E.P.A.R s  Editing

Raloxifene Teva

What is Raloxifene Teva?

Raloxifene Teva is a medicine that contains the active substance raloxifene hydrochloride. It is available as tablets (60 mg).Raloxifene Teva is a 'generic medicine'. This means that Raloxifene Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called Evista. For more information on generic medicines, see the question-and-answer document here.

What is Raloxifene Teva used for?

Raloxifene Teva is used for the treatment and prevention of osteoporosis (a disease that makes bones fragile) in women who have been through the menopause. Raloxifene Teva has been shown to significantly reduce vertebral fractures (breaks in the spine), but not hip fractures. The medicine can only be obtained with a prescription.

How is Raloxifene Teva used?

The recommended dose of Raloxifene Teva is one tablet taken once a day. Patients may also receive calcium and vitamin D supplements if they do not get enough from their diet. Raloxifene Teva is intended for long-term use.

How does Raloxifene Teva work?

Osteoporosis happens when not enough new bone grows to replace the bone that is naturally broken down. Gradually, the bones become thin and fragile, and more likely to break (fracture). Osteoporosis is more common in women after the menopause, when the levels of the female hormone oestrogen fall: oestrogen slows down bone breakdown and makes the bones less likely to fracture.The active substance in Raloxifene Teva, raloxifene, is a selective oestrogen receptor modulator (SERM). Raloxifene acts as an 'agonist' of the oestrogen receptor (a substance that stimulates the receptor for oestrogen) in some tissues in the body. Raloxifene has the same effect as oestrogen in the bone, but it does not have an effect in the breast or the womb.

How has Raloxifene Teva been studied?

Because Raloxifene Teva is a generic medicine, studies in people have been limited to tests to determine that it is bioequivalent to the reference medicine, Evista. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefit and risk of Raloxifene Teva?

Because Raloxifene Teva is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why has Raloxifene Teva been approved?

The CHMP concluded that, in accordance with EU requirements, Raloxifene Teva has been shown to have comparable quality and to be bioequivalent to Evista. Therefore, the CHMP's view was that, as for Evista, the benefit outweighs the identified risk. The Committee recommended that Raloxifene Teva be given marketing authorisation.

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Ranexa

What is Ranexa and what is it used for?

Ranexa is a medicine used to treat the symptoms of stable angina pectoris (chest pain caused by reduced blood flow to the heart). It is used as an add-on to existing treatment in patients whose disease is not adequately controlled by other medicines, such as beta blockers or calcium antagonists, or in patients who cannot take these medicines.Ranexa contains the active substance ranolazine.

How is Ranexa used?

Ranexa can only be obtained with a prescription and is available as prolonged-release tablets (375 mg, 500 mg and 750 mg). 'Prolonged release' means that ranolazine is released slowly from the tablet over a few hours.The recommended starting dose of Ranexa is 375 mg twice a day. After two to four weeks, the dose should be increased to 500 mg twice a day, and then to 750 mg twice a day, depending on the patient's response. The maximum dose is 750 mg twice a day. Doses may need to be lower in patients who have certain side effects. Dose increases should be carried out carefully in the elderly, in patients who weigh less than 60 kg, and in patients who have problems with their kidneys, liver or heart.For more information about using Ranexa, see the package leaflet or contact your doctor or pharmacist.

How does Ranexa work?

The active substance in Ranexa, ranolazine, is thought to work by reducing the flow of calcium ions into the heart muscle cells. Calcium ions normally cause the heart muscle to contract. By reducing the flow of calcium into the cells, ranolazine is thought to help the heart to relax, improving blood flow to the heart muscle and relieving the symptoms of angina pectoris.

What benefits of Ranexa have been shown in studies?

Ranexa has been investigated in one main study involving 823 patients with an average age of 64 years who had had angina pectoris for at least three months. In the study, two doses of Ranexa (750 and 1,000 mg twice a day) were compared with placebo (a dummy treatment) as an add-on to commonly used medicines for angina pectoris (atenolol, amlodipine or diltiazem). Ranexa was shown to be more effective than placebo at increasing the length of time the patients could exercise. At the start of the study, the patients could exercise for about 7 minutes. After 12 weeks, this increased by an average of 1 minute 56 seconds in the patients adding either dose of Ranexa, and by an average of 1 minute 32 seconds in those adding placebo.

What are the risks associated with Ranexa?

The most common side effects with Ranexa (which may affect up to 1 in 10 people) are dizziness, headache, constipation, vomiting, nausea (feeling sick) and weakness. For the full list of side effects of Ranexa, see the package leaflet.Ranexa must not be used in patients who have severe problems with their kidneys or moderate or severe problems with their liver. It must also not be used in patients who are taking other medicines that are broken down in the same way as ranolazine, or certain other medicines that are used to correct the heart rhythm. For the full list of restrictions, see the package leaflet.

Why is Ranexa authorised in the EU?

The European Medicines Agency noted that the effectiveness of Ranexa in improving the symptoms of patients with stable angina pectoris is modest but that it could be of value in patients who have not responded fully to other medicines. The Agency therefore decided that Ranexa's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Ranexa?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ranexa have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ranexa are continuously monitored. Side effects reported with Ranexa are carefully evaluated and any necessary action taken to protect patients.

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Ranivisio

What is Ranivisio and what is it used for?

Ranivisio is a medicine used to treat adults with certain sight problems caused by damage to the retina (the light-sensing layer at the back of the eye), and more specifically its central region, known as the macula. The macula provides the vision needed to see detail for everyday tasks such as driving, reading and recognising faces. Ranivisio is used to treat:• 'wet' form of age-related macular degeneration (AMD). The wet form of AMD is caused by choroidal neovascularisation (abnormal growth of blood vessels beneath the retina, which may leak fluid and blood and cause swelling);• macular oedema (swelling of the macula) caused by diabetes or by occlusion (blockage) of the veins behind the retina;• proliferative diabetic retinopathy (growth of abnormal tiny blood vessels in the eye, associated with diabetes);• other sight problems associated with choroidal neovascularisation.Ranivisio is a 'biosimilar medicine'. This means that Ranivisio is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Ranivisio is Lucentis. For more information on biosimilar medicines, see here.Ranivisio contains the active substance ranibizumab.

How is Ranivisio used?

Ranivisio is a solution for injection of 0.5 mg into the vitreous humour, the jelly-like fluid in the eye. It can only be obtained with a prescription and must be given by a qualified eye doctor who is experienced in giving injections into the eye.Treatment is started with one injection every month, with regular checks of the patient's vision and examination of the back of the eye, until maximum vision is achieved and/or there are no signs of disease activity. The interval between two injections of Ranivisio into the same eye must be at least four weeks. Treatment with Ranivisio should be stopped if the patient is not benefitting from it.For more information about using Ranivisio, see the package leaflet or contact your doctor or pharmacist.

How does Ranivisio work?

The active substance in Ranivisio, ranibizumab, is a small piece of a monoclonal antibody. A monoclonal antibody is a type of protein that has been designed to recognise and attach to a specific target (called an antigen) that is found in certain cells in the body.Ranibizumab has been designed to attach to and block a substance called vascular endothelial growth factor A (VEGF-A). VEGF-A is a protein that makes blood vessels grow and leak fluid and blood, damaging the macula. By blocking VEGF-A, ranibizumab reduces the growth of the blood vessels and controls the leakage and swelling.

What benefits of Ranivisio have been shown in studies?

Laboratory studies comparing Ranivisio with Lucentis have shown that the active substance in Ranivisio is highly similar to that in Lucentis in terms of structure, purity and biological activity. Studies have also shown that giving Ranivisio produces similar levels of the active substance in the body to giving Lucentis.In addition, a study involving 477 patients with age-related macular degeneration found that Ranivisio produced comparable improvements in the condition to those seen with Lucentis. In this study, the average number of letters patients could recognise on a standard eye test improved by 5 in patients treated with Ranivisio and by 6 in patients given Lucentis after 8 weeks of treatment.Because Ranivisio is a biosimilar medicine, the studies on effectiveness and safety of ranibizumab carried out with Lucentis do not all need to be repeated for Ranivisio.

What are the risks associated with Ranivisio?

The safety of Ranivisio has been evaluated, and on the basis of all the studies carried out the side effects of the medicine are considered to be comparable to those of the reference medicine Lucentis.The most common side effects with ranibizumab (which may affect more than 1 in 10 people) are increased intraocular pressure (pressure within the eye), headache, vitritis (inflammation in the eye), vitreous detachment (separation of the vitreous from the back of the eye), retinal haemorrhage (bleeding at the back of the eye), visual disturbance, eye pain, vitreous floaters (spots in the vision), conjunctival haemorrhage (bleeding at the front of the eye), eye irritation, sensation of a foreign body in the eye, increased lacrimation (watery eyes), blepharitis (inflammation of the eyelids), dry eye, ocular hyperaemia (increased blood supply to the eye, leading to redness of the eye), eye pruritis (itching), arthralgia (joint pain) and nasopharyngitis (inflammation of the nose and throat). Rarely, endophthalmitis (an infection inside the eye), blindness, serious damage to the retina and cataract (clouding of the lens) can occur.Ranivisio must not be used in patients who may have an infection of the eye or of the area around the eye, or who have severe inflammation within the eye. For the full list of side effects and restrictions of Ranivisio, see the package leaflet.

Why is Ranivisio authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Ranivisio has a highly similar structure, purity and biological activity to Lucentis and is distributed in the body in the same way. In addition, studies in patients with age-related macular degeneration have shown that the safety and effectiveness of Ranivisio is equivalent to that of Lucentis in this indication.All these data were considered sufficient to conclude that Ranivisio will behave in the same way as Lucentis in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Lucentis, the benefits of Ranivisio outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Ranivisio?

The company that markets Ranivisio will provide information packs to patients to help them prepare for treatment, recognise serious side effects and know when to seek urgent attention from their doctor.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ranivisio have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ranivisio are continuously monitored. Suspected side effects reported with Ranivisio are carefully evaluated and any necessary action taken to protect patients.

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Rapamune

What is Rapamune and what is it used for?

Rapamune is a medicine used to prevent the body from rejecting a newly transplanted kidney. It is used in adults who are at a low to moderate risk of rejection. It is recommended that Rapamune is used with ciclosporin and corticosteroids (other medicines to prevent organ rejection) for two to three months. Rapamune can then be used for continuing treatment with corticosteroids, but only if ciclosporin treatment can be stopped.Rapamune is also used for treating patients with sporadic lymphangioleiomyomatosis (S-LAM) with moderate lung disease or worsening lung function. S-LAM is a rare lung disease that causes worsening symptoms such as shortage of breath and occurs mainly in women who are at an age when they can have children.Rapamune contains the active substance sirolimus.

How is Rapamune used?

Rapamune treatment should be started by and remain under the guidance of a doctor who is a qualified specialist in transplantation. The medicine can only be obtained with a prescription.Rapamune is available as an oral solution (1 mg/ml) and tablets (0.5, 1 and 2 mg).To prevent organ rejection, the first dose is usually 6 mg given soon after the transplantation followed by 2 mg once a day. The doctor will adjust the dose to achieve appropriate levels of sirolimus in the patient's blood.To treat patients with S-LAM, the dose of Rapamune is 2 mg daily and after 10 to 20 days the doctor will adjust the dose to achieve appropriate levels of sirolimus in the patient's blood.For more information about using Rapamune, see the package leaflet or contact your doctor or pharmacist.

How does Rapamune work?

The active substance in Rapamune, sirolimus, is an immunosuppressant (a medicine that reduces the activity of the immune system). In the body, sirolimus attaches to a protein inside cells to make a 'complex'. This complex then blocks another protein called 'mammalian target of rapamycin' (mTOR). Since mTOR is involved in the multiplication of activated T-lymphocytes (white blood cells that are responsible for attacking the transplanted organ), Rapamune reduces the number of these cells, reducing the risk of organ rejection.In S-LAM, mTOR is overactive, causing excessive multiplication of cells that cause the disease. By blocking mTOR, Rapamune reduces the multiplication of these cells.

What benefits of Rapamune have been shown in studies?

Prevention of rejectionRapamune was more effective than placebo (a dummy treatment) or azathioprine (another immunosuppressive medicine) in two main studies involving a total of 1,295 patients who were having a kidney transplant. All patients were also treated with ciclosporin and corticosteroids and were at low to moderate risk of rejection. The main measure of effectiveness was the number of treatment failures (rejection or loss of the new kidney, or death) after 6 months. In the first study, treatment failed in19% (53 out of 284) of the patients adding Rapamune after 6 months, compared with 32% (52 out of 161) of those adding azathioprine. In the second study, treatment failed in 30% (68 out of 277) of the patients adding Rapamune, compared with 48% (62 out of 130) of those adding placebo.Two additional studies looked at Rapamune as continuing treatment for up to 5 years in 765 patients who were able to stop ciclosporin after 2 to 3 months. Rapamune was effective in helping the new kidney to survive, with an improvement in how well it worked and an improvement in blood pressure when ciclosporin treatment was stopped.Treatment of S-LAMRapamune was more effective than placebo in improving lung function in a study involving 81 patients with S-LAM. The main measure of effectiveness was a change of FEV1 (the maximum volume of air a person can breathe out in 1 second). FEV1 improved by an average of 1 ml per month in patients treated with Rapamune compared with a worsening by 12 ml per month in patients receiving placebo.

What are the risks associated with Rapamune?

The most common side effects with Rapamune (which may affect more than 1 in 10 people) are infections, fever, slow wound healing, low counts of various blood cells, blood tests showing altered levels of various substances (including low potassium and phosphate; raised fats, cholesterol, glucose and markers for tissue breakdown and for liver and kidney function), diabetes, lymphocele (collection of lymph fluid usually in the lower belly), pain in various parts of the body, rapid heartbeat, raised blood pressure, problems affecting the gut, proteinuria (protein in the urine), menstrual disorders, oedema (swelling because of fluid build-up), rash and acne.Patients allergic to peanut or soya must not take Rapamune oral solution because the solution contains soya oil.For the full list of side effects and restrictions of Rapamune, see the package leaflet.Rapamune Rapamune (sirolimus)

Why is Rapamune authorised in the EU?

The European Medicines Agency considered that Rapamune is effective for the prevention of rejection of a transplanted kidney in patients at low to moderate risk of rejection. The Agency noted that no medicinal product has been approved for the treatment of S-LAM and Rapamune's effect on lung function is considered important. The Agency decided that Rapamune's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rapamune?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rapamune have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rapamune are continuously monitored. Side effects reported with Rapamune are carefully evaluated and any necessary action taken to protect patients.

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Rapilysin

What is Rapilysin?

Rapilysin is a powder and solvent that are made up into a solution for injection. It contains the active substance reteplase.

What is Rapilysin used for?

Rapilysin is used within 12 hours of a suspected heart attack to help dissolve the blood clots obstructing the flow of blood to the heart muscle.The medicine can only be obtained with a prescription.

How is Rapilysin used?

Rapilysin should be prescribed by doctors who have experience in using medicines that dissolve blood clots and who can monitor its use.Treatment with Rapilysin should be started as soon as possible after the start of heart attack symptoms. Rapilysin is given as two injections, 30 minutes apart. Each injection is given into a vein slowly, but in less than two minutes. Other medicines that prevent clotting (aspirin and heparin) should be given before and after the Rapilysin injection to stop clots from forming again. However, Rapilysin and heparin or aspirin must not be given in the same syringe.

How does Rapilysin work?

The active substance in Rapilysin, reteplase, is a copy of a natural enzyme called t-PA that has been modified so that it starts working faster and for longer. Reteplase activates the production of an enzyme called plasmin, which breaks up blood clots. Following a heart attack, Rapilysin can help dissolve blood clots that have formed in the arteries supplying the heart muscle, thereby restoring normal blood flow to the heart.

How has Rapilysin been studied?

Rapilysin has been studied in more than 21,000 patients in four studies. Rapilysin has been compared with other medicines used to dissolve blood clots: streptokinase in 6,000 patients and alteplase in about 15,000 patients. The studies looked at the number of patients who had died 30 to 35 days after treatment, and at the number of patients who had heart failure (an inability of the heart to pump enough blood around the body) or a stroke.

What benefit has Rapilysin shown during the studies?

Rapilysin was more effective than streptokinase in reducing the number of patients with heart failure, and it was as effective as streptokinase in preventing death. Rapilysin was also as effective as alteplase in preventing death and stroke.

What is the risk associated with Rapilysin?

The most common side effects with Rapilysin (seen in more than 1 patient in 10) are bleeding at the injection site, recurrent ischaemia (reduced blood supply to parts of the body) or angina (severe chest pain), hypotension (low blood pressure), heart failure or pulmonary oedema (build-up of fluid on the lungs), and reactions at the site of the injection, such as burning sensations. For the full list of all side effects reported with Rapilysin, see the package leaflet.Rapilysin must also not be used in patients who are at risk of bleeding because of other diseases, treatment with other medicines, high blood pressure, previous bleeding or recent surgery. For the full list of restrictions, see the package leaflet.

Why has Rapilysin been approved?

The CHMP decided that Rapilysin's benefits are greater than its risks for and recommended that it be given marketing authorisation.

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Rapiscan

What is Rapiscan?

Rapiscan is a solution for injection that contains the active substance regadenoson.

What is Rapiscan used for?

Rapiscan is for diagnostic use only. It is used in a type of heart scan called 'radionuclide myocardial perfusion imaging' to see the blood flow in the heart muscle.Before this type of scan, the patient's heart is usually put under stress by exercise such as walking or running on a treadmill to help dilate (widen) the blood vessels in the heart and increase the blood flow to the heart muscle. Rapiscan is used as a 'stress agent' that has a similar effect on the heart as exercise. It is used in adult patients (aged 18 years or over) who are unable to exercise enough for a stress test.The medicine can only be obtained with a prescription.

How is Rapiscan used?

Rapiscan must only be used in a hospital that has equipment for resuscitation and monitoring the patient.It is given as a 10-second injection of 400 micrograms into a vein immediately followed by an injection of sodium chloride (salt) solution. The patient then undergoes the procedures for radionuclide myocardial perfusion imaging, starting with an injection of a radioactive substance 10 to 20 secondsafter the sodium chloride injection. Because Rapiscan causes a rapid increase in heart rate and a fall in blood pressure, patients should remain sitting or lying down and be monitored frequently until the effects of the medicine have worn off.Rapiscan should only be used once within any 24-hour period. Patients must not take any medicines or products that contain methylxanthines (such as caffeine or theophylline) for at least 12 hours before receiving Rapiscan. They should also stop receiving dipyridamole (a medicine used to prevent blood clots) for at least two days before receiving Rapiscan. For further information on the use of Rapiscan, see the summary of product characteristics (also part of the EPAR).

How does Rapiscan work?

The active substance in Rapiscan, regadenoson, is an A2A adenosine receptor agonist. It works by attaching to A2A adenosine receptors in the walls of the blood vessels in the heart, causing the blood vessels to widen and increasing blood flow into the heart muscle. This enables the blood flow in the heart to be seen more easily during myocardial perfusion imaging.

How has Rapiscan been studied?

In two main studies, around 2,000 adult patients first had a myocardial perfusion imaging scan performed using adenosine (another medicine used as a stress agent) followed by a second scan with either adenosine or Rapiscan. The main measure of effectiveness was based on the similarity between the results of the scans with Rapiscan and adenosine.

What benefit has Rapiscan shown during the studies?

The results of scans using Rapiscan and adenosine were comparable. The 'agreement rates' between the first and second scans were similar regardless of which of the two medicines were used for the second scan.

What is the risk associated with Rapiscan?

The most common side effects with Rapiscan (seen in more than 1 patient in 10) are headache, dizziness, ST segment changes (an abnormal reading on the electrocardiogram or ECG), flushing (reddening of the skin), dyspnoea (difficulty breathing), gastrointestinal (stomach and gut) discomfort and chest pain. For the full list of all side effects reported with Rapiscan, see the package leaflet.Rapiscan must not be used in patients with slow heart rate unless they have a pacemaker, unstable angina (a type of chest pain that changes in severity) that has not been controlled with treatment, severe hypotension (low blood pressure) or decompensated heart failure (when the heart does not work as well as it should). For the full list of restrictions, see the package leaflet.

Why has Rapiscan been approved?

The CHMP decided that Rapiscan's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Rapiscan?

A risk management plan has been developed to ensure that Rapiscan is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rapiscan, including the appropriate precautions to be followed by healthcare professionals and patients.

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Rasagiline Mylan

What is Rasagiline Mylan and what is it used for?

Rasagiline Mylan is a medicine used to treat adults with Parkinson's disease (a progressive brain disorder that causes shaking, slow movement and muscle stiffness).Rasagiline Mylan can be used either alone, or as an add-on to levodopa (another medicine used in Parkinson's disease) in patients who are having fluctuations in the control of their condition. Fluctuations happen when the effects of the medication wear off and symptoms re-emerge before the next dose is due. They are linked to a reduction in the effect of levodopa, when the patient experiences sudden switches between being 'on' and able to move, and being 'off' and having difficulty moving about.Rasagiline Mylan is a 'generic medicine'. This means that Rasagiline Mylan is similar to a 'reference medicine' already authorised in the European Union (EU) called Azilect. For more information on generic medicines, see the question-and-answer document here.Rasagiline Mylan contains the active substance rasagiline.

How is Rasagiline Mylan used?

Rasagiline Mylan is available as tablets (1 mg). The standard dose is one tablet once a day.The medicine can only be obtained with a prescription.

How does Rasagiline Mylan work?

The active substance in Rasagiline Mylan, rasagiline, is a 'monoamine oxidase B inhibitor'. It blocks the enzyme monoamine oxidase type B, which breaks down a substance called dopamine in the brain. Dopamine is important for controlling movement and coordination. In patients with Parkinson's disease, the cells that produce dopamine begin to die and the amount of dopamine in the brain decreases. The patients then lose their ability to control their movements reliably. By increasing levels of dopamine in the parts of the brain that control movement and coordination, Rasagiline Mylan reduces the symptoms of Parkinson's disease, such as stiffness and slowness of movement.

How has Rasagiline Mylan been studied?

Because Rasagiline Mylan is a generic medicine, studies in people have been limited to tests to determine that it is bioequivalent to the reference medicine, Azilect. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Rasagiline Mylan?

Because Rasagiline Mylan is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Rasagiline Mylan approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements, Rasagiline Mylan has been shown to have comparable quality and to be bioequivalent to Azilect. Therefore, the CHMP's view was that, as for Azilect, the benefit outweighs the identified risk. The Committee recommended that Rasagiline Mylan be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Rasagiline Mylan?

A risk management plan has been developed to ensure that Rasagiline Mylan is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rasagiline Mylan, including the appropriate precautions to be followed by healthcare professionals and patients.

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Rasagiline Ratiopharm

What is Rasagiline ratiopharm and what is it used for?

Rasagiline ratiopharm is a medicine used to treat adults with Parkinson's disease (a progressive brain disorder that causes shaking, slow movement and muscle stiffness).Rasagiline ratiopharm can be used either alone, or as an add-on to levodopa (another medicine used in Parkinson's disease) in patients who are having 'fluctuations' towards the end of the period between levodopa doses. Fluctuations happen when the effects of the medication wear off and symptoms reemerge. They are linked to a reduction in the effect of levodopa, when the patient experiences sudden switches between being 'on' and able to move, and being 'off' and having difficulty moving about.This medicine is the same as Azilect, which is already authorised in the European Union (EU). The company that makes Azilect has agreed that its scientific data can be used for Rasagiline ratiopharm ('informed consent').Rasagiline ratiopharm contains the active substance rasagiline.

How is Rasagiline ratiopharm used?

Rasagiline ratiopharm is available as tablets (1 mg). The standard dose is one tablet once a day.The medicine can only be obtained with a prescription.

How does Rasagiline ratiopharm work?

The active substance in Rasagiline ratiopharm, rasagiline, is a 'monoamine oxidase B inhibitor'. It blocks the enzyme monoamine oxidase type B, which breaks down the neurotransmitter dopamine in the brain. Neurotransmitters are chemicals that allow nerve cells to communicate with one another. In patients with Parkinson's disease, the cells that produce dopamine die and the amount of dopamine in the brain decreases. The patients then lose their ability to control their movements reliably. By increasing levels of dopamine in the parts of the brain that control movement and coordination, Rasagiline ratiopharm improves the signs and symptoms of Parkinson's disease, such as stiffness and slowness of movement.

What benefits of Rasagiline ratiopharm have been shown in studies?

Rasagiline ratiopharm has been shown in three studies, involving 1,563 patients, to be effective in both relieving the symptoms of Parkinson's disease and in reducing the time patients spend in their 'off' periods. In one of the studies, a 26-week treatment with Rasagiline ratiopharm resulted in an average fall of 0.13 points in UPDRS (a standard scale for assessing symptoms of Parkinson's disease) from a starting value of 24.69 compared with a rise of 4.07 points in the patients taking placebo from astarting value of 24.54. A fall in the UPDRS score indicates an improvement in symptoms, while a rise indicates a worsening of symptoms.In the two other studies, Rasagiline ratiopharm was given as 'add-on' to patients with later stage disease who were already being treated with levodopa, and compared with placebo and another medicine entacapone (also used as add-ons). The studies included 1,159 patients and lasted 26 and 18 weeks, respectively. In both studies, patients taking Rasagiline ratiopharm spent an average of around one hour less in the 'off' state than those taking placebo. Similar reductions in time spent in the 'off' state were seen in patients taking entacapone.

What are the risks associated with Rasagiline ratiopharm?

The most common side effect with Rasagiline ratiopharm (seen in more than 1 patient in 10) is headache. For the full list of all side effects reported with Rasagiline ratiopharm, see the package leaflet.Rasagiline ratiopharm must not be used with other monoamine oxidase inhibitors including medicines and herbal preparations without prescription such as St John's wort (used to treat depression). It must also not be used with pethidine (a painkiller). There should be at least 14 days between stopping treatment with Rasagiline ratiopharm and starting treatment with another monoamine-oxidase inhibitor or with pethidine. Rasagiline ratiopharm must not be used in patients who have severe problems with their liver. It is not recommended for patients with moderate liver problems. Patients with mild liver problems should use Rasagiline ratiopharm with caution and should stop treatment if their liver problems get worse.For the full list of all side effects and restrictions with Rasagiline ratiopharm, see the package leaflet.

Why is Rasagiline ratiopharm approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Rasagiline ratiopharm's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Rasagiline ratiopharm?

A risk management plan has been developed to ensure that Rasagiline ratiopharm is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rasagiline ratiopharm, including the appropriate precautions to be followed by healthcare professionals and patients.Further information can be found in the summary of the risk management plan.

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Rasilez

What is Rasilez?

Rasilez is a medicine that contains the active substance aliskiren. It is available as tablets (150 and 300 mg).

What is Rasilez used for?

Rasilez is used to treat essential hypertension (high blood pressure) in adults. 'Essential' means that the hypertension has no obvious cause.The medicine can only be obtained with a prescription.

How is Rasilez used?

The recommended dose of Rasilez is 150 mg once a day. Rasilez may be taken alone or in combination with other medicines for hypertension, with the exception of 'angiotensin converting enzyme (ACE) inhibitors' or 'angiotensin receptor blockers' (ARBs) in patients with diabetes, or moderate or severe kidney impairment. Rasilez should not be taken together with fruit juice or drinks containing plant extracts such as herbal teas. The dose of Rasilez may be increased to 300 mg once a day in patients whose blood pressure is not adequately controlled.

How does Rasilez work?

The active substance in Rasilez, aliskiren, is a renin inhibitor. It blocks the activity of a human enzyme called renin, which is involved in the production of a substance called angiotensin I in the body.Angiotensin I is converted into the hormone angiotensin II, which is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the production of angiotensin I, levels of both angiotensin I and angiotensin II fall. This causes vasodilation (widening of the blood vessels), so that the blood pressure drops. This may reduce the risks associated with high blood pressure, such as having a stroke.

How has Rasilez been studied?

Rasilez has been studied in 14 main studies involving over 10,000 patients with essential hypertension. Thirteen of the studies included patients with mild to moderate hypertension, and one included patients with severe hypertension. In five of the studies, the effects of Rasilez taken alone were compared with those of placebo (a dummy treatment). Rasilez, taken alone or in combination with other medicines, was also compared with other medicines for hypertension. Combination studies looked at Rasilez used with an ACE inhibitor (ramipril), an ARB (valsartan), a beta-blocker (atenolol), a calcium-channel blocker (amlodipine) and a diuretic (hydrochlorothiazide). The studies lasted between six and 52 weeks and the main measure of effectiveness was the change in blood pressure during either the resting phase of the heartbeat ('diastolic') or when the chambers of the heart were contracting ('systolic'). The blood pressure was measured in 'millimetres of mercury' (mmHg).

What benefit has Rasilez shown during the studies?

Rasilez on its own was more effective than placebo and as effective as comparator treatments in reducing blood pressure. When the results of the five studies comparing Rasilez taken alone with placebo were looked at together, patients aged under 65 years had an average fall in diastolic blood pressure of 9.0 mmHg after eight weeks of taking 150 mg Rasilez, from an average of 99.4 mmHg at the start of the study. This was compared with a fall of 5.8 mmHg from 99.3 mmHg in the patients taking placebo.Larger falls were seen in patients aged 65 years or over and those taking higher doses of Rasilez. Rasilez also reduced blood pressure in patients with diabetes and patients who were overweight. The medicine's effects were maintained for up to a year in two of the studies.The studies with Rasilez taken in combination with other medicines showed additional decreases in blood pressure compared with the decreases produced by these medicines alone.

What is the risk associated with Rasilez?

The most common side effects with Rasilez (seen in between 1 and 10 patients in 100) are dizziness, diarrhoea, arthralgia (joint pain) and hyperkalaemia (high blood potassium levels). For the full list of all side effects reported with Rasilez, see the package leaflet.Rasilez must not be used in patients who have had angioedema (swelling under the skin) with aliskiren, hereditary angioedema or angioedema of no obvious cause, or in women who are more than three months pregnant. Its use during the first three months of pregnancy and in women planning to become pregnant is not recommended. Rasilez must also not be taken with ciclosporin, itraconazole or other medicines known as 'potent P-glycoprotein inhibitors' (such as quinidine). Rasilez in combination with an ACE inhibitor or an ARB must not be used in patients with diabetes, or moderate or severe kidney impairment. Rasilez is for use in adults only; it must not be used in children aged less than 2 years and is not recommended for older children. For the full list of restrictions, see the package leaflet.

Why has Rasilez been approved?

The CHMP noted that Rasilez is effective in reducing blood pressure when used alone or in combination. The CHMP therefore decided that the benefits of Rasilez are greater than its risks and recommended that it be given marketing authorisation. However, in February 2012, following the review of a study called ALTITUDE, the CHMP recommended that Rasilez should not be used together with an ACE inhibitor or ARB in patients with diabetes or with moderate or severe kidney impairment because of an increase in the risk of cardiovascular and kidney problems.

What measures are being taken to ensure the safe and effective use of Rasilez?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rasilez have also been included in the summary of product characteristics and the package leaflet.

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Ratiograstim

What is Ratiograstim?

Ratiograstim is a solution for injection or for infusion (drip into a vein). It contains the active substance filgrastim.Ratiograstim is a 'biosimilar' medicine. This means that Ratiograstim is similar to a biological medicine that is already authorised in the European Union (EU) and contains the same active substance (also known as the 'reference medicine'). The reference medicine for Ratiograstim is Neupogen. For more information on biosimilar medicines, see the question-and-answer document here.

What is Ratiograstim used for?

Ratiograstim is used to stimulate the production of white blood cells in the following situations:• to reduce the duration of neutropenia (low levels of neutrophils, a type of white blood cell) and the occurrence of febrile neutropenia (neutropenia with fever) in patients receiving chemotherapy (cancer treatment) that is cytotoxic (cell-killing);• to reduce the duration of neutropenia in patients undergoing treatment to destroy the bone marrow cells before a bone marrow transplant (such as in some patients with leukaemia) if they are at a risk of long-term, severe neutropenia;• to increase levels of neutrophils and reduce the risk of infections in patients with neutropenia who have a history of severe, repeated infections;•Ratiograstim can also be used in patients who are about to donate blood stem cells for transplant, to help release these cells from the bone marrow.The medicine can only be obtained with a prescription.

How is Ratiograstim used?

Ratiograstim is given by injection under the skin or infusion into a vein. How it is given, the dose and the duration of treatment depend on why it is being used, the patient's body weight and the response to treatment. Ratiograstim is usually given in a specialised treatment centre, although patients who receive it by injection under the skin may inject themselves once they have been trained appropriately.For more information, see the package leaflet.

How does Ratiograstim work?

The active substance in Ratiograstim, filgrastim, is very similar to a human protein called granulocyte colony stimulating factor (G CSF). Filgrastim is produced by a method known as 'recombinant DNA technology': it is made by bacteria into which a gene (DNA) has been introduced, which makes them able to produce filgrastim. The replacement acts in same way as naturally produced G CSF by encouraging the bone marrow to produce more white blood cells.

How has Ratiograstim been studied?

Ratiograstim was studied to show that it is comparable to the reference medicine, Neupogen.Ratiograstim was compared with Neupogen and with placebo (a dummy treatment) in one main study involving 348 patients with breast cancer. The study looked at the duration of severe neutropenia during the patients' first cycle of cytotoxic chemotherapy.To study the safety of Ratiograstim, two further studies were carried out in patients with lung cancer and with non-Hodgkin's lymphoma.

What benefit has Ratiograstim shown during the studies?

Treatment with Ratiograstim and Neupogen brought about similar reductions in duration of severe neutropenia. During the first 21-day chemotherapy cycle, patients treated with either Ratiograstim or Neupogen had severe neutropenia for an average of 1.1 days, compared with 3.8 days in those receiving placebo. Therefore, the effectiveness of Ratiograstim was shown to be equivalent to that of Neupogen.

What is the risk associated with Ratiograstim?

The most common side effect with Ratiograstim (seen in more than 1 patient in 10) is musculoskeletal pain (pain in the muscles and bones). Other side effects may be seen in more than 1 patient in 10, depending on the condition that Ratiograstim is being used for. For the full list of all side effects and restrictions, see the package leaflet.

Why has Ratiograstim been approved?

The CHMP decided that, in accordance with EU requirements, Ratiograstim has been shown to have a comparable quality, safety and efficacy profile to Neupogen. Therefore, the CHMP's view was that, asfor Neupogen, the benefit outweighs the identified risk. The Committee recommended that Ratiograstim be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Ratiograstim?

A risk management plan has been developed to ensure that Ratiograstim is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ratiograstim, including the appropriate precautions to be followed by healthcare professionals and patients.

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Ravicti

What is Ravicti and what is it used for?

Ravicti is a medicine used to manage urea cycle disorders in adults and children, when the diseases cannot be managed by changes in diet alone. Patients with urea cycle disorders are not able to get rid of waste nitrogen from the body because they lack some liver enzymes. In the body, waste nitrogen is turned into ammonia, which is harmful when it accumulates. Ravicti is used in patients who lack one or more of the following enzymes: carbamoyl phosphate synthase-I, ornithine carbamoyltransferase, argininosuccinate synthetase, argininosuccinate lyase, arginase I and ornithine translocase.Ravicti contains the active substance glycerol phenylbutyrate.Urea cycle disorders are rare, and Ravicti was designated an 'orphan medicine' (a medicine used in rare diseases) for several forms of the disease on 10 June 2010. Further information on the orphan designations can be found on the European Medicines Agency's website ema.europa.eu/en/medicines/ /ema_group_types/ema_orphan.

How is Ravicti used?

Ravicti is available as a liquid (1.1 g/ml) to be taken by mouth, or given through a tube that goes from the nose to the stomach or through the belly into the stomach. It can only be obtained with a prescription and should be prescribed by a doctor who has experience in treating patients with urea cycle disorders.Since proteins are a source of nitrogen, Ravicti must be used together with a special low-protein diet, and sometimes with dietary supplements (depending on the daily protein intake needed for growth and development).The dose of Ravicti depends on the patient's diet, height and weight. Regular blood tests are needed to adjust the dose. The total daily dose of Ravicti should be divided into equal amounts and given with each meal. Ravicti may be a life-long treatment unless the patient has a successful liver transplant.For more information about using Ravicti, see the package leaflet or contact your doctor or pharmacist.

How does Ravicti work?

The active substance in Ravicti, glycerol phenylbutyrate, is converted to phenylacetate in the body. Phenylacetate attaches to the amino acid glutamine found in proteins to form a substance that the kidneys can remove from the body. This removal of proteins decreases the levels of nitrogen in the body, reducing the amount of ammonia produced.

What benefits of Ravicti have been shown in studies?

Ravicti has been compared with sodium phenylbutyrate (another medicine used to treat urea cycle disorders) in a study involving 88 adults with urea cycle disorders. The main measure of effectiveness was the change in the blood level of ammonia after 4 weeks of treatment. The study showed that Ravicti was at least as effective as the comparator in controlling the blood level of ammonia: the estimated average ammonia level was about 870 micromoles per litre in patients treated with Ravicti, compared with about 980 micromoles per litre in patients treated with sodium phenylbutyrate. Data from additional studies showed a similar effect in children treated with Ravicti from birth.

What are the risks associated with Ravicti?

The most common side effects with Ravicti (which may affect more than 1 in 20 people) are diarrhoea, flatulence (passing gas), headache, decreased appetite, vomiting, tiredness, feeling sick and abnormal skin smell.Ravicti must not be used to treat acute hyperammonaemia (sudden rise of blood ammonia levels). For the full list of side effects and restrictions with Ravicti, see the package leaflet.

Why is Ravicti authorised in the EU?

The European Medicines Agency decided that the benefits of Ravicti are greater than its risks and it can be authorised for use in the EU.Ravicti is effective in reducing the blood level of ammonia in patients with urea cycle disorders. Ravicti is a sustained-release medicine, meaning the active substance is released throughout the day. Therefore, this results in a better control of blood ammonia levels over the whole day. For this same reason Ravicti must not be used to treat acute hyperammonaemia as more rapidly acting treatments are needed in these cases.Additionally, the Agency considered that since Ravicti is available as a liquid this could make the medicine more palatable especially for children, compared with other medicines available as granules to be added to food; the liquid formulation also facilitates giving it through a tube to patients unable to swallow.The side effects of Ravicti affect mainly the gut and are considered manageable. However, further data on the long-term safety of Ravicti are awaited.

What measures are being taken to ensure the safe and effective use of Ravicti?

The company that markets Ravicti will set up a registry of patients to obtain further information on the long-term benefits and safety of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ravicti have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ravicti are continuously monitored. Side effects reported with Ravicti are carefully evaluated and any necessary action taken to protect patients.

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Raxone

What is Raxone and what is it used for?

Raxone is a medicine used to treat visual impairment in adults and adolescents aged 12 years and over with Leber's hereditary optic neuropathy (LHON), an inherited disease characterised by progressive loss of sight. Raxone contains the active substance idebenone.Because the number of patients with Leber's hereditary optic neuropathy is low, the disease is considered 'rare', and Raxone was designated an 'orphan medicine' (a medicine used in rare diseases) on 15 February 2007.Raxone is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Raxone contains idebenone at a different strength. The reference medicine for Raxone is Mnesis (45 mg tablets).

How is Raxone used?

Raxone can only be obtained with a prescription and treatment should be started and supervised by a doctor with experience in LHON. Raxone is available as 150 mg tablets, and the recommended dose is two tablets taken three times a day with food.

How does Raxone work?

The active substance in Raxone, idebenone, is an anti-oxidant agent that acts on mitochondria (the structures inside cells that produce the energy necessary for cells to function). Patients affected by LHON have mutations (defects) in the genetic material of mitochondria. This means that mitochondria do not work properly to generate energy, and produce toxic forms of oxygen (free radicals) that damage nerve cells in the eye that are needed for vision. Idebenone is thought to help improve production of energy by restoring mitochondrial function, thereby preventing the cellular damage and the loss of sight seen in LHON.

What benefits of Raxone have been shown in studies?

Raxone has been investigated in one main study involving 85 patients with LHON, in which it was compared with placebo (a dummy treatment) over 24 weeks. The main measure of effectiveness was improvement in vision, mostly based on the numbers of letters patients were able to read on a standard eye test chart. By the end of the study, patients treated with Raxone were able to read on average 3 to 6 letters more compared with patients receiving placebo. Furthermore, some patients who were classified as 'off chart' (unable to read any letters on the chart) at the beginning of the study were able to read at least one line during the eye test after treatment, and this was also considered clinically important. Additionally, 30% of patients treated with Raxone (16 out of 53) had a clinically relevant recovery of vision in at least one eye, compared with 10% of patients (3 out of 29) in the placebo group.Additional supportive data on the benefits of Raxone came from an expanded access program through which Raxone was made available to individual patients not participating in a clinical study, and from a case record survey, which included data from patients with LHON who did not receive any treatment.Analyses of all these data showed a consistent pattern whereby generally a larger proportion of patients treated with Raxone had vision improvement compared with untreated or placebo-treated patients.

What are the risks associated with Raxone?

The most common side effects with Raxone (which may affect more than 1 in 10 people) are nasopharyngitis and cough; mild to moderate diarrhoea and back pain are also common (affecting up to 1 in 10 people).For the full list of all side effects and restrictions with Raxone, see the package leaflet.

Why is Raxone approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Raxone are greater than its risks and recommended that it be approved for use in the EU.The Committee noted the lack of treatments for preventing or reversing the vision loss in patients with LHON. The results of the main study showed an improvement in vision in patients treated with Raxone, and this trend towards a beneficial effect was confirmed by additional data from an expanded access program and a case record survey. With regard to the safety of Raxone, the majority of side effects seen with the medicine were mild or moderate in intensity.Raxone has been authorised under 'exceptional circumstances'. This is because it has not been possible to obtain complete information about Raxone due to the rarity of the disease. Every year, theRaxoneEuropean Medicines Agency will review any new information that becomes available and this summary will be updated as necessary.

What information is still awaited for Raxone?

Since Raxone has been approved under exceptional circumstances, the company that markets Raxone will conduct additional studies on the long-term effects and safety of Raxone, and will establish and maintain a registry of LHON patients treated with Raxone.

What measures are being taken to ensure the safe and effective use of Raxone?

A risk management plan has been developed to ensure that Raxone is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Raxone, including the appropriate precautions to be followed by healthcare professionals and patients.Further information can be found in the summary of the risk management plan.

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Rayvow

What is Rayvow and what is it used for?

Rayvow is a medicine used to treat migraine with or without aura (unusual visual or other sensory experiences) in adults.Rayvow contains the active substance lasmiditan.

How is Rayvow used?

Rayvow is available as a tablet and is taken by mouth. The recommended starting dose is 100 mg. The dose may be adjusted depending on the patient's response to treatment.If the migraine resolves after a first dose of 50 mg or 100 mg and then comes back within 24 hours, a second dose of the same strength may be taken at least two hours after the first dose. No more than 200 mg should be taken in any 24-hour period.If the migraine does not resolve after the first dose, a second dose for the same attack is unlikely to be effective.The medicine can only be obtained with a prescription.For more information about using Rayvow, see the package leaflet or contact your doctor or pharmacist.

How does Rayvow work?

Migraine symptoms can be reduced through the action of a chemical messenger called serotonin (5-hydroxytriptamine, 5-HT) at specific receptors (target sites) in the brain, including the 5-HT1F receptor. The active substance in Rayvow, lasmiditan, is a 5-HT1F receptor agonist, meaning that it activates one such serotonin receptor. The exact way in which the medicine works is not fully understood, but by binding to these receptors, lasmiditan is thought to both lower the amount of other chemical messengers in the brain known to play role in migraine and suppress pain pathways.

What benefits of Rayvow have been shown in studies?

Three main studies involving a total of around 7,000 adults showed that Rayvow is more effective than placebo (a dummy treatment) at treating migraine. Patients with a migraine attack causing moderate to severe headache recorded the level of pain 2 hours after treatment using a 4-point scale.In the first study, 28% (142 out of 503) of patients who took 100 mg Rayvow and 32% (167 out of 518) of those who took 200 mg reported no pain 2 hours after treatment, compared with 15% of those who took placebo (80 out of 524).In the second study, 31% of patients who took 100 mg (167 out of 532) and 39% of those who took 200 mg (205 out of 528) reported no pain after 2 hours, compared with 21% of those who took placebo(115 out of 540). Another group of patients received 50 mg Rayvow, and the medicine was effective in 29% of these patients (159 out of 556).In the last study, 26% of patients who took 100 mg Rayvow (108 out of 419) and 29% of those who took 200 mg (127 out of 434) reported no pain after 2 hours, compared with 8%, of those who took placebo (37 out of 443). This study also showed that Rayvow remained effective across multiple attacks. Of patients taking 100 mg or 200 mg Rayvow, 14% (49 out of 340) and 24% (82 out of 336), respectively, reported no pain after two hours in at least two out of three attacks, compared with 4% of those treated with placebo (16 out of 373).

What are the risks associated with Rayvow?

The most common side effect with Rayvow (which may affect more than 1 in 10 people) is dizziness. Other side effects (which may affect up to 1 in 10 people) are somnolence (sleepiness), tiredness, paraesthesia (abnormal sensations like pins and needles), nausea, vertigo (feeling dizzy), hypoaesthesia (reduced sense of touch) and muscle weakness.For the full list of side effects and restrictions of Rayvow, see the package leaflet.

Why is Rayvow authorised in the EU?

Three main studies have shown that Rayvow is effective at treating headache in patients suffering from migraines. The side effects are considered manageable. The European Medicines Agency therefore decided that Rayvow's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rayvow?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rayvow have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rayvow are continuously monitored. Suspected side effects reported with Rayvow are carefully evaluated and any necessary action taken to protect patients.

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Reagila

What is Reagila and what is it used for?

Reagila is an antipsychotic medicine used to treat schizophrenia in adults. Schizophrenia is a mental illness with symptoms such as delusions, disorganised thinking and speech, suspiciousness and hallucinations (hearing or seeing things that are not there).Reagila contains the active substance cariprazine.

How is Reagila used?

Reagila is available as capsules (1.5, 3, 4.5 and 6 mg) to be taken by mouth. The recommended starting dose is 1.5 mg once a day. The dose can be increased by 1.5 mg at a time up to a maximum of 6 mg per day. The lowest dose that works well for the patient should be maintained. Because the medicine's effects may take time to show, patients should be monitored for several weeks after starting treatment or changing the dose.Reagila can only be obtained with a prescription. For further information, see the package leaflet.

How does Reagila work?

The active substance in Reagila, cariprazine, attaches to receptors (targets) in the brain for two neurotransmitters called dopamine and serotonin, which nerve cells use to communicate withneighbouring cells. Since dopamine and serotonin play a role in schizophrenia, by attaching to their receptors, cariprazine helps normalise the activity of the brain. This reduces symptoms of schizophrenia and prevents them from returning.

What benefits of Reagila have been shown in studies?

Studies showed that Reagila improves symptoms of schizophrenia and prevents symptoms from returning.In three main studies in a total of 1,795 adults, Reagila was more effective than placebo (a dummy treatment) at reducing symptoms on a standard rating scale called PANSS (positive and negative syndrome scale). The PANSS score, which ranges from a minimum of 30 (no symptoms) to a maximum of 210 (severest symptoms), was around 96 at the start of treatment. After 6 weeks, depending on the study, the PANSS score fell by 17 to 23 points with Reagila compared with 9 to 14 points with placebo.A fourth main study in 461 patients who mostly had 'negative' symptoms (such as lack of drive, social withdrawal, and problems with attention and memory) and only few 'positive' symptoms (such as delusions and hallucinations) showed that Reagila was effective at treating negative symptoms: after 26 weeks of treatment Reagila lowered the PANSS score for negative symptoms by around 9 points compared with around 7 points with another medicine, risperidone.Finally, a fifth main study in 200 patients showed that Reagila was more effective than placebo at preventing symptoms from coming back after initial treatment. Over a 72 week period, symptoms returned in a quarter of patients taking Reagila compared with around half of those taking placebo.

What are the risks associated with Reagila?

The most common side effects with Reagila are akathisia (a constant urge to move) and parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement). Side effects are mostly mild or moderate.Reagila must not be taken at the same time as certain other medicines called strong or moderate CYP3A4 inhibitors or inducers.For the full list of all side effects and restrictions with Reagila, see the package leaflet.

Why is Reagila approved?

As well as studies showing that Reagila improves the positive symptoms of schizophrenia both in the short and longer term, one study also showed that the medicine improved the negative symptoms of the disease which have a large impact on patients' quality of life. Most of the side effects are as expected with antipsychotic medicines and many can be treated. Therefore, the European Medicines Agency decided that Reagila's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Reagila?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Reagila have been included in the summary of product characteristics and the package leaflet.

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Rebetol

What is Rebetol?

Rebetol is a medicine that contains the active substance ribavirin. It is available as capsules (200 mg) and as an oral solution (40 mg/ml).

What is Rebetol used for?

Rebetol is used in combination with other medicines to treat adults with long-term hepatitis C (a disease of the liver due to infection with the hepatitis C virus). It can also be used in previously untreated patients aged three years and over whose livers are working properly.The medicine can only be obtained with a prescription.

How is Rebetol used?

Treatment with Rebetol should be started and monitored by a doctor who has experience in the management of long-term hepatitis C.The dose of Rebetol is based on the patient's body weight, and ranges from five to six capsules a day in adults. In children weighing between 47 and 65 kg the dose ranges from 3 to 4 capsules. Children above 3 years of age and adolescents who weigh less than 47 kg or who cannot swallow capsules should take the oral solution at a dose of 15 mg per kilogram body weight a day. Rebetol is taken with food each day in two divided doses (morning and evening). The duration of treatment depends on the patient's condition and response to treatment, and ranges from six months to a year. The dose mayneed to be adjusted for patients who experience side effects. For more information, see the package leaflet.

How does Rebetol work?

The active substance in Rebetol, ribavirin, is an antiviral belonging to the class 'nucleoside analogues'. Rebetol is thought to interfere with the production or action of viral DNA and RNA, which are needed for viruses to survive and multiply. Rebetol on its own has no effect on eliminating the hepatitis C virus from the body.

How has Rebetol been studied?

Rebetol has been studied in a total of over 6,000 adults who had not been treated before, including 328 patients with cirrhosis and 507 patients also infected with HIV. It has also been studied in 1,699 adults whose disease had come back after previous treatment or whose previous treatment had failed. Rebetol has also been studied in 177 children and adolescents aged between three and 17 years who had not been treated before. In all of the studies, Rebetol was given in combination with interferon alfa-2b or peginterferon alfa-2b. In most of the studies, the main measure of effectiveness was the amount of virus in the blood before and after six months or a year of treatment, and at 'follow-up', six months later. Some studies also looked at signs of improvement of the condition of the liver.Two main studies involving 1,503 adult patients with type 1 hepatitis C and compensated liver disease investigated the effect of ribavirin in a triple therapy combination with peginterferon alfa-2b and boceprevir. The main measure of effectiveness in these studies was the number of patients who had no detectable hepatitis C virus in their blood 24 weeks after the end of the treatment and could therefore be considered to be cured.Additional data from the published literature show the positive effects of ribavirin-containing medicines when taken in different combinations, including combinations with peginterferon alfa-2a and a class of medicines known as direct acting antivirals (or DAAs).

What benefit has Rebetol shown during the studies?

In adults who had not been treated before, Rebetol in combination with interferon alfa 2b was more effective than interferon alfa 2b on its own, with 41% of the patients responding to the combination treatment and 16% to the interferon alone. Response rates were higher when Rebetol was used with peginterferon alfa 2b. Rebetol in combination with peginterferon alfa 2b was also effective in adults with cirrhosis or HIV. Combination treatment including Rebetol was effective in around a quarter of the adults whose disease had come back after previous treatment or whose previous treatment did not work, and over half of the children and adolescents treated.In the studies on triple therapy in patients with type 1 hepatitis C and compensated liver disease, ribavirin in combination with peginterferon alfa 2b and boceprevir was shown to be more effective than the dual combination with peginterferon alfa 2b alone. Triple therapy led to a 30% increase in the number of previously untreated early responders who were cured after six months. A 40% increase was seen among patients who had been treated before.

What is the risk associated with Rebetol?

Haemolytic anaemia (anaemia caused by abnormal breakdown of red blood cells) is a common side effect (seen in between 1 and 10 patients in 100), usually during the first few weeks of treatment. The haemolytic anaemia may affect a patient's heart function and lead to abnormal test values for substances such as uric acid and bilirubin in the blood. There are several other side effects of Rebetol, some of which are very common (occurring in more than 1 in 10 patients). For the full list of side effects reported with Rebetol, see the package leaflet.Rebetol must not be used in patients with severe heart disease and blood disorders such as thalassaemia and sickle cell anaemia or in pregnant or breast-feeding women. For a full list of restrictions, see the package leaflet.

Why has Rebetol been approved?

The CHMP decided that Rebetol's benefits are greater than its risks and recommended that it be given marketing authorisation.The Committee noted that Rebetol in combination with other medicines, including peginterferon alfa and DAAs is effective against long-term hepatitis C virus infection in adults and children.

What measures are being taken to ensure the safe and effective use of Rebetol?

A risk management plan has been developed to ensure that Rebetol is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rebetol, including the appropriate precautions to be followed by healthcare professionals and patients.

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Rebif

What is Rebif and what is it used for?

Rebif is a medicine used to treat patients with relapsing multiple sclerosis (MS). MS is a disease in which inflammation damages the protective insulation around nerves (demyelination) as well as the nerves themselves. Relapsing MS is the type of MS where the patient has attacks (relapses) between periods with no symptoms. Rebif's effectiveness has not been shown in patients with secondary progressive MS (the type of MS that comes after relapsing MS) that is not relapsing.Rebif can also be used in patients who have had a single attack of demyelination accompanied by inflammation. It is used when the patient is considered to be at high risk of developing MS. Before using Rebif, doctors need to exclude other causes for the symptoms.Rebif contains the active substance interferon beta-1a.

How is Rebif used?

Rebif can only be obtained with a prescription and treatment should be started by a doctor who has experience in the management of MS.Rebif is available as a solution for injection in prefilled syringes, prefilled pens and cartridges for use in an electronic injection device.The recommended dose of Rebif is 44 micrograms given three times a week by injection under the skin. A 22-microgram dose is recommended for patients who cannot tolerate the higher dose.When first starting treatment with Rebif, the dose should be slowly increased from a starting dose of8.8 micrograms three times a week to avoid side effects.The patients can inject Rebif themselves once they have been trained. The doctor may advise the patient to take a fever-reducing painkiller before each injection and for 24 hours after injection to reduce the influenza (flu)-like symptoms that may occur as a side effect of treatment. All patients should be assessed at least once every two years.For more information about using Rebif, see the package leaflet or contact your doctor or pharmacist.

How does Rebif work?

The active substance in Rebif is the protein interferon beta-1a, one of a group of interferons that can be naturally produced by the body to help it fight against viruses and other attacks. In MS, the immune system (the body's natural defences) malfunctions and attacks parts of the central nervous system (the brain, spinal cord and optic nerve [nerve that sends signals from the eye to the brain]), causing inflammation that damages the nerves and the insulation around them. The exact way that Rebif works in MS is not yet known but the active substance, interferon beta-1a, seems to calm down the immune system, and prevents relapses of MS.

What benefits of Rebif have been shown in studies?

Rebif has been studied in 560 patients with relapsing MS. The patients had experienced at least two relapses in the previous two years. Patients received either Rebif (22 or 44 micrograms) or placebo (a dummy treatment) for two years. The study was then extended to four years. Rebif was more effective than placebo in reducing the number of relapses in relapsing MS. Relapses were reduced by about 30% over two years for both Rebif 22 and 44 micrograms compared with placebo, and by 22% (Rebif 22 micrograms) and 29% (Rebif 44 micrograms) over four years.Rebif has also been studied in patients with secondary progressive MS. Rebif had no significant effect on the progression of disability, but the relapse rate was reduced by about 30%. Some effect on progression of disability could be seen, but only in the patients who had relapses in the two years before the start of the study.Rebif (44 micrograms given once or three times a week) has also been compared with placebo in 515 patients who had experienced a single attack of demyelination. The probability of developing MS over 24 months was 62.5% for patients given Rebif three times a week and 75.5% for patients given Rebif once a week compared with 85.8% for patients given placebo.

What are the risks associated with Rebif?

The most common side effects with Rebif (which may affect more than 1 in 10 people) are flu-like symptoms, neutropenia, lymphopenia and leucopenia (low white blood cell counts), thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), headache, inflammation and other reactions at the injection site, and increases in transaminases (liver enzymes).Rebif must not be used in patients who have severe depression or have thoughts of suicide.For the full list of side effects and restrictions with Rebif, see the package leaflet.

Why is Rebif authorised in the EU?

The European Medicines Agency decided that Rebif's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rebif?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rebif have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rebif are continuously monitored. Side effects reported with Rebif are carefully evaluated and any necessary action taken to protect patients.

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Reblozyl

What is Reblozyl and what is it used for?

Reblozyl is a medicine used to treat anaemia (low red blood cell counts) in adults with the following blood disorders:• Myelodysplastic syndromes, a group of conditions where too few blood cells are produced by the bone marrow. Reblozyl is used in patients who need regular blood transfusions and who have a very low to moderate risk of their condition developing into acute myeloid leukaemia (a blood cancer) or of dying. It is used in patients in whom another medicine, erythropoietin, is unsuitable or does not work.• Beta thalassaemia, a genetic condition in which patients cannot make enough beta globin, acomponent of haemoglobin (the protein in red blood cells that carries oxygen around the body).These diseases are rare, and Reblozyl was designated an 'orphan medicine' (a medicine used in rare diseases). Further information on the orphan designations can be found on the European Medicines Agency's website (myelodysplastic syndromes: 22 August 2014; beta thalassaemia: 29 July 2014).The medicine contains the active substance luspatercept.

How is Reblozyl used?

The medicine is available for injection under the skin and can only be obtained with a prescription.Treatment should be started by a doctor experienced in the treatment of blood diseases.The injection is given under the skin of the upper arm, thigh or belly. The recommended dose depends on the patient's weight and is adjusted depending on the patient's response. Treatment is given once every 3 weeks. If the patient develops serious side effects, treatment should be delayed until side effects have improved.For more information about using Reblozyl, see the package leaflet or contact your doctor or pharmacist.

How does Reblozyl work?

The active substance in Reblozyl, luspatercept, regulates the maturation of red blood cells. It does this by blocking a signalling pathway called Smad2/3 that slows down the maturation of red blood cells and is overactive in patients with beta thalassaemia and myelodysplastic syndromes. Blocking Smad2/3 increases the production of red blood cells and allows them to develop normally.

What benefits of Reblozyl have been shown in studies?

Myelodysplastic syndromesThe main study involved 229 adults with myelodysplastic syndromes requiring regular blood transfusions. Patients received either Reblozyl or placebo (a dummy treatment) in addition to normal standard of care. 58 out of 153 patients (38%) taking Reblozyl did not need a blood transfusion for at least 8 weeks compared with 10 out of 76 (13%) patients receiving placebo. Beta thalassaemiaThe main study involved 336 patients with beta thalassaemia requiring regular blood transfusions. Patients received either Reblozyl or placebo in addition to standard treatment. Blood transfusion needs were reduced by at least one third (33%) in 48 out of 224 patients (21%) taking Reblozyl compared with 5 out of 112 (4.5%) patients receiving placebo.A second main study involved patients with beta thalassaemia not requiring regular blood transfusions.Patients received either Reblozyl or placebo together with standard treatment for at least 48 weeks. After 12 weeks, 74 out of 96 patients receiving Reblozyl (77%) had a rise of at least 1 g/dL in their haemoglobin level over the next 12 weeks without needing transfusions, compared with none of the 49 patients who received placebo.

What are the risks associated with Reblozyl?

The most common side effects with Reblozyl in patients with myelodysplastic syndromes (which may affect more than 15 in 100 people) are tiredness, diarrhoea, weakness, nausea (feeling sick), dizziness, back pain and headache. The most common serious or severe side effects (affecting more than 2 in 100 people) include syncope (fainting), tiredness, hypertension (high blood pressure), weakness, urinary tract infection (infection of the structures that carry the urine) and back pain.The most common side effects of Reblozyl in patients with beta thalassaemia requiring transfusion (which may affect more than 15 in 100 people) are headache, bone pain and joint pain. The most common serious or severe side effects are hyperuricaemia (high levels of uric acid in the blood), stroke, effects due to blood clots in the veins such as deep vein thrombosis, portal vein thrombosis (clots in the veins supplying the liver) and pulmonary embolism (clots in the veins supplying the lungs).The most common side effects of Reblozyl in patients with beta thalassaemia not requiring regular transfusion (which may affect more than 15 in 100 people) are headache, bone, back and joint pain, and prehypertension and hypertension (high blood pressure). The most common serious or severe side effect is traumatic fracture (a fracture caused for example by a fall or an accident).Reblozyl must not be given during pregnancy. Women who can become pregnant must use effective contraception during treatment and for at least 3 months after the last dose. Patients requiring treatment to control the growth of extramedullary haemopoiesis masses (the formation of blood cells outside the bone marrow) must not use Reblozyl. For the full list of side effects and restrictions of Reblozyl, see the package leaflet.

Why is Reblozyl authorised in the EU?

Treatment with frequent blood transfusions can lead to accumulation of iron in the body, which can damage organs. Reblozyl reduces the need for blood transfusions in myelodysplastic syndromes and beta thalassaemia while its side effects are considered manageable. In patients with beta thalassaemia not requiring regular transfusions, higher haemoglobin levels are expected to improve outcomes for patients. The European Medicines Agency therefore decided that Reblozyl's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Reblozyl?

The company that markets Reblozyl will provide educational packs for doctors who prescribe Reblozyl explaining that the medicine can be harmful to the unborn child and detailing the steps that need to be taken for the medicine to be used safely. It will also supply cards to women who can become pregnant about the safety measures they should take to avoid pregnancy.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Reblozyl have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Reblozyl are continuously monitored. Side effects reported with Reblozyl are carefully evaluated and any necessary action taken to protect patients.

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Recarbrio

What is Recarbrio and what is it used for?

Recarbrio is an antibiotic for treating adults with the following infections:• lung infections caught in hospital (hospital-acquired pneumonia), including ventilator-associated pneumonia (pneumonia caught while on a ventilator, which is a machine that helps a patient to breathe);• infection that has spread into the blood (bacteraemia) as a likely complication of hospital-acquired pneumonia or ventilator-associated pneumonia;• infections caused by bacteria classed as aerobic Gram-negative bacteria when other treatments might not work.Official guidance on the appropriate use of antibiotics should be considered when using the medicine.Recarbrio contains the active substances imipenem, cilastatin and relebactam.

How is Recarbrio used?

Recarbrio can only be obtained with a prescription and it should be used only after consulting a doctor with experience of managing infectious diseases.Recarbrio is given by infusion (drip) into a vein over 30 minutes. It is given every 6 hours for 5 to 14 days, depending on the nature of the infection.For more information about using Recarbrio, see the package leaflet or contact your doctor or pharmacist.

How does Recarbrio work?

One of the active substances in Recarbrio, imipenem, kills bacteria and the other two, cilastatin and relebactam, increase imipenem's effectiveness in different ways.Imipenem interferes with bacterial proteins that are important for building the bacterial cell wall. This results in defective cell walls that collapse and cause the bacteria to die. Imipenem is quickly broken down by the kidneys and the cilastatin in Recarbrio prevents this breakdown and so allows imipenemto work for longer. The third active substance, relebactam, blocks enzymes in the bacteria called betalactamases. These enzymes break down antibiotics such as imipenem and stop them working.

What benefits of Recarbrio have been shown in studies?

In a main study in 47 adults with infections caused by Gram-negative bacteria, 71% of patients treated with Recarbrio had a favourable outcome (based on their symptoms and test results) compared with 70% of patients treated with another combination (colistin, imipenem and cilastatin). Patients in this study had serious infections that were resistant to treatment with imipenem plus cilastatin. Patients were treated for hospital-acquired pneumonia, complicated intra-abdominal infection (infection that has spread in the belly with swelling and build-up of pus) and complicated urinary tract infection (infection extending beyond the bladder into the kidneys).In a second main study involving 537 patients with hospital-acquired or ventilator-associated pneumonia, 61% of patients treated with Recarbrio were cured (assessed 7 to 14 days after the end of treatment) compared with 56% of patients treated with piperacillin and tazobactam (another antibiotic combination).

What are the risks associated with Recarbrio?

The most common side effects with Recarbrio (which may affect up to 1 in 10 people) are diarrhoea and blood test results showing disturbances in liver enzymes (suggesting stress on the liver).Recarbrio must not be used in patients who are hypersensitive (allergic) to imipenem and other carbapenem antibiotics (such as ertapenem and meropenem) or in patients who have had a severe allergic reaction to the broader class of beta-lactam antibiotics (such as penicillins and cephalosporins).For the full list of side effects and restrictions of Recarbrio, see the package leaflet.

Why is Recarbrio authorised in the EU?

There were too few patients in the main study of infections caused by Gram-negative bacteria to show conclusively that Recarbrio is effective against bacteria that have become resistant to imipenem. However, studies on how the medicine works in the body provided more evidence of its effectiveness. Recarbrio can therefore be useful when there is limited choice of treatment for bacterial infections resistant to imipenem and other carbapenem antibiotics.The study in patients with hospital-acquired or ventilator-associated pneumonia found Recarbrio at least as effective as the antibiotic combination piperacillin with tazobactam. The European Medicines Agency noted that imipenem plus cilastatin is already authorised for treating bacteraemia linked to hospital-acquired or ventilator-associated pneumonia.Recarbrio's side effects, which are similar to those of imipenem with cilastatin, are acceptable.The Agency therefore decided that Recarbrio's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Recarbrio?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Recarbrio have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Recarbrio are continuously monitored. Side effects reported with Recarbrio are carefully evaluated and any necessary action taken to protect patients.

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Refacto Af

What is ReFacto AF?

ReFacto AF is a powder and solvent used to make up a solution for injection. ReFacto AF contains the active substance moroctocog alfa. It is available as vials or pre-filled syringes.

What is ReFacto AF used for?

ReFacto AF is used for the treatment and prevention of bleeding in patients with haemophilia A (an inherited bleeding disorder). ReFacto AF can be used in patients of all ages, including newborns.The medicine can only be obtained with a prescription.

How is ReFacto AF used?

ReFacto AF should be started under the supervision of a doctor who has experience in the treatment of haemophilia A.ReFacto AF is given by injection into a vein over several minutes. The dose and the frequency of treatment depend on whether ReFacto AF is used to treat or prevent bleeding, the seriousness of the condition, the extent and location of the bleeding or the type of surgery, and the patient's bodyweight. Full details on how to calculate the dose are included in the summary of product characteristics (also part of the EPAR).Patients or their carers can give injections of ReFacto AF, provided that they have been trained appropriately.

How does ReFacto AF work?

Patients with haemophilia A lack factor VIII, a protein needed for normal clotting of the blood, and as a result, they bleed readily and may have problems, such as bleeding in the joints, muscles and internal organs. The active substance in ReFacto AF, moroctocog alfa, works in the body in the same way as human factor VIII. It replaces the missing factor VIII, thereby helping the blood to clot and giving temporary control of bleeding.The human coagulation factor VIII in ReFacto AF is not extracted from human blood but is produced by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA), which makes it able to produce human coagulation factor VIII.

How has ReFacto AF been studied?

ReFacto AF was first authorised as ReFacto in April 1999, for use in previously treated and untreated patients with haemophilia A, based on the results of three main studies. In February 2009, a number of changes to the way ReFacto is made were introduced. These included removal of the use of aprotein called albumin, which is produced from human blood, from the manufacturing process. The name of the medicine was also changed from ReFacto to ReFacto AF.Following these changes, the company carried out a study to show that ReFacto and ReFacto AF were treated by the body in the same way. It also carried out two main studies looking at the effectiveness of ReFacto AF: the first looked at the prevention and treatment of bleeding episodes in 94 previously treated patients and the second looked at the prevention of bleeding in 22 patients having surgery.

What benefit has ReFacto AF shown during the studies?

The studies showed that ReFacto AF was as safe and effective as ReFacto in preventing and treating bleeding episodes in patients with haemophilia A.

What is the risk associated with ReFacto AF?

The most common side effects with ReFacto AF (seen in more than 1 patient in 10) are headache, cough, pain in the joints and fever. Patients may also develop antibodies against factor VIII medicines such as Refacto AF. These are known as inhibitors as they can prevent the medicine from working effectively, which may result in a loss of bleeding control. Uncommonly, patients may also develop allergic reactions. For the full list of all side effects reported with ReFacto AF, see the package leaflet.ReFacto AF must not be used in people who are hypersensitive (allergic) to human coagulation factor VIII, to any of the other ingredients or to hamster proteins.

Why has ReFacto AF been approved?

The CHMP noted that ReFacto AF was comparable to ReFacto, the original form of the medicine. Therefore, the Committee decided that the benefits of ReFacto AF are greater than its risks and recommended that it be given marketing authorisation.ReFacto AF

What measures are being taken to ensure the safe and effective use of ReFacto AF?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Refacto AF have been included in the summary of product characteristics and the package leaflet.

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Refixia

What is Refixia and what is it used for?

Refixia is a medicine used to treat and prevent bleeding in patients with haemophilia B, an inherited bleeding disorder caused by lack of a clotting protein called factor IX. It can be used in adults and children from 12 years of age.Refixia contains the active substance nonacog beta pegol.

How is Refixia used?

Refixia can only be obtained with a prescription and treatment should be under the supervision of a doctor who has experience in the treatment of haemophilia.Refixia is available as a powder and a liquid that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on whether Refixia is used to treat or prevent bleeding, or to reduce bleeding during surgery, the extent and location of the bleeding, and the patient's bodyweight. For further information on how to use this medicine, see the summary of product characteristics (also part of the EPAR).Patients or their carers may be able to inject Refixia themselves at home once they have been trained appropriately. For full details, see the package leaflet.

How does Refixia work?

Patients with haemophilia B lack factor IX, a protein needed for normal clotting of the blood, and as a result, they bleed readily. The active substance in Refixia, nonacog beta pegol, works in the body in the same way as human factor IX. It replaces the missing factor IX, thereby helping the blood to clot and giving temporary control of bleeding.

What benefits of Refixia have been shown in studies?

Refixia has been shown to be effective at both treating bleeding episodes and keeping the number of episodes low.In a study involving 74 adults and adolescents aged 13 or above, 29 patients given Refixia as a weekly preventive treatment had around 1 bleeding episode a year, and 15 patients given Refixia for treating bleedings 'on demand' had around 16 bleeding episodes a year. In addition, when bleeding did occur, Refixia was rated excellent or good at treating around 92% of bleeding episodes. 87% of bleeding episodes resolved with one injection of Refixia.In the second study in 25 children aged below 13 years, all patients were given Refixia as a weekly preventive treatment. Patients had around 1 bleeding episode per year and Refixia was rated excellent or good at treating around 93% of bleeding episodes. Around 86% of bleeding episodes resolved with one injection.

What are the risks associated with Refixia?

Hypersensitivity (allergic) reactions are uncommon with Refixia (may affect up to 1 in 100 patients) and may include: swelling, burning and stinging at the injection site, chills, flushing, itchy rash, headache, hives, low blood pressure, lethargy, nausea and vomiting, restlessness, a fast heartbeat, tightness of the chest and wheezing. In some cases these reactions can become severe.Some patients taking factor IX medicines may develop inhibitors (antibodies) against factor IX, causing the medicine to stop working and resulting in a loss of bleeding control. Factor IX medicines can also potentially cause problems due to the formation of blood clots in the blood vessels.Refixia must not be used in patients allergic to hamster proteins. For the full list of side effects and restrictions, see the package leaflet.

Why is Refixia approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Refixia's benefits are greater than its risks and recommended that it be approved for use in the EU.Studies show that Refixia is effective at preventing and treating bleeding episodes in patients with haemophilia B and its safety is comparable to that of other factor IX products. However, part of the active substance in Refixia (called PEG) may accumulate in the body, including in a structure in the brain called choroid plexus, following long-term treatment. Since this could potentially cause problems especially in children below 12 years of age, Refixia is only approved for use in in adults and children from 12 years of age.Refixia

What measures are being taken to ensure the safe and effective use of Refixia?

The company that markets Refixia will conduct a study to investigate the potential effects of PEG accumulation in the choroid plexus of the brain and other organs.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Refixia have been included in the summary of product characteristics and the package leaflet.

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Regkirona

What is Regkirona and what is it used for?

Regkirona is a medicine used for treating COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of their disease becoming severe.Regkirona contains the active substance regdanvimab.

How is Regkirona used?

Regkirona is given as a single infusion (drip) into a vein within 7 days of the start of COVID-19 symptoms; the dose depends on the patient's body weight.The medicine can only be obtained with a prescription and should be given in healthcare facilities where patients can be monitored while receiving the infusion and for at least 1 hour afterwards, and where they can be adequately managed in case they develop severe allergic reactions, including anaphylaxis.For more information about using Regkirona, see the package leaflet or contact your healthcare provider.

How does Regkirona work?

The active substance in Regkirona, regdanvimab, is a monoclonal antibody with activity against SARSCoV-2, the virus that causes COVID 19. A monoclonal antibody is a type of protein that has been designed to attach to a specific structure (called an antigen). Regdanvimab has been designed to attach to the spike protein of SARS-CoV-2. When regdanvimab attaches to the spike protein, the virus is unable to enter the body's cells.

What benefits of Regkirona have been shown in studies?

A main study involving 1,315 patients with COVID-19 showed that Regkirona led to fewer patients requiring hospitalisation or oxygen therapy, or dying, when compared with placebo (a dummy treatment). Among the patients at increased risk of their illness becoming severe, 3.1% of patients treated with Regkirona (14 out 446) were hospitalised, required supplemental oxygen or died within 28 days of treatment compared with 11.1% of patients on placebo (48 out of 434).The majority of patients in the study were infected with the original SARS-CoV-2 virus or the Alpha variant; data on the efficacy of Regkirona against some circulating SARS-CoV-2 variants is currently limited.

What are the risks associated with Regkirona?

Infusion-related reactions, including allergic reactions and anaphylaxis, may affect up to 1 in 1,000 people given Regkirona.For the full list of side effects and restrictions of Regkirona, see the package leaflet.

Why is Regkirona authorised in the EU?

Regkirona was shown to be effective at reducing the risk of hospitalisation or death in patients with COVID-19 at increased risk of the disease becoming severe. The safety profile of Regkirona is considered favourable. The European Medicines Agency therefore decided that Regkirona's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Regkirona?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Regkirona have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Regkirona are continuously monitored. Suspected side effects reported with Regkirona are carefully evaluated and any necessary action taken to protect patients.

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Rekambys

What is Rekambys and what is it used for?

Rekambys is used together with another medicine called cabotegravir to treat adults infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS). It is used in adults whose infection is under control with other HIV medicines.Rekambys contains the active substance rilpivirine.

How is Rekambys used?

Rekambys is available as a prolonged-release suspension for injection. 'Prolonged release' means that the active substance is released slowly over a few weeks after being injected. The medicine is given by injection into the hip or buttock muscle by a doctor or nurse.Before starting treatment, the doctor ensures that the patient agrees to keep to the schedule of injections, because this is important to keep the virus under control and there is a risk that levels of the virus could increase or the virus could become resistant to treatment if doses are missed.Rilpivirine and cabotegravir tablets are taken daily by mouth for one month, after which Rekambys and cabotegravir injections are given monthly or every 2 months.If treatment with Rekambys is stopped, another treatment to supress the virus must be started to minimise the risk that the virus could become resistant to treatment.Rekambys can only be obtained with a prescription, and treatment should be started by a doctor who has experience in the management of HIV infection.For more information about using Rekambys, including the schedule for the injections, see the package leaflet or contact your doctor or pharmacist.

How does Rekambys work?

Rekambys is a type of HIV medicine called a non-nucleoside reverse transcriptase inhibitor (NNRTI). It blocks the activity of reverse transcriptase, an enzyme produced by HIV-1 that allows it to make more viruses in the cells it has infected. By blocking this enzyme, Rekambys, taken in combination with cabotegravir, reduces the amount of HIV in the blood and keeps it at a low level. Rekambys does notcure HIV infection or AIDS, but it can hold off damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Rekambys have been shown in studies?

Rekambys, taken together with cabotegravir, was as effective as other HIV medicines in maintaining the HIV-1 level in the blood (viral load) below a defined level (less than 50 HIV-1 RNA copies/ml) in 3 main studies involving patients with HIV-1 infection. The studies involved patients who had not taken HIV medicines before or who had been taking these medicines for at least 6 months.In two studies, patients were treated with Rekambys and cabotegravir or with combinations of other medicines. After 48 weeks, the HIV-1 level was above the limit in 1.9% of patients (11 out of 591) taking monthly injections of Rekambys and cabotegravir and in 1.7% of patients (10 out of 591) taking other medicines.One study showed that injections of Rekambys and cabotegravir given monthly or every 2 months were similarly effective. After 48 weeks for patients taking the injections every 2 months, the HIV-1 level was above the limit in 1.7% of patients (9 out of 522) compared with 1% of patients (5 out of 523) who had monthly injections.

What are the risks associated with Rekambys?

The most common side effects with Rekambys (which may affect more than 1 in 10 people) are injection site reactions, headache and fever.Rekambys must not be used with the following medicines as they may lead to reduced blood levels of the medicine, reducing its effectiveness:• carbamazepine, oxcarbazepine, phenobarbital, phenytoin (medicines for epilepsy);• rifabutin, rifampicin, rifapentine (antibiotics);• systemic dexamethasone (a steroid anti-inflammatory and immunosuppressant medicine), except when used as a single dose treatment;• St John's wort (a herbal antidepressant medicine).For the full list of side effects and restrictions with Rekambys, see the package leaflet.

Why is Rekambys authorised in the EU?

Injections every month or every 2 months may be more convenient for patients than taking medicines every day. Studies showed that the injections were as effective at keeping the virus level low as other standard medicines. It is important that patients keep to the schedule of injections to avoid the virus becoming resistant to treatment, and further studies will determine whether this is happening once the medicine is on the market. The European Medicines Agency decided that Rekambys's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rekambys?

The company that markets Rekambys will carry out 2 studies on how the medicine is used and its effectiveness. The outcomes for patients who switch to other treatments after taking Rekambys will also be studied.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rekambys have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rekambys are continuously monitored. Side effects reported with Rekambys are carefully evaluated and any necessary action taken to protect patients.

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Rekovelle

What is Rekovelle and what is it used for?

Rekovelle is a medicine given to women who are having fertility treatments such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). It is used to stimulate the ovaries to produce several eggs at the time, which can then be collected and fertilised in the laboratory.Rekovelle contains the active substance follitropin delta.

How is Rekovelle used?

Rekovelle is available as a solution for injection, contained in a cartridge to be used with Rekovelle injection pen. The medicine can only be obtained with a prescription and treatment should be started under the supervision of a doctor who has experience in the treatment of fertility problems.Rekovelle is given by injection under the skin once a day for several consecutive days during the woman's menstrual cycle starting on day 2 or 3 of the cycle and is continued until sufficient eggs have developed. The starting dose of Rekovelle depends on the woman's bodyweight and on the blood level of the anti-Mόllerian hormone (a hormone which indicates how well the ovaries will respond to stimulation). The dose can then be modified in subsequent cycles according to the woman's response. After the first injection, the woman or their partner may be able to give the injections themselves, if they have been trained and have access to expert advice.For further information, see the package leaflet.

How does Rekovelle work?

The active substance in Rekovelle, follitropin delta, is a copy of the natural hormone called folliclestimulating hormone (FSH) which plays a key role in fertility in women by stimulating the production of eggs in the ovaries. Giving extra stimulation with Rekovelle helps increase the number of eggs produced in the ovaries, which means that more eggs can then be collected and fertilised in the laboratory.

What benefits of Rekovelle have been shown in studies?

Rekovelle was compared with GONAL-f (follitropin alfa), another fertility medicine, in one study involving 1,326 women who were undergoing controlled ovarian stimulation for IVF or ICSI. The main measure of effectiveness was the rate of implantation and pregnancy.The study showed that Rekovelle was as effective as GONAL-f at stimulating the ovaries: around 31% of women (204 out of 665) treated with Rekovelle became pregnant compared with around 32% of women (209 out of 661) treated with GONAL-f. Implantation rates were also similar: around 35% with Rekovelle versus around 36% with GONAL-f.

What are the risks associated with Rekovelle?

The most common side effects with Rekovelle (which may affect between 1 and 10 people in 100) are headache, discomfort and pain in the pelvic area which may arise from the ovaries, nausea (feeling sick) and tiredness and ovarian hyperstimulation syndrome (OHSS). OHSS is when a woman's ovaries over-respond to stimulation, causing symptoms such as vomiting, diarrhoea and pain. In severe cases OHSS may lead to difficulty breathing and problems with blood clotting. The frequency of side effects may decrease with repeated treatment cycles. For the full list of all side effects reported with Rekovelle, see the package leaflet.Rekovelle must not be used in women with tumours of the pituitary gland or hypothalamus, or cancer of the breast, womb or ovary. Rekovelle must not be used when there is enlargement of an ovary or a cyst that is caused by something other than polycystic ovarian syndrome, or when there is unexplained bleeding from the vagina. For the full list of restrictions, see the package leaflet.

Why is Rekovelle approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Rekovelle's benefits are greater than its risks and recommended that it be approved for use in the EU.The CHMP considered that Rekovelle was effective in obtaining several eggs at the same time following stimulation in women undergoing fertility treatment. The safety profile of Rekovelle was considered acceptable and similar to that of GONAL-f.

What measures are being taken to ensure the safe and effective use of Rekovelle?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rekovelle have been included in the summary of product characteristics and the package leaflet.

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Relistor

What is Relistor and what is it used for?

Relistor is used to treat constipation caused by opioid painkillers (such as morphine) when laxative medicines have not worked well enough.Relistor contains the active substance methylnaltrexone bromide.

How is Relistor used?

Relistor can only be obtained with a prescription. It is available as a solution for injection in vials or in prefilled syringes.In patients who are receiving palliative care (treatment of the symptoms of a serious disease that is not intended to lead to cure), Relistor is given as an injection under the skin, once every two days, in addition to the usual laxative medicines. The dose depends on the patient's body weight. In patients not on palliative care, Relistor is given as an injection under the skin at a dose of 12 mg once a day, for at least 4 days per week and up to 7 days per week as needed; treatment with usual laxatives should be stopped when starting Relistor. Relistor is usually injected under the skin of the upper legs, belly or upper arms.The dose of Relistor should be reduced in patients who have severe kidney problems. Relistor is not recommended for patients who have very severe kidney problems that require dialysis (a blood clearance technique).Patients can inject Relistor themselves once they have been trained appropriately.

How does Relistor work?

Opioids relieve pain by attaching to 'opioid receptors' in the brain and spinal cord. These receptors are also found in the gut. When opioids attach to the gut receptors, the mobility of the gut is reduced, leading to constipation.The active substance in Relistor, methylnaltrexone bromide, is a 'mu-opioid receptor antagonist'. This means that it blocks a specific type of opioid receptor called the 'mu-opioid receptor'. Methylnaltrexone bromide is derived from naltrexone, a well-known substance that is used to block the action of opioids. Methylnaltrexone bromide is less able to enter the brain than naltrexone, meaning that it blocks the mu-opioid receptors in the gut but not in the brain. By blocking these receptors, Relistor reduces the constipation due to opioids, but does not interfere with their painkilling effects.

What benefits of Relistor have been shown in studies?

Relistor was shown to be more effective than placebo (a dummy treatment) at stimulating bowel movement in two main studies involving a total of 288 patients with an advanced illness and constipation caused by opioids. The main measure of effectiveness in both studies was the number of patients who had a bowel movement within four hours of the first dose. The second study also looked at the number of patients who had a bowel movement at least twice within four hours of the first four doses. Looking at the results of the two studies taken together, 55% of the patients receiving Relistor had a bowel movement within four hours of the first dose (91 out of 165), compared with 15% of the patients receiving placebo (18 out of 123). In the second study, 52% of the patients receiving Relistor had a bowel movement at least twice within four hours of the first four doses (32 out of 62), compared with 8% of those receiving placebo (6 out of 71).Relistor has also been compared with placebo in a third study involving 496 patients with constipation caused by opioids, but no advanced illness. The main measures of effectiveness were the number of patients who had a bowel movement within four hours of the first dose, and the percentage of injections that were successful in producing a bowel movement. Results showed that 34% of patients receiving Relistor (102 out of 298) had a bowel movement within four hours after the first injection, compared with 10% of those receiving placebo (16 out of 162). The percentages of successful injections for the two groups were around 30% and 9%, respectively.

What are the risks associated with Relistor?

The most common side effects with Relistor (seen in more than 1 patient in 10) are abdominal pain (stomach ache), nausea (feeling sick), diarrhoea and flatulence. These side effects are generally mild or moderate. For the full list of all side effects reported with Relistor, see the package leaflet.Relistor must not be used in patients whose bowel is blocked, who are at risk of recurrent bowel blockage or who have a condition that needs immediate bowel surgery. For the full list of restrictions, see the package leaflet.

Why is Relistor approved?

The Agency's Committee for Medicinal Products for Human Use decided that Relistor's benefits are greater than its risks and recommended that it be given marketing authorisation.Relistor

What measures are being taken to ensure the safe and effective use of Relistor?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Relistor have been included in the summary of product characteristics and the package leaflet.

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Relvar Ellipta

What is Relvar Ellipta and what is it used for?

Relvar Ellipta is an inhaler for treating asthma and chronic obstructive pulmonary disease (COPD).In asthma, it is used for regular treatment of patients from 12 years of age:• whose symptoms are not controlled with an inhaled corticosteroid and an inhaled short-acting beta-2 agonist;• whose symptoms are adequately controlled with both inhaled corticosteroids and a long-acting beta-2 agonist.In COPD, it is used in adults who have flare-ups of the disease despite regular bronchodilator treatment (treatment to widen the airways).Relvar Ellipta contains the active substances fluticasone furoate and vilanterol.

How is Relvar Ellipta used?

Relvar Ellipta is available as an inhaler in two strengths (92/22 micrograms and 184/22 micrograms). The doctor will decide which inhaler the patient should use. The dose is one inhalation ('puff') into the mouth once a day at the same time each day.Relvar Ellipta can only be obtained with a prescription. For more information about using Relvar Ellipta, see the package leaflet or contact your doctor or pharmacist.

How does Relvar Ellipta work?

Relvar Ellipta contains two active substances that work in different ways to improve breathing in patients with asthma and COPD.Fluticasone furoate is a corticosteroid. It works on various types of immune cells, blocking the release of substances involved in inflammation. This reduces inflammation in the airways and improves the patient's breathing.Vilanterol is a long-acting beta-2 agonist. It attaches to beta-2 receptors in the airways and causes the muscles of the airways to relax and widen, allowing the patient to breathe more easily.

What benefits of Relvar Ellipta have been shown in studies?

AsthmaThree studies in over 3,200 patients showed that Relvar Ellipta improves breathing and reduces flareups in patients with asthma.In two of the studies, Relvar Ellipta 92/22 increased the volume of air a patient could breathe out in one second (FEV1) by 36 ml more than fluticasone furoate alone and 172 ml more than placebo (a dummy treatment). Relvar Ellipta 184/22 also improved FEV1 by 193 ml more than fluticasone furoate and 210 ml more than another inhaler containing fluticasone propionate.In a third study, fewer patients taking Relvar Ellipta 92/22 had at least one severe flare-up after a year of treatment than those taking fluticasone furoate alone (13% versus 16%).A fourth study in 1,522 patients showed that Relvar Ellipta was as effective as another medicine containing a corticosteroid (fluticasone propionate) and a long-acting beta-2 agonist (salmeterol). These patients were already well controlled with the comparator medicine and Relvar Ellipta treatment was able to maintain their FEV1.COPDFour studies in over 5,500 patients showed that Relvar Ellipta improves breathing and reduces flareups of symptoms in patients with COPD.The first study showed that Relvar Ellipta 92/22 improved average FEV1 by 115 ml more than placebo, and a second study showed that Relvar Ellipta 184/22 improved average FEV1 by 131 ml more than placebo.In two further studies, Relvar Ellipta reduced the number of flare-ups by between 13 and 34% more than vilanterol alone.

What are the risks associated with Relvar Ellipta?

The most common side effects with Relvar Ellipta (which may affect more than 1 in 10 people) are headache and nasopharyngitis (inflammation of the nose and throat). More serious side effects include pneumonia and fractures (seen in up to 1 in 10 people), which were reported more often in patients with COPD than those with asthma. For the full list of side effects of Relvar Ellipta, see the package leaflet.

Why is Relvar Ellipta authorised in the EU?

Relvar Ellipta improves breathing and reduces flare ups of symptoms in patients with asthma and COPD. Regarding its safety, the most frequent side effects reported with Relvar Ellipta were similar to those seen with other COPD and asthma treatments; an increased incidence of pneumonia was observed in patients with COPD.The European Medicines Agency concluded that Relvar Ellipta's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Relvar Ellipta?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Relvar Ellipta have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Relvar Ellipta are continuously monitored. Side effects reported with Relvar Ellipta are carefully evaluated and any necessary action taken to protect patients.

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Remicade

What is Remicade and what is it used for?

Remicade is an anti-inflammatory medicine. It is usually used when other medicines or treatments have failed, in adults with the following diseases:• rheumatoid arthritis (an immune system disease causing inflammation of the joints). Remicade is used with methotrexate (a medicine that acts on the immune system);• Crohn's disease (a disease causing inflammation of the digestive tract), when the disease is moderate to severe or fistulising (with the formation of fistulae, abnormal passageways between the gut and other organs);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• ankylosing spondylitis (a disease causing inflammation and pain in the joints of the spine); •• psoriasis (a disease causing red, scaly patches on the skin).Remicade is also used in patients aged between 6 and 17 years with severe, active Crohn's disease or severely active ulcerative colitis, when they have not responded to or cannot take other medicines or treatments.Remicade contains the active substance infliximab.

How is Remicade used?

Remicade is available as a powder that is made up into a solution for infusion (drip into a vein). Remicade can only be obtained with a prescription and must be given under the supervision and monitoring of a specialised doctor who has experience in the diagnosis and treatment of the diseases that Remicade can be used to treat.Remicade is usually given as 3 mg per kilogram body weight in rheumatoid arthritis, although the dose can be increased if necessary. The dose is 5 mg per kilogram for the other diseases. How often the treatment is repeated depends on which disease is being treated, and on the patient's response to the medicine.Remicade is given as an infusion lasting one or two hours. All patients are monitored for any reactions during the infusion and for at least one to two hours afterwards. To reduce the risk of infusion-related reactions, patients may be given other medicines before or during treatment with Remicade or the infusion time may be slowed down. For more information about using Remicade, see the package leaflet or contact your doctor or pharmacist.

How does Remicade work?

The active substance in Remicade, infliximab, is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Infliximab has been designed to attach to a chemical messenger in the body called tumour necrosis factor-alpha (TNF-alpha). This messenger is involved in causing inflammation and is found at high levels in patients with the diseases that Remicade is used to treat. By blocking TNF-alpha, infliximab improves the inflammation and other symptoms of the diseases.

What benefits of Remicade have been shown in studies?

Rheumatoid arthritisRemicade has been studied in a total of 1,432 patients with rheumatoid arthritis in two studies. In these studies, more patients taking Remicade in combination with methotrexate showed a reduction in symptoms than those taking methotrexate alone, as well as less damage to the joints and greater improvements in physical function.Crohn's diseaseIn Crohn's disease in adults, Remicade was compared with placebo (a dummy treatment) in 1,090 adults in four studies. In these studies Remicade produced a greater improvement in symptoms, led to fistulae healing in more patients and increased the time that patients continued to respond to treatment.The effects of adding Remicade to existing treatment have also been studied in 103 children and adolescents with Crohn's disease who were aged between 6 and 17 years. Most of the patients showed a reduction in symptoms after adding Remicade to their existing treatment.A sixth study in 508 adult patients looked at the number of patients whose symptoms improved and who did not need additional treatment with corticosteroids (other medicines used in Crohn's disease). The patients were treated for 6 months with Remicade, another medicine azathioprine, or the combination of Remicade and azathioprine. Remicade alone and in combination with azathioprine was more effective than azathioprine alone.Ulcerative colitis, ankylosing spondylitis and psoriatic arthritisFor ulcerative colitis (728 adults), ankylosing spondylitis (70 adults) and psoriatic arthritis (104 adults), Remicade has been compared with placebo. More adult patients receiving Remicade had a reduction in symptoms than those receiving placebo.In a study with 60 children aged between 6 and 17 years with ulcerative colitis 73% of patients responded to treatment with Remicade at week eight (44 out of 60).PsoriasisIn a study in 627 adults with psoriasis, Remicade led to a greater improvement in symptoms than placebo.

What are the risks associated with Remicade?

The most common side effects with Remicade (seen in more than 1 patient in 10) are viral infections (such as flu or cold sores), headache, upper respiratory tract infection (colds), sinusitis (inflammation of the sinuses), nausea (feeling sick), abdominal pain (stomach ache), infusion-related reactions and pain. Some side effects, including infections, may be more common in children than in adults. For the full list of side effects of Remicade, see the package leaflet.Remicade must not be used in patients who have experienced hypersensitivity (allergy) to infliximab in the past, or who are hypersensitive (allergic) to mouse proteins or any of the other ingredients of Remicade. Remicade must not be used in patients with tuberculosis, other severe infections, or moderate or severe heart failure (an inability of the heart to pump enough blood around the body).

Why is Remicade authorised in the EU?

The European Medicines Agency decided that Remicade's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Remicade?

Patients who receive Remicade must be given a special reminder card. The card will include safety information about the medicine and a record of the dates and results of specific tests that the patient has had so these can be shared with any treating doctor.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Remicade have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Remicade are continuously monitored. Side effects reported with Remicade are carefully evaluated and any necessary action taken to protect patients.

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Remsima

What is Remsima and what is it used for?

Remsima is an anti-inflammatory medicine that contains the active substance infliximab. It is usually used when other medicines or treatments have failed, in adults with the following immune-system diseases:• rheumatoid arthritis (a disease causing inflammation of the joints). Remsima is used with methotrexate (another medicine that acts on the immune system);• Crohn's disease (a disease causing inflammation of the digestive tract), when the disease is moderate to severe or fistulising (with the formation of fistulas, abnormal passageways between the gut and other organs);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• ankylosing spondylitis (a disease causing inflammation and pain in the joints of the spine); •• psoriasis (a disease causing red, scaly patches on the skin).Remsima is also used in patients aged between 6 and 17 years with severe, active Crohn's disease or severely active ulcerative colitis, when they have not responded to or cannot take other medicines or treatments.Remsima is a 'biosimilar' medicine. This means that Remsima is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Remsima is Remicade. For more information on biosimilar medicines, see here.

How is Remsima used?

Remsima can only be obtained with a prescription and treatment should be started and supervised by a specialised doctor who has experience in the diagnosis and treatment of the diseases that Remsima can be used to treat.Classified as internal/staff & contractors by the European Medicines AgencyRemsima is available as a powder to be made up into a solution for infusion (drip) into a vein. For treatment of rheumatoid arthritis, Remsima is also available as a solution for injection under the skin in a pre-filled syringe or pen.Remsima is given as an infusion into a vein lasting one or two hours. All patients are monitored for any reactions during the infusion and for at least one to two hours afterwards. To reduce the risk of infusion-related reactions, patients may be given other medicines before or during treatment with Remsima or the infusion may be slowed down. How often the treatment is repeated depends on which disease is being treated, and on the patient's response to the medicine.For rheumatoid arthritis, after two treatments with infliximab have been given by infusion, Remsima can be given by injection under the skin for subsequent treatments. Patients can inject Remsima themselves once they have been trained.For more information about using Remsima, see the package leaflet or contact your doctor or pharmacist.

How does Remsima work?

The active substance in Remsima, infliximab, is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Infliximab has been designed to attach to a chemical messenger in the body called tumour necrosis factor-alpha (TNF-alpha). This messenger is involved in causing inflammation and is found at high levels in patients with the diseases that Remsima is used to treat. By blocking TNF-alpha, infliximab improves the inflammation and other symptoms of the diseases.

What benefits of Remsima have been shown in studies?

Laboratory studies comparing Remsima with Remicade have shown that the active substance in Remsima is highly similar to that in Remicade in terms of structure, purity and biological activity. In addition, Remsima and Remicade given by infusion into a vein were compared in one main study involving 606 adults with rheumatoid arthritis. Patients received either Remsima or Remicade in addition to methotrexate for 30 weeks. The main measure of effectiveness was the change in symptoms. After 30 weeks of treatment, Remsima was as effective as Remicade with around 60% of patients responding to treatment with either medicine.A study was also carried out in 250 patients with ankylosing spondylitis to show that Remsima given by infusion into a vein produces levels of the active substance in the body that are comparable to the reference medicine, Remicade.Because Remsima is a biosimilar medicine, the studies on effectiveness and safety of infliximab carried out with Remicade do not all need to be repeated for Remsima.Remsima injection to be given under the skin was shown to be as effective as Remsima given by infusion into a vein in a study involving 343 patients with rheumatoid arthritis. Patients received Remsima by infusion twice, two weeks apart and subsequent treatments were given either by infusion or injection under the skin. After 22 weeks, the reduction of symptoms was comparable for treatment given by infusion into a vein and by injection under the skin.

What are the risks associated with Remsima?

The safety of Remsima has been evaluated, and on the basis of all the studies carried out, the side effects of the medicine are considered to be comparable to those of the reference medicine Remicade.Classified as internal/staff & contractors by the European Medicines AgencyThe most common side effects with Remsima (which may affect more than 1 in 10 people) are viral infections (such as flu or cold sores), headache, upper respiratory-tract infection (nose and throat infections), sinusitis (inflammation of the sinuses), nausea (feeling sick), abdominal pain (stomach ache), infusion-related reactions and pain. Some side effects, including infections, may be more common in children than in adults. For the full list of all side effects of Remsima, see the package leaflet.Remsima must not be used in patients who have experienced hypersensitivity (allergy) to infliximab in the past, or who are hypersensitive (allergic) to mouse proteins or any of the other ingredients of Remsima. Remsima must not be used in patients with tuberculosis, other severe infections, or moderate or severe heart failure (an inability of the heart to pump enough blood around the body).

Why is Remsima authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Remsima has a highly similar structure, purity and biological activity to Remicade and is distributed in the body in the same way. In addition, studies in rheumatoid arthritis and ankylosing spondylitis have shown that the safety and effectiveness of Remsima are equivalent to those of Remicade in the conditions.All these data were considered sufficient to conclude that Remsima will behave in the same way as Remicade in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Remicade, the benefits of Remsima outweigh the identified risks and it can be authorised for use in the EU.Remsima given by injection under the skin for rheumatoid arthritis is as effective as Remsima given by infusion and the safety profile is acceptable. It also allows patients the convenience of having their treatment at home.

What measures are being taken to ensure the safe and effective use of Remsima?

The company that markets Remsima will provide a card to patients that includes information about the medicine and can be used to record tests they have taken.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Remsima have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Remsima are continuously monitored. Side effects reported with Remsima are carefully evaluated and any necessary action taken to protect patients.

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Renagel

What is Renagel?

Renagel is a medicine that contains the active substance sevelamer hydrochloride. It is available as tablets (400 and 800 mg).

What is Renagel used for?

Renagel is used to control hyperphosphataemia (high blood phosphate levels) in adults on dialysis (a blood clearance technique used in patients with kidney disease). It can be used in patients undergoing haemodialysis (dialysis using a blood filtration machine) or peritoneal dialysis (where fluid is pumped into the abdomen and an internal body membrane filters the blood). Renagel should be used with other treatments such as calcium or vitamin D supplements to control the development of bone disease.The medicine can only be obtained with a prescription.

How is Renagel used?

The recommended starting dose of Renagel depends on the level of phosphate in the blood and ranges from 800 to 1,600 mg three times a day. The dose of Renagel should be adjusted to ensure that the blood phosphate level stays below 1.76 mmol/l. Patients should take Renagel tablets whole with meals and stick to their prescribed diets.

How does Renagel work?

Patients with long-term kidney disease cannot eliminate phosphate from their bodies. This leads to hyperphosphataemia, which, in the long term, can cause complications such as heart and bone disease. The active substance in Renagel, sevelamer hydrochloride, is a phosphate binder. When taken with meals, it attaches to phosphate from food within the gut, preventing it from being absorbed into the body. This helps to reduce the phosphate levels in the blood.

How has Renagel been studied?

In haemodialysis, Renagel has been studied in two short-term studies lasting eight weeks and one longer study lasting 44 weeks. The first study compared Renagel with calcium acetate (another phosphate-lowering medicine) in 84 patients. The second, which did not compare Renagel with any other medicines, included 172 patients. The longer study looked at the use of Renagel in 192 patients, the majority of whom had taken Renagel in previous studies.In peritoneal dialysis, there has been one study comparing Renagel with calcium acetate in 143 patients over 12 weeks.In all of the studies, the main measure of effectiveness was the change in blood phosphate levels between the start and the end of treatment.

What benefit has Renagel shown during the studies?

Renagel produced a significant decrease in serum phosphate in all of the studies.In the comparative study of patients undergoing haemodialysis, there was an average fall of 0.65 mmol/l over the eight weeks of Renagel treatment, compared with 0.68 mmol/l when the patients were taking calcium acetate. Patients taking Renagel had a similar fall in phosphate levels in the second study. In the third, there was an average fall of 0.71 mmol/l over 44 weeks.In the study of patients undergoing peritoneal dialysis, the patients receiving Renagel had similar falls in phosphate as the patients receiving calcium acetate (0.52 and 0.58 mmol/l, respectively).

What is the risk associated with Renagel?

The most common side effects with Renagel (seen in more than 1 patient in 10) are nausea (feeling sick) and vomiting. For the full list of all side effects reported with Renagel, see the package leaflet.Renagel must not be used in people with hypophosphataemia (low blood phosphate levels) or with bowel obstruction (a blockage in the gut).

Why has Renagel been approved?

The CHMP decided that Renagel's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Renagel?

A risk management plan has been developed to ensure that Renagel is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Renagel, including the appropriate precautions to be followed by healthcare professionals and patients.

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Renvela

What is Renvela and what is it used for?

Renvela is a medicine used to control hyperphosphataemia (high blood phosphate levels) in:• adult patients on dialysis (a technique to remove unwanted substances from the blood);• adults and children from 6 years of age with chronic (long-term) kidney disease.Renvela should be used with other treatments such as calcium supplements and vitamin D to prevent the development of bone disease.It contains the active substance sevelamer carbonate.

How is Renvela used?

Renvela is available as tablets (800 mg) and as powder (0.8 g, 1.6 g and 2.4 g) in a sachet to be taken 3 times a day with meals.The dose to take depends on the patient's level of blood phosphate and, in case of children, their height and weight. Renvela must not be taken on an empty stomach and patients should keep to their prescribed diets.The medicine can only be obtained with a prescription. For more information about using Renvela, see the package leaflet or contact your doctor or pharmacist.

How does Renvela work?

The active substance in Renvela, sevelamer carbonate, is a phosphate binder. When taken with meals, it attaches in the gut to phosphate from food, thereby preventing the phosphate from being absorbed into the body and helping reduce phosphate levels in the blood.

What benefits of Renvela have been shown in studies?

Renvela has been shown in studies to be effective at lowering levels of blood phosphate in patients with hyperphosphataemia.SendIn two main studies in 110 adults with kidney disease who were on dialysis, Renvela brought phosphate levels down to around 1.5-1.6 mmol/l (which is within or close to the normal range) and was as effective as another authorised medicine Renagel.In a third main study in 49 adults who were not on dialysis, Renvela reduced phosphate levels from 2.0 mmol/l to 1.6 mmol/l.Finally, a main study also showed that Renvela was effective at lowering phosphate levels in 100 children: children who took Renvela had a greater reduction in phosphorous (0.87 mg/dl) than those taking placebo (a dummy treatment) who had a rise in phosphorous of 0.04 mg/dl.

What are the risks associated with Renvela?

The most common side effects with Renvela (which may affect more than 1 in 10 people) are nausea (feeling sick), vomiting, upper abdominal (belly) pain and constipation. For the full list of side effects with Renvela, see the package leaflet.Renvela must not be used in people with low blood phosphate levels or with bowel obstruction (a blockage in the gut). For the full list of restrictions, see the package leaflet.

Why is Renvela authorised in the EU?

Studies show that Renvela is effective at reducing levels of blood phosphate in patients with hyperphosphataemia, and its side effects are considered manageable. The European Medicines Agency therefore concluded that Renvela's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Renvela?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Renvela have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Renvela are continuously monitored. Side effects reported with Renvela are carefully evaluated and any necessary action taken to protect patients.

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Repaglinide Accord

What is Repaglinide Accord?

Repaglinide Accord is a medicine that contains the active substance repaglinide. It is available as round tablets (0.5 mg, 1 mg and 2 mg).Repaglinide Accord is a 'generic medicine'. This means that Repaglinide Accord is similar to a 'reference medicine' already authorised in the European Union (EU) called NovoNorm. For more information on generic medicines, see the question-and-answer document here.

What is Repaglinide Accord used for?

Repaglinide Accord is used in patients who have type 2 diabetes (non-insulin-dependent diabetes). It is used together with diet and exercise to lower blood glucose (sugar) levels in patients whose hyperglycaemia (high blood glucose levels) cannot be controlled by diet, weight reduction and exercise. Repaglinide Accord may also be used with metformin (another anti-diabetes medicine) in type 2 diabetes patients whose blood glucose levels are not satisfactorily controlled on metformin alone.The medicine can only be obtained with a prescription.

How is Repaglinide Accord used?

Repaglinide Accord is taken before meals, normally up to 15 minutes before each main meal. The dose is adjusted to give the best control. A doctor should regularly test the patient's blood glucose to find the lowest effective dose. Repaglinide Accord can also be used for type 2 diabetes patients whoseblood glucose levels are usually controlled well on diet, but are experiencing temporary loss of blood glucose control.The recommended starting dose is 0.5 mg. This dose may need to be increased after one or two weeks.If patients are transferred from another anti-diabetes medicine, the recommended starting dose is 1 mg.Repaglinide Accord is not recommended for patients below 18 years of age because of a lack of information on safety and effectiveness in this age group.

How does Repaglinide Accord work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. Repaglinide Accord helps the pancreas to produce more insulin at mealtimes and is used to control type 2 diabetes.

How has Repaglinide Accord been studied?

Because Repaglinide Accord is a generic medicine, studies in patients have been limited to tests to determine that it is bioequivalent to the reference medicine. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Repaglinide Accord?

Because Repaglinide Accord is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why has Repaglinide Accord been approved?

The CHMP concluded that, in accordance with EU requirements, Repaglinide Accord has been shown to have comparable quality and to be bioequivalent to the reference medicine. Therefore, the CHMP's view was that, as for NovoNorm, the benefit outweighs the identified risk. The Committee recommended that Repaglinide Accord be given marketing authorisation.

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Repaglinide Krka

What is Repaglinide Krka?

Repaglinide Krka is a medicine that contains the active substance repaglinide. It is available as round tablets (white: 0.5 mg; yellow: 1 mg; pink: 2 mg).Repaglinide Krka is a 'generic medicine'. This means that Repaglinide Krka is similar to a 'reference medicine' already authorised in the European Union (EU) called NovoNorm. For more information on generic medicines, see the question-and-answer document here.

What is Repaglinide Krka used for?

Repaglinide Krka is used in patients who have type 2 diabetes (non-insulin-dependent diabetes). It is used together with diet and exercise to lower blood glucose (sugar) levels in patients whose hyperglycaemia (high blood glucose levels) cannot be controlled by diet, weight reduction and exercise.The medicine can only be obtained with a prescription.

How is Repaglinide Krka used?

Repaglinide Krka is taken before meals, normally up to 15 minutes before each main meal. The dose is adjusted to give the best control. A doctor should regularly test the patient's blood glucose to find the lowest effective dose. Repaglinide Krka can also be used for type 2 diabetes patients whose blood glucose levels are usually controlled well on diet, but are experiencing temporary loss of blood glucose control.The recommended starting dose is 0.5 mg. This dose may need to be increased after one or two weeks. If patients are transferred from another anti-diabetes medicine, the recommended starting dose is 1 mg.Repaglinide Krka is not recommended for patients below 18 years of age because of a lack of information on safety and effectiveness in this age group.

How does Repaglinide Krka work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. Repaglinide Krka helps the pancreas to produce more insulin at mealtimes and is used to control type 2 diabetes.

How has Repaglinide Krka been studied?

Because Repaglinide Krka is a generic medicine, studies have been limited to tests to determine that it is bioequivalent to the reference medicine, NovoNorm. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefit and risk of Repaglinide Krka?

Because Repaglinide Krka is a generic medicine and is bioequivalent to the reference medicine, its benefit and risk are taken as being the same as the reference medicine.

Why has Repaglinide Krka been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements, Repaglinide Krka has been shown to have comparable quality and to be bioequivalent to NovoNorm. Therefore, the CHMP's view was that, as for NovoNorm, the benefit outweighs the identified risk. The Committee recommended that Repaglinide Krka be given marketing authorisation.

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Repaglinide Teva

What is Repaglinide Teva?

Repaglinide Teva is a medicine that contains the active substance repaglinide. It is available as round tablets (blue: 0.5 mg; yellow: 1 mg; peach: 2 mg).Repaglinide Teva is a 'generic medicine'. This means that Repaglinide Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called NovoNorm. For more information on generic medicines, see the question-and-answer document here.

What is Repaglinide Teva used for?

Repaglinide Teva is used in patients who have type 2 diabetes (non-insulin-dependent diabetes). It is used together with diet and exercise to lower blood glucose (sugar) levels in patients whose hyperglycaemia (high blood glucose levels) cannot be controlled by diet, weight reduction and exercise. Repaglinide Teva may also be used with metformin (another anti-diabetes medicine) in type 2 diabetes patients whose blood glucose levels are not satisfactorily controlled on metformin alone.

How is Repaglinide Teva used?

Repaglinide Teva is taken before meals, normally up to 15 minutes before each main meal. The dose is adjusted to give the best control. A doctor should regularly test the patient's blood glucose to find the lowest effective dose. Repaglinide Teva can also be used for type 2 diabetes patients whose blood glucose levels are usually controlled well on diet, but are experiencing temporary loss of blood glucose control.The recommended starting dose is 0.5 mg. This dose may need to be increased after one or two weeks. If patients are transferred from another anti-diabetes medicine, the recommended starting dose is 1 mg.

How does Repaglinide Teva work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. Repaglinide Teva helps the pancreas to produce more insulin at mealtimes and is used to control type 2 diabetes.

How has Repaglinide Teva been studied?

Because Repaglinide Teva is a generic medicine, studies have been limited to tests to determine that it is bioequivalent to the reference medicine (this means that the two medicines produce the same levels of the active substance in the body).

What are the benefit and risk of Repaglinide Teva?

Because Repaglinide Teva is a generic medicine and is bioequivalent to the reference medicine, its benefit and risk are taken as being the same as those of the reference medicine.

Why has Repaglinide Teva been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements, Repaglinide Teva has been shown to have comparable quality and to be bioequivalent to NovoNorm. Therefore, the CHMP's view was that, as for NovoNorm, the benefit outweighs the identified risk. The Committee recommended that Repaglinide Teva be given marketing authorisation.

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Repatha

What is Repatha and what is it used for?

Repatha is a medicine for lowering levels of fats in the blood.It is used to reduce blood fat levels in patients with primary hypercholesterolaemia (high blood cholesterol levels caused by a genetic abnormality), homozygous familial hypercholesterolaemia (a severe form of high blood cholesterol inherited from both parents) and mixed dyslipidaemia (abnormal levels of different fats, including cholesterol).It is also used to reduce the risk of heart problems in patients with atherosclerosis (thickened arterial walls) who have had a heart attack, stroke or other problems of the circulatory system (atherosclerotic heart disease).Repatha is used in combination with a statin or a statin and other fat-lowering medicines. Repatha can also be used without a statin in patients who cannot take statins. Some patients are required to be on a low-fat diet.Repatha contains the active substance evolocumab.

How is Repatha used?

Before starting treatment with Repatha, other causes of excess cholesterol and abnormal fat levels in the blood should be ruled out.Repatha is available as a solution for injection in pre-filled syringes, pre-filled pens and cartridges. The cartridges are to be used together with an automated dosing device called a mini-doser. Injections are given under the skin of the abdomen, thigh or upper arm.The recommended dose for adults with mixed dyslipidaemia or atherosclerotic heart disease and adults and children aged 10 years and above with primary hypercholesterolaemia is either 140 mg every two weeks or 420 mg once a month.For adults and children aged 10 years and above with homozygous familial hypercholesterolaemia, the initial recommended dose is 420 mg once a month. If the desired response is not achieved after 12 weeks of treatment, the dose can be increased up to 420 mg every two weeks.The medicine can only be obtained with a prescription. Patients can self-administer the medicine once they have been properly trained.For more information about using Repatha, see the package leaflet or contact your doctor or pharmacist.

How does Repatha work?

The active substance in Repatha, evolocumab, is a monoclonal antibody (a type of protein) that has been designed to attach to a protein called PCSK9. PCSK9 attaches to cholesterol receptors on the surface of liver cells, causing the receptors to be absorbed and broken down inside the cells. By attaching to PCSK9, Repatha blocks it from interacting with cholesterol receptors on the surface of liver cells. This prevents the receptors from being broken down and therefore increases their numbers on the cell surface, where they can attach to LDL-cholesterol ('bad' cholesterol) and remove it from the bloodstream. This helps to reduce the amount of cholesterol in the blood. Repatha also helps to reduce other fatty substances in the blood of patients with mixed dyslipidaemia.

What benefits of Repatha have been shown in studies?

Hypercholesterolaemia and mixed dyslipidaemiaIn primary hypercholesterolaemia and mixed dyslipidaemia, Repatha was studied in nine main studies involving around 7,400 adult patients, including patients with heterozygous familial disease. Some of the studies looked at Repatha taken on its own, while others studied Repatha in combination with other fat-lowering medicines, including patients on the maximum recommended doses of statins. Some studies compared Repatha with placebo (a dummy treatment) and others with another medicine (ezetimibe). These studies found a substantial reduction in blood levels of LDL-cholesterol (around 60 to 70% more than placebo, and around 40% more than ezetimibe) from week 10 to week 12 of the study and at the end of 12 weeks.Repatha was also studied in a main study involving 157 children aged 10 to 17 years with heterozygous familial hypercholesterolaemia. The study compared Repatha with placebo, both in combination with optimal fat-lowering therapy. This study found that Repatha reduced LDL-cholesterol in the blood by around 38% more than placebo after 24 weeks of treatment.In homozygous familial hypercholesterolaemia, Repatha was studied in two main studies involving 155 patients, which included 14 children older than 12 years. One of these studies showed that Repatha given together with other fat-lowering medicines reduced fat levels in the blood after 12 weeks of treatment (around 15 to 32% more than placebo given on top of other fat-lowering medicines). A second study showed that long-term use of Repatha achieved a sustained reduction of fat levels in the blood in these patients during 28 weeks of treatment.Repatha was also studied in a main study involving 13 children aged 10 to 17 years with homozygous familial hypercholesterolaemia. This study found that long-term use of Repatha, in combination with optimal fat-lowering therapy, achieved a sustained reduction in LDL-cholesterol in these children during 80 weeks of treatment.Atherosclerotic heart diseaseRepatha was studied in more than 27,500 patients with a history of established cardiovascular disease. They received either Repatha or placebo, both with an optimal fat-lowering therapy, for over 2 years on average. In the Repatha group, less than 10% (1,344 of 13,784 patients) had a cardiovascular event (meaning death, heart attack, stroke, hospitalization or surgery due to problems with the blood flow to the heart) during the study compared with just over 11% in the placebo group (1,563 of 13,780 patients).

What are the risks associated with Repatha?

The most common side effects with Repatha (which may affect up to 1 in 100 people) are nasopharyngitis (inflammation of the nose and throat), upper respiratory tract infection (nose and throat infection), back pain, joint pain, flu and reactions at the site of injection. For the full list of side effects and restrictions with Repatha, see the package leaflet.

Why is Repatha authorised in the EU?

The European Medicines Agency decided that Repatha's benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted that across all studies in patients with primary hypercholesterolaemia and mixed dyslipidaemia, Repatha showed an important reduction in LDLcholesterol levels, which is a known risk factor for cardiovascular disease. In patients with atherosclerotic heart disease, Repatha reduced the number of cardiovascular events, in particular heart attacks and strokes. The Agency also noted that for patients with homozygous familial disease there are limited treatment options, and these patients have a higher risk of cardiovascular disease. In this population, including some children over 10 years old, Repatha showed a consistent reduction in LDLcholesterol levels beyond what can be achieved with existing fat-lowering medicines. Repatha's side effects are considered acceptable and manageable.

What measures are being taken to ensure the safe and effective use of Repatha?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Repatha have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Repatha are continuously monitored. Side effects reported with Repatha are carefully evaluated and any necessary action taken to protect patients.

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Replagal

What is Replagal?

Replagal is medicine that contains the active substance agalsidase alfa. It is available as a concentrate to be made into solution for infusion (drip) into a vein.

What is Replagal used for?

Replagal is used to treat patients who have Fabry disease, a rare inherited disorder. Patients with Fabry disease do not have enough of an enzyme called alpha-galactosidase A. This enzyme normally breaks down a fatty substance called globotriaosylceramide (Gb3 or GL-3). If the enzyme is not present, Gb3 cannot be broken down and it builds up in the body's cells, such as kidney cells.People with Fabry disease may have a wide range of signs and symptoms, including severe conditions such as kidney failure, heart problems, and stroke.The medicine can only be obtained with a prescription.

How is Replagal used?

Only a doctor who has experience in treating patients with Fabry disease or other inherited metabolic diseases should give Replagal.Replagal is given once every 2 weeks as an infusion of 0.2 mg per kilogram body weight over 40 minutes. It is intended for long-term use.

How does Replagal work?

Replagal is an enzyme replacement therapy. Enzyme replacement therapy provides patients with the enzyme they are lacking. Replagal is designed to replace the human enzyme alpha-galactosidase A, which is lacking in people with Fabry disease. The active substance in Replagal, agalsidase alfa, is a copy of the human enzyme, produced by a method known as 'recombinant DNA technology': it is made by cells that have received a gene (DNA), which makes them able to produce the enzyme. The replacement enzyme helps to break down the Gb3 and stops it building up in the cells.

How has Replagal been studied?

Replagal has been compared with placebo (a dummy treatment) in two main studies involving a total of 40 male patients. The first study measured the effects of Replagal on pain while the second study measured its effect on the mass of the left ventricle (heart muscle), a measure of the amount of Gb3 in the heart cells. The effect of giving doses weekly rather than every two weeks was also investigated. A further study was carried out in 15 female patients. Replagal has also been evaluated in additional studies involving 38 children aged 7 years or above.

What benefit has Replagal shown during the studies?

After 6 months of treatment, Replagal significantly reduced pain in patients compared with placebo. Replagal reduced left ventricle mass by an average of 11.5 g while patients receiving placebo had an increase in left ventricular mass of 21.8 g. The effects in female patients were comparable to those in male patients and weekly dosing had no advantage over standard doses. Children who received Replagal had no unexpected increase in heart mass, and the levels of Gb3 in their blood were reduced.

What is the risk associated with Replagal?

The most common side effects with Replagal (seen in more than 1 patient in 10) are infusionassociated reactions. These include chills, headache, nausea, pyrexia (fever), pain and discomfort, flushing and fatigue (tiredness), and are rarely severe. For the full list of all side effects and restrictions with Replagal, see the package leaflet.

Why has Replagal been approved?

The CHMP decided that for patients with Fabry disease treatment with Replagal might provide longterm clinical benefits. The CHMP decided that Replagal's benefits are greater than its risks and recommended that it be given marketing authorisation.Replagal was originally authorised under 'exceptional circumstances', because as the disease is rare, limited information was available at the time of approval. As the company had supplied the additional information requested, the 'exceptional circumstances' ended on 20 July 2015.

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Resolor

What is Resolor?

Resolor is a medicine that contains the active substance prucalopride. It is available as tablets (1 and 2 mg).

What is Resolor used for?

Resolor is used to treat symptoms of chronic (long-term) constipation in adults for whom laxatives (medicines that trigger bowel movements) do not work well enough.The medicine can only be obtained with a prescription.

How is Resolor used?

The recommended dose of Resolor is 2 mg taken once a day. Patients aged over 65 years should start with a 1 mg dose once a day, and this can be increased to 2 mg once a day if needed.

How does Resolor work?

The active substance in Resolor, prucalopride, is a '5-HT4 receptor agonist'. This means that it works like a substance in the body called 5-hydroxytryptamine (5-HT, also known as serotonin) and attaches to receptors for 5-HT in the gut called '5-HT4 receptors'.When 5-HT binds to these receptors, it normally stimulates movement in the gut. In the same way, when prucalopride attaches to and stimulates these receptors, it increases this movement and allows the bowels to empty faster.

How has Resolor been studied?

Resolor (2 or 4 mg once a day) was compared with placebo (a dummy treatment) in three main studies involving 1,999 patients with chronic constipation, 88% of whom were women. The patients had not responded well enough to previous treatment with laxatives.Resolor 2 mg once a day was also compared with placebo in another main study involving 374 men with chronic constipation.The main measure of effectiveness in the studies was the number of patients who completely emptied their bowels at least three times a week over a 12 week period without the help of laxatives.

What benefit has Resolor shown during the studies?

Resolor was more effective than placebo at treating chronic constipation. Over the 12-week period, 24% (151 out of 640) of patients who received Resolor 2 mg completely emptied their bowels at least three times a week, compared with 11% (73 out of 645) of patients who received placebo. The result from patients who received Resolor at the higher dose of 4 mg was similar to those who took the 2 mg dose.In the study of men with chronic constipation, 38% of patients treated with Resolor 2 mg (67 out of 177) completely emptied their bowels at least three times a week, compared with 18% of those given placebo (32 out of 181).

What is the risk associated with Resolor?

The most common side effects with Resolor (seen in more than 1 patient in 10) are headache, nausea (feeling sick), diarrhoea and abdominal (tummy) pain. For the full list of all side effects reported with Resolor, see the package leaflet.Resolor must not be used in patients with kidney problems requiring dialysis (a blood clearance technique). It must also not be used in patients with intestinal perforation or obstruction, severe inflammatory conditions of the intestines such as Crohn's disease, ulcerative colitis (inflammation of the large intestine causing ulceration and bleeding) and toxic megacolon and megarectum (very serious complications of colitis). For the full list of restrictions, see the package leaflet.

Why has Resolor been approved?

The CHMP decided that Resolor's benefits are greater than its risks and recommended that it be given marketing authorisation..

What measures are being taken to ensure the safe and effective use of Resolor?

A risk management plan has been developed to ensure that Resolor is used as safely as possible.Based on this plan, safety information has been included in the summary of product characteristics andthe package leaflet for Resolor, including the appropriate precautions to be followed by healthcare professionals and patients.

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Respreeza

What is Respreeza and what is it used for?

Respreeza is a medicine used in adults with alpha1-proteinase inhibitor deficiency, an inherited disorder that can cause lung problems such as increasing shortness of breath and which may also affect the liver. Respreeza is used to slow down damage to the lungs in patients with severe disease.Respreeza contains the active substance human alpha1-proteinase inhibitor.

How is Respreeza used?

Respreeza is available as a powder and solvent to be made into a solution for infusion (drip) into a vein. The first infusion should be given under the supervision of a healthcare professional experienced in the treatment of alpha1-proteinase inhibitor deficiency. Subsequent infusions can be given by a caregiver or by the patient.The recommended dose of Respreeza is 60 mg per kilogram body weight, given once a week. The infusion should last around 15 minutes.The medicine can only be obtained with a prescription. For further information, see the package leaflet.

How does Respreeza work?

The active substance in Respreeza, human alpha1-proteinase inhibitor, is a natural protein in the blood which protects lung tissue from damage. It is obtained from human blood and works by replacing the protein that is lacking in patients with alpha1-proteinase inhibitor deficiency.

What benefits of Respreeza have been shown in studies?

Respreeza has been shown to slow down lung damage in one main study involving 180 patients with lung damage due to alpha1-proteinase inhibitor deficiency. In the study, Respreeza was compared with placebo (a dummy treatment) and the main measure of effectiveness was the decrease in lung density. Lung density is an indicator of the extent of lung damage: the bigger the decrease in lung density, the greater is the damage to the lung. The decrease in lung density after 24 months was around 2.6 g/l in patients who received Respreeza, compared with a decrease of around 4.2 g/l in patients receiving placebo.

What are the risks associated with Respreeza?

The most common side effects with Respreeza (which may affect up to 1 in 10 people) are dizziness, headache, dyspnoea (shortness of breath) and nausea. Allergic reactions have been observed during treatment, some of which were severe.Because of the risk of severe allergic reactions, Respreeza must not be used in patients who are lacking IgA, a protein in the blood, and who have developed antibodies against it because these patients are more prone to allergic reactions. For the full list of all side effects and restrictions with Respreeza, see the package leaflet.

Why is Respreeza approved?

The main study with Respreeza showed that the medicine is effective at slowing down the damage to the lungs in patients with alpha1-proteinase inhibitor deficiency, and this effect is considered relevant for patients with severe disease. Allergic reactions were the main safety concern with Respreeza, but advice on how to manage this risk has been included in the product information. No other major concerns have been identified about the safety of the medicine.Therefore, the Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Respreeza's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Respreeza?

The company that markets Respreeza will carry out a further study to assess whether an increased dose of 120 mg/kg may lead to improved effects compared with the currently recommended dose.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Respreeza have also been included in the summary of product characteristics and the package leaflet.

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Retacrit

What is Retacrit?

Retacrit is a solution for injection. It is available in prefilled syringes containing between 1,000 and 40,000 international units (IU) of the active substance, epoetin zeta.Retacrit is a 'biosimilar' medicine. This means that Retacrit is similar to a biological medicine (the 'reference medicine') that is already authorised in the European Union (EU), and contains a similar active substance to the reference medicine. The reference medicine for Retacrit is Eprex/Erypo, which contains epoetin alfa. For more information on biosimilar medicines, see the question-and-answer document here.

What is Retacrit used for?

Retacrit is used in the following situations:• to treat anaemia (low red blood cell counts) that is causing symptoms in patients with chronic renal failure (long-term, progressive decrease in the ability of the kidneys to work properly) or other kidney problems;• to treat anaemia in adults receiving chemotherapy to treat certain types of cancer and to reduce the need for blood transfusions;• to increase the amount of blood that patients with moderate anaemia can self-donate before surgery, so that their own blood can be given back to them during or after surgery;• to reduce the need for blood transfusions in patients with moderate anaemia about to undergo major bone surgery (such as a hip or knee replacement).The medicine can only be obtained with a prescription.

How is Retacrit used?

Treatment with Retacrit must be started under the supervision of doctors who have experience in the management of patients with the conditions that the medicine is used for.For patients with kidney problems, Retacrit can be injected into a vein or under the skin. For patients receiving chemotherapy, it must be injected under the skin, and for patients about to undergo surgery, it must be injected into a vein. The dose, the frequency of injection and how long Retacrit is used for depend on why it is being used, and are adjusted according to the patient's response. For patients with chronic renal failure or receiving chemotherapy, haemoglobin levels should remain within the recommended range (between 10 and 12 grams per decilitre in adults and between 9.5 and 11 g/dl in children). Haemoglobin is the protein in red blood cells that carries oxygen around the body. The lowest dose that provides adequate control of symptoms should be used.The iron levels of all patients should be checked before treatment to make sure that they are not too low, and iron supplements should be used throughout treatment. Retacrit can be injected under the skin by the patient or their carer if they have been trained appropriately. For full details, see the package leaflet.

How does Retacrit work?

A hormone called erythropoietin stimulates the production of red blood cells from the bone marrow. Erythropoietin is produced by the kidneys. In patients receiving chemotherapy or with kidney problems, anaemia can be caused by a lack of erythropoietin, or by the body not responding enough to the erythropoietin it has naturally. In these cases, erythropoietin is used to replace the missing hormone or to increase red blood cell counts. Erythropoietin is also used before surgery to increase the number of red blood cells to help patients produce more blood for self-donation.The active substance in Retacrit, epoetin zeta, is a copy of human erythropoietin and works in exactly the same way as the natural hormone to stimulate red blood cell production. It is produced by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA), which makes it able to produce epoetin zeta.

How has Retacrit been studied?

Retacrit was studied to show that it is comparable with the reference medicine, Eprex/Erypo, in experimental models and in humans.Retacrit, injected into a vein, was compared with the reference medicine in two main studies involving 922 patients who had anaemia associated with chronic renal failure requiring haemodialysis (a technique for removing waste products from the blood). The first study compared the effects of Retacrit with those of Eprex/Erypo in correcting red blood cell counts in 609 patients over 24 weeks. The second study compared the effects of Retacrit with those of Eprex/Erypo in maintaining red blood cell counts in 313 patients. All of the patients in the second study had been receiving treatment with Eprex/Erypo for at least three months before they were either switched to Retacrit or remained on Eprex/Erypo for 12 weeks. After that, the two groups switched to receiving the other medicine for a further 12 weeks. In both studies, the main measures of effectiveness were the levels of haemoglobin during treatment, as well as the dose of epoetin received.The company also presented the results of two studies looking at the effects of Retacrit injected under the skin: one involved 261 cancer patients receiving chemotherapy, and the other compared Retacrit with Eprex/Erypo in 462 patients with anaemia caused by kidney problems.

What benefit has Retacrit shown during the studies?

Retacrit was as effective as Eprex/Erypo in correcting and maintaining red blood cell counts. In the correction study, haemoglobin levels were around 11.6 g/dl during the last four weeks of the study, having risen from around 8.0 g/dl before treatment. In the study of patients already being treated with an epoetin, haemoglobin levels were maintained at around 11.4 g/dl when the patients were receiving Retacrit and when they were receiving Eprex/Erypo. In both studies, the dose of epoetin received was similar with both medicines.Retacrit was also effective when it was injected under the skin. The study in patients receiving chemotherapy showed that Retacrit brought about similar improvements in haemoglobin levels as those reported in the scientific literature for other epoetins. Retacrit was also as effective as the reference medicine in patients with kidney problems.

What is the risk associated with Retacrit?

As with other medicines containing an epoetin, the most common side effect with Retacrit is an increase in blood pressure, which can sometimes lead to symptoms of encephalopathy (brain problems) such as sudden stabbing migraine-like headache and confusion. Retacrit can also lead to skin rash and influenza (flu)-like symptoms. For the full list of all side effects reported with Retacrit, see the package leaflet.Retacrit should not be used in people who may be hypersensitive (allergic) to epoetin zeta or any of the other ingredients. It must not be used in patients who have developed pure red cell aplasia (reduced or stopped red blood cell production) following treatment with any erythropoietin, patients with hypertension (high blood pressure) that is not controlled, patients about to undergo surgery who have severe cardiovascular (heart and blood vessel) problems including a recent heart attack or stroke, or patients who cannot receive medicines to prevent blood clots.Retacrit must not be used prior to major bone surgery in patients who have a severe disease affecting their arteries or their blood vessels in the heart, neck or brain, including patients who have recently had a heart attack or stroke.

Why has Retacrit been approved?

The CHMP concluded that, in accordance with EU requirements, Retacrit has been shown to have a comparable quality, safety and efficacy profile to Eprex/Erypo. Therefore, the CHMP's view was that, as for Eprex/Erypo, the benefit outweighs the identified risks. The Committee recommended that Retacrit be given marketing authorisation.

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Retsevmo

What is Retsevmo and what is it used for?

Retsevmo is a cancer medicine for use in patients whose cancer is caused by changes in a gene called RET. It can be used for:• advanced non-small cell lung cancer in adults not previously treated with a RET inhibitor;• advanced thyroid cancer in adults who had previously been treated with the cancer medicines sorafenib or lenvatinib or both;• advanced medullary thyroid cancer in patients aged from 12 years.Retsevmo contains the active substance selpercatinib.

How is Retsevmo used?

Retsevmo is available as capsules. The medicine can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the use of cancer treatments.The dose of Retsevmo is 160 mg twice daily, reduced to 120 mg twice daily in patients weighing less than 50 kg. Treatment with Retsevmo can continue until it stops working or the patient has severe side effects.For more information about using Retsevmo, see the package leaflet or contact your doctor or pharmacist.

How does Retsevmo work?

The active substance in Retsevmo, selpercatinib, is a RET inhibitor, which belongs to a broader class of cancer medicines known as tyrosine kinase inhibitors. It blocks the activity of abnormal proteins, which are made by the body due to changes in the RET gene. In patients with such changes, these abnormal proteins can lead to uncontrolled cell growth and cancer. By blocking the proteins, selpercatinib helps to reduce the growth and spread of the cancer cells.

What benefits of Retsevmo have been shown in studies?

In one main study in patients with cancers caused by abnormalities in the RET gene, Retsevmo was effective at reducing tumour size. In this study, Retsevmo was not compared with other medicines or placebo (a dummy treatment).Advanced non-small cell lung cancerIn adults with non-small cell lung cancer who had previously received treatment with platinum-based chemotherapy, the cancer shrank in 64% (67 out of 105) of patients treated with Retsevmo. In previously untreated patients, 84% (58 out of 69) had a complete (no signs of cancer) or partial (shrinkage of the tumour) response to treatment with Retsevmo.Advanced thyroid cancerIn 19 adults with thyroid cancer who had previously been treated with sorafenib or lenvatinib or both, the cancer shrank in 79% of patients.Advanced medullary thyroid cancerIn adults and adolescents aged from 15 years with medullary thyroid cancer, the cancer shrank in 73.5% (111 out of 151) of patients who had previously been treated with cabozantinib or vandetanib, and in 81% (115 out of 142) of patients who had not previously received treatment with cabozantinib or vandetanib.Retsevmo is also expected to be effective in adolescents from 12 years of age with medullary thyroid cancer because the medicine is distributed in, and removed from, the body of these patients in the same way as for adults.

What are the risks associated with Retsevmo?

The most common side effects with Retsevmo (which may affect more than 1 in 10 people) are loss of appetite, headache, dizziness, prolonged QT interval (changes in the heart's electrical activity), high blood pressure, abdominal (belly) pain, diarrhoea, nausea (feeling sick), vomiting, constipation, dry mouth, rash, fever, tiredness, oedema (swelling caused by fluid build-up), bleeding, and blood tests showing changes in liver enzymes (indicating stress on the liver), decreased platelet (components that help the blood clot) and white blood cell counts, decreased magnesium and increased creatinine (indicating kidney problems).The most common serious side effects are abdominal pain, hypersensitivity (allergic reactions), diarrhoea and blood tests showing changes in liver enzymes.For the full list of side effects and restrictions of Retsevmo, see the package leaflet.

Why is Retsevmo authorised in the EU?

Retsevmo was found to be effective at treating cancers involving changes to the RET gene, reducing the size of the cancer in most patients. Its side effects are considered manageable. The European Medicines Agency therefore decided that Retsevmo's benefits are greater than its risks and it can be authorised for use in the EU.Retsevmo has been given 'conditional authorisation'. This means that although the European Medicines Agency decided that the benefits of Retsevmo are greater than its risks, the company will have to provide additional evidence after authorisation. Conditional authorisation is granted on the basis of less comprehensive data than are normally required. It is granted for medicines that fulfil an unmetmedical need to treat serious diseases and when the benefits of having them available earlier outweigh any risks associated with using the medicines while waiting for further evidence. Every year, the Agency will review any new information that becomes available and this overview will be updated as necessary.

What information is still awaited for Retsevmo?

Since Retsevmo has been given conditional authorisation, the company that markets Retsevmo will provide results of studies to confirm its long-term effectiveness and safety, particularly in comparison with other medicines that are used for the cancers for which Retsevmo has been authorised.

What measures are being taken to ensure the safe and effective use of Retsevmo?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Retsevmo have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Retsevmo are continuously monitored. Side effects reported with Retsevmo are carefully evaluated and any necessary action taken to protect patients.

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Revatio

What is Revatio and what is it used for?

Revatio is a medicine used to treat adults and children from 1 year of age with pulmonary arterial hypertension (PAH, abnormally high blood pressure in the arteries of the lungs). In adults, Revatio is used in patients with class II (slight limitation of physical activity) or class III (marked limitation of physical activity) PAH.Revatio contains the active substance sildenafil.

How is Revatio used?

Revatio can only be obtained with a prescription and treatment should only be started and monitored by a doctor who has experience in the treatment of PAH.Revatio is available as tablets (20 mg), a solution for injection (0.8 mg/ml) and a powder to be made up into an oral suspension (10 mg/ml). The solution for injection is for adults who cannot take Revatio tablets or oral suspension for a short period, but whose condition is stable.In adults, Revatio is taken at a dose of 20 mg three times a day. Lower doses of Revatio may be needed in patients taking some medicines that affect the way Revatio is broken down in the body. In adults who cannot take the tablets or oral suspension, the solution for injection is injected into a vein by a doctor or nurse at a dose of 10 mg (12.5 ml) three times a day.In children aged 1 to 17 years, the recommended dose is 10 mg three times a day in children weighing less than 20 kg and 20 mg three times a day in those over 20 kg. Higher doses should not be used.

How does Revatio work?

PAH is a debilitating disease where there is severe constriction (narrowing) of the blood vessels of the lungs. This leads to high blood pressure in the vessels taking blood from the heart to the lungs and reduces the amount of oxygen that can get into the blood in the lungs, making physical activity more difficult.The active substance in Revatio, sildenafil, belongs to a group of medicines called 'phosphodiesterase type 5 (PDE5) inhibitors', which means that it blocks the PDE5 enzyme. This enzyme is found in the blood vessels of the lungs. When it is blocked, a substance called 'cyclic guanine monophosphate' (cGMP) cannot be broken down, so that it remains in the vessels where it causes relaxation and widening of the blood vessels. In patients with PAH, sildenafil widens the blood vessels of the lungs, which lowers the blood pressure and improves symptoms.

What benefits of Revatio have been shown in studies?

Revatio was more effective than placebo (a dummy treatment) at improving exercise capacity in one main study in adults and another main study in children.The main study in adults involved 277 patients with PAH, most of whom had class II or class III disease. Change in exercise capacity was measured as the improvement in the distance patients could walk in 6 minutes after 12 weeks of treatment. Before treatment, adults with class II disease could walk an average of 378m in 6 minutes. After 12 weeks, this distance had increased by 49 m more in the patients taking 20 mg Revatio than in the patients taking placebo. Adults with class III disease could walk an average of 326 m at the start of the study. This distance had increased by 45 m more in the patients taking 20 mg Revatio than in those taking placebo after 12 weeks.The main study in children involved 235 children aged 1 to 17 years with PAH. Change in exercise capacity in this study was measured as the improvement in the maximum volume of oxygen used during exercise after 16 weeks of treatment, in children able to perform the exercise tests. After 16 weeks, the maximum volume of oxygen the children used during exercise increased on average by 10.2% with Revatio compared with 0.5% with placebo.The company also presented the results of studies showing that the tablets were equivalent to the oral suspension (produced similar levels of sildenafil in the blood), and that a 10 mg injection was equivalent to a 20 mg tablet.

What are the risks associated with Revatio?

The most common side effects with Revatio in adults (which may affect more than 1 patient in 10) are headache, flushing (reddening of the skin), dyspepsia (heartburn), diarrhoea and pain in arm or leg. Side effects are similar with the solution for injection. In children, the most common side effects (which may affect up to 1 patient in 10) are throat and nose infections, headache, vomiting, fever, diarrhoea, flu and nosebleeds. For the full list of all side effects reported with Revatio, see the package leaflet.Revatio must not be taken by patients who have ever had a problem with blood flow in the eye called non-arteritic anterior ischaemic optic neuropathy (NAION). Revatio must not be taken with nitrates (medicines used to treat angina), or with medicines that could affect the way that Revatio is brokendown in the body, such as ketoconazole or itraconazole (antifungal medicines) and ritonavir (used to treat HIV infection). It must not be started in patients with severe liver disease or severe hypotension (very low blood pressure), or who have recently had a stroke or heart attack, because Revatio has not been studied in these groups of patients. For the full list of restrictions, see the package leaflet.

Why is Revatio approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Revatio's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded that Revatio provides an alternative treatment option for PAH.

What measures are being taken to ensure the safe use of Revatio?

The company that markets Revatio will agree with each European Union Member State on how the solution for injection will be distributed. It will also ensure that doctors and pharmacists who will prescribe or dispense the solution for injection in each Member State receive information about how it should be used and how to report side effects such as low blood pressure.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Revatio have also been included in the summary of product characteristics and the package leaflet.

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Revestive

What is Revestive and what is it used for?

Revestive is a medicine for treating short bowel syndrome (or short gut) in adults and children aged 4 months and above.Short bowel syndrome is a condition in which nutrients and fluids are not properly absorbed by the gut, usually because a large part of the intestine has been surgically removed.Short bowel syndrome is rare, and Revestive was designated an 'orphan medicine' (a medicine used in rare diseases) on 11 December 2001. Further information on the orphan designation can be found on the EMA website.Revestive contains the active substance teduglutide.

How is Revestive used?

The medicine can only be obtained with a prescription, and treatment should be started under the supervision of a doctor with experience in treating short bowel syndrome.Revestive is given once a day as an injection under the skin of the abdomen (belly). Patients or their carers can inject the medicines once they have received adequate training. Treatment should be stopped if a benefit is not observed.For more information about using Revestive, see the package leaflet or contact your doctor or pharmacist.

How does Revestive work?

The active substance in Revestive, teduglutide, is similar to human glucagon-like peptide 2 (GLP-2), a hormone made in the gut that increases absorption of nutrients from the intestine.Teduglutide works in a similar way to GLP-2 and increases intestinal absorption by increasing blood flow to and from the gut, reducing the speed at which food passes through the intestine and reducingacid secretions in the stomach which can interfere with absorption. Teduglutide has the advantage of lasting longer than GLP-2 in the body.

What benefits of Revestive have been shown in studies?

Patients with short bowel syndrome are usually given nutrients as an infusion directly into their veins (parenteral nutrition). Revestive has been shown in three studies to reduce the amount of parenteral nutrition that patients need.In one study in adults, 63% (27 out of 43) of those who received Revestive had their parenteral nutrition at 20 weeks reduced by at least a fifth and maintained this reduced intake at 24 weeks. This compares with 30% (13 out of 43) of those given placebo (a dummy treatment).In a second study in children, 53% (8 out of 15) of those who received Revestive had their parenteral nutrition at 12 weeks reduced by at least a tenth, while none (0 out of 5) of the patients who received a standard treatment achieved the same.In a third study in infants aged 4 to 12 months (corrected for gestational age), 60% (3 out of 5) of infants given Revestive had their parenteral nutrition at 24 weeks reduced by at least a fifth, while 20% (1 out of 5) of the infants who received a standard treatment achieved the same.Additional data in young children suggest that the medicine can be expected to behave in the same way across age groups.

What are the risks associated with Revestive?

For the full list of side effects and restrictions with Revestive, see the package leaflet.The most common side effects with Revestive (which may affect more than 1 in 10 people) include belly ache and swollen stomach, respiratory tract infections (infections of the throat, sinuses, airways or lungs), reddening, pain or swelling at the site of injection, nausea, headache and vomiting. In addition, patients with a stoma (an artificial opening at the front of the abdomen to collect faeces or urine) commonly experienced complications, such as swelling of the stoma.Revestive must not be used in patients who have, or are suspected to have, cancer. It must also not be used in patients who have had a gastrointestinal cancer (cancer of the stomach, gut or liver) in the last five years.

Why is Revestive authorised in the EU?

Studies show that Revestive is beneficial for patients with short bowel syndrome as it significantly reduces the amount of parenteral nutrition they need. Patients who need high volumes of parenteral nutrition may benefit from a significant reduction, whereas patients in need of low amounts may have the chance to be weaned off completely. Furthermore, Revestive showed an acceptable safety profile, with the majority of side effects being mild to moderate.The European Medicines Agency therefore decided that Revestive's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Revestive?

The company will provide more data about the medicine's safety from a registry of patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Revestive have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Revestive are continuously monitored. Suspected side effects reported with Revestive are carefully evaluated and any necessary action taken to protect patients.

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Revinty Ellipta

What is Revinty Ellipta and what is it used for?

Revinty Ellipta is an inhaler for treating asthma and chronic obstructive pulmonary disease (COPD).In asthma, it is used for regular treatment of patients from 12 years of age:• whose symptoms are not controlled with an inhaled corticosteroid and an inhaled short-acting beta-2 agonist;• whose symptoms are adequately controlled with both inhaled corticosteroids and a long-acting beta-2 agonist.In COPD, it is used in adults who have flare-ups of the disease despite regular bronchodilator treatment (treatment to widen the airways).Revinty Ellipta contains the active substances fluticasone furoate and vilanterol.This medicine is the same as Relvar Ellipta, which is already authorised in the EU. The company that makes Relvar Ellipta has agreed that its scientific data can be used for Revinty Ellipta ('informed consent').

How is Revinty Ellipta used?

Relvar Ellipta is available as an inhaler in two strengths (92/22 micrograms and 184/22 micrograms). The doctor will decide which inhaler the patient should use. The dose is one inhalation ('puff') into the mouth once a day at the same time each day.Revinty Ellipta can only be obtained with a prescription. For more information about using Revinty Ellipta, see the package leaflet or contact your doctor or pharmacist.

How does Revinty Ellipta work?

Revinty Ellipta contains two active substances that work in different ways to improve breathing in patients with asthma and COPD.Fluticasone furoate is a corticosteroid. It works on various types of immune cells, blocking the release of substances involved in inflammation. This reduces inflammation in the airways and improves the patient's breathing.Vilanterol is a long-acting beta-2 agonist. It attaches to beta-2 receptors in the airways and causes the muscles of the airways to relax and widen, allowing the patient to breathe more easily.

What benefits of Revinty Ellipta have been shown in studies?

AsthmaThree studies in over 3,200 patients showed that Revinty Ellipta improves breathing and reduces flare- ups in patients with persistent asthma.In two of the studies, Revinty Ellipta 92/22 increased the volume of air a patient could breathe out in one second (FEV1) by 36 ml more than fluticasone furoate alone and 172 ml more than placebo (a dummy treatment). Revinty Ellipta 184/22 also improved FEV1 by 193 ml more than fluticasone furoate and 210 ml more than another inhaler containing fluticasone propionate.In a third study, fewer patients taking Revinty Ellipta 92/22 had at least one severe flare-up after a year of treatment than those taking fluticasone furoate alone (13% versus 16%).A fourth study in 1,522 patients showed that Revinty Ellipta was as effective as another medicine containing a corticosteroid (fluticasone propionate) and a long-acting beta-2 agonist (salmeterol). These patients were already well controlled with the comparator medicine and Revinty Ellipta treatment was able to maintain their FEV1.COPDFour studies in over 5,500 patients showed that Revinty Ellipta improves breathing and reduces flare ups of symptoms in patients with COPD.The first study showed that Revinty Ellipta 92/22 improved average FEV1 by 115 ml more than placebo, and a second study showed that Revinty Ellipta 184/22 improved average FEV1 by 131 ml more than placebo.In two further studies, Revinty Ellipta reduced the number of flare-ups by between 13 and 34% more than vilanterol alone

What are the risks associated with Revinty Ellipta?

The most common side effects with Revinty Ellipta (which may affect more than 1 in 10 people) are headache and nasopharyngitis (inflammation of the nose and throat). More serious side effects include pneumonia and fractures (seen in up to 1 in 10 people), which were reported more often in patients with COPD than those with asthma. For the full list of side effects of Revinty Ellipta, see the package leaflet.

Why is Revinty Ellipta authorised in the EU?

Revinty Ellipta improves breathing and reduces flare ups of symptoms in patients with asthma and COPD. Regarding its safety, the most frequent side effects reported with Revinty Ellipta were similar to those seen with other COPD and asthma treatments; an increased incidence of pneumonia was observed in patients with COPD.The European Medicines Agency concluded that Revinty Ellipta's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Revinty Ellipta?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Revinty Ellipta have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Revinty Ellipta are continuously monitored. Side effects reported with Revinty Ellipta are carefully evaluated and any necessary action taken to protect patients.

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Revlimid

What is Revlimid and what is it used for?

Revlimid is a medicine used for the treatment of certain cancers and serious conditions affecting blood cells and bone marrow, namely multiple myeloma, myelodysplastic syndromes and mantle cell and follicular lymphoma.In multiple myeloma, a cancer of a type of white blood cells called plasma cells, Revlimid is used:• in adults who have had a stem cell transplant (a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from a donor);• in adults with previously untreated (newly diagnosed) multiple myeloma, who cannot have stem cell transplantation. It is used in combination with dexamethasone, or bortezomib and dexamethasone, or melphalan and prednisone;• in adults whose disease has been treated at least once. It is used in combination with dexamethasone.In myelodysplastic syndromes, a group of bone marrow disorders that cause anaemia (low red blood cell counts), Revlimid is used in patients who need blood transfusions to manage their anaemia. It is used in patients with a genetic abnormality (called deletion 5q) when other treatments are not adequate.In mantle cell lymphoma and follicular lymphoma, blood cancers that affect a type of white blood cell called B lymphocytes, Revlimid is used in adults whose disease has come back after treatment or does not improve with treatment. In follicular lymphoma it is used with the medicine rituximab.Revlimid contains the active substance lenalidomide.

How is Revlimid used?

Revlimid can only be obtained with a prescription and treatment should be supervised by doctors who have experience in the use of cancer medicines. It is available as capsules (2.5, 5, 7.5, 10, 15, 20 and 25 mg) to be taken by mouth.Treatment is given in cycles, with Revlimid being used once a day on certain days of the cycles.Treatment cycles are continued until the disease is no longer being controlled or side effects becomeunacceptable. The dose of Revlimid depends on the disease it is being used for, the patient's overall health and blood test results. The dose may need to be reduced or treatment interrupted in case of certain side effects.For more information about using Revlimid, see the package leaflet or contact your doctor or pharmacist.

How does Revlimid work?

The active substance in Revlimid, lenalidomide, is an immunomodulator. This means that it affects the activity of the immune system (the body's natural defences). Lenalidomide works in several ways: it blocks the development of abnormal cells, prevents the growth of blood vessels within tumours and also stimulates specialised cells of the immune system to attack the abnormal cells.

What benefits of Revlimid have been shown in studies?

Multiple myelomaRevlimid was more effective than placebo (a dummy treatment) in two main studies in 1,074 patients with newly diagnosed multiple myeloma and who had had stem cell transplantation. In the first study, patients taking Revlimid lived longer on average without their disease getting worse (57 months) than patients in the placebo group (29 months). In the second study, patients taking Revlimid also lived longer without their disease getting worse (44 months) than patients in the placebo group (24 months).In newly diagnosed multiple myeloma, Revlimid has been studied in two main studies involving 2,082 patients. The first study compared Revlimid with placebo, both taken with melphalan and prednisone. In this study, patients taking Revlimid (plus melphalan and prednisone) lived longer without their disease getting worse (27 months) than patients receiving placebo (13 months). In the second study, Revlimid taken with low-dose dexamethasone was compared with standard treatment of melphalan, prednisone and thalidomide. It took 26 months for the disease to get worse in patients taking Revlimid plus dexamethasone, compared with 22 months for those on standard treatment.Another main study involved 523 patients with multiple myeloma who had not been treated previously and for whom stem cell transplantation had not been planned. Patients treated with Revlimid and dexamethasone lived for around 30 months on average without their disease getting worse compared with around 43 months for those who also received bortezomib.Revlimid was also studied in two main studies involving 704 patients with previously treated multiple myeloma. In both studies, Revlimid was compared with placebo, both taken with dexamethasone. The results of the two studies taken together showed that, on average, patients taking Revlimid lived longer without their disease getting worse (48 weeks) than patients receiving placebo (20 weeks).Myelodysplastic syndromesTwo main studies have also been carried out involving a total of 353 patients with lower risk myelodysplastic syndromes. The first study did not compare Revlimid with any other treatment, while the second study compared it with placebo. In the first study, 97 out of 148 patients (66%) taking 10 mg Revlimid did not need a blood transfusion for at least 8 weeks. In the second study, 38 out of 69 patients (55%) taking 10 mg Revlimid did not need a blood transfusion for at least 26 weeks, compared with 4 out of 67 patients (6%) taking placebo.Mantle cell lymphomaOne main study involved 254 patients with mantle cell lymphoma that had come back after previous treatment or had not improved on previous treatment. Revlimid was compared with a medicine chosen by the patients' doctors. The average time before the disease got worse was 38 weeks in those treated with Revlimid, compared with 23 weeks in those given other treatments.Follicular lymphomaThe main study involved 358 patients with slow-growing blood cancers (marginal zone lymphoma or follicular lymphoma) that had come back or not improved after previous treatment: 295 of them had follicular lymphoma. The study compared Revlimid with placebo when added to another cancer medicine, rituximab. The average length of time that patients lived without follicular lymphoma getting worse was around 39 months with Revlimid plus rituximab, compared with 14 months with the placebo plus rituximab.

What are the risks associated with Revlimid?

The most common side effects with Revlimid when used for the treatment of multiple myeloma are: bronchitis (inflammation of the airways in the lungs), nasopharyngitis (inflammation of the nose and throat), cough, gastroenteritis (inflammation of the stomach and intestines with diarrhoea and vomiting), upper respiratory tract infection (nose and throat infections), tiredness, neutropenia (low levels of neutrophils, a type of white blood cell), constipation, diarrhoea, muscle cramps, anaemia, thrombocytopenia (low platelet counts), rash, back pain, insomnia (difficulty sleeping), decreased appetite, fever, peripheral oedema (swelling of the limbs due to fluid retention), leucopenia (low white blood cell counts), weakness, peripheral neuropathy (nerve damage in the hands and feet) and hypocalcaemia (low levels of calcium in the blood).The most common side effects with Revlimid when used for the treatment of myelodysplastic syndromes are neutropenia, thrombocytopenia, diarrhoea, constipation, nausea (feeling sick), itching, rash, tiredness and muscle spasms.The most common side effects with Revlimid when used for the treatment of mantle cell lymphoma are neutropenia, anaemia, diarrhoea, tiredness, constipation, fever and rash.The most common side effects with Revlimid when used to treat follicular lymphoma are neutropenia, leucopenia, diarrhoea, constipation, tiredness and cough.The most serious side effects with Revlimid are: neutropenia, venous thromboembolism (blood clots in the veins) including pulmonary embolism (blood clots in the lungs), lung infections including pneumonia, hypotension (low blood pressure), dehydration, kidney failure, febrile neutropenia (neutropenia with fever), diarrhoea and anaemia.Lenalidomide can be harmful to the unborn child. Therefore, Revlimid must not be used in women who are pregnant. It must also not be used in women who could become pregnant, unless they take all the necessary steps to ensure that they are not pregnant before treatment and that they do not become pregnant during or soon after treatment.For the full list of side effects and restrictions of Revlimid, see the package leaflet.

Why is Revlimid authorised in the EU?

Revlimid prolongs the time patients live without their cancer getting worse and reduces the need for blood transfusions in myelodysplastic syndromes. Side effects are considered manageable. Therefore, the European Medicines Agency decided that Revlimid's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Revlimid?

The company that makes Revlimid will provide a letter and educational kits for healthcare professionals, and brochures for patients, explaining that the medicine can be harmful to the unborn child and detailing the steps that need to be taken for the medicine to be used safely. It will also supply cards to patients about the safety measures patients should take.The company has also set up a pregnancy prevention programme in each member state and will collect information on the medicine's use outside its approved uses. The boxes containing Revlimid capsules also include a warning stating that lenalidomide can be harmful to the unborn child.In addition, the company will carry out a study in patients with myelodysplastic syndromes to gather further safety data, as well as a safety study in patients with newly diagnosed multiple myeloma not eligible for transplantation.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Revlimid have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Revlimid are continuously monitored. Side effects reported with Revlimid are carefully evaluated and any necessary action taken to protect patients.

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Revolade

What is Revolade and what is it used for?

Revolade is a medicine that is used for the treatment of:• primary immune thrombocytopenia (ITP), a disease in which the patient's immune system destroys platelets (components in the blood that help it to clot). Patients with ITP have low platelet counts in the blood (thrombocytopenia) and are at risk of bleeding. Revolade is used in patients from 1 year of age for whom treatment with medicines such as corticosteroids or immunoglobulins has not worked. In children and adolescents, the medicine is used when they have had the disease for at least 6 months;• thrombocytopenia in adults with chronic (long-term) hepatitis C, a liver disease caused by the hepatitis C virus. Revolade is used when the thrombocytopenia is too severe to allow interferonbased therapy (a type of treatment for hepatitis C);• acquired severe aplastic anaemia (a disease in which the bone marrow does not make enough blood cells or platelets). Revolade is used in adult patients whose disease is not controlled by immunosuppressive therapy (medicines that lower the body's immune defences) and cannot receive haematopoietic stem cell transplantation (where the patient's bone marrow is replaced by stem cells from a donor to form new bone marrow).Revolade contains the active substance eltrombopag.

How is Revolade used?

Revolade is available as tablets and as a powder to prepare a suspension (a liquid) to be taken by mouth. The medicine can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in treating blood diseases or chronic hepatitis C and its complications.The dose depends on the patient's age and the disease for which Revolade is being used; it is adjusted as needed to maintain the appropriate platelet level.For more information about using Revolade, see the package leaflet or contact your doctor or pharmacist.Send us a

How does Revolade work?

In the body, a hormone called 'thrombopoietin' stimulates the production of platelets by attaching to certain receptors (targets) in the bone marrow. The active substance in Revolade, eltrombopag, also attaches to and stimulates the thrombopoietin receptors. This increases the production of platelets, improving platelet counts.

What benefits of Revolade have been shown in studies?

ITP in adultsFor the treatment of ITP in adults, Revolade was compared with placebo (a dummy treatment) in two main studies involving a total of 311 patients who had previously been treated, but those treatments had not worked or the disease had come back.Revolade was more effective than placebo: in the first study, 59% of the patients who took Revolade (43 out of 73) achieved a platelet count of at least 50,000 per microlitre (which is considered adequate to prevent bleeding complications) after 6 weeks of treatment, compared with 16% of those who took placebo (6 out of 37). In the second study, the 135 patients taking Revolade were around 8 times more likely to reach the target platelet count of between 50,000 and 400,000 per microlitre during the 6 months of treatment than the 62 patients who were given placebo.A separate analysis of these data, in addition to data from another study, examined if the response to the medicine differed depending on when adult patients were diagnosed before they started treatment.In almost 400 patients with ITP, the number of patients who achieved a platelet count of at least 50,000 per microlitre after 6 weeks of treatment was generally comparable between patients diagnosed less than 6 months and those diagnosed more than 6 months before starting treatment.Data from scientific literature supported these findings.ITP in childrenIn children with ITP, Revolade was more effective than placebo in one main study involving 92 children between 1 and 17 years of age who had previously been treated for ITP. This study lasted 13 weeks and looked at the proportion of patients whose platelet count had increased to at least 50,000 per microlitre for at least 6 out of 8 weeks, between week 5 to 12 of the study in the absence of rescue medication. This occurred in around 40% of those taking Revolade (25 out of 63) compared with around 3% (1 out of 29) of those who took placebo. An extension of the study found that Revolade was effective at maintaining adequate levels of platelets in the long term.Thrombocytopenia associated with hepatitis CFor the treatment of thrombocytopenia associated with hepatitis C, two main studies involving a total of 1,441 adults were carried out. These compared Revolade with placebo for allowing the starting and maintenance of antiviral treatment in patients with hepatitis C whose platelet count was initially too low to allow starting such treatment (less than 75,000 per microlitre). In both studies, the main measure of effectiveness was the number of patients whose blood tests did not show any sign of hepatitis C virus 6 months after the end of treatment.In these two studies, a higher proportion of patients who took Revolade tested negative for hepatitis C, compared with those who took placebo (23% versus 14% in the first study, and 19% versus 13% in the second study).Severe aplastic anaemiaFor the treatment of severe aplastic anaemia, Revolade was studied in 43 patients and was not compared with any other medicine. The main measure of effectiveness was the number of patients who responded to Revolade (whose platelet, red or white blood cell count remained above pre-set levels) after 12 or 16 weeks of treatment.In this study, 40% of patients (17 out of 43) responded to treatment after 12 weeks, and in 65% of them (11 out of 17) the platelet count either increased by at least 20,000 per microliter or was stable without a need for blood transfusions. Preliminary data from a supportive study are consistent with the result of the main study, with 46% of patients responding to treatment after 12 weeks.

What are the risks associated with Revolade?

The most common side effects with Revolade in adults with ITP (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea and abnormal blood levels of certain liver enzymes. The most important serious side effects are liver problems and thromboembolic complications (problems with clots in blood vessels). In children with ITP, the most common side effects include nose and throat infection, cough, fever, pain in the belly or in the mouth and throat, toothache and runny nose.In adults with severe aplastic anaemia the most common side effects include headache, dizziness, cough, pain in the belly or in the mouth and throat, nausea, diarrhoea, joint pain, pain in limbs, tiredness, fever and abnormal blood levels of certain liver enzymes.In patients with thrombocytopenia and advanced chronic hepatitis C who are treated with interferon and Revolade, the most common side effects include headache, anaemia (low red blood cell counts), decreased appetite, cough, nausea, diarrhoea, high levels of bilirubin in the blood, hair loss, itching, muscle pain, fever, tiredness, flu-like illness, weakness, chills and swelling (because of build-up of water in the body). Important serious side effects are liver problems and thromboembolic complications.For the full list of restrictions and side effects of Revolade, see the package leaflet.

Why is Revolade authorised in the EU?

The European Medicines Agency decided that Revolade's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Revolade?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Revolade have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Revolade are continuously monitored. Side effects reported with Revolade are carefully evaluated and any necessary action taken to protect patients.

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Reyataz

What is Reyataz?

Reyataz is an antiviral medicine that contains the active substance atazanavir. It is available as capsules (100 mg, 150 mg, 200 mg and 300 mg) and oral powder (50 mg).

What is Reyataz used for?

Reyataz is used together with low-dose ritonavir and other antiviral medicines to treat adults and children aged 3 months and over and weighing at least 5 kg who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).For patients who have received HIV medicines before, doctors should prescribe Reyataz only after they have looked at which medicines the patient has taken and carried out tests to establish that the virus is likely to respond to Reyataz. The medicine is not expected to work in patients in whom many medicines in the same class as Reyataz (protease inhibitors) do not work.The medicine can only be obtained with a prescription.

How is Reyataz used?

Treatment with Reyataz should be started by a doctor who has experience in the treatment of HIV infection.For adults (aged 18 years or over), the recommended dose is 300 mg once a day. In younger patients, the dose of Reyataz depends on body weight. Reyataz oral powder can be used for children aged atleast 3 months and weighing at least 5 kg, and for patients who cannot swallow capsules. Each dose must be taken with food.Reyataz is normally given with ritonavir to boost its action but doctors can consider stopping ritonavir in adults in some specific situations.

How does Reyataz work?

The active substance in Reyataz, atazanavir, is a protease inhibitor. It blocks an enzyme called protease, which is needed for the virus to multiply. Blocking the enzyme prevents the virus from multiplying, slowing down the spread of infection. A small dose of another medicine, ritonavir, is normally given at the same time as a 'booster'. Ritonavir slows down the break-down of atazanavir, increasing the levels of atazanavir in the blood. This allows a lower dose of atazanavir to be used for the same antiviral effect. Reyataz, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Reyataz does not cure HIV infection or AIDS, but it may delay the damage to the immune system and the development of infections and diseases associated with AIDS.

How has Reyataz been studied?

Reyataz capsules have been assessed in four main studies involving patients aged 16 years and over. One study compared ritonavir-boosted Reyataz with ritonavir-boosted lopinavir (another antiviral medicine) in 883 patients who had not taken treatment for HIV infection before. The other three studies involved a total of 743 patients who had taken treatment for HIV infection before: the first two compared Reyataz, taken with saquinavir (another antiviral medicine) but without ritonavir, with ritonavir-boosted saquinavir or ritonavir-boosted lopinavir. The final study compared Reyataz plus either ritonavir or saquinavir with ritonavir-boosted lopinavir in 358 patients. The main measure of effectiveness was the change in the levels of HIV in the patients' blood (viral load).Reyataz capsules boosted with ritonavir have also been studied in 41 patients aged between 6 and 18 years. More than half of these patients had taken HIV treatment in the past. The study looked at the effect of the medicine on viral load and on the immune system, among other measures.A further main study involved 172 patients who had achieved undetectable viral load (below 50 copies/ml) after treatment with Reyataz capsules and ritonavir. It compared continued treatment with either a higher dose of Reyataz without ritonavir or the boosted combination.Reyataz oral powder with ritonavir has been assessed in two main studies involving 155 children aged from 3 months up to 11 years. More than half of these patients had taken HIV treatment in the past. A measure of effectiveness was the viral load after treatment for 48 weeks.In all of the studies, the patients also took two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs, a type of antiviral medicine).

What benefit has Reyataz shown during the studies?

In patients who had not been treated before, ritonavir-boosted Reyataz capsules were as effective as ritonavir-boosted lopinavir. At the start of the study, the patients' viral loads were around 88,100 copies/ml, but after 48 weeks, 78% of the patients taking Reyataz (343 out of 440) had viral loads below 50 copies/ml, compared with 76% of those taking lopinavir (338 out of 443).In patients who had been treated before, the results of the first study could not be interpreted, as a large number of patients left the study before its planned end. In the second study, ritonavir-boosted lopinavir caused a greater reduction in viral load than Reyataz capsules taken without ritonavir after 24 weeks. In the third study, patients taking ritonavir-boosted Reyataz capsules had similar falls in viral load after 24 and 48 weeks as those taking ritonavir-boosted lopinavir: they had fallen by around 99% after 48 weeks. This finding was maintained after 96 weeks.In the patients aged between 6 and 18 years, 81% of those who had not taken HIV treatment in the past (13 out of 16) and 24% of those who had taken it in the past (6 out of 25) had viral loads below 50 copies/ml after 48 weeks. The patients also had improvements in their immune systems.In the study in patients who already had undetectable viral loads with ritonavir-boosted Reyataz capsules, these were maintained in 68 of 87 patients (78%) who continued treatment with a higher dose of Reyataz without ritonavir, and in 64 of 85 (75%) who continued with the boosted combination.In the two studies in children aged from 3 months up to 11 years taking boosted Reyataz oral powder, the viral load was undetectable in about half the children after treatment for 48 weeks.

What is the risk associated with Reyataz?

In adults, the most common side effects with Reyataz (seen in between 1 and 10 patients in 100) are headache, ocular icterus (yellowing of the eyes), vomiting, diarrhoea, abdominal pain (stomach ache), nausea (feeling sick), dyspepsia (heartburn), rash, fatigue (tiredness) and jaundice (yellowing of the skin and eyes because of liver problems). In studies, side effects were similar in younger patients. For the full list of all side effects reported with Reyataz, see the package leaflet.Reyataz must not be used in patients who have severe reductions in their liver function; if given with ritonavir it must not be used in patients with moderate reduction in liver function. In addition, Reyataz must not be given to patients taking rifampicin (used to treat tuberculosis), sildenafil (when this medicine is used to treat pulmonary arterial hypertension), St John's wort (a herbal medicine used to treat depression) or medicines that are broken down in the body in the same way as Reyataz and are harmful at high levels in the blood. For the full list of restrictions with Reyataz see the package leaflet.

Why has Reyataz been approved?

The CHMP considered that Reyataz's effectiveness had been shown in patients aged at least 3 months and weighing at least 5 kg. The Committee decided that Reyataz's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Reyataz?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Reyataz have been included in the summary of product characteristics and the package leaflet.

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Rezolsta

What is Rezolsta and what is it used for?

Rezolsta is a medicine usedfor treating patients human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS). It is given in combination with other HIV medicines for treating adults and adolescents from 12 years of age (and weighing at least 40 kg).Rezolsta contains the active substances darunavir and cobicistat. The medicine is for use only in patients who have not received HIV treatment before or in previously treated patients whose disease is not expected to be resistant to darunavir and who are healthy enough and have HIV virus levels below a certain threshold.

How is Rezolsta used?

Rezolsta can only be obtained with a prescription and treatment should be started by a doctor experienced in managing HIV infection. Rezolsta is available as tablets that contain 800 mg of darunavir and 150 mg of cobicistat. The recommended dose is one tablet a day, taken with food. For more information about using Rezolsta, see the package leaflet or contact your doctor or pharmacist.

How does Rezolsta work?

Rezolsta contains two active substances. Darunavir is a protease inhibitor. It blocks an enzyme called protease, which the virus needs to make new copies of itself. When the enzyme is blocked, the virus does not reproduce normally and its increase and spread slows down. Cobicistat acts as a 'booster' to enhance the effects of darunavir, by prolonging its activity in the body.Rezolsta, taken in combination with other HIV medicines, reduces the amount of HIV in the blood and keeps it at a low level. Rezolsta does not cure HIV infection, but it can delay or reverse the damage to the immune system and the development of infections and diseases associated with AIDS.Darunavir is currently authorised as Prezista and cobicistat as Tybost.

What benefits of Rezolsta have been shown in studies?

Because darunavir and cobicistat have both previously been shown to be effective and are authorised for the treatment of HIV infection, studies were mainly carried out to show that Rezolsta producedsimilar effects and levels of darunavir in the blood to the two active substances given separately, and to darunavir given with a different booster medicine, ritonavir (an established combination).In addition, one main study examined the safety and effectiveness of darunavir and cobicistat given with other HIV medicines, in 313 adults with HIV who had not been treated previously or who had been treated and whose infection was not expected to be resistant to darunavir. Effectiveness was measured by a reduction in viral load (the amount of HIV-1 virus in the blood) to less than 50 copies/ml. Overall, 258 patients (82%) achieved this response after 24 weeks of treatment, and 253 patients (81%) at 48 weeks, which was comparable to results with darunavir plus ritonavir.Further data indicated that darunavir and cobicistat also led to acceptable reductions in the viral load in adolescents between 12 and 17 years of age.

What are the risks associated with Rezolsta?

The most common side effects with Rezolsta (which may affect more than 1 in 10 people) are diarrhoea, nausea (feeling sick), headache and rash. The most serious side effects were rash, diabetes, hypersensitivity (allergic) reactions, vomiting, Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals) and immune reconstitution syndrome. With immune reconstitution syndrome, the patient's immune system starts working again and fights existing infections (causing inflammation) and may attack healthy tissue such as the liver and thyroid gland. For the full list of all side effects of Rezolsta, see the package leaflet.Rezolsta must not be taken by patients who have severely reduced liver function. It must also not be used with certain other medicines as they may reduce the effectiveness of treatment or increase side effects. For the full list of restrictions, see the package leaflet.

Why is Rezolsta authorised in the EU?

The European Medicines Agency decided that Rezolsta's benefits are greater than its risks and recommended that it can be authorised for use in the EU. Both active substances have already been shown to be effective, and combining them into a single tablet was considered to be more convenient than taking them separately, reducing the risk of errors. There was no evidence of unexpected side effects.

What measures are being taken to ensure the safe and effective use of Rezolsta?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rezolsta have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rezolsta are continuously monitored. Side effects reported with Rezolsta are carefully evaluated and any necessary action taken to protect patients.

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Rhokiinsa

What is Rhokiinsa and what is it used for?

Rhokiinsa is an eye-drop solution that is used to reduce pressure inside the eye in adults who have open-angle glaucoma (a disease where the pressure in the eye rises because fluid cannot drain out of the eye) or ocular hypertension (when the pressure in the eye is higher than normal).Rhokiinsa contains the active substance netarsudil.

How is Rhokiinsa used?

Rhokiinsa is only available on prescription and should be started by an eye specialist. It is available as an eye-drop solution (200 microgram/ml) and the dose is one drop in the affected eye once a day, in the evening.For more information about using Rhokiinsa, see the package leaflet or contact your doctor or pharmacist.

How does Rhokiinsa work?

When pressure in the eye is raised, it can cause damage to the retina (the light-sensitive membrane at the back of the eye) and to the optic nerve that sends signals from the eye to the brain. This can result in serious vision loss and even blindness.The active substance in Rhokiinsa, netarsudil, is a Rho kinase inhibitor. This means that it blocks the activity of an enzyme called Rho kinase, which has a role in controlling drainage of fluid from the eye. When it blocks this enzyme, Rhokiinsa increases the flow of fluid out of the eyeball, thereby lowering pressure inside the eye. Rhokiinsa is also thought to lower eye pressure by reducing pressure in the veins around the eyes.

What benefits of Rhokiinsa have been shown in studies?

A main study of 708 patients with open-angle glaucoma or ocular hypertension showed that Rhokiinsa is effective at lowering eye pressure. In patients with moderately high eye pressure (up to 25 mmHg), Rhokiinsa was as effective as timolol (another medicine), lowering the pressure by around 3.9 mmHg to 4.7 mmHg, compared with reductions of 3.8 mmHg to 5.2 mmHg for patients using timolol.In patients whose eye pressure was higher than 25 mmHg, Rhokiinsa was less effective than timolol. However, when these results were combined with results from other studies, decreases in eye pressure with Rhokiinsa were larger than those seen in the main study only.

What are the risks associated with Rhokiinsa?

The most common side effect with Rhokiinsa (which may affect around 5 in 10 people) is conjunctival hyperaemia (increased blood supply to the eye, leading to redness). Other common side effects (which may affect up to 2 in 10 people) are: cornea verticillata (deposits in the cornea, the transparent layer in front of the eye that covers the pupil and iris), eye pain, conjunctival haemorrhage (bleeding in the surface layer of the eye), erythema (reddening) at the site where the medicine was applied and the eyelid, corneal staining, blurred vision and increased lacrimation (watery eyes).For the full list of side effects and restrictions with Rhokiinsa, see the package leaflet.

Why is Rhokiinsa authorised in the EU?

Rhokiinsa, which has a different mode of action from previously authorised treatments, provides another treatment option for patients with open-angle glaucoma and ocular hypertension. Rhokiinsa showed good effects across a range of eye pressures. The effect of Rhokiinsa was less pronounced in patients whose eye pressure was more than 30 mmHg, but these results were considered less important because Rhokiinsa is not expected to be used on its own in this group.In terms of safety, the side effects of Rhokiinsa are considered manageable and were more likely to be confined to the eye. However, side effects on the eye were more frequent than those of timolol, and this may lead people to stop treatment. The safety of Rhokiinsa will be further investigated in a study.The European Medicines Agency therefore decided that Rhokiinsa's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rhokiinsa?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rhokiinsa have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rhokiinsa are continuously monitored. Side effects reported with Rhokiinsa are carefully evaluated and any necessary action taken to protect patients.

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Riarify

What is Riarify and what is it used for?

Riarify is a medicine used in adults to relieve the symptoms of moderate to severe chronic obstructive pulmonary disease (COPD). COPD is a long-term disease in which the airways and air sacs inside the lungs become damaged or blocked, leading to difficulty breathing.Riarify is used for maintenance (continuing) treatment in patients whose disease is not adequately controlled despite treatment with a combination of two COPD medicines consisting of a long-acting beta-2 agonist plus either an inhaled corticosteroid or a long-acting muscarinic receptor antagonist. Beta-2 agonists and muscarinic receptor antagonists help to widen the airways; corticosteroids reduce inflammation in the airways and lungs.This medicine is the same as Trimbow, which is already authorised in the EU. The company that makes Trimbow has agreed that its scientific data can be used for Riarify ('informed consent').Riarify contains the active substances beclometasone, formoterol and glycopyrronium bromide.

How is Riarify used?

Riarify is available as a liquid in a portable inhaler device. The recommended dose is two inhalations twice a day.Patients should be shown how to use the inhaler correctly by a doctor or another healthcare professional, who should also regularly check that the patient's inhalation technique is correct.The medicine can only be obtained with a prescription. For more information about using Riarify, see the package leaflet or contact your doctor or pharmacist.

How does Riarify work?

The three active substances in Riarify work in different ways to reduce inflammation and keep the airways open, allowing the patient to breathe more easily.Beclometasone belongs to anti-inflammatory medicines known as corticosteroids. It works in a similar way to naturally occurring corticosteroid hormones, reducing the activity of the immune system. This leads to a reduction in the release of substances involved in the inflammation process, such as histamine, thereby helping to keep the airways clear and allowing the patient to breathe more easily.Formoterol is a long-acting beta-2 agonist. It attaches to receptors (targets) known as beta-2 receptors in the muscles of the airways. By attaching to these receptors, it causes the muscles to relax, which keeps the airways open and helps with the patient's breathing.Glycopyrronium bromide is a long-acting muscarinic receptor antagonist. It opens the airways by blocking muscarinic receptors in muscle cells in the lungs. Because these receptors help control the contraction of the airway muscles, blocking them causes the muscles to relax, helping to keep the airways open and allowing the patient to breathe more easily.

What benefits of Riarify have been shown in studies?

Riarify has been shown to be effective at relieving symptoms of COPD in three main studies involving over 5,500 patients whose symptoms were not controlled well enough either by combinations of two other COPD medicines or by a muscarinic receptor antagonist alone.In the first study lasting a year, after 26 weeks of treatment Riarify improved patients' FEV1 (the maximum volume of air a person can breathe out in one second) by 82 ml before a dose and 261 ml after a dose. By comparison, the FEV1 increased by 1 and 145 ml before and after dosing in patients treated with a medicine containing only 2 of the active substances found in Riarify (beclometasone plus formoterol).In the second study lasting a year, patients treated with Riarify had 20% fewer exacerbations (flareups of symptoms) per year than patients treated with tiotropium (a long-acting muscarinic receptor antagonist). In this study, Riarify was as effective as tiotropium plus a combination of beclometasone and formoterol at reducing the number of exacerbations.In the third study lasting a year, patients treated with Riarify had 15% fewer exacerbations a year than patients treated with a combination of indacaterol (a long-acting beta-2 agonist) and glycopyrronium bromide.

What are the risks associated with Riarify?

Side effects with Riarify include oral candidiasis (a fungal infection of the mouth caused by a yeast called Candida), muscle spasms and dry mouth.For the full list of side effects and restrictions with Riarify, see the package leaflet.

Why is Riarify authorised in the EU?

Riarify is effective at reducing the frequency of exacerbations and improving lung function of patients with COPD. No major safety concerns have been reported with Riarify, with side effects being manageable and similar to other COPD medicines. The European Medicines Agency therefore decided that Riarify's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Riarify?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Riarify have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Riarify is continuously monitored. Side effects reported with Riarify are carefully evaluated and any necessary action taken to protect patients.

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Riltrava Aerosphere

What is Riltrava Aerosphere and what is it used for?

Riltrava Aerosphere is a medicine used to treat patients with moderate to severe chronic obstructive pulmonary disease (COPD), a long-term disease in which the airways and air sacs in the lungs become damaged or blocked, leading to difficulty breathing.Riltrava Aerosphere is used for maintenance (regular) treatment in adults whose disease is not controlled well enough with a combination of inhaled medicines consisting of a long-acting beta-2 agonist plus either a corticosteroid or a long-acting muscarinic antagonist.Riltrava Aerosphere contains the active substances formoterol, glycopyrronium bromide and budesonide.This medicine is the same as Trixeo Aerosphere, which is already authorised in the EU. The company that makes Trixeo Aerosphere has agreed that its scientific data can be used for Riltrava Aerosphere ('informed consent').

How is Riltrava Aerosphere used?

Riltrava Aerosphere can only be obtained with a prescription. It is available in a portable inhaler device. The recommended dose is two inhalations twice a day (two in the morning and two in the evening). Patients should be shown how to use the inhaler correctly by a doctor or other healthcare professional.For more information about using Riltrava Aerosphere, see the package leaflet or contact your doctor or pharmacist.

How does Riltrava Aerosphere work?

Riltrava Aerosphere contains three active substances, which work in different ways to widen the airways and improve breathing in COPD.Formoterol is a long-acting beta-2 agonist. It attaches to receptors (targets) known as beta-2 receptors in the muscles of the airways. When it attaches to these receptors, it causes the muscles to relax, which keeps the airways open and helps with the patient's breathing.Glycopyrronium bromide is a long-acting muscarinic receptor antagonist. This means that it blocks muscarinic receptors in muscle cells in the airways. Because these receptors help control the contraction of muscles, glycopyrronium causes the muscles of the airways to relax, helping to keep the airways open.Budesonide belongs to a group of anti-inflammatory medicines known as corticosteroids. It works in a similar way to naturally occurring corticosteroid hormones, reducing the activity of the immune system (the body's natural defences) by attaching to receptors in various types of immune cell. This leads to a reduction in the release of substances that are involved in the inflammation process, such as histamine, thereby keeping the airways clear and allowing the patient to breathe more easily.

What benefits of Riltrava Aerosphere have been shown in studies?

Two main studies in over 10,000 patients with moderate to very severe COPD have shown that Riltrava Aerosphere is effective at improving patients' FEV1 (the maximum volume of air they can breathe out in one second) and at reducing the number of exacerbations (flare-ups) of the disease.In the first study, patients treated with Riltrava Aerosphere for 24 weeks had FEV1 increases of around147 ml, compared with 125 ml for patients treated with glycopyrronium/formoterol, and 73 ml and 88 ml for patients treated with two different inhalers containing budesonide/formoterol.The second study, which lasted one year, showed that patients treated with Riltrava Aerosphere had fewer COPD exacerbations (1.08 per year) than patients treated with with glycopyrronium/formoterol (1.42) or budesonide/formoterol (1.24).

What are the risks associated with Riltrava Aerosphere?

The most common side effects with Riltrava Aerosphere (which may affect up to 1 in 10 people) are pneumonia (lung infection), headache and urinary tract infection.For the full list of side effects and restrictions of Riltrava Aerosphere, see the package leaflet.

Why is Riltrava Aerosphere authorised in the EU?

Riltrava Aerosphere improved lung function in patients with moderate to severe COPD, and reduced disease exacerbations. The safety profile of Riltrava Aerosphere is considered similar to that of medicines containing combinations of a corticosteroid, beta-2 agonist and antimuscarinic. The European Medicines Agency therefore decided that Riltrava Aerosphere's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Riltrava Aerosphere?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Riltrava Aerosphere have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Riltrava Aerosphere are continuously monitored. Side effects reported with Riltrava Aerosphere are carefully evaluated and any necessary action taken to protect patients.

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Rilutek

What is Rilutek?

Rilutek is a medicine containing the active substance riluzole. It is available as 50 mg tablets.

What is Rilutek used for?

Rilutek is used in patients with amyotrophic lateral sclerosis (ALS). ALS is a form of motor neuron disease where the nerve cells responsible for sending instructions to the muscles gradually deteriorate, leading to weakness, muscle wasting and paralysis. Rilutek is used to extend the patient's life or to delay the need for mechanical ventilation.Rilutek should not be used in patients with any other form of motor neuron disease.The medicine can only be obtained with a prescription.

How is Rilutek used?

Treatment with Rilutek should only be started by a specialist doctor with experience in the management of motor neuron diseases. The recommended dose is 100 mg per day (given as one 50 mg tablet every 12 hours). For more information, see the package leaflet.

How does Rilutek work?

The active substance in Rilutek, riluzole, acts on the nervous system. The exact way in which it works in ALS is not known. It is thought that the destruction of nerve cells in motor neuron disease may be caused by too much of the neurotransmitter glutamate. Neurotransmitters are substances that nerve cells use to communicate with neighbouring cells. Riluzole stops the release of glutamate and this may help in preventing the nerve cells being damaged.

How has Rilutek been studied?

Rilutek has been compared with placebo (a dummy treatment) in three studies involving a total of 1,282 patients. One of these studies was in older patients (over 75) and in patients with advanced disease. Across the studies, Rilutek was given as 50, 100 or 200 mg per day, and for up to 18 months. The main measure of effectiveness was the average survival time.

What benefit has Rilutek shown during the studies?

The average survival time was significantly longer for patients who received Rilutek compared with patients who received placebo. Looking at the results of the three studies together, over 18 months, patients who received Rilutek 100 mg/day had an average survival time that was about 2 months longer than the survival time for patients who received placebo. Rilutek 50 mg/day was no more effective than placebo and 200 mg/day was no more effective than 100 mg/day. The medicine was not more effective than placebo in the late stages of ALS.

What is the risk associated with Rilutek?

The most common side effects seen with Rilutek (in more than 1 patient in 10) are nausea (feeling sick), asthenia (weakness) and abnormal liver tests. For the full list of all side effects reported with Rilutek, see the package leaflet.Rilutek must not be used in patients who have liver disease or who have abnormally high levels of liver enzymes. Rilutek must also not be given to women who are pregnant or breastfeeding. For the full list of restrictions, see the package leaflet.

Why has Rilutek been approved?

The CHMP decided that Rilutek's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Riluzole Zentiva

What is Riluzole Zentiva?

Riluzole Zentiva is a medicine containing the active substance riluzole. It is available as tablets (50 mg).This medicine is the same as Rilutek, which is already authorised in the European Union (EU). The company that makes Rilutek has agreed that its scientific data can be used for Riluzole Zentiva ('informed consent').

What is Riluzole Zentiva used for?

Riluzole Zentiva is used in patients with amyotrophic lateral sclerosis (ALS). ALS is a form of motor neurone disease where attacks of the nerve cells responsible for sending instructions to the muscles lead to weakness, muscle waste and paralysis. Riluzole Zentiva is used to extend the patient's life, or the time before they need to use mechanical ventilation.Riluzole Zentiva should not be used in patients with any other form of motor neurone disease.The medicine can only be obtained with a prescription.

How is Riluzole Zentiva used?

Treatment with Riluzole Zentiva should only be started by a specialist doctor with experience in the management of motor neurone diseases. In adult and elderly patients, it is given as 100 mg a day (50 mg every 12 hours). For more information please see the package leaflet.

How does Riluzole Zentiva work?

The active substance in Riluzole Zentiva, riluzole, acts on the nervous system. The exact way in which it works in ALS is not known. It is thought that the destruction of nerve cells in motor neurone disease may be caused by too much glutamate, a neurotransmitter (chemical messenger). Riluzole stops the release of glutamate and this may help in preventing the nerve cells being damaged.

How has Riluzole Zentiva been studied?

The effectiveness of Riluzole Zentiva has been compared with that of placebo (a dummy treatment) in three studies involving a total of 1,282 patients. One of these studies was in older patients (over 75) and in patients with advanced disease. Across the studies, Riluzole Zentiva was given as 50, 100 or 200 mg per day, and for up to 18 months. The main measure of effectiveness was the average survival time.

What benefit has Riluzole Zentiva shown during the studies?

The average survival time was significantly longer for patients who received Riluzole Zentiva compared with patients who received placebo. Looking at the results of the three studies together, over 18 months, patients who received Riluzole Zentiva 100 mg/day had an average survival time that was about two months longer than the survival time for patients who received placebo. Riluzole Zentiva 50 mg/day was no more effective than placebo and 200 mg/day was no more effective than 100 mg/day.The medicine was not more effective than placebo in the late stages of ALS.

What is the risk associated with Riluzole Zentiva?

The most common side effects seen with Riluzole Zentiva (in more than 1 patient in 10) are nausea (feeling sick), asthenia (weakness) and abnormal liver tests (increased in liver enzymes levels). For the full list of all side effects reported with Riluzole Zentiva, see the package leaflet.Riluzole Zentiva must not be used in people who are hypersensitive (allergic) to riluzole or any of the other ingredients. Riluzole Zentiva must not be used in patients who have liver disease or who have abnormally high levels of liver enzymes. Riluzole Zentiva must also not be given to women who are pregnant or breast-feeding.

Why has Riluzole Zentiva been approved?

The CHMP decided that Riluzole Zentiva's benefits are greater than its risks to extend life or the time to mechanical ventilation for patients with amyotrophic lateral sclerosis. They noted that there is no evidence that Riluzole Zentiva exerts a therapeutic effect on motor function, lung function, fasciculations, muscle strength and motor symptoms, and that it has not been shown to be effective in the late stages of ALS. The Committee recommended that Riluzole Zentiva be given marketing authorisation.

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Rinvoq

What is Rinvoq and what is it used for?

Rinvoq is a medicine for treating adults with rheumatoid arthritis, a disease that causes inflammation of the joints.Rinvoq is used for moderate or severe rheumatoid arthritis that cannot be controlled well enough with disease-modifying anti-rheumatic medicines or if the patient cannot take these medicines. It can be used on its own or with methotrexate, another medicine for rheumatoid arthritis.Rinvoq contains the active substance upadacitinib.

How is Rinvoq used?

Rinvoq can only be obtained with a prescription. Treatment with the medicine should be started and supervised by a doctor experienced in diagnosing and treating rheumatoid arthritis. It is available as 15 mg tablets.The recommended dose of Rinvoq is one tablet once a day. The doctor may interrupt treatment in case of certain side effects, including falls in blood cell counts. For more information about using Rinvoq, see the package leaflet or contact your doctor or pharmacist.

How does Rinvoq work?

In patients with rheumatoid arthritis, the immune system (the body's defences) attacks healthy tissue, causing inflammation in the joints.Upadacitinib, the active substance in Rinvoq, is an immunosuppressant. This means that it reduces the activity of the immune system. Upadacitinib works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

What benefits of Rinvoq have been shown in studies?

Five studies involving a total of nearly 4,400 patients found Rinvoq effective in reducing symptoms in patients with moderate to severe rheumatoid arthritis. These studies involved rating disease activity in 28 joints in the body on a standard scale.The first study was in patients who had not previously been treated with methotrexate. It found that after 24 weeks, 48% of patients were in remission (clear of symptoms) after treatment with Rinvoq compared with 19% of patients receiving methotrexate.The second study was in patients whose disease was not well controlled with disease-modifying antirheumatic medicines. It found that of patients treated with Rinvoq, 48% had low disease activity after 12 weeks compared with 17% of patients receiving placebo (a dummy treatment).The third study was in patients whose disease was not controlled well with methotrexate. It found that 45% of patients treated with methotrexate plus Rinvoq had low disease activity after 12 weeks compared with 29% of patients treated with methotrexate plus adalimumab (a biological diseasemodifying anti-rheumatic medicine) and 14% of patients receiving methotrexate plus placebo.The fourth study was also in patients whose disease was not controlled well enough with methotrexate. It found that 45% of the patients treated with Rinvoq on its own had low disease activity after 14 weeks compared with 19% of patients continuing their methotrexate treatment.The fifth study involved patients for whom a biological disease-modifying anti-rheumatic medicine was either not suitable or did not work well enough. The patients were being treated with conventional disease-modifying anti-rheumatic medicines (chloroquine, hydroxychloroquine, leflunomide or sulfasalazine, often combined with methotrexate). Of the patients who also received Rinvoq, 43% had low disease activity compared with 14% of patients receiving placebo.

What are the risks associated with Rinvoq?

The most common side effects with Rinvoq (which may affect more than 1 in 10 people) are upper respiratory tract infections (nose and throat infections). The most important serious side effects are serious infections. For the full list of side effects of Rinvoq, see the package leaflet.Rinvoq must not be used in patients with tuberculosis or serious infections. It must also not be used in patients with severe liver problems or during pregnancy. For the full list of restrictions, see the package leaflet.

Why is Rinvoq authorised in the EU?

Rinvoq was effective at controlling moderate to severe rheumatoid arthritis in patients whose disease had not improved enough with other disease-modifying anti-rheumatic medicines. Studies found that it reduced disease activity when used alone or combined with other medicines. Patients treated with Rinvoq may have side effects that include infection, neutropenia (low count of a type of white blood cell), and blood tests that suggest liver or muscle damage and raised blood lipids. However, these side effects are considered manageable.The European Medicines Agency therefore decided that Rinvoq's benefits are greater than its risks and that it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rinvoq?

The company that markets Rinvoq will provide information to healthcare professionals about the risks of infection, harm to the unborn baby if Rinvoq is taken during pregnancy, and problems affecting the heart and circulation. The company will also supply a patient alert card describing warning signs of Rinvoq's serious side effects and how to get help, and a reminder not to use it during pregnancy.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rinvoq have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rinvoq are continuously monitored. Side effects reported with Rinvoq are carefully evaluated and any necessary action taken to protect patients.

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Ristaben

What is Ristaben?

Ristaben is a diabetes medicine that contains the active substance sitagliptin. It is available as tablets (25, 50 and 100 mg).

What is Ristaben used for?

Ristaben is used in patients with type 2 diabetes to improve the control of blood glucose (sugar) levels.It is used in addition to diet and exercise in the following ways:• on its own, in patients who are not satisfactorily controlled on diet and exercise and in whom metformin (a diabetes medicine) is not suitable;• in combination with metformin or a PPAR-gamma agonist (a type of diabetes medicine) such as a thiazolidinedione, in patients who are not satisfactorily controlled on metformin or the PPARgamma agonist used on its own;• in combination with a sulphonylurea (another type of diabetes medicine) in patients who are not satisfactorily controlled with a sulphonylurea used on its own and in whom metformin is not suitable;• in combination with both metformin, and a sulphonylurea or a PPAR-gamma agonist, in patients who are not satisfactorily controlled on the two medicines;• in combination with insulin, with or without metformin, in patients who are not satisfactorily controlled on a stable dose of insulin.The medicine can only be obtained with a prescription.

How is Ristaben used?

Ristaben is taken at a dose of 100 mg once a day. If Ristaben is taken with a sulphonylurea or insulin, the dose of the sulphonylurea or insulin may need to be lowered to reduce the risk of hypoglycaemia (low blood sugar levels).In patients with moderately or severely reduced kidney function the dose of Ristaben should be reduced.

How does Ristaben work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. The active substance in Ristaben, sitagliptin, is a dipeptidyl-peptidase-4 (DPP 4) inhibitor. It works by blocking the breakdown of 'incretin' hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By increasing levels of incretin hormones in the blood, sitagliptin stimulates the pancreas to produce more insulin when blood glucose levels are high. Sitagliptin does not work when the blood glucose is low. Sitagliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon. Together, these processes reduce blood glucose levels and help to control type 2 diabetes.

How has Ristaben been studied?

Ristaben was studied in nine studies involving almost 6,000 patients with type 2 diabetes whose blood glucose levels were not adequately controlled:• four of the studies compared Ristaben with placebo (a dummy treatment). Ristaben or placebo were used on their own in two studies involving 1,262 patients, as an add-on to metformin in one study involving 701 patients, and as an add-on to pioglitazone (a PPAR-gamma agonist) in one study involving 353 patients;• two studies compared Ristaben with other diabetes medicines. One study compared Ristaben with glipizide (a sulphonylurea), when they were used as an add-on to metformin in 1,172 patients. The other study compared Ristaben with metformin, used on their own, in 1,058 patients;• three additional studies compared Ristaben with placebo when they were added to other diabetes medicines: glimepiride (another sulphonylurea), with or without metformin, in 441 patients; the combination of metformin and rosiglitazone (a PPAR-gamma agonist) in 278 patients; and a stable dose of insulin, with or without metformin, in 641 patients.In all of the studies, the main measure of effectiveness was the change in the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.

What benefit has Ristaben shown during the studies?

Ristaben was more effective than placebo when it was taken alone or in combination with other diabetes medicines. In patients taking Ristaben on its own, HbA1c levels fell from around 8.0% at the start of the studies by 0.48% after 18 weeks and 0.61% after 24 weeks. In contrast, they rose by 0.12% and 0.18%, respectively, in the patients taking placebo. Adding Ristaben to metformin reducedHbA1c levels by 0.67% after 24 weeks, compared with a fall of 0.02% in the patients adding placebo. When added to pioglitazone, Ristaben reduced HbA1c levels by 0.85% after 24 weeks, compared with a fall of 0.15% in the patients adding placebo.In the studies comparing Ristaben with other medicines, the effectiveness of adding Ristaben to metformin was similar to that of adding glipizide. When taken on their own, Ristaben and metformin produced similar reductions in HbA1c levels, but the effectiveness of Ristaben seemed to be slightly lower than that of metformin.In the additional studies, adding Ristaben to glimepiride (with or without metformin) led to a reduction in HbA1c levels of 0.45% after 24 weeks, compared with an increase of 0.28% in the patients adding placebo. HbA1c levels were reduced by 1.03% after 18 weeks in patients adding Ristaben to metformin and rosiglitazone, compared with a fall of 0.31% in those adding placebo. Finally, they were reduced by 0.59% in patients adding Ristaben to insulin (with or without metformin), compared with a fall of 0.03% in those adding placebo.

What is the risk associated with Ristaben?

Serious side effects reported with Ristaben include pancreatitis (inflammation of the pancreas) and hypersensitivity (allergic reactions). Hypoglycaemia has been reported in combination with a sulphonylurea in 4.7-13.8% of patients and with insulin in 9.6% of patients. For the full list of all side effects and restrictions with Ristaben, see the package leaflet.

Why has Ristaben been approved?

The CHMP decided that Ristaben's benefits are greater than its risks and recommended that it be given marketing authorisation.What measures are being taken to ensure the safe and effective use of RistabenA risk management plan has been developed to ensure that Ristaben is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ristaben, including the appropriate precautions to be followed by healthcare professionals and patients.

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Ristfor

What is Ristfor?

Ristfor is a diabetes medicine that contains two active substances, sitagliptin and metformin hydrochloride. It is available as tablets (50 mg sitagliptin and 850 mg metformin hydrochloride; 50 mg sitagliptin and 1,000 mg metformin hydrochloride).

What is Ristfor used for?

Ristfor is used in patients with type 2 diabetes to improve the control of blood glucose (sugar) levels. It is used in addition to diet and exercise in the following ways:• in patients who are not satisfactorily controlled on metformin (a diabetes medicine) used on its own;• in patients who are already taking a combination of sitagliptin and metformin as separate tablets;• in combination with a sulphonylurea, a PPAR-gamma agonist such as a thiazolidinedione, or insulin (other types of diabetes medicine) in patients who are not satisfactorily controlled on this medicine and metformin.The medicine can only be obtained with a prescription.

How is Ristfor used?

Ristfor is taken twice a day. The strength of tablet to use depends on the dose of the other diabetes medicines that the patient was taking before. If Ristfor is taken with a sulphonylurea or insulin, the dose of the sulphonylurea or insulin may need to be lowered, to avoid hypoglycaemia (low blood sugar levels).The maximum dose of sitagliptin is 100 mg a day. Ristfor should be taken with food to avoid any stomach problems caused by metformin.

How does Ristfor work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the level of glucose in the blood or when the body is unable to use insulin effectively. The active substances in Ristfor, sitagliptin and metformin hydrochloride, each have a different mode of action.Sitagliptin is a dipeptidyl-peptidase-4 (DPP 4) inhibitor. It works by blocking the breakdown of 'incretin' hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By increasing the levels of incretin hormones in the blood, sitagliptin stimulates the pancreas to produce more insulin when blood glucose levels are high. Sitagliptin does not work when the blood glucose is low. Sitagliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon. Sitagliptin has been authorised in the European Union (EU) as Januvia and Xelevia since 2007 and as Tesavel since 2008.Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut. Metformin has been available in the EU since the 1950s.As a result of the action of both active substances, blood glucose levels are reduced and this helps to control type 2 diabetes.

How has Ristfor been studied?

Sitagliptin on its own as Januvia/Xelevia/Tesavel can be used with metformin, and with both metformin and a sulphonylurea, in type 2 diabetes patients. The company presented the results of three studies of Januvia/Xelevia to support the use of Ristfor in patients who were not satisfactorily controlled on their existing metformin treatment. Two of the studies looked at sitagliptin as an add-on to metformin: the first compared it with placebo (a dummy treatment) in 701 patients, and the second compared it with glipizide (a sulphonylurea) in 1,172 patients. The third study compared sitagliptin with placebo, when used as an add-on to glimepiride (another sulphonylurea), with or without metformin, in 441 patients.The results of three further studies were used to support the use of Ristfor. The first included 1,091 patients who were not satisfactorily controlled on diet and exercise alone and compared the effect of Ristfor with that of metformin or sitagliptin alone. The second included 278 patients who were not satisfactorily controlled on the combination of metformin and rosiglitazone (a PPAR-gamma agonist) and compared the effects of adding sitagliptin or placebo. The third included 641 patients who were not satisfactorily controlled on a stable dose of insulin, three-quarters of whom were also taking metformin. This study also compared the effects of adding sitagliptin or placebo.In all of the studies, the main measure of effectiveness was the change in the levels of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.The company carried out additional studies to show that the active substances in Ristfor are absorbed by the body in the same way as the two medicines given separately.

What benefit has Ristfor shown during the studies?

Ristfor was more effective than metformin alone. Adding 100 mg sitagliptin to metformin reduced HbA1c levels by 0.67% (from around 8.0%) after 24 weeks, compared with a fall of 0.02% in the patients adding placebo. The effectiveness of adding sitagliptin to metformin was similar to that of adding glipizide. In the study in which sitagliptin was added to glimepiride and metformin, the levels of HbA1c were reduced by 0.59% after 24 weeks, compared with an increase of 0.30% in the patients adding placebo.In the first of the three further studies, Ristfor was more effective than metformin or sitagliptin alone. In the second, HbA1c levels were reduced by 1.03% after 18 weeks in patients adding sitagliptin to metformin and rosiglitazone, compared with a fall of 0.31% in those adding placebo. Finally, they were reduced by 0.59% after 24 weeks in patients adding sitagliptin to insulin, compared with a fall of0.03% in those adding placebo. There was no difference in this effect between the patients also taking metformin and those not taking it.

What is the risk associated with Ristfor?

Serious side effects reported with Ristfor include pancreatitis (inflammation of the pancreas) and hypersensitivity (allergic reactions). Hypoglycaemia has been reported in combination with a sulphonylurea in 13.8% of patients and with insulin in 10.9% of patients. For the full list of all side effects reported with Ristfor, see the package leaflet.Ristfor must not be used in patients who have diabetic ketoacidosis or pre coma (dangerous conditions that can occur in diabetes), problems with the kidneys or liver, conditions that may affect the kidneys, or a disease that causes a reduced supply of oxygen to the tissues such as failure of the heart or lungs or a recent heart attack. It must also not be used in patients who consume excessive amounts of alcohol or are alcoholic, or in women who are breast-feeding. For the full list of restrictions, see the package leaflet.

Why has Ristfor been approved?

The CHMP decided that Ristfor's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Ristfor?

A risk management plan has been developed to ensure that Ristfor is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Ristfor, including the appropriate precautions to be followed by healthcare professionals and patients.

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Ritonavir Mylan

What is Ritonavir Mylan and what is it used for?

Ritonavir Mylan is used in combination with other medicines to treat patients over two years of age who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).Ritonavir Mylan contains the active substance ritonavir and is a 'generic medicine'. This means that Ritonavir Mylan contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Norvir. For more information on generic medicines, see the question-and-answer document here.

How is Ritonavir Mylan used?

Ritonavir Mylan can only be obtained with a prescription and treatment with Ritonavir Mylan should be given by a doctor who has experience in the treatment of HIV infection. It is available as tablets (100 mg) and should be taken with food.Ritonavir Mylan can be used as a 'pharmacokinetic enhancer' (booster) to increase the blood levels of other antiviral medicines that belong to the same group as Ritonavir Mylan (protease inhibitors) including amprenavir, atazanavir, darunavir, fosamprenavir, lopinavir, saquinavir, and tipranavir. The usual dose of Ritonavir Mylan for adults is 100 or 200 mg, once or twice a day. The dose depends onwhich other protease inhibitor is being taken. For more information, see the package leaflet provided with the other medicine.Ritonavir Mylan can also be used in larger doses for a direct antiviral effect on HIV. The recommended dose for adults (aged 18 years or over) is 600 mg twice a day. For younger patients, the recommended dose depends on the patient's height and weight. Treatment should start with a low dose that is gradually increased over the first 14 days of treatment.

How does Ritonavir Mylan work?

As a 'booster', the active substance ritonavir slows the breakdown of other protease inhibitor antivirals. This increases the levels of these protease inhibitors in the blood and enhances their antiviral effect.At higher antiviral doses, ritonavir is a 'protease inhibitor'. This means that it blocks a viral enzyme called protease, which is involved in the multiplication of HIV. When the enzyme is blocked, the virus can no longer multiply normally, slowing down its spread. Ritonavir Mylan, taken in combination with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. Ritonavir Mylan does not cure HIV infection or AIDS, but it may hold off damage to the immune system and the development of infections and diseases associated with AIDS.

How has Ritonavir Mylan been studied?

Studies on the benefits and risks of the active substance in the approved uses have already been carried out with the reference medicine, Norvir, and do not need to be repeated for Ritonavir Mylan.As for every medicine, the company provided studies on the quality of Ritonavir Mylan. The company also carried out a study that showed that it is 'bioequivalent' to the reference medicine. Two medicines are bioequivalent when they produce the same levels of the active substance in the body and are therefore expected to have the same effect.

What are the benefits and risks of Ritonavir Mylan?

Because Ritonavir Mylan is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Ritonavir Mylan approved?

The European Medicines Agency concluded that, in accordance with EU requirements, Ritonavir Mylan has been shown to have comparable quality and to be bioequivalent to Norvir. Therefore, the Agency's view was that, as for Norvir, the benefit outweighs the identified risk. The Agency recommended that Ritonavir Mylan be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Ritonavir Mylan?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ritonavir Mylan have been included in the summary of product characteristics and the package leaflet.

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Rivaroxaban Accord

What is Rivaroxaban Accord and what is it used for?

Rivaroxaban Accord is an anticoagulant medicine (a medicine that prevents blood clotting) used in adults:• to treat deep vein thrombosis (DVT, a blood clot in a deep vein, usually in the leg) and pulmonary embolism (a clot in a blood vessel supplying the lungs), and to prevent DVT and pulmonary embolism from re-occuring;• to prevent venous thromboembolism (VTE, the formation of blood clots in the veins) in patients who are undergoing surgery to replace a hip or knee;• to prevent stroke (caused by a blood clot in the brain) and systemic embolism (a blood clot in another organ) in patients with non-valvular atrial fibrillation (irregular rapid contractions of the upper chambers of the heart);• to prevent atherothrombotic events (such as heart attack, stroke or death from heart disease) in patients:> after an acute coronary syndrome, when it is used with an antiplatelet medicine (which prevents the formation of blood clots). Acute coronary syndrome consists of conditions such as unstable angina (a severe type of chest pain) and heart attack;> at high risk of ischaemic events (problems caused by restricted blood supply) who have coronary artery disease (disease caused by obstructed blood supply to the heart muscle) or peripheral artery disease (disease caused by defective blood flow in the arteries). It is used with aspirin.Rivaroxaban Accord contains the active substance rivaroxaban.Rivaroxaban Accord is a 'generic medicine'. This means that Rivaroxaban Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Xarelto. For more information on generic medicines, see the question-and-answer document here.

How is Rivaroxaban Accord used?

Rivaroxaban Accord is available as tablets (2.5, 10, 15 and 20 mg). The dose and duration of treatment with Rivaroxaban Accord depend on what it is being used for and the patient's risk of bleeding. It is given at a lower dose (2.5 mg twice daily) when used in combination with an antiplatelet medicine such as acetylsalicylic acid (aspirin) or ticlopidine. The doctor will regularly evaluate the benefits of ongoing treatment against the risk of excessive or internal bleeding.The medicine can only be obtained with a prescription. For more information about using Rivaroxaban Accord, see the package leaflet or contact your doctor or pharmacist.

How does Rivaroxaban Accord work?

The active substance in Rivaroxaban Accord, rivaroxaban, is a 'factor Xa inhibitor'. This means that it blocks factor Xa, an enzyme that is involved in the production of thrombin. Thrombin is central to the process of blood clotting. By blocking factor Xa, the levels of thrombin decrease, which reduces the risk of blood clots forming in the veins and arteries, and also treats existing clots.

How has Rivaroxaban Accord been studied?

Studies on the benefits and risks of the active substance in the authorised uses have already been carried out with the reference medicine, Xarelto, and do not need to be repeated for Rivaroxaban Accord.As for every medicine, the company provided studies on the quality of Rivaroxaban Accord. The company also carried out studies that showed that it is 'bioequivalent' to the reference medicine. Two medicines are bioequivalent when they produce the same levels of the active substance in the body and are therefore expected to have the same effect.

What are the benefits and risks of Rivaroxaban Accord?

Because Rivaroxaban Accord is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Rivaroxaban Accord authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, RivaroxabanAccord has been shown to have comparable quality and to be bioequivalent to Xarelto. Therefore, the Agency's view was that, as for Xarelto, the benefits of Rivaroxaban Accord outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rivaroxaban Accord?

The company that markets Rivaroxaban Accord will provide an educational pack for doctors who prescribe Rivaroxaban Accord, containing important safety information including on the risk of bleeding during treatment with Rivaroxaban Accord and how to manage this risk. In addition, prescribers will receive a patient alert card to give to patients receiving Rivaroxaban Accord containing key safety reminders for patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rivaroxaban Accord have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rivaroxaban Accord are continuously monitored. Side effects reported with Rivaroxaban Accord are carefully evaluated and any necessary action taken to protect patients.

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Rivaroxaban Mylan

What is Rivaroxaban Mylan and what is it used for?

Rivaroxaban Mylan is an anticoagulant medicine (a medicine that prevents blood clotting) used:• to treat deep vein thrombosis (DVT, a blood clot in a deep vein, usually in the leg) and pulmonary embolism (a clot in a blood vessel supplying the lungs), and to prevent DVT and pulmonary embolism from re-occurring in adults;• to prevent venous thromboembolism (VTE, the formation of blood clots in the veins) in adults who are undergoing surgery to replace a hip or knee;• to treat VTE and prevent VTE from re-occurring in children and adolescents aged less than 18 years weighing more than 30 kg;• to prevent stroke (caused by a clot in a blood vessel in the brain) and systemic embolism (a clot in other blood vessels) in adults with non-valvular atrial fibrillation (irregular rapid contractions of the upper chambers of the heart);• to prevent atherothrombotic events (such as heart attack, stroke or death from heart disease) in adults:
− after an acute coronary syndrome, when it is used with an antiplatelet medicine (which prevents the formation of blood clots). Acute coronary syndrome consists of conditions such as unstable angina (a severe type of chest pain) and heart attack;
− at high risk of ischaemic events (problems caused by restricted blood supply) who have coronary artery disease (disease caused by obstructed blood supply to the heart muscle) or peripheral artery disease (disease caused by defective blood flow in the arteries). It is used with aspirin.
Rivaroxaban Mylan contains the active substance rivaroxaban and is a 'generic medicine'. This means that Rivaroxaban Mylan contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Xarelto. For more information on generic medicines, see the question-and-answer document here.Send

How is Rivaroxaban Mylan used?

Rivaroxaban Mylan is available as tablets of various strengths. The dose and duration of treatment with Rivaroxaban Mylan depend on what it is being used for and the patient's risk of bleeding. For children, the form, dose and duration of treatment also depend on the patient's age and weight. Rivaroxaban Mylan is given at a lower dose when used in combination with an antiplatelet medicine such as aspirin, clopidogrel or ticlopidine. The doctor will regularly evaluate the benefits of ongoing treatment against the risk of excessive or internal bleeding.The medicine can only be obtained with a prescription. For more information about using Rivaroxaban Mylan, see the package leaflet or contact your doctor or pharmacist.

How does Rivaroxaban Mylan work?

The active substance in Rivaroxaban Mylan, rivaroxaban, is a 'factor Xa inhibitor'. This means that it blocks factor Xa, an enzyme that is involved in the production of thrombin. Thrombin is central to the process of blood clotting. By blocking factor Xa, the levels of thrombin decrease, which reduces the risk of blood clots forming in the veins and arteries, and also treats existing clots.

How has Rivaroxaban Mylan been studied?

Studies on the benefits and risks of the active substance in the authorised uses have already been carried out with the reference medicine, Xarelto, and do not need to be repeated for Rivaroxaban Mylan.As for every medicine, the company provided data on the quality of Rivaroxaban Mylan. The company also carried out studies that showed that it is 'bioequivalent' to the reference medicine. Two medicines are bioequivalent when they produce the same levels of the active substance in the body and are therefore expected to have the same effect.

What are the benefits and risks of Rivaroxaban Mylan?

Because Rivaroxaban Mylan is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Rivaroxaban Mylan authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, RivaroxabanMylan has been shown to have comparable quality and to be bioequivalent to Xarelto. Therefore, the Agency's view was that, as for Xarelto, the benefits of Rivaroxaban Mylan outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rivaroxaban Mylan?

The company that markets Rivaroxaban Mylan will provide an educational pack for doctors who prescribe Rivaroxaban Mylan, containing important safety information including on the risk of bleeding during treatment with Rivaroxaban Mylan and how to manage this risk. In addition, prescribers will receive a patient alert card to give to patients receiving Rivaroxaban Mylan containing key safety reminders for patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rivaroxaban Mylan have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rivaroxaban Mylan are continuously monitored. Suspected side effects reported with Rivaroxaban Mylan are carefully evaluated and any necessary action taken to protect patients.

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Rivastigmine 1 A Pharma

What is Rivastigmine 1 A Pharma?

Rivastigmine 1 A Pharma is a medicine containing the active substance rivastigmine. It is available as capsules (1.5 mg, 3 mg, 4.5 mg and 6 mg) and as an oral solution (2 mg/ml).

What is Rivastigmine 1 A Pharma used for?

Rivastigmine 1 A Pharma is used for the treatment of patients with mild to moderately severe Alzheimer's dementia, a progressive brain disorder that gradually affects memory, intellectual ability and behaviour. Rivastigmine 1 A Pharma is also used to treat mild to moderately severe dementia in patients with Parkinson's disease.The medicine can only be obtained with a prescription.

How is Rivastigmine 1 A Pharma used?

Treatment with Rivastigmine 1 A Pharma should be initiated and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer's disease or dementia in patients with Parkinson's disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Rivastigmine 1 A Pharma by the patient. Treatment should continue as long as the medicine has a benefit, but the dose can be reduced or treatment interrupted if the patient has side effects.Rivastigmine 1 A Pharma should be given twice a day, with morning and evening meals. The capsules should be swallowed whole. The starting dose is 1.5 mg twice a day. In patients who tolerate this dose, it can be increased in 1.5-mg steps no more frequently than every two weeks, to a regular dose of 3 to 6 mg twice a day. The highest tolerated dose should be used to get the maximum benefit, but the dose should not exceed 6 mg twice a day.

How does Rivastigmine 1 A Pharma work?

The active substance in Rivastigmine 1 A Pharma, rivastigmine, is an antidementia medicine. In patients with Alzheimer's dementia or dementia due to Parkinson's disease, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a chemical that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes,Rivastigmine 1 A Pharma allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer's dementia and dementia due to Parkinson's disease.

How has Rivastigmine 1 A Pharma been studied?

Rivastigmine 1 A Pharma has been studied in three main studies involving 2,126 patients with mild to moderately severe Alzheimer's disease. Rivastigmine 1 A Pharma was also studied in 541 patients with dementia due to Parkinson's disease. All of the studies lasted six months and compared the effects of Rivastigmine 1 A Pharma with those of placebo (a dummy treatment). The main measures of effectiveness were the change in symptoms in two main areas: cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).An additional study in 27 patients was used to show that Rivastigmine 1 A Pharma capsules and oral solution produced similar levels of the active substance in the blood.

What benefit has Rivastigmine 1 A Pharma shown during the studies?

Rivastigmine 1 A Pharma was more effective than placebo at controlling symptoms. In the three studies of Rivastigmine 1 A Pharma in patients with Alzheimer's dementia, patients taking doses of Rivastigmine 1 A Pharma between 6 and 9 mg per day had an average increase in cognitive symptoms of 0.2 points from a baseline of 22.9 points at the start of the study, where a lower score indicates better performance. This was compared with an increase of 2.6 points from 22.5 in the patients taking placebo. For the global score, patients taking Rivastigmine 1 A Pharma had an increase in symptoms of 4.1 points, compared with 4.4 in those taking placebo.The patients with dementia due to Parkinson's disease taking Rivastigmine 1 A Pharma capsules showed an improvement in cognitive symptoms of 2.1 points, compared with a worsening of 0.7 points in those taking placebo, from a baseline of around 24 points. The global symptom score also improved more in the patients taking Rivastigmine 1 A Pharma.

What is the risk associated with Rivastigmine 1 A Pharma?

The types of side effects seen with Rivastigmine 1 A Pharma depend on the type of dementia it is being used to treat. Overall, the most common side effects include nausea (feeling sick, seen in 38 patients in 100) and vomiting (seen in 23 patients in 100), particularly during the phase when the dose of Rivastigmine 1 A Pharma is being increased. For the full list of all side effects reported with Rivastigmine 1 A Pharma, see the package leaflet.Rivastigmine 1 A Pharma must not be used in people who are hypersensitive (allergic) to rivastigmine, other carbamate derivatives or any of the other ingredients. It must also not be used in patients who are suspected to have had in the past an allergic reaction called 'allergic contact dermatitis' to Exelon patch.

Why has Rivastigmine 1 A Pharma been approved?

The CHMP concluded that Rivastigmine 1 A Pharma has a modest effectiveness in treating the symptoms of Alzheimer's dementia, although this does reflect an important benefit in some patients. The Committee initially concluded that for the treatment of dementia due to Parkinson's disease, Rivastigmine 1 A Pharma's benefits did not outweigh its risks. However, following a re-examination of this opinion, the Committee concluded that the medicine's modest effectiveness could also be of benefit to some of these patients.Therefore, the Committee decided that Rivastigmine 1 A Pharma's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Rivastigmine Actavis

What is Rivastigmine Actavis?

Rivastigmine Actavis is a medicine containing the active substance rivastigmine. It is available as capsules (1.5, 3, 4.5 and 6 mg).Rivastigmine Actavis is a 'generic medicine'. This means that Rivastigmine Actavis is similar to a 'reference medicine' already authorised in the European Union (EU) called Exelon. For more information on generic medicines, see the question-and-answer document here.

What is Rivastigmine Actavis used for?

Rivastigmine Actavis is used for the treatment of patients with mild to moderately severe Alzheimer's dementia, a progressive brain disorder that gradually affects memory, intellectual ability and behaviour.It can also be used to treat mild to moderately severe dementia in patients with Parkinson's disease.The medicine can only be obtained with a prescription.

How is Rivastigmine Actavis used?

Treatment with Rivastigmine Actavis should be initiated and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer's disease or dementia in patients with Parkinson's disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Rivastigmine Actavis by the patient. Treatment should continue as long as the medicine has a benefit, but the dose can be reduced or treatment interrupted if the patient has side effects.Rivastigmine Actavis should be given twice a day, with morning and evening meals. The starting dose is 1.5 mg twice a day. In patients who tolerate this dose, it can be increased in 1.5 mg steps no more frequently than every two weeks, to a regular dose of 3 to 6 mg twice a day. The highest tolerated dose should be used to get the maximum benefit, but the dose should not exceed 6 mg twice a day.

How does Rivastigmine Actavis work?

The active substance in Rivastigmine Actavis, rivastigmine, is a dementia medicine. In patients with Alzheimer's dementia or dementia due to Parkinson's disease, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a chemical that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes, Rivastigmine Actavis allows levels of acetylcholine to increase in the brain, helping to reduce the symptoms of Alzheimer's dementia and dementia due to Parkinson's disease.

How has Rivastigmine Actavis been studied?

Because Rivastigmine Actavis is a generic medicine, studies in people have been limited to tests to determine that it is bioequivalent to the reference medicine, Exelon. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Rivastigmine Actavis?

Because Rivastigmine Actavis is a generic medicine and is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why has Rivastigmine Actavis been approved?

The CHMP concluded that, in accordance with EU requirements, Rivastigmine Actavis has been shown to have comparable quality and to be bioequivalent to Exelon. Therefore, the CHMP's view was that, as for Exelon, the benefit outweighs the identified risk. The Committee recommended that Rivastigmine Actavis be given marketing authorisation.

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Rivastigmine Hexal

What is Rivastigmine Hexal?

Rivastigmine Hexal is a medicine containing the active substance rivastigmine. It is available as capsules (1.5 mg, 3 mg, 4.5 mg and 6 mg) and as an oral solution (2 mg/ml).

What is Rivastigmine Hexal used for?

Rivastigmine Hexal is used for the treatment of patients with mild to moderately severe Alzheimer's dementia, a progressive brain disorder that gradually affects memory, intellectual ability and behaviour. Rivastigmine Hexal is also used to treat mild to moderately severe dementia in patients with Parkinson's disease.The medicine can only be obtained with a prescription.

How is Rivastigmine Hexal used?

Treatment with Rivastigmine Hexal should be initiated and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer's disease or dementia in patients with Parkinson's disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Rivastigmine Hexal by the patient. Treatment should continue as long as the medicine has a benefit, but the dose can be reduced or treatment interrupted if the patient has side effects.Rivastigmine Hexal should be given twice a day, with morning and evening meals. The capsules should be swallowed whole. The starting dose is 1.5 mg twice a day. In patients who tolerate this dose, it canbe increased in 1.5-mg steps no more frequently than every two weeks, to a regular dose of 3 to 6 mg twice a day. The highest tolerated dose should be used to get the maximum benefit, but the dose should not exceed 6 mg twice a day.

How does Rivastigmine Hexal work?

The active substance in Rivastigmine Hexal, rivastigmine, is an antidementia medicine. In patients with Alzheimer's dementia or dementia due to Parkinson's disease, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a chemical that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes,Rivastigmine Hexal allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer's dementia and dementia due to Parkinson's disease.

How has Rivastigmine Hexal been studied?

Rivastigmine Hexal has been studied in three main studies involving 2,126 patients with mild to moderately severe Alzheimer's disease. Rivastigmine Hexal was also studied in 541 patients with dementia due to Parkinson's disease. All of the studies lasted six months and compared the effects of Rivastigmine Hexal with those of placebo (a dummy treatment). The main measures of effectiveness were the change in symptoms in two main areas: cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).An additional study in 27 patients was used to show that Rivastigmine Hexal capsules and oral solution produced similar levels of the active substance in the blood.

What benefit has Rivastigmine Hexal shown during the studies?

Rivastigmine Hexal was more effective than placebo at controlling symptoms. In the three studies of Rivastigmine Hexal in patients with Alzheimer's dementia, patients taking doses of Rivastigmine Hexal between 6 and 9 mg per day had an average increase in cognitive symptoms of 0.2 points from a baseline of 22.9 points at the start of the study, where a lower score indicates better performance. This was compared with an increase of 2.6 points from 22.5 in the patients taking placebo. For the global score, patients taking Rivastigmine Hexal had an increase in symptoms of 4.1 points, compared with 4.4 in those taking placebo.The patients with dementia due to Parkinson's disease taking Rivastigmine Hexal capsules showed an improvement in cognitive symptoms of 2.1 points, compared with a worsening of 0.7 points in those taking placebo, from a baseline of around 24 points. The global symptom score also improved more in the patients taking Rivastigmine Hexal.

What is the risk associated with Rivastigmine Hexal?

The types of side effects seen with Rivastigmine Hexal depend on the type of dementia it is being used to treat. Overall, the most common side effects include nausea (feeling sick, seen in 38 patients in100) and vomiting (seen in 23 patients in 100), particularly during the phase when the dose of Rivastigmine Hexal is being increased. For the full list of all side effects reported with Rivastigmine Hexal, see the package leaflet.Rivastigmine Hexal must not be used in people who are hypersensitive (allergic) to rivastigmine, other carbamate derivatives or any of the other ingredients. It must also not be used in patients who aresuspected to have had in the past an allergic reaction called 'allergic contact dermatitis' to Exelon patch.

Why has Rivastigmine Hexal been approved?

The CHMP concluded that Rivastigmine Hexal has a modest effectiveness in treating the symptoms of Alzheimer's dementia, although this does reflect an important benefit in some patients. The Committee initially concluded that for the treatment of dementia due to Parkinson's disease, Rivastigmine Hexal's benefits did not outweigh its risks. However, following a re-examination of this opinion, the Committee concluded that the medicine's modest effectiveness could also be of benefit to some of these patients.Therefore, the Committee decided that Rivastigmine Hexal's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Rivastigmine Sandoz

What is Rivastigmine Sandoz?

Rivastigmine Sandoz is a medicine containing the active substance rivastigmine. It is available as capsules (1.5 mg, 3 mg, 4.5 mg and 6 mg) and as an oral solution (2 mg/ml).

What is Rivastigmine Sandoz used for?

Rivastigmine Sandoz is used for the treatment of patients with mild to moderately severe Alzheimer's dementia, a progressive brain disorder that gradually affects memory, intellectual ability and behaviour. Rivastigmine Sandoz is also used to treat mild to moderately severe dementia in patients with Parkinson's disease.The medicine can only be obtained with a prescription.

How is Rivastigmine Sandoz used?

Treatment with Rivastigmine Sandoz should be initiated and supervised by a doctor who has experience in the diagnosis and treatment of Alzheimer's disease or dementia in patients with Parkinson's disease. Treatment should only be started if a caregiver is available who will regularly monitor the use of Rivastigmine Sandoz by the patient. Treatment should continue as long as the medicine has a benefit, but the dose can be reduced or treatment interrupted if the patient has side effects.Rivastigmine Sandoz should be given twice a day, with morning and evening meals. The capsules should be swallowed whole. The starting dose is 1.5 mg twice a day. In patients who tolerate this dose, it can be increased in 1.5-mg steps no more frequently than every two weeks, to a regular dose of 3 to 6 mg twice a day. The highest tolerated dose should be used to get the maximum benefit, but the dose should not exceed 6 mg twice a day.

How does Rivastigmine Sandoz work?

The active substance in Rivastigmine Sandoz, rivastigmine, is an antidementia medicine. In patients with Alzheimer's dementia or dementia due to Parkinson's disease, certain nerve cells die in the brain, resulting in low levels of the neurotransmitter acetylcholine (a chemical that allows nerve cells to communicate with each other). Rivastigmine works by blocking the enzymes that break down acetylcholine: acetylcholinesterase and butyrylcholinesterase. By blocking these enzymes,Rivastigmine Sandoz allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer's dementia and dementia due to Parkinson's disease.

How has Rivastigmine Sandoz been studied?

Rivastigmine Sandoz has been studied in three main studies involving 2,126 patients with mild to moderately severe Alzheimer's disease. Rivastigmine Sandoz was also studied in 541 patients with dementia due to Parkinson's disease. All of the studies lasted six months and compared the effects of Rivastigmine Sandoz with those of placebo (a dummy treatment). The main measures of effectiveness were the change in symptoms in two main areas: cognitive (the ability to think, learn and remember) and global (a combination of several areas including general function, cognitive symptoms, behaviour and the ability to carry out everyday activities).An additional study in 27 patients was used to show that Rivastigmine Sandoz capsules and oral solution produced similar levels of the active substance in the blood.

What benefit has Rivastigmine Sandoz shown during the studies?

Rivastigmine Sandoz was more effective than placebo at controlling symptoms. In the three studies of Rivastigmine Sandoz in patients with Alzheimer's dementia, patients taking doses of Rivastigmine Sandoz between 6 and 9 mg per day had an average increase in cognitive symptoms of 0.2 points from a baseline of 22.9 points at the start of the study, where a lower score indicates better performance. This was compared with an increase of 2.6 points from 22.5 in the patients taking placebo. For the global score, patients taking Rivastigmine Sandoz had an increase in symptoms of 4.1 points, compared with 4.4 in those taking placebo.The patients with dementia due to Parkinson's disease taking Rivastigmine Sandoz capsules showed an improvement in cognitive symptoms of 2.1 points, compared with a worsening of 0.7 points in those taking placebo, from a baseline of around 24 points. The global symptom score also improved more in the patients taking Rivastigmine Sandoz.

What is the risk associated with Rivastigmine Sandoz?

The types of side effects seen with Rivastigmine Sandoz depend on the type of dementia it is being used to treat. Overall, the most common side effects (seen in more than 1 patient in 10) include nausea (feeling sick, seen in 38 patients in 100) and vomiting (seen in 23 patients in 100), particularly during the phase when the dose of Rivastigmine Sandoz is being increased. For the full list of all side effects reported with Rivastigmine Sandoz, see the package leaflet.Rivastigmine Sandoz must not be used in people who are hypersensitive (allergic) to rivastigmine, other carbamate derivatives or any of the other ingredients. It must also not be used in patients who are suspected to have had in the past an allergic reaction called 'allergic contact dermatitis' to Exelon patch.

Why has Rivastigmine Sandoz been approved?

The CHMP concluded that Rivastigmine Sandoz has a modest effectiveness in treating the symptoms of Alzheimer's dementia, although this does reflect an important benefit in some patients. The Committee initially concluded that for the treatment of dementia due to Parkinson's disease, Rivastigmine Sandoz's benefits did not outweigh its risks. However, following a re-examination of this opinion, the Committee concluded that the medicine's modest effectiveness could also be of benefit to some of these patients.Therefore, the Committee decided that Rivastigmine Sandoz's benefits are greater than its risks and recommended that it be given marketing authorisation.

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Rixathon

What is Rixathon and what is it used for?

Rixathon is a medicine used to treat the following blood cancers and inflammatory conditions:• follicular lymphoma and diffuse large B cell non-Hodgkin's lymphoma (two types of non-Hodgkin's lymphoma, a blood cancer);• chronic lymphocytic leukaemia (CLL, another blood cancer affecting white blood cells);• severe rheumatoid arthritis (an inflammatory condition of the joints);• granulomatosis with polyangiitis (GPA or Wegener's granulomatosis) and microscopic polyangiitis(MPA), which are inflammatory conditions of the blood vessels;• pemphigus vulgaris, a serious condition involving widespread blistering of the skin and lining of the mouth, nose, throat and genitals.Depending on the condition it is used to treat, Rixathon may be given on its own, or with chemotherapy (cancer medicines) or medicines used for inflammatory disorders (methotrexate or a corticosteroid).Rixathon contains the active substance rituximab.Rixathon is a 'biosimilar medicine'. This means that Rixathon is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Rixathon is MabThera. For more information on biosimilar medicines, see here.

How is Rixathon used?

Rixathon can only be obtained with a prescription. It should be given under the close supervision of an experienced healthcare professional and in a place where facilities for resuscitating patients are immediately available. The medicine is available for infusion (drip) into a vein.Before each infusion, the patient should be given an antihistamine (to prevent allergic reactions) and an antipyretic (a medicine to reduce fever). Depending on the condition being treated, the patients are also given other medicines to manage side effects.For more information about using Rixathon, see the package leaflet or contact your doctor or pharmacist.

How does Rixathon work?

The active substance in Rixathon, rituximab, is a monoclonal antibody designed to attach to a protein called CD20, which is present on B cells. When rituximab attaches to CD20, it causes the B cells to die, which helps in lymphoma and CLL (where B cells have become cancerous) and in rheumatoid arthritis and pemphigus (where B cells are involved in inflammation). In GPA and MPA, destroying B cells lowers the production of antibodies thought to play an important role in attacking the blood vessels and causing inflammation.

What benefits of Rixathon have been shown in studies?

Laboratory studies comparing Rixathon with the reference medicine MabThera have shown that the active substance in Rixathon is highly similar to that in MabThera in terms of structure, purity and biological activity. Studies have also shown that giving Rixathon produces similar levels of the active substance in the body to giving MabThera.In addition, Rixathon was as effective as MabThera in one main study involving 629 patients with advanced, untreated follicular lymphoma, where Rixathon or MabThera were added to other chemotherapy for part of the treatment. The cancer improved in just over 87% of those given Rixathon (271 of 311 patients), and in similar numbers of those given MabThera (274 of 313 patients). A supportive study in patients with rheumatoid arthritis also indicated similar effectiveness between MabThera and Rixathon.Because Rixathon is a biosimilar medicine, the studies on effectiveness and safety of rituximab carried out with MabThera do not all need to be repeated for Rixathon.

What are the risks associated with Rixathon?

The safety of Rixathon has been evaluated, and on the basis of all the studies carried out, the side effects of the medicine are considered to be comparable to those of the reference medicine MabThera.The most common side effects with Rixathon are reactions related to the infusion (such as fever, chills and shivering) while most common serious side effects are infusion reactions, infections and heartrelated problems.Rixathon must not be used in people who are hypersensitive (allergic) to rituximab, mouse proteins or any of the other ingredients or in patients with a severe infection or a severely weakened immune system (the body's defences). Patients with rheumatoid arthritis, GPA, MPA or pemphigus vulgaris must also not receive Rixathon if they have severe heart problems.For the full list of side effects and restrictions of Rixathon, see the package leaflet.

Why is Rixathon authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Rixathon has a highly similar structure, purity and biological activity to MabThera and is distributed in the body in the same way. In addition, a study in patients with follicular lymphoma has shown that the safety and effectiveness of Rixathon are equivalent to those of MabThera.Rixathon Rixathon (rituximab)All these data were considered sufficient to conclude that Rixathon will behave in the same way as MabThera in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for MabThera, the benefits of Rixathon outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rixathon?

The company marketing Rixathon will provide doctors with additional information about giving the medicine correctly. It will also provide doctors and patients using the medicine for rheumatoid arthritis, GPA, MPA or pemphigus with educational material on the risk of infection including that of a rare severe infection, progressive multifocal leukoencephalopathy (PML). These patients are also to receive an alert card, which they are to carry at all times, instructing them to contact their doctor immediately if they have symptoms of infection.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rixathon have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rixathon are continuously monitored. Side effects reported with Rixathon are carefully evaluated and any necessary action taken to protect patients.

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Riximyo

What is Riximyo and what is it used for?

Riximyo is a medicine used to treat the following blood cancers and inflammatory conditions:• follicular lymphoma and diffuse large B cell non-Hodgkin's lymphoma (two types of non-Hodgkin's lymphoma, a blood cancer);• chronic lymphocytic leukaemia (CLL, another blood cancer affecting white blood cells);• granulomatosis with polyangiitis (GPA or Wegener's granulomatosis) and microscopic polyangiitis(MPA), which are inflammatory conditions of the blood vessels;• pemphigus vulgaris, a serious condition involving widespread blistering of the skin and lining of the mouth, nose, throat and genitals.Depending on the condition it is used to treat, Riximyo may be given on its own, or with chemotherapy (cancer medicines) or medicines used for inflammatory disorders (corticosteroids).Riximyo contains the active substance rituximab.Riximyo is a 'biosimilar medicine'. This means that Riximyo is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Riximyo is MabThera. For more information on biosimilar medicines, see here.

How is Riximyo used?

Riximyo can only be obtained with a prescription. It should be given under the close supervision of an experienced healthcare professional and in a place where facilities for resuscitating patients are immediately available. The medicine is available for infusion (drip) into a vein.Before each infusion, the patient should be given an antihistamine (to prevent allergic reactions) and an antipyretic (a medicine to reduce fever). Depending on the condition being treated, the patients are also given other medicines to manage side effects.For more information about using Riximyo, see the package leaflet or contact your doctor or pharmacist.

How does Riximyo work?

The active substance in Riximyo, rituximab, is a monoclonal antibody designed to attach to a protein called CD20, which is present on B cells. When rituximab attaches to CD20, it causes the B cells to die, which helps in lymphoma and CLL (where B cells have become cancerous) and in pemphigus (where B cells are involved in inflammation). In GPA and MPA, destroying B cells lowers the production of antibodies thought to play an important role in attacking the blood vessels and causing inflammation.

What benefits of Riximyo have been shown in studies?

Laboratory studies comparing Riximyo with the reference medicine MabThera have shown that the active substance in Riximyo is highly similar to that in MabThera in terms of structure, purity and biological activity. Studies have also shown that giving Riximyo produces similar levels of the active substance in the body to giving MabThera.In addition, Riximyo was as effective as MabThera in one main study involving 629 patients with advanced, untreated follicular lymphoma, where Riximyo or MabThera were added to other chemotherapy for part of the treatment. The cancer improved in just over 87% of those given Riximyo (271 of 311 patients), and in similar numbers of those given MabThera (274 of 313 patients).Because Riximyo is a biosimilar medicine, the studies on effectiveness and safety of rituximab carried out with MabThera do not all need to be repeated for Riximyo.

What are the risks associated with Riximyo?

The safety of Riximyo has been evaluated, and on the basis of all the studies carried out, the side effects of the medicine are considered to be comparable to those of the reference medicine MabThera.The most common side effects with Riximyo are reactions related to the infusion (such as fever, chills and shivering) while most common serious side effects are infusion reactions, infections and heartrelated problems.Riximyo must not be used in people who are hypersensitive (allergic) to rituximab, mouse proteins or any of the other ingredients or in patients with a severe infection or a severely weakened immune system (the body's defences). Patients with GPA, MPA or pemphigus vulgaris must also not receive Riximyo if they have severe heart problems.For the full list of side effects and restrictions of Riximyo, see the package leaflet.

Why is Riximyo authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Riximyo has a highly similar structure, purity and biological activity to MabThera and is distributed in the body in the same way. In addition, a study in patients with follicular lymphoma has shown that the safety and effectiveness of Riximyo are equivalent to those of MabThera.All these data were considered sufficient to conclude that Riximyo will behave in the same way as MabThera in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for MabThera, the benefits of Riximyo outweigh the identified risks and it can be authorised for use in the EU.Riximyo Riximyo (rituximab)

What measures are being taken to ensure the safe and effective use of Riximyo?

The company marketing Riximyo will provide doctors with additional information about giving the medicine correctly. It will also provide doctors and patients using the medicine for GPA, MPA or pemphigus with educational material on the risk of infection including that of a rare severe infection, progressive multifocal leukoencephalopathy (PML). These patients are also to receive an alert card, which they are to carry at all times, instructing them to contact their doctor immediately if they have symptoms of infection.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Riximyo have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Riximyo are continuously monitored. Side effects reported with Riximyo are carefully evaluated and any necessary action taken to protect patients.

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Rixubis

What is Rixubis and what is it used for?

Rixubis is a medicine used to treat and prevent bleeding in patients with haemophilia B, an inherited bleeding disorder caused by lack of factor IX. It can be used in patients of all ages, and for short-term or long-term use. Rixubis contains the active substance nonacog gamma.

How is Rixubis used?

Rixubis can only be obtained with a prescription and treatment should be started under the supervision of a doctor who has experience in the treatment of haemophilia.Rixubis is available as a powder and solvent that are mixed together to make a solution for injection into a vein. The dose and frequency of treatment depend on the patient's bodyweight and whether Rixubis is used to treat or prevent bleeding, as well as the seriousness of the haemophilia, the extent and location of the bleeding and the patient's age and health. For further information, see the summary of product characteristics (also part of the EPAR).Patients or their carers may be able to administer Rixubis themselves at home once they have been trained appropriately. For full details, see the package leaflet.

How does Rixubis work?

Patients with haemophilia B lack factor IX, which is needed for blood to clot properly. This lack causes blood clotting problems, such as bleeding in the joints, muscles or internal organs. The active substance in Rixubis, nonacog gamma, is a version of human factor IX and helps the blood to clot in the same way. Rixubis can therefore be used to replace the missing factor IX, giving temporary control of the bleeding disorder.Nonacog gamma is not extracted from human blood but is made by a method known as 'recombinant DNA technology': it is made by hamster cells into which a gene (DNA) has been introduced that makes the cells able to produce the human clotting factor.

What benefits of Rixubis have been shown in studies?

The benefits of Rixubis in treating and preventing bleeding episodes have been shown in three main studies involving patients with severe or moderately severe haemophilia B. None of the studies compared the effectiveness of Rixubis directly with another medicine. Effectiveness in stopping bleeding was measured on a standard scale in which 'excellent' meant complete relief of pain and no signs of bleeding after a single dose of the medicine, and 'good' meant relief of pain and signs of improvement with a single dose, although further doses might be needed for complete resolution.In the first study, involving 73 patients aged 12 to 59 years, 249 bleeding episodes were treated with Rixubis. The effect of treatment in stopping bleeding episodes was rated excellent in 41% of cases and good in a further 55%. With respect to prevention of bleeding, the average bleeding rate during treatment was 4.26 bleeds a year, compared with an average of about 17 per year before enrolment. A second study involved 23 children aged from just under 2 to nearly 12 years of age, who experienced 26 bleeding episodes during the study: treatment of bleeding episodes was rated as excellent in 50% of cases and good in another 46%, and the average bleeding rate was reduced from 6.8 to 2.7 bleeds per year. In a third study, Rixubis was given to 14 patients undergoing surgery; treatment with Rixubis kept blood loss during the surgery to levels expected in patients without haemophilia B.The evaluation of these studies also indicated that Rixubis was distributed in the body similarly to another approved factor IX product.

What are the risks associated with Rixubis?

The most common side effects with Rixubis (which may affect up to 1 in 10 people) are dysgeusia (taste disturbances) and pain in the limbs. Hypersensitivity (allergic) reactions may occur rarely, and can include angioedema (swelling of tissues under the skin), burning and stinging at the injection site, chills, flushing, itchy rash, headache, hives, hypotension (low blood pressure), feeling tired or restless, nausea (feeling sick) or vomiting, tachycardia (rapid heartbeat), tightness of the chest, wheezing and tingling sensations. In some cases, reactions become severe (anaphylaxis) and may be associated with dangerously steep falls in blood pressure. For the full list of all side effects with Rixubis see the package leaflet.Rixubis must not be used in patients who are hypersensitive (allergic) to nonacog gamma or any of its other ingredients, or who are known to be allergic to hamster protein.

Why is Rixubis approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Rixubis's benefits are greater than its risks and recommended that it be approved for use in the EU. The Committee considered that Rixubis had been shown to be effective in preventing and treating bleeding episodes inRixubisadults and children with haemophilia B, and was also effective in allowing them to undergo surgery safely. The safety profile was considered acceptable and was outweighed by the beneficial effects.

What measures are being taken to ensure the safe and effective use of Rixubis?

A risk management plan has been developed to ensure that Rixubis is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rixubis, including the appropriate precautions to be followed by healthcare professionals and patients.Further information can be found in the summary of the risk management plan.

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Rizmoic

What is Rizmoic and what is it used for?

Rizmoic is a medicine for treating constipation caused by opioid pain relief medicines in patients who have previously been treated with a laxative (a medicine that triggers bowel movements).It contains the active substance naldemedine.

How is Rizmoic used?

Rizmoic is available as 200 microgram tablets. The recommended dose is one tablet once daily, which the patient can take with or without a laxative.The patient must stop taking Rizmoic when they are no longer taking an opioid. Rizmoic can only be obtained with a prescription. For more information about using Rizmoic, see the package leaflet or contact your doctor or pharmacist.

How does Rizmoic work?

The active substance in Rizmoic, naldemedine, works by attaching to and blocking receptors in the gut (mu-, delta- and kappa-opioid receptors), through which opioid medicines cause constipation.Because molecules of naldemedine were designed not be able to enter into the brain, the medicine does not block opioids from working on pain receptors in the brain and therefore does not interfere with pain relief.

What benefits of Rizmoic have been shown in studies?

Studies have shown that Rizmoic is effective at improving bowel movement in patients who are currently taking laxatives or had taken laxatives in the past.The studies compared Rizmoic with placebo (a dummy treatment) to see if treatment would consistently increase the number of patients who can pass stools and allow them to do so at least 3 times a week during treatment.In two of the studies, involving 1095 patients taking opioids for chronic (long-term) pain caused by a condition other than cancer, 50% of patients taking Rizmoic for 12 weeks achieved the desired outcome, compared with 34% of patients taking placebo.In two other studies, involving 307 patients taking opioids for cancer pain, 74% of patients taking Rizmoic for two weeks achieved the desired outcome compared with 36% of patients taking placebo.

What are the risks associated with Rizmoic?

The most common side effects with Rizmoic in patients without cancer (which may affect up to 1 in 10 people) are abdominal pain (belly ache), diarrhoea, nausea and vomiting. In patients with cancer, the most common side effects were diarrhoea (seen in more than 1 in 10 people) and abdominal pain (seen in up to 1 in 10 people). The majority of side effects in patients with or without cancer were mild to moderate.Rizmoic must not be used in patients with a blocked or perforated bowel or patients at high risk of bowel blockage. For the full list of side effects and restrictions, see the package leaflet.

Why is Rizmoic authorised in the EU?

Constipation is the most common side effect of opioid pain medicines and many standard laxatives are not effective in treating the condition.Rizmoic has been shown to improve bowel movement in patients taking opioids pain medicines for long-term pain (including cancer pain). Furthermore, the side effects of Rizmoic, which mainly affected the gut, were mostly mild or moderate.The European Medicines Agency therefore decided that Rizmoic's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rizmoic?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rizmoic have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rizmoic are continuously monitored. Side effects reported with Rizmoic are carefully evaluated and any necessary action taken to protect patients.

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Roactemra

What is RoActemra and what is it used for?

RoActemra is a medicine used to treat:• adults with severe rheumatoid arthritis that is getting worse who have not been previously treated with a medicine called methotrexate;• adults with moderate to severe active rheumatoid arthritis whose previous treatments with disease modifying antirheumatic drugs (DMARDs), such as methotrexate or medicines known as tumour necrosis factor (TNF) blockers, have not worked well enough or were not tolerated;• children from 1 year of age with active systemic juvenile idiopathic arthritis in whom other treatments (with anti-inflammatory medicines called NSAIDs and corticosteroids) have not worked well enough;• children from 2 years of age with juvenile idiopathic polyarthritis in whom treatment with methotrexate has not worked well enough.RoActemra is used in combination with methotrexate for these conditions but it can be used on its own in patients for whom methotrexate is inappropriate.RoActemra is also used to treat:• adults with giant cell arteritis, a disease in which arteries, usually of the head, are swollen;• adults and children from 2 years of age for the treatment of severe or life-threatening cytokine release syndrome (CRS, a condition that can cause nausea, vomiting, pain and low blood pressure). CRS is a side effect of certain cancer treatments and RoActemra is used for CRS caused by medicines known as chimeric antigen receptors (CAR) T-cell medicines.RoActemra can also be used in adults with COVID-19 who are receiving treatment with corticosteroid medicines by mouth or injection and require extra oxygen or mechanical ventilation (breathing assisted by a machine).RoActemra contains the active substance tocilizumab.

How is RoActemra used?

RoActemra can only be obtained with a prescription and treatment should be started by a doctor who has experience in the diagnosis and treatment of the relevant condition.RoActemra is available as a solution to be injected under the skin and as a concentrate for making a solution for infusion (drip) into a vein. How RoActemra is given, its dose and how often it is given depends on the condition it is used to treat. For COVID-19 and CRS, RoActemra must only be given as an infusion.For more information about using RoActemra, see the package leaflet or contact your doctor or pharmacist.

How does RoActemra work?

The active substance in RoActemra, tocilizumab, is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific target (called an antigen) in the body. Tocilizumab attaches to the receptor for a messenger molecule or 'cytokine' called interleukin-6. This messenger is involved with inflammation and is found at high levels in patients with rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, CRS and COVID-19. By preventing interleukin-6 from attaching to its receptors, tocilizumab reduces the inflammation and other symptoms of these diseases.

What benefits of RoActemra have been shown in studies?

Rheumatoid arthritisIn severe rheumatoid arthritis not previously treated with methotrexate, RoActemra given by infusion was investigated in one main study involving 1,162 patients. RoActemra, on its own or in combination with methotrexate, was compared with placebo (a dummy treatment) plus methotrexate. After six months of treatment, 45% of patients taking RoActemra in combination with methotrexate (130 out of 290) and 39% of patients taking RoActemra on its own (113 out of 292) achieved remission (did not show symptoms of the disease), compared with 15% of those taking placebo plus methotrexate (43 out of 287).For the treatment of moderate to severe rheumatoid arthritis where other medicines were unsuccessful, RoActemra given by infusion was studied in five main studies involving a total of over 4,000 adults. In three of these studies, RoActemra was compared with placebo, as an add-on to failing treatment with conventional rheumatoid arthritis medicines in a total of over 3,000 patients. Results showed that patients adding RoActemra were around four times more likely to respond to treatment than those adding placebo. One of the studies, which involved 1,196 patients, also showed that the combination of RoActemra and methotrexate slowed down the damage to the joints and improved physical function after up to two years, when compared with the combination of placebo and methotrexate. In the fourth study, which included 498 patients who had an inadequate response to TNF blockers, patients receiving RoActemra with methotrexate were around nine times more likely to respond than those receiving placebo with methotrexate. The fifth study involving 673 patients showed that patients receiving RoActemra on its own were more likely to respond than those taking methotrexate on its own. Almost 4,000 patients from these five studies went on to enter studies looking at the long-term effects of RoActemra treatment and results showed that response to RoActemra is maintained for at least two years.RoActemra given by injection under the skin was investigated in two studies involving 1,918 patients with moderate to severe rheumatoid arthritis where previous treatment with DMARD had not worked well. In the first study, RoActemra was more effective than placebo in treating rheumatoid arthritis: after six months of treatment with RoActemra, 61% of patients responded to treatment compared with 32% on placebo. The other study, which compared RoActemra injected under the skin with RoActemra given by infusion, showed that RoActemra injected under the skin was no less effective in achieving a response after six months.Juvenile idiopathic arthritisIn systemic juvenile idiopathic arthritis, RoActemra given by infusion was compared with placebo in one main study involving 112 children in whom treatment with NSAID and corticosteroids did not work well enough. In this study 85% (64 out of 75) of patients treated with RoActemra responded to treatment and no longer had fever after three months, compared with 24% (9 out of 37) of patients receiving placebo.Another study involving 51 children from 1 year of age showed that RoActemra given by injection under the skin had a similar distribution in the body and effect on the disease to that previously seen with RoActemra given by infusion.Juvenile idiopathic polyarthritisIn juvenile idiopathic polyarthritis, RoActemra given by infusion was compared with placebo in one main study involving 166 children from 2 years of age who could not take methotrexate or for whom methotrexate did not work well enough. Patients were allowed to continue treatment with methotrexate during the study. After 4 to 6 months of treatment, 26% of patients on RoActemra (21 out of 82) had a flare-up of symptoms during treatment, compared with 48% of patients taking placebo (39 out of 81).Giant cell arteritisIn giant cell arteritis, RoActemra given by injection under the skin was found more effective than placebo in one main study involving 251 adults. All patients were also treated with a corticosteroid, which was stopped after reducing the dose gradually over 6 or 12 months. One year after starting treatment, 56% of patients treated with RoActemra once a week did not have symptoms compared with 14% patients receiving placebo.Cytokine release syndrome (CRS)RoActemra given by infusion was considered to be effective at treating severe CRS based on a review of data from 66 patients who experienced this condition after they were given CAR-T cell medicines to treat a blood cancer. The main measure of effectiveness was based on the number of patients whose CRS resolved within 14 days from the first dose of RoActemra, and who needed no more than two doses of the medicine, and no additional treatment other than corticosteroid medicines. Out of 51 patients who had CRS after being given the CAR-T cell medicine tisagenlecleucel, 39 responded to treatment with RoActemra (76.5%), while 8 out 15 patients (53.3%) who had CRS after being given axicabtagene ciloleucel responded.COVID-19In severe COVID-19, one main study showed that treatment with RoActemra given by infusion in addition to standard treatment reduces the risk of death when compared with standard treatment alone. Overall, 31% of patients treated with RoActemra plus standard treatment (621 out of 2,022) died within 28 days of treatment compared with 35% of patients receiving standard treatment alone (729 out of 2,094). In addition, 57% of patients (1,150 out of 2,022) who received RoActemra were able to leave the hospital within 28 days compared with 50% of patients (1,044 out of 2,094) who received standard treatment alone.

What are the risks associated with RoActemra?

In patients with rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis or cytokine release syndrome, the most common side effects (which may affect up to 1 patient in 10) with RoActemra are upper respiratory tract infections (nose and throat infection), nasopharyngitis (inflammation of the nose and throat), headache, hypertension (high blood pressure) and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis (a disease affecting the gut) and hypersensitivity (allergic) reactions.In patients with COVID-19, the most common side effects (which may affect up to 1 patient in 10) with RoActemra are high levels of transaminases in the blood (a sign of possible liver problems), constipation, and urinary tract infections (infections of the structures that carry urine).RoActemra must not be used in patients who have an active, severe infection (except COVID-19).Doctors should monitor patients carefully for signs of infection during treatment, and should prescribe RoActemra with caution in patients who have had recurring or long-term infections, or diseases that could increase the risk of infections, such as diverticulitis or diabetes.For the full list of side effects and restrictions, see the package leaflet.

Why is RoActemra authorised in the EU?

Studies show RoActemra is effective at reducing symptoms of several inflammatory conditions. When added to standard treatment, it is also effective at reducing the risk of dying from COVID-19 and the amount of time COVID-19 patients stay in hospital. The European Medicines Agency decided that RoActemra's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of RoActemra?

The company that markets RoActemra must supply all doctors expected to prescribe the medicine for rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis and giant cell arteritis with an educational pack containing important information on the safety and correct use of RoActemra. The pack will also include a patient alert card with key safety information for patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of RoActemra have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of RoActemra are continuously monitored. Side effects reported with RoActemra are carefully evaluated and any necessary action taken to protect patients.

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Roclanda

What is Roclanda and what is it used for?

Roclanda is an eye-drop solution for reducing pressure inside the eye in adults who have open-angle glaucoma (a disease where the pressure in the eye rises because fluid cannot drain out of the eye) or ocular hypertension (when the pressure in the eye is higher than normal). It is for patients in whom treatment with either a prostaglandin medicine or netarsudil alone did not sufficiently reduce the pressure.Roclanda contains the active substances latanoprost and netarsudil.

How is Roclanda used?

The medicine can only be obtained with a prescription and treatment should be started by an eye specialist. It is available as an eye-drop solution and the dose is one drop in the affected eye, in the evening.For more information about using Roclanda, see the package leaflet or contact your healthcare provider.

How does Roclanda work?

Raised pressure in the eye can cause damage to the retina (the light-sensitive membrane at the back of the eye) and to the optic nerve that sends signals from the eye to the brain. This can result in serious vision loss and even blindness.Roclanda contains two active substances, netarsudil and latanoprost, which lower the pressure in the eye in different ways. Latanoprost is a prostaglandin analogue (a copy of the natural substance prostaglandin) that works by increasing the drainage of fluid out of the eye. Netarsudil blocks the activity of an enzyme called Rho kinase, which has a role in controlling fluid drainage from the eye. By blocking this enzyme, netarsudil increases the flow of fluid out of the eyeball, thereby lowering pressure inside the eye. Together, the two active substances reduce the pressure inside the eye more than either medicine alone.

What benefits of Roclanda have been shown in studies?

Two main studies involving a total of 1,468 adults with glaucoma or ocular hypertension showed that Roclanda is more effective at lowering eye pressure than either of its two active substances given alone.Both studies measured the pressure inside the eye at 9 different time points over a period of 3 months. Taken together, the results from the two studies showed that pressure inside the eye in patients treated with Roclanda was between 15.03 and 16.38 mmHg, compared with between 17.35 and 19.39 mmHg in those treated with netarsudil and between 16.93 and 17.96 mmHg in those treated with latanoprost.

What are the risks associated with Roclanda?

The most common side effects with Roclanda (which may affect more than 1 in 10 people) are conjunctival hyperaemia (red eye), pain at the site where the medicine was applied and cornea verticillata (deposits in the cornea, the transparent layer in front of the eye that covers the pupil and iris).Other common side effects (which may affect up to 1 in 10 people) are eye pruritus (itching of the eye), erythema (reddening) and discomfort in the eye, increased lacrimation (watery eyes), and conjunctival haemorrhage (bleeding in the surface layer of the eye).For the full list of side effects and restrictions of Roclanda, see the package leaflet.

Why is Roclanda authorised in the EU?

Roclanda, which combines two medicines to reduce pressure inside the eye, is more effective than the individual medicines given alone. This offers another treatment option for patients with open-angle glaucoma or ocular hypertension in whom a prostaglandin analogue or netarsudil alone have not sufficiently reduced the pressure. Reducing pressure inside the eye can prevent eye pain and loss of vision.The side effects of Roclanda are generally mild to moderate and considered manageable.The European Medicines Agency decided that Roclanda's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Roclanda?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Roclanda have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Roclanda are continuously monitored. Side effects reported with Roclanda are carefully evaluated and any necessary action taken to protect patients.

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Roctavian

What is Roctavian and what is it used for?

Roctavian is a medicine for treating severe haemophilia A, an inherited bleeding disorder caused by the lack of a clotting protein known as factor VIII. It is used in adults who do not have inhibitors(antibodies) against factor VIII and who have no antibodies against adeno-associated virus serotype 5 (AAV5).Roctavian contains the active substance valoctocogene roxaparvovec and is a type of advanced therapy medicine called a 'gene therapy product'. This is a type of medicine that works by delivering genes into the body.Haemophilia A is rare, and Roctavian was designated an 'orphan medicine' (a medicine used in rare diseases) on 21 March 2016. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/EU3161622.

How is Roctavian used?

The medicine can only be obtained with a prescription and treatment should be started under supervision of a doctor experienced in the treatment of haemophilia or bleeding disorders. The medicine should be given in a facility equipped to promptly treat infusion-related reactions.Roctavian is given as a single infusion (drip) into a vein over a number of hours. The dose depends on the patient's body weight. Patients may be given other medicines to reduce the risk of infusion-related reactions.For more information about using Roctavian, see the package leaflet or contact your doctor or pharmacist.

How does Roctavian work?

Roctavian is made of a virus (AAV5) that has been modified to contain the gene for factor VIII, which is lacking in patients with haemophilia A. After being given to the patient, the virus is expected to carry the factor VIII gene into the liver cells, enabling them to produce the missing factor VIII for a long period. This is expected to control the bleeding disorder.The type of virus used in this medicine (adeno-associated virus) does not cause disease in humans.

What benefits of Roctavian have been shown in studies?

A main study involving 134 adult male patients with severe haemophilia A found that Roctavian was effective at increasing the level of factor VIII activity and that this increase was sustained for at least 2 years. 104 weeks after receiving a single dose of the medicine, 75.4% of the patients had an average factor VIII activity level of at least 5 international units per decilitre (IU/dL), which is a measure of mild haemophilia. In addition, the yearly number of bleeding episodes decreased by 85.5% and the need for additional factor VIII replacement treatment dropped by 97.5%.

What are the risks associated with Roctavian?

The most common side effects with Roctavian (which may affect more than 3 in 10 people) are increased levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase (signs of possible liver problems), increased levels of the enzyme lactate dehydrogenase (sign of possible tissue damage), nausea (feeling sick) and headache. For the full list of side effects of Roctavian, see the package leaflet.Roctavian must not be given to people who are hypersensitive (allergic) to any of its ingredients, or who have an active or chronic (long-term) infection that is not controlled by medicines or significant liver fibrosis or liver cirrhosis (scarring of the liver).

Why is Roctavian authorised in the EU?

Patients with haemophilia A require lifelong treatment with one or more injections per week or month to replace or mimic the missing factor VIII. Roctavian has been shown to be effective at increasing the level of factor VIII activity in patients with haemophilia A, and this increase is sustained for at least 2 years. The European Medicines Agency also considered that, as Roctavian is given as a single infusion, it would reduce the treatment burden for patients with severe haemophilia A for at least 2 years.Although the long-term safety data are limited, the safety profile was considered acceptable.Roctavian has been given 'conditional authorisation'. This means that the Agency decided that the benefits of Roctavian are greater than its risks, but the company will have to provide additional evidence after authorisation.Conditional authorisation is granted on the basis of less comprehensive data than are normally required. It is granted for medicines that fulfil an unmet medical need to treat serious diseases and when the benefits of having them available earlier outweigh any risks associated with using the medicines while waiting for further evidence. Every year, the Agency will review any new information that becomes available until data become comprehensive and this overview will be updated as necessary.

What information is still awaited for Roctavian?

Since Roctavian has been given conditional authorisation, the company that markets Roctavian will provide additional data from ongoing studies on the long-term safety and effectiveness of the medicine in patients with severe haemophilia A and will carry out a study on when to best start corticosteroid treatment in these patients to avoid liver problems. The company will also provide data from a registry of patients treated with Roctavian to study its long-term safety and effectiveness.

What measures are being taken to ensure the safe and effective use of Roctavian?

The company that markets Roctavian will provide patients and healthcare professionals with educational material explaining the benefits, risks and uncertainties about the long-term effects of the medicine. Patients will also be given a patient card to inform healthcare professionals that they have received Roctavian to treat haemophilia A.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Roctavian have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Roctavian are continuously monitored. Suspected side effects reported with Roctavian are carefully evaluated and any necessary action taken to protect patients.

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Rolufta Ellipta

What is Rolufta Ellipta and what is it used for?

Rolufta Ellipta is a medicine used to relieve the symptoms of chronic obstructive pulmonary disease (COPD) in adults. COPD is a long-term disease in which the airways and air sacs inside the lungs become damaged or blocked, leading to difficulty breathing. Rolufta Ellipta is used for maintenance (regular) treatment.Rolufta Ellipta contains the active substance umeclidinium bromide.

How is Rolufta Ellipta used?

Rolufta Ellipta is available as an inhalation powder in a portable inhaler device. Each inhalation provides 65 micrograms of umeclidinium bromide equivalent to 55 micrograms of umeclidinium. The recommended dose is one inhalation per day at the same time each day. For detailed information on how to use the inhaler correctly, see the instructions in the package leaflet or contact your doctor or pharmacist.The medicine can only be obtained with a prescription.

How does Rolufta Ellipta work?

The active substance in Rolufta Ellipta, umeclidinium bromide, is a muscarinic receptor antagonist. It works by blocking the action of so-called muscarinic receptors, which control the contraction of muscles. When umeclidinium bromide is inhaled, it relaxes the muscles of the airways. This helps to keep the airways open and allows the patient to breathe more easily.

What benefits of Rolufta Ellipta have been shown in studies?

Rolufta Ellipta was investigated in four main studies involving over 4,000 patients. Three studies compared Rolufta Ellipta with placebo (a dummy treatment), while one study compared Rolufta Ellipta with tiotropium (another medicine for COPD). The main measure of effectiveness was based on1 Previously known as Rolufta.changes in the patients' forced expiratory volumes (FEV1, the maximum volume of air a person can breathe out in one second).Results showed that Rolufta Ellipta improved lung function by an average FEV1 by 127 ml more than placebo after 12 weeks of treatment and by 115 ml after 24 weeks of treatment. A double dose of Rolufta Ellipta only showed small improvements compared with a single dose, which were not considered relevant. In the study comparing Rolufta Ellipta with tiotropium, FEV1 improvements over 24 weeks were similar for both medicines.The studies also showed an improvement in symptoms such as breathlessness and wheezing.

What are the risks associated with Rolufta Ellipta?

The most common side effects with Rolufta Ellipta (which may affect up to 1 in 10 people) are headache, nasopharyngitis (inflammation of the nose and throat), upper respiratory tract infection(nose and throat infection), sinusitis (inflammation of the sinuses), cough, urinary tract infection (infection of the structures that carry urine), and tachycardia (increased heart rate).For the full list of side effects and restrictions with Rolufta Ellipta, see the package leaflet.

Why is Rolufta Ellipta authorised in the EU?

The European Medicines Agency decided that Rolufta Ellipta's benefits are greater than its risks and it can be authorised for use in the EU. The Agency concluded that Rolufta Ellipta was shown to be effective at improving the lung function and symptoms of COPD. The Agency also noted that there were no major safety concerns with Rolufta Ellipta, with side effects being manageable and similar to other medicines of the same class (antimuscarinic bronchodilators).

What measures are being taken to ensure the safe and effective use of Rolufta Ellipta?

As medicines of the same class as Rolufta Ellipta may have an effect on the heart and blood vessels, the company that markets Rolufta Ellipta will carry out a long-term study in patients to collect further information on its safety in comparison with tiotropium.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rolufta Ellipta have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rolufta Ellipta are continuously monitored. Side effects reported with Rolufta Ellipta are carefully evaluated and any necessary action taken to protect patients.

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Ronapreve

What is Ronapreve and what is it used for?

Ronapreve is a medicine used for treating COVID-19 in adults and adolescents (from 12 years of age and weighing at least 40 kilograms) who do not require supplemental oxygen and who are at increased risk of their disease becoming severe.The medicine can also be used to prevent COVID-19 in people aged 12 years and older weighing at least 40 kilograms. Ronapreve contains two active substances, casirivimab and imdevimab.

How is Ronapreve used?

Ronapreve is given as a single treatment by infusion (drip) into a vein or by injection under the skin.The recommended dose is 600 mg of casirivimab and 600 mg of imdevimab.When used for treatment, it should be given within 7 days of the patient developing symptoms of COVID-19.When used for prevention after contact with a person with COVID-19, Ronapreve should be given as soon as possible after contact occurred. Ronapreve may also be given to prevent COVID-19 when no contact has occurred. In these cases, following an initial dose of 600 mg casirivimab and 600 mg imdevimab, a dose of 300 mg of casirivimab and 300 mg of imdevimab may be given every four weeks until prevention is no longer required.The medicine can only be obtained with a prescription and should be given in healthcare facilities where patients can be adequately monitored and managed in case they develop severe allergic reactions, including anaphylaxis.For more information about using Ronapreve, see the package leaflet or contact your healthcare provider.

How does Ronapreve work?

This medicine is made of casirivimab and imdevimab, two monoclonal antibodies. A monoclonal antibody is a type of protein that has been designed to recognise and attach to a specific structure (called an antigen). Casirivimab and imdevimab have been designed to attach to the spike protein ofSARS-CoV-2 (the virus causing COVID-19) at two different sites. When the active substances attach to the spike protein, the virus is unable to enter the body's cells.

What benefits of Ronapreve have been shown in studies?

Treatment of COVID-19A main study (COV-2067) involving patients with COVID-19 who did not require oxygen and were at increased risk of their illness becoming severe showed that Ronapreve at the authorised dose led to fewer hospitalisations or deaths when compared with placebo (dummy treatment). Overall, 0.9% of patients treated with Ronapreve (11 out of 1,192 patients) were hospitalised or died within 29 days of treatment compared with 3.4% of patients on placebo (40 out of 1,193 patients).Prevention of COVID-19A main study (COV-2069) looked at the benefits of Ronapreve for prevention of COVID-19 in people who had close contact with an infected household member.Ronapreve was found to be effective at preventing people from getting infected and developing symptoms after contact: amongst people who tested negative for SARS-CoV-2 following contact, fewer people given Ronapreve developed symptoms within 29 days of their test results compared with people given placebo (1.5% (11 out of 753) for Ronapreve compared with 7.8% (59 out of 752 people) for placebo).Ronapreve was also found to be effective at preventing symptoms in infected people. Amongst the people who tested positive for SARS-CoV-2 after contact, 29% (29 out of 100) of people who received Ronapreve developed symptoms compared with 42.3% (44 out of 104 people) of people who received a placebo.

What are the risks associated with Ronapreve?

The most common side effects with Ronapreve (which may affect up to 1 in 10 people) are allergic reactions, which include infusion related reactions and injection site reactions.For the full list of side effects and restrictions of Ronapreve, see the package leaflet.

Why is Ronapreve authorised in the EU?

Ronapreve showed a clinically meaningful effect in preventing hospitalisation and death in patients with COVID-19, while also showing benefits in preventing COVID-19. Although vaccination is the main way of preventing COVID-19, there is an unmet medical need in people who have been exposed to COVID19 as well as in people who cannot be vaccinated and who require long-term prevention. The safety profile of Ronapreve is favourable. The European Medicines Agency decided that Ronapreve's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Ronapreve?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ronapreve have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ronapreve are continuously monitored. Suspected side effects reported with Ronapreve are carefully evaluated and any necessary action taken to protect patients.

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Rotarix

What is Rotarix?

Rotarix is a vaccine that is given by mouth. It is available in three forms:• a powder and solvent that are made up into an oral suspension in an oral applicator;• an oral suspension in a prefilled oral applicator;• an oral suspension in a squeezable tube.Rotarix contains a live attenuated (weakened) form of the human rotavirus (RIX4414 strain).

What is Rotarix used for?

Rotarix is used in babies aged from 6 to 24 weeks to protect against gastroenteritis (diarrhoea and vomiting) caused by rotavirus infections. Rotarix is given according to official recommendations.The vaccine can only be obtained with a prescription.

How is Rotarix used?

Rotarix is given as two doses, at least four weeks apart. The first dose is given when the baby is older than six weeks. Ideally, both doses should be given before the baby is aged 16 weeks and they must be given by the time the baby is 24 weeks old. The same vaccination course can be used in babies born up to 13 weeks prematurely (from 27 weeks gestational age).If the powder and solvent are used, they should be mixed together just before the vaccine is given, and the resulting suspension given directly into the mouth of the baby using the oral applicator provided. If the ready-made oral suspension is used, the contents of the prefilled oral applicator or tube should be given into the mouth of the baby. Rotarix can be given at the same time as other vaccines.

How does Rotarix work?

Rotarix contains small amounts of rotavirus, a virus that causes gastroenteritis. The virus is alive, but it has been weakened so that it does not cause the disease, which makes it suitable for use in a vaccine. When an infant is given the vaccine, the immune system (the system that fights diseases) recognises the weakened virus as 'foreign' and makes defences against it. After vaccination, the immune system is able to respond more quickly when it is exposed to the virus again. This helps to protect against gastroenteritis caused by rotavirus.

How has Rotarix been studied?

Overall, the clinical studies of Rotarix involved over 75,000 babies and took place in various countries worldwide. The main study compared Rotarix with placebo (a dummy vaccine) in over 63,000 babies who were born at full term (after a pregnancy of at least 36 weeks). The benefit of the vaccine was measured by looking at how many babies developed severe rotavirus gastroenteritis in the months after they had been vaccinated and before they had reached one year of age.A further study looked at the safety of Rotarix and its ability to stimulate the production of antibodies in 1,009 babies born up to 13 weeks prematurely. These results were compared with the findings of a study in babies born at full term who were vaccinated with Rotarix.Four additional studies were carried out in over 3,000 infants, to confirm that the ready-for-use forms of the vaccine were as safe and as effective as the powder and solvent formulation in stimulating the production of antibodies against rotavirus.

What benefit has Rotarix shown during the studies?

Rotarix was more effective than placebo in preventing severe gastroenteritis due to rotavirus. In the main study, the number of cases of severe rotavirus gastroenteritis was lower following vaccination with Rotarix: 0.1% of the babies vaccinated with Rotarix in whom effectiveness was assessed developed severe rotavirus gastroenteritis (12 out of over 9,000) compared with 0.9% of the babies who received placebo (77 out of almost 9,000).The study in premature babies showed that Rotarix was well tolerated and produced similar levels of antibodies as in infants born at full term.

What is the risk associated with Rotarix?

The most common side effects with Rotarix (seen in between 1 and 10 patients in 100) are diarrhoea and irritability. Very rarely (seen in less than 1 patient in 10,000), a serious condition called intussusception (in which part of the bowel becomes enfolded within another part of the bowel, leading to a blockage) has been reported after the use of rotavirus vaccines. For the full list of all side effects reported with Rotarix, see the package leaflet.Rotarix must not be used in babies who are hypersensitive (allergic) to any of the ingredients of the vaccine or those who showed signs of allergy after receiving a dose of rotavirus vaccine in the past. It must also not be given to patients who have disorders that cause severe abnormalities of the immune system called 'severe combined immunodeficiency', who have had intussusception in the past, or who have problems with their bowel that could put them at risk of intussusception. Vaccination with Rotarix should be postponed in babies who have a sudden high fever, diarrhoea or vomiting.Rotarix should never be injected under any circumstances.

Why has Rotarix been approved?

The CHMP decided that Rotarix's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Rotarix?

A risk management plan has been developed to ensure that Rotarix is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Rotarix, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Rotarix is developing a vaccine free of porcine circovirus type 1 (PCV-1) after a very small amount of viral particles was found in the vaccine in 2010. PCV-1 is not known to cause any disease.

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Rotateq

What is RotaTeq?

RotaTeq is a vaccine that is taken by mouth. It is available as a solution in a single-dose tube. It contains five live rotavirus strains, each carrying a different antigen (G1, G2, G3, G4 and P1[8]).

What is RotaTeq used for?

RotaTeq is used in babies from 6 to 32 weeks of age to protect against gastroenteritis (diarrhoea and vomiting) caused by rotavirus infections. RotaTeq is given according to official recommendations.The vaccine can only be obtained with a prescription.

How is RotaTeq used?

RotaTeq is given as three doses, with at least four weeks between each dose. The contents of the tube of RotaTeq are given directly into the baby's mouth. The first dose is given when the baby is between 6 and 12 weeks of age. It is recommended that the last dose be given to the child by the age of 20 to 22 weeks. If necessary it may be given up to the age of 32 weeks. RotaTeq can be given at the same time as other vaccinations (except the oral polio vaccine, when a two-week interval is needed between the two vaccines).RotaTeq can be given to premature babies, as long as the pregnancy lasted at least 25 weeks. The first dose should be given six weeks after birth at the earliest.

How does RotaTeq work?

There are various types of rotaviruses that cause gastroenteritis. They vary in that they may carry different antigens. An antigen is a specific structure that the body can recognise as 'foreign' and against which the body can make an antibody, a special protein that can neutralise or destroy the antigen. RotaTeq contains viruses that carry the antigens for some of the most commonly occurring types of rotaviruses. When a baby is given the vaccine, the immune system (the system that fights diseases) makes antibodies against these antigens, which help prevent infections caused by rotaviruses that occur naturally and carry the same or very similar antigens.

How has RotaTeq been studied?

Overall, the studies of RotaTeq involved over 72,000 babies, including about 2,000 premature babies. About half of the babies received RotaTeq, and the others received placebo (a dummy vaccine). The main measure of effectiveness, which was studied in 6,000 babies, was the number of babies who developed rotavirus gastroenteritis during the following rotavirus season (the time of the year when rotaviruses are known to circulate and cause infection, generally during the cooler months in winter to early spring).

What benefit has RotaTeq shown during the studies?

The number of cases of rotavirus gastroenteritis due to viruses with the same antigens as in the vaccine decreased following vaccination with RotaTeq. Among the almost 6,000 babies in whom the main measure of effectiveness was studied, 82 of the babies vaccinated with RotaTeq developed rotavirus gastroenteritis (one with severe gastroenteritis) compared with 315 of the babies who received placebo (51 severe cases). The study also showed that there were fewer hospital admissions or visits to emergency clinics for rotavirus gastroenteritis in babies vaccinated with RotaTeq.

What is the risk associated with RotaTeq?

The most common side effects with RotaTeq (seen in more than 1 patient in 10) are pyrexia (fever), diarrhoea and vomiting. Very rarely (seen in less than 1 patient in 10,000), a serious condition called intussusception (in which part of the bowel becomes enfolded within another part of the bowel, leading to a blockage) has been reported after the use of rotavirus vaccines. For the full list of all side effects reported with RotaTeq, see the package leaflet.RotaTeq must not be used in babies who are hypersensitive (allergic) to the active substance or any of the other ingredients, or who showed signs of allergy after receiving a dose of RotaTeq or another vaccine against rotavirus in the past. RotaTeq must not be given to babies who have had intussusception in the past or who have problems with their bowel that could put them at risk of intussusception. It must also not be used in babies whose immune system is weakened. Vaccination with RotaTeq should be postponed in babies who have a sudden high fever, diarrhoea or vomiting.RotaTeq should never be injected under any circumstances.

Why has RotaTeq been approved?

The CHMP decided that RotaTeq's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of RotaTeq?

A risk management plan has been developed to ensure that RotaTeq is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for RotaTeq, including the appropriate precautions to be followed by healthcare professionals and patients.

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Roteas

What is Roteas and what is it used for?

Roteas is an anticoagulant medicine (a medicine that prevents blood clotting) used in adults:• to prevent stroke (caused by blood clots in the brain) and systemic embolism (blood clots in other organs) in patients with non-valvular atrial fibrillation (irregular rapid contractions of the upper chambers of the heart). It is used in patients who have one or more risk factors, such as high blood pressure, diabetes, heart failure, having had a stroke or being 75 years old or over;• to treat deep-vein thrombosis (DVT, a blood clot in a deep vein, usually in the leg) and pulmonary embolism (a clot in a blood vessel supplying the lungs), and to prevent DVT and pulmonary embolism from re-occurring.Roteas contains the active substance edoxaban.This medicine is the same as Lixiana, which is already authorised in the European Union (EU). The company that makes Lixiana has agreed that its scientific data can be used for Roteas ('informed consent').

How is Roteas used?

Roteas is available as tablets and can only be obtained with a prescription. The usual dose is 60 mg once a day but doses may be adjusted for kidney function, low body weight or in those who are also taking certain medicines (known as P-gp inhibitors) that can interfere with the removal of edoxaban from the body. Dose adjustments may also need to be made in patients who are switched between Roteas and other anticoagulant medicines. Treatment is continued while the benefit outweighs the risk of bleeding, which depends on the condition being treated and any existing risk factors. For more information about using Roteas, see the package leaflet or contact your doctor or pharmacist.

How does Roteas work?

The active substance in Roteas, edoxaban, is a 'factor Xa inhibitor'. This means that it blocks factor Xa, an enzyme that is involved in the production of thrombin. Thrombin is essential for blood clotting. By blocking factor Xa, the medicine reduces the levels of thrombin in the blood, which helps treat clotsand reduce the risk of them forming in the arteries and veins and leading to DVT, pulmonary embolism, stroke or other organ damage.

What benefits of Roteas have been shown in studies?

Roteas has been shown to be as effective as the standard anticoagulant warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation. The effects were studied in one main study, which involved over 21,000 patients for an average of 2.5 years. The main measure of effectiveness was the rate of stroke or systemic embolism among the patients each year. A first systemic embolism or stroke occurred in around 1.2% of those given standard doses of Roteas and 1.5% of those given warfarin respectively. When another recommended definition of the type of stroke was used, embolism or stroke due to blood clots was seen in 0.9% of patients given Roteas and 1% of those given warfarin. There was a trend for better results in patients with reduced kidney function than those whose kidney function was normal.In the treatment and prevention of blood clots in patients with DVT or pulmonary embolism, Roteas was also found to be as effective as warfarin, in a study involving over 8,200 patients. The main measure of effectiveness was the number of patients who had another episode of DVT or pulmonary embolism during the study period. Further episodes were seen in 130 of 4,118 patients given edoxaban (3.2%) and in 146 of 4,122 given warfarin (3.5%).

What are the risks associated with Roteas?

The most common side effects with Roteas (which may affect up to 1 in 10 people) are nose bleeds (epistaxis), blood in the urine (haematuria) and anaemia (low levels of red blood cells). Bleeding can occur at any site and can be severe or even fatal. For the full list of side effects of Roteas, see the package leaflet.Roteas must not be used in patients who are actively bleeding, have liver diseases that affect blood clotting, have severe uncontrolled high blood pressure or who have a condition putting them at significant risk of major bleeding. It must also not be used in pregnant or breastfeeding women or together with another anticoagulant. For the full list of restrictions, see the package leaflet.

Why is Roteas authorised in the EU?

The European Medicines Agency decided that Roteas's benefits are greater than its risks and it can be authorised for use in the EU. The medicine has been shown to be at least as effective as warfarin in reducing stroke rates in patients with atrial fibrillation and in preventing further episodes of DVT or pulmonary embolism.With respect to safety, overall the risk of serious bleeding such as bleeding into the brain was reduced compared with warfarin, although there may be less difference where warfarin treatment is well managed. Although there was greater a risk of bleeding from the mucosa (tissues lining body cavities such as the nose, gut and vagina), the Agency considered that the risk could be managed with appropriate measures.

What measures are being taken to ensure the safe and effective use of Roteas?

The company that markets Roteas will provide educational materials for doctors prescribing the medicine and an alert card for patients, explaining the risks of bleeding with the medicine and how to manage them.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Roteas have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Roteas are continuously monitored. Side effects reported with Roteas are carefully evaluated and any necessary action taken to protect patients.

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Rozlytrek

What is Rozlytrek and what is it used for?

Rozlytrek is a cancer medicine. It can be used for treating patients from 12 years of age with solid tumours (cancer growths) that have a genetic abnormality called NTRK gene fusion. Rozlytrek is for use in patients with tumours that have spread nearby or to other parts of the body (metastatic cancer) or when removing the tumour by surgery could cause severe harm. It should be used only if the patient has not been treated previously with a medicine that works in the same way as Rozlytrek and other treatments are not suitable.Rozlytrek can also be used for treating adults with advanced non-small-cell lung cancer that has a genetic abnormality called ROS1 gene fusion. It should be used only if the patient has not been treated previously with a medicine that blocks ROS1.Rozlytrek contains the active substance entrectinib.

How is Rozlytrek used?

Rozlytrek can only be obtained with a prescription and treatment should be started by a doctor who is experienced in the use of cancer medicines. It is available as capsules.The recommended dose of Rozlytrek for adults is 600 mg once daily. The dose for children is based on the child's height and weight. Treatment with Rozlytrek is continued until it stops working. The doctor may reduce the dose, interrupt treatment or stop it altogether if the patient has certain side effects.For more information about using Rozlytrek, see the package leaflet or contact your doctor or pharmacist.

How does Rozlytrek work?

Cancers with NTRK gene fusion or ROS1 gene fusion produce abnormal proteins that cause uncontrolled increase of cancer cells. Entrectinib, the active substance in Rozlytrek, blocks the action of these proteins and so prevents the increase in cancer cells, thereby slowing down cancer growth.

What benefits of Rozlytrek have been shown in studies?

Solid tumours with NTRK gene fusionOngoing studies involved a total of 74 adults with advanced solid tumours with NTRK gene fusion in whom previous treatment had stopped working or other treatment was not suitable. Patients received Rozlytrek until it stopped working or caused unacceptable side effects. Out of a total of 74 patients, the cancer shrank in 64% of patients and the average duration of response (period during which the size of the cancer was under control) was 12.9 months. Rozlytrek was not compared with another treatment for solid tumours.Supporting studies indicate that the medicine is expected to work in the same way in patients from 12 years of age.Non-small-cell lung cancer with ROS1 gene fusionStudies involved a total of 94 patients with advanced or metastatic non-small-cell lung cancer with ROS1 gene fusion. Patients were followed up for more than 12 months and they received Rozlytrek until it stopped working or caused unacceptable side effects. The cancer shrank in 73% of patients and the average duration of response was 16.5 months. The studies did not compare Rozlytrek with another treatment for non-small-cell lung cancer.

What are the risks associated with Rozlytrek?

The most common side effects with Rozlytrek (which may affect more than 1 in 5 people) are tiredness, constipation, dysgeusia (taste disturbances), oedema (swelling with fluid retention), dizziness, diarrhoea, nausea (feeling sick), dysaesthesia (unpleasant and abnormal feeling when touched), dyspnoea (difficulty breathing), anaemia (low red blood cell count), increased weight, increased blood creatinine (possible sign of kidney problems), pain, cognitive disorders (problems with ability to think, learn and remember), vomiting, cough, and fever.The most common serious side effects with Rozlytrek (which may affect more than 1 in 50 people) are lung infection, dyspnoea, cognitive disorders and pleural effusion (build-up of fluid around the lungs).For the full list of restrictions and side effects of Rozlytrek, see the package leaflet.

Why is Rozlytrek authorised in the EU?

The European Medicines Agency considered that in patients with solid tumours with NTRK gene fusion, treatment with Rozlytrek is of benefit when other treatment is not available or does not work. However, more information is needed on the medicine's effect on tumours in different sites and also when other gene abnormalities are present. For non-small-cell lung cancer with ROS1 gene fusion, results currently available suggest that treatment with Rozlytrek can reduce the size of tumours. The side effects of Rozlytrek are considered manageable.Therefore, the Agency decided that Rozlytrek's benefits are greater than its risks and it can be authorised for use in the EU. Rozlytrek has been given 'conditional authorisation'. This means that there is more evidence to come about the medicine, which the company is required to provide. Every year, the Agency will review any new information that becomes available and this overview will be updated as necessary.

What information is still awaited for Rozlytrek?

Since Rozlytrek has been given conditional authorisation, the company that markets Rozlytrek will provide further data from ongoing studies on the effectiveness and safety of Rozlytrek in adults and children who have solid tumours with NTRK gene fusion.

What measures are being taken to ensure the safe and effective use of Rozlytrek?

The company that markets Rozlytrek will provide results from a study comparing the effectiveness of Rozlytrek with crizotinib (another cancer medicine) in patients with non-small-cell lung cancer with ROS1 fusion whose disease has spread to the brain.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rozlytrek have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rozlytrek are continuously monitored. Side effects reported with Rozlytrek are carefully evaluated and any necessary action taken to protect patients.

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Rubraca

What is Rubraca and what is it used for?

Rubraca is a cancer medicine for treating high-grade cancers of the ovary, fallopian tubes (the tubes connecting ovaries to the uterus) and the peritoneum (the membrane lining the abdomen).It is used as maintenance treatment in patients whose recurring cancer has cleared (partially or completely) after treatment with platinum-based cancer medicines.Rubraca contains the active substance rucaparib.

How is Rubraca used?

Rubraca can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in the treatment of cancer.Rubraca is available as tablets to be taken twice a day. Treatment should continue until the cancer progresses or the patient has unacceptable side effects. Treatment with Rubraca should be started no later than 8 weeks after the patient has finished their treatment with a platinum-based medicine.For more information about using Rubraca, see the package leaflet or contact your doctor or pharmacist.

How does Rubraca work?

The active substance in Rubraca, rucaparib, blocks the activity of a family of proteins called poly(ADPribose) polymerases (PARPs) that help to repair damaged DNA in cells (both normal and cancer cells). In normal cells there is an alternative mechanism for repairing DNA but this alternative mechanism does not work properly in cancer cells with mutations in the BRCA genes. Therefore, when PARP proteins are blocked, the damaged DNA in these cancer cells cannot be repaired, and, as a result, the cancer cells die.

What benefits of Rubraca have been shown in studies?

Rubraca was investigated in a main study of 564 patients with ovarian cancer which had cleared (partially or completely) after treatment with platinum-based cancer medicines. Patients given Rubraca lived for 11 months without the disease coming back or getting worse compared with 5 months in patients given placebo (a dummy treatment).

What are the risks associated with Rubraca?

For the full list of side effects and restrictions with Rubraca, see the package leaflet.The most common side effects with Rubraca (which may affect more than 1 in 5 people) include tiredness or weakness, nausea (feeling sick), vomiting, anaemia (low red blood cell counts), abdominal pain (belly ache), dysgeusia (taste disturbances), increased levels of liver enzymes in the blood (which may indicate liver damage), decreased appetite, diarrhoea and thrombocytopenia (low levels of platelets).Women must not breastfeed during treatment with Rubraca and for at least 2 weeks after treatment.

Why is Rubraca authorised in the EU?

Rubraca has been shown to delay worsening or return of the disease in patients whose cancer had cleared partially or completely after treatment with platinum-based medicines. This benefit was seen in patients with or without the BRCA mutation. Regarding safety, side effects occur frequently but are generally not serious and are manageable with appropriate treatment. In addition, fewer liver and blood-related problems occur with Rubraca than with other existing treatments for these patients.The European Medicines Agency decided that Rubraca's benefits are greater than its risks and it can be authorised for use in the EU.Rubraca was originally given 'conditional authorisation' because there was more evidence to come about the use of Rubraca outside maintenance treatment of patients. This use has since been restricted.1 The authorisation has therefore been switched from a conditional to a standard marketing authorisation.

What measures are being taken to ensure the safe and effective use of Rubraca?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rubraca have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rubraca are continuously monitored. Side effects reported with Rubraca are carefully evaluated and any necessary action taken to protect patients.

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Ruconest

What is Ruconest and what is it used for?

Ruconest is a medicine used to treat attacks of hereditary angioedema in adults and adolescents. Patients with angioedema have attacks of swelling that can occur anywhere in the body, such as in the face or limbs, or around the gut, causing discomfort and pain. Ruconest is used in patients with hereditary angioedema that is linked to naturally low levels of a protein called 'C1 esterase inhibitor'.Ruconest contains the active substance conestat alfa.

How is Ruconest used?

Ruconest can only be obtained with a prescription and treatment should be started under the supervision of a doctor with experience in diagnosing and treating hereditary angioedema.Ruconest is available as a powder (with or without solvent) that is made up into a solution for injection. It is given by slow injection into a vein lasting around five minutes. The dose depends on the patient's body weight. One injection is usually enough to treat an attack, but a second injection may be given if the patient does not improve enough after the first one. A patient should not be given more than two injections within any 24-hour period. Patients may be able to inject the medicine themselves after they have been properly trained. In this case the powder that comes with the solvent should be used.

How does Ruconest work?

The C1 esterase inhibitor protein is required to control the 'complement' and 'contact' systems, collections of proteins in the blood that fight against infection and cause inflammation. Patients with low levels of this protein have excessive activity of these two systems, which leads to the symptoms of angioedema. The active substance in Ruconest, conestat alfa, is a copy of the C1 esterase inhibitor protein and wor ks in the same way as the natural human protein. When it is given during an angioedema attack, conestat alfa stops this excessive activity, helping to relieve the patient's symptoms.

What benefits of Ruconest have been shown in studies?

Ruconest was studied in two main studies involving a total of 70 adults and adolescents with hereditary angioedema caused by low levels of C1 esterase inhibitor protein. When an attack occurred, the patients were given Ruconest or placebo (a dummy treatment). The main measure of effectiveness was how long it took for the symptoms to start to improve. Improvement was measured by the patients rating the severity of their symptoms on a scale from 0 to 100.Ruconest was more effective than placebo at improving the symptoms of patients having an attack of angioedema. Patients receiving Ruconest at doses of 50 units/kg and 100 units/kg started to improve after one and two hours. Patients receiving placebo started to improve after four hours in one study and after over eight hours in the other.

What is the risk associated with Ruconest?

The most common side effect with Ruconest (seen in between 1 and 10 patients in 100) is headache. For the full list of all side effects reported with Ruconest, see the package leaflet.Ruconest must not be used in patients with known or suspected allergy to rabbits. For the full list of restrictions, see the package leaflet.

Why is Ruconest approved?

The CHMP decided that Ruconest's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Ruconest?

The company that markets Ruconest will ensure that healthcare professionals who are expected to prescribe Ruconest are provided with an educational pack containing information on the proper use of the medicine and warnings about the risk of allergy. The company will also provide prescribers with an alert card for their patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ruconest have also been included in the summary of product characteristics and the package leaflet.

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Rukobia

What is Rukobia and what is it used for?

Rukobia is a medicine used to treat adults infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS). Rukobia is given with other HIV medicines when none of the standard combinations work well enough to control the infection because the virus is resistant to them (multi-drug resistant HIV-1).

How is Rukobia used?

Rukobia can only be obtained with a prescription. It should be prescribed by a doctor who is experienced in the treatment of HIV infection.The medicine is available as prolonged-release tablets, which release the active substance slowly over a few hours. One tablet should be taken twice a day.For more information about using Rukobia, see the package leaflet or contact your doctor or pharmacist.

How does Rukobia work?

When in the body, the medicine attaches to a protein on the outer envelope of the HIV-1 virus. This prevents the virus from interacting with immune cells called T cells, which are the main target of the HIV-1 virus. By preventing the virus from entering the T cells and reproducing inside them, Rukobia slows down the spread of infection.Rukobia does not cure HIV-1 infection or AIDS, but it may hold off damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Rukobia have been shown in studies?

Rukobia taken with other HIV medicines was shown to be effective at reducing viral load (blood levels of HIV-1 virus) in patients with multi-drug resistant HIV-1.In a main study involving adults with multi-drug resistant HIV-1, patients were given Rukobia or placebo (a dummy treatment) in addition to their usual HIV medicines. At the start of treatment,patients had a viral load of at least 400 copies/ml. After 8 days, 65% of patients who were taking Rukobia had a decrease in the viral load compared with 19% of patients receiving placebo.After around 22 months taking Rukobia, the viral load had fallen to below 40 copies/ml in 60% of patients taking at least one other HIV medicine that worked and in 37% of patients in whom no other HIV medicines were working.

What are the risks associated with Rukobia?

The most common side effects with Rukobia (which may affect more than 1 in 10 people) are diarrhoea, headache, nausea (feeling sick), rash, belly pain and vomiting.The most serious side effect (which may affect more than 1 in 100 people) is immune reconstitution inflammatory syndrome (when the immune system starts working again, leading to inflammation and damage to healthy tissue).Rukobia must not be taken with certain medicines called 'strong CYP3A inducers', including epilepsy medicines carbamazepine and phenytoin, cancer medicines mitotane and enzalutamide, the antibiotic medicine rifampicin and the herbal medicine St John's wort (Hypericum perforatum).For the full list of side effects and restrictions with Rukobia, see the package leaflet.

Why is Rukobia authorised in the EU?

Rukobia suppressed the HIV-1 virus in patients for whom other HIV medicines were not working and no major safety concerns were identified. The European Medicines Agency therefore decided that Rukobia's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rukobia?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rukobia have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rukobia are continuously monitored. Side effects reported with Rukobia are carefully evaluated and any necessary action taken to protect patients.

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Ruxience

What is Ruxience and what is it used for?

Ruxience is a medicine used to treat the following blood cancers and inflammatory conditions:• follicular lymphoma and diffuse large B cell non-Hodgkin's lymphoma (two types of nonHodgkin's lymphoma, a blood cancer);• chronic lymphocytic leukaemia (CLL, another blood cancer affecting white blood cells);• severe rheumatoid arthritis (an inflammatory condition of the joints);• granulomatosis with polyangiitis (GPA or Wegener's granulomatosis) and microscopic polyangiitis (MPA), which are inflammatory conditions of the blood vessels;• pemphigus vulgaris, a serious condition involving widespread blistering of the skin and lining of the mouth, nose, throat and genitals.Depending on the condition it is used to treat, Ruxience may be given on its own, or with chemotherapy (cancer medicines) or medicines used for inflammatory disorders (methotrexate or a corticosteroid).Ruxience contains the active substance rituximab.Ruxience is a 'biosimilar medicine'. This means that Ruxience is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Ruxience is MabThera. For more information on biosimilar medicines, see here.

How is Ruxience used?

Ruxience can only be obtained with a prescription. It should be given under the close supervision of an experienced healthcare professional and in a place where facilities for resuscitating patients are immediately available. The medicine is given by infusion (drip) into a vein.Before each infusion, the patient should be given an antihistamine (to prevent allergic reactions) and an antipyretic (a medicine to reduce fever). Depending on the condition being treated, the patients are also given other medicines to manage side effects.For more information about using Ruxience, see the package leaflet or contact your doctor or pharmacist.

How does Ruxience work?

The active substance in Ruxience, rituximab, is a monoclonal antibody designed to attach to a protein called CD20, which is present on B cells. When rituximab attaches to CD20, it causes the B cells to die, which helps in lymphoma and CLL (where B cells have become cancerous) and in rheumatoid arthritis and pemphigus (where B cells are involved in inflammation). In GPA and MPA, destroying B cells lowers the production of antibodies thought to play an important role in attacking the blood vessels and causing inflammation.

What benefits of Ruxience have been shown in studies?

Laboratory studies comparing Ruxience with MabThera have shown that the active substance inRuxience is highly similar to that in MabThera in terms of structure, purity and biological activity. Studies have also shown that giving Ruxience produces similar levels of the active substance in the body to giving MabThera.In addition, Ruxience was as effective as MabThera in a study in 394 patients with follicular lymphoma, who were given an infusion of Ruxience or MabThera once a week for 4 weeks; after 26 weeks, the disease had responded partially or completely (disappearance of all signs of disease) in 148 of 196 given Ruxience (76%) and in a comparable proportion of those given MabThera (140 of 198; 71%).Because Ruxience is a biosimilar medicine, the studies on effectiveness and safety of rituximab carried out with MabThera do not all need to be repeated for Ruxience.

What are the risks associated with Ruxience?

The safety of Ruxience has been evaluated, and on the basis of all the studies carried out the side effects of the medicine are considered to be comparable to those of the reference medicine MabThera.The most common side effects with Ruxience are reactions related to the infusion (such as fever, chills and shivering) while most common serious side effects are infusion reactions, infections and heartrelated problems.Ruxience must not be used in people who are hypersensitive (allergic) to rituximab, mouse proteins or any of the other ingredients or in patients with a severe infection or a severely weakened immune system (the body's defences). Patients with rheumatoid arthritis, GPA, MPA or pemphigus vulgaris must also not receive Ruxience if they have severe heart problems.For the full list of side effects and restrictions of Ruxience, see the package leaflet.

Why is Ruxience authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Ruxience has a highly similar structure, purity and biological activity to MabThera and is distributed in the body in the same way. In addition, a study in follicular lymphoma has shown that the safety and effectiveness of Ruxience are equivalent to those of MabThera.All these data were considered sufficient to conclude that Ruxience will behave in the same way as MabThera in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for MabThera, the benefits of Ruxience outweigh the identified risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Ruxience?

The company marketing Ruxience will provide doctors with additional information about giving the medicine correctly. It will also provide doctors and patients using the medicine for rheumatoid arthritis, GPA, MPA or pemphigus with educational material on the risk of infection including that of a rare severe infection, progressive multifocal leukoencephalopathy (PML). These patients are also to receive an alert card, which they are to carry at all times, instructing them to contact their doctor immediately if they have symptoms of infection.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ruxience have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ruxience are continuously monitored. Side effects reported with Ruxience are carefully evaluated and any necessary action taken to protect patients.

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Rxulti

What is Rxulti and what is it used for?

Rxulti is an antipsychotic medicine used to treat schizophrenia in adults. Schizophrenia is a mental illness with symptoms such as delusions, disorganised thinking and speech, suspiciousness and hallucinations (seeing, hearing or feeling things that are not there).Rxulti contains the active substance brexpiprazole.

How is Rxulti used?

Rxulti is available as tablets (0.25, 0.5, 1, 2, 3 and 4 mg) to be taken by mouth. The recommended starting dose is 1 mg once daily for the first 4 days. The dose is then increased to 2 mg once daily taken on days 5, 6 and 7 and increased again if necessary to 4 mg once daily on day 8. The recommended dose is between 2 and 4 mg daily and 4 mg is the maximum recommended daily dose.In patients with moderately or severely reduced kidney or liver function the dose should be limited to 3 mg once a day. In patients taking certain other medicines the doctor may need to adjust the dose of Rxulti.Rxulti can only be obtained with a prescription.For more information about using Rxulti, see the package leaflet or contact your doctor or pharmacist.

How does Rxulti work?

The active substance in Rxulti, brexpiprazole, is thought to attach to receptors (targets) in the brain for several neurotransmitters (substances nerve cells use to communicate with neighbouring cells) including dopamine, serotonin and noradrenaline. These neurotransmitters play a role in schizophrenia, and by acting at their receptors, brexpiprazole helps normalise the activity of the brain and reduce symptoms of schizophrenia.

What benefits of Rxulti have been shown in studies?

Rxulti has been shown to be effective at reducing symptoms of schizophrenia in 5 main studies involving 2,404 adults with schizophrenia, although there were some inconsistent results.In 4 of the studies, Rxulti was compared with placebo (a dummy treatment) and the main measure of effectiveness was reduction of symptoms on a standard rating scale called PANSS (positive and negative syndrome scale) which ranges from a minimum of 30 (no symptoms) to a maximum of 210 (severest symptoms) after 6 weeks of treatment.In the first study, the PANSS score fell by around 21 and 20 points with 2 mg and 4 mg Rxulti respectively compared with 12 points with placebo.In the second study, the PANSS score fell by around 20 points with 4 mg Rxulti compared with 14 points with placebo. However, there was not considered to be a difference between 2 mg Rxulti and placebo.In the third study, the PANSS score fell by around 15 points with 2 mg Rxulti compared with 8 points with placebo and there was not considered to be a difference between 4 mg Rxulti and placebo.In the fourth study, doses of Rxulti ranging from 2 to 4 mg were compared with placebo and with another antipsychotic medicine, quetiapine. After 6 weeks, there was not considered to be a difference between Rxulti and placebo. Results at 2, 3 and 4 weeks showed improvement in symptoms with Rxulti compared with placebo. Quetiapine showed improvement in symptoms at 6 weeks compared with placebo.The fifth study compared Rxulti with placebo over one year, and the main measure of effectiveness was the risk of relapse (worsening of symptoms). Rxulti was more effective than placebo in preventing relapse: after a year, 14% of patients taking Rxulti had relapsed compared with 38% of patients taking placebo.

What are the risks associated with Rxulti?

The most common side effects with Rxulti are akathisia (a constant urge to move, which may affect around 6 in 100 people) and weight gain (which may affect around 4 in 100 people).For the full list of side effects and restrictions with Rxulti, see the package leaflet.

Why is Rxulti authorised in the EU?

Rxulti was effective at reducing symptoms of schizophrenia. Although the reductions in symptoms were not consistent across the studies, this often occurs in studies with antipsychotic medicines and the European Medicines Agency considered that the effects were sufficient to conclude that Rxulti is beneficial to patients with schizophrenia. Based on available data, it is not possible to say how Rxulti compares with other medicines of the same type. The safety profile of Rxulti is similar to other antipsychotic medicines. The Agency decided that Rxulti's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rxulti?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rxulti have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rxulti are continuously monitored. Side effects reported with Rxulti are carefully evaluated and any necessary action taken to protect patients.

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Rybelsus

What is Rybelsus and what is it used for?

Rybelsus is a medicine used to control blood glucose (sugar) levels in adults whose type 2 diabetes is not controlled well enough. It can be used on its own when metformin (another medicine for diabetes) cannot be used, or in combination with other diabetes medicines. It should be used with an appropriate diet and physical exercise.Rybelsus contains the active substance semaglutide.

How is Rybelsus used?

Rybelsus is available as tablets (3, 7 and 14 mg) and can only be obtained with a prescription. The starting dose is 3 mg once daily. After one month, the dose should be increased to 7 mg once daily. If needed, the dose can be further increased up to a maximum of 14 mg once daily.For more information about using Rybelsus, see the package leaflet or contact your doctor or pharmacist.

How does Rybelsus work?

Type 2 diabetes is a disease in which the body does not make enough insulin to control the level of glucose in the blood or when the body cannot use insulin effectively. The result is a high level of glucose in the blood.The active substance in Rybelsus, semaglutide, is a 'GLP-1 receptor agonist'. It acts in the same way as GLP-1 (a hormone produced in the gut) by increasing the amount of insulin that the pancreas releases in response to food. This helps with the control of blood glucose levels.

What benefits of Rybelsus have been shown in studies?

Rybelsus was effective at controlling blood glucose levels in 7 main studies involving a total of over 5,500 patients with type 2 diabetes.Depending on the dose, Rybelsus lowered HbA1c (showing improved blood glucose control) by between 0.6 and 1.4 percentage points. The results compared favourably with those with three otherdiabetes treatments empagliflozin, sitagliptin or liraglutide, which led to reductions of 0.9, 0.8, 0.9 percentage points, respectively. Rybelsus was also more effective than placebo (a dummy treatment).In addition to better controlled blood glucose, patients taking Rybelsus had a beneficial reduction in body weight after 6 months. A further study in close to 3,200 patients suggested that Rybelsus may reduce the number of heart attacks and strokes compared to placebo, however, the difference was not statistically significant (it may be due to chance).

What are the risks associated with Rybelsus?

The most common side effects with Rybelsus (which may affect more than 1 in 10 people) are nausea (feeling sick), diarrhoea and low blood sugar levels (when used with insulin or a sulphonylurea).For the full list of side effects and restrictions of Rybelsus, see the package leaflet.

Why is Rybelsus authorised in the EU?

Rybelsus is effective at controlling blood glucose levels in patients with type 2 diabetes and can also help patients reduce their weight. The most common side effects with Rybelsus affect the digestive system; the side effects are generally manageable and similar to those with an authorised injectable form of semaglutide (Ozempic).As with the injectable form, there is a risk that Rybelsus could worsen some patients' diabetic retinopathy (damage to the retina in the eye). Patients with this condition will therefore be monitored carefully.The European Medicines Agency concluded that Rybelsus' benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Rybelsus?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rybelsus have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rybelsus are continuously monitored. Side effects reported with Rybelsus are carefully evaluated and any necessary action taken to protect patients.

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Rybrevant

What is Rybrevant and what is it used for?

Rybrevant is a cancer medicine used to treat adults with advanced non-small cell lung cancer (NSCLC) whose cancer cells have certain genetic changes. These changes are in the gene for a protein that controls cell growth, epidermal growth factor receptor (EGFR), and are known as 'activating EGFR exon 20 insertion mutations'. The medicine is given when cancer treatment with platinum-based medicines has not worked well enough.Rybrevant contains the active substance amivantamab.

How is Rybrevant used?

The medicine can only be obtained with a prescription. Treatment with Rybrevant should be started and supervised by a doctor who is experienced in using cancer medicines and given in a setting where any infusion-related side effects can be managed.Rybrevant is given as an infusion (drip) into a vein. The first week's dose is split over two successive days, and then it is given once weekly for the next three weeks and after that once every two weeks. The dose of the medicine depends on the patient's bodyweight. Treatment is continued until the disease gets worse or side effects become too severe. Treatment should be stopped temporarily or permanently, and subsequent doses may be reduced if the patient experiences certain side effects.Patients should be given antihistamines (allergy medicines), antipyretics (fever-reducing medicines), and corticosteroids before the first treatment to reduce infusion-related reactions. In the following treatment sessions, patients should be given antihistamines and antipyretics.For more information about using Rybrevant, see the package leaflet or contact your doctor or pharmacist.

How does Rybrevant work?

In NSCLC cells, EGFR is often overactive, causing uncontrolled growth of cancer cells.Amivantamab is a monoclonal antibody (a type of protein) designed to recognise and attach to two receptors (targets) on the surface of the NSCLC cells simultaneously. One part of the antibody attaches to EGFR with activating EGFR Exon 20 insertion mutations. The other part attaches to MET, a receptorimportant for cancer growth and metastasis (cancer that spreads to another part of the body). By attaching to the two proteins, amivantamab blocks them from receiving the messages the cancer cells need for growing and spreading. The attached antibody also attracts and activates immune cells to kill the targeted cancer cells.

What benefits of Rybrevant have been shown in studies?

In one main study, Rybrevant was effective at reducing the size of the cancer in patients with NSCLC with activating EGFR exon 20 insertion mutations who had previously been treated with platinumbased cancer medicines. Rybrevant was not compared with any other treatment or placebo (a dummy treatment).Response to treatment (shrinkage in size of the cancer) was assessed using body imaging. In around 37% (42 out of 114) of the patients, the cancer shrank after treatment with Rybrevant. On average, responses lasted for just over 12 months.

What are the risks associated with Rybrevant?

The most common side effects with Rybrevant (which may affect more than 1 in 5 people) are rash, infusion-related reactions, nail toxicity (nail abnormalities with pain or discomfort), hypoalbuminaemia (low blood levels of the protein albumin), oedema (fluid retention), tiredness, stomatitis (inflammation of the lining of the mouth), nausea (feeling sick), and constipation. The most common serious side effects (which may affect more than 1 in 100 people) are interstitial lung disease (disorders causing scarring in the lungs), infusion-related reactions and rash.For the full list of side effects and restrictions of Rybrevant, see the package leaflet.

Why is Rybrevant authorised in the EU?

Patients with NSCLC with EGFR Exon 20 insertion mutations have few available treatment options if their cancer gets worse or does not respond to platinum-based therapy. Although the main trial included a relatively small number of patients and did not compare Rybrevant with another cancer treatment, it showed that the medicine can provide clinically significant benefits in a group of patients who have limited treatment options. Its side effects were considered manageable with appropriate measures, such as changing the dose or, for infusion-related reactions, modifying the infusion and treating the symptoms.The European Medicines Agency, therefore, decided that Rybrevant's benefits are greater than its risks and it can be authorised for use in the EU.Rybrevant has been given 'conditional authorisation'. This means that there is more evidence to come about the medicine, which the company is required to provide. Every year, the European Medicines Agency will review any new information that becomes available and this overview will be updated as necessary.

What information is still awaited for Rybrevant?

Since Rybrevant has been given conditional authorisation, the company that markets Rybrevant will provide additional results from an ongoing study in patients with advanced or metastatic NSCLC with activating EGFR Exon 20 insertion mutations. The study will compare the effectiveness of adding Rybrevant to platinum-based chemotherapy versus platinum-based therapy alone for initial treatment.

What measures are being taken to ensure the safe and effective use of Rybrevant?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rybrevant have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Rybrevant are continuously monitored. Suspected side effects reported with Rybrevant are carefully evaluated and any necessary action taken to protect patients.

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Rydapt

What is Rydapt and what is it used for?

Rydapt is a cancer medicine used to treat adults with newly diagnosed acute myeloid leukaemia (AML), a cancer of white blood cells. It is used with other cancer medicines (chemotherapy) initially and on its own once the chemotherapy is completed if the disease has responded to treatment. Rydapt is only given when the AML has a particular genetic change called an FLT3 mutation.Rydapt is also used on its own in adults with the following disorders of a type of white blood cell known as mast cell: aggressive systemic mastocytosis, systemic mastocytosis associated with a haematological neoplasm (blood cancer), and mast cell leukaemia.Because the number of patients with these diseases is low, they are considered 'rare', and Rydapt was designated an 'orphan medicine' (a medicine used in rare diseases) on various dates (see below).Rydapt contains the active substance midostaurin.

How is Rydapt used?

Rydapt can only be obtained with a prescription and treatment should be started by a doctor experienced in the use of cancer medicines. Rydapt is available as capsules containing 25 mg of midostaurin. The usual starting dose is 50 mg (two capsules) twice a day for AML, on days 8 to 21 of a 28-day treatment cycle, and then every day once the disease has responded. Treatment is continuedfor up to 12 cycles depending on how patients respond. For mast cell disorders, the starting dose is 100 mg (four capsules) twice daily; treatment is continued for as long as the patient benefits. If apatient develops certain severe side effects, the doctor may decide to reduce subsequent doses or delay or stop treatment.For further information, see the package leaflet.

How does Rydapt work?

The active substance in Rydapt, midostaurin, is a 'tyrosine kinase inhibitor'. This means that it blocks the action of certain enzymes known as receptor tyrosine kinases. In patients with an FLT3 mutation, an abnormal form of the FLT3 tyrosine kinase stimulates the survival and growth of AML cells. By blocking the abnormal FLT3 enzyme, Rydapt helps to bring about the death of the abnormal cells and control the spread of the cancer. Rydapt also blocks a mutated form of another enzyme, KIT kinase, which plays an important role in stimulating the abnormal growth of mast cells in patients with mast cell disorders.

What benefits of Rydapt have been shown in studies?

Rydapt has been shown to improve survival in patients with AML associated with an FLT3 mutation. One main study, involving 717 such patients, compared Rydapt with placebo (a dummy treatment) initially as an addition to other cancer medicines, followed by treatment with Rydapt or placebo alone in those whose disease responded. About 51% of those given Rydapt and 43% of those given placebo were still alive after 5 years.Another main study involving 116 patients with mast cell disorders also showed benefit. The study looked at the response to Rydapt treatment in patients with aggressive systemic mastocytosis, systemic mastocytosis associated with blood cancer, or mast cell leukaemia. Overall, using the most stringent, up-to-date criteria, the disease responded to treatment in about 28% of patients (32 of 113). When looked at separately the response rate was highest (60%) in those with aggressive systemic mastocytosis.

What are the risks associated with Rydapt?

When used to treat AML, the most common side effects with Rydapt (which may affect more than 1 in 10 people) are febrile neutropenia (fever and low white blood cell count, seen in nearly all patients), exfoliative dermatitis (inflamed, peeling skin), vomiting, headache, petechiae (tiny blood spots under the skin) and fever. The most frequent severe side effects were febrile neutropenia, lymphopenia (low counts of lymphocytes, a particular type of white blood cell), infections at the site of a catheter (a tube inserted in a vein), exfoliative dermatitis, high blood sugar and nausea (feeling sick).When used for mast cell disorders, the commonest side effects (affecting one third or more of all patients) were nausea, vomiting, diarrhoea, peripheral oedema (swelling of the ankles and feet) and tiredness. The commonest severe side effects were tiredness, sepsis (blood poisoning), pneumonia (lung infection), febrile neutropenia and diarrhoea.For the full list of all side effects reported with Rydapt, see the package leaflet.Rydapt must not be given to patients taking certain other medicines that affect the way it is handled in the body. For the full list of restrictions, see the package leaflet.

Why is Rydapt approved?

Rydapt has been shown to be of benefit in patients with AML associated with an FTL3 mutation. The safety of the medicine was acceptable in such a severe condition and was considered manageable.In mast cell disorders there was also important evidence of effectiveness. Although Rydapt had not been compared with other treatments, given the rarity of the conditions and the unmet medical need of patients who have them, the clinical benefits were clear, and the adverse effects acceptable.The European Medicines Agency therefore decided that Rydapt's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Rydapt?

The company that markets Rydapt will complete three further studies to provide the Agency with evidence to support the effectiveness of the medicine in elderly patients with AML.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Rydapt have been included in the summary of product characteristics and the package leaflet.

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Ryeqo

What is Ryeqo and what is it used for?

Ryeqo is a medicine used to treat moderate to severe symptoms of uterine fibroids (non-cancerous growths in the womb) in women of reproductive age.Ryeqo contains the active substances relugolix, estradiol and norethisterone acetate.

How is Ryeqo used?

Ryeqo is available as tablets. The recommended dose is one tablet a day at around the same time each day. Treatment should begin within 5 days from the start of a menstrual period to avoid initial irregular or heavy bleeding. After starting the treatment, Ryeqo can be taken without interruption.All other hormonal contraceptive methods must be stopped before starting Ryeqo, which provides adequate contraception after at least one month of use.The medicine can only be obtained with a prescription. For more information about using Ryeqo, see the package leaflet or contact your doctor or pharmacist.

How does Ryeqo work?

One of the active substances in Ryeqo, relugolix, blocks the pituitary gland (a gland that controls many other hormone-producing glands in the body) from releasing luteinizing hormone and folliclestimulating hormone, which in turn prevents the production of progesterone and decreases the production of oestrogen. Progesterone and oestrogen are hormones that are involved in fibroid growth.Another active substance of Ryeqo, estradiol, is a natural sex hormone that helps to reduce symptoms related to the lowered levels of oestrogen, such as hot flushes and bone density loss. However, estradiol used alone can cause hyperplasia (growth) of the endometrium (the lining of the womb), which could lead to endometrial cancer. Ryeqo, therefore, also contains the active substance norethisterone acetate, a synthetic progesterone replacement that blocks the effects of estradiol on the womb, reducing the risk of endometrial growth.

What benefits of Ryeqo have been shown in studies?

Ryeqo has been shown to be effective in treating symptoms linked to uterine fibroids in two studies involving pre-menopausal women aged 18 to 50 with heavy menstrual bleeding. In both studies, around 500 women received either Ryeqo or placebo (a dummy treatment) for 24 weeks.In the first study, 73% (94 out of 128) of women using Ryeqo reported monthly menstrual blood loss of fewer than 80 mL and at least 50% less blood loss than before the treatment, compared with 19% (24 out of 128) of those taking placebo. In the second study, 71% (89 out of 126) achieved this reduction in the volume of blood lost while using Ryeqo, compared with 15% (19 out of 129) of those given the placebo.

What are the risks associated with Ryeqo?

The most common side effects with Ryeqo (which may affect up to 1 in 10 people) are hot flushes and bleeding from the womb.Ryeqo must not be used in women who have, or have had, venous thromboembolism (blood clots in the veins) or those who have had a stroke or a heart attack. It must also not be used in women who have a blood clotting disorder, osteoporosis, migraines or headaches with neurological symptoms, cancers that are influenced by sex hormones (such as breast cancer or genital cancer), liver tumours, or abnormal liver function, or in those who are pregnant, breastfeeding or have genital bleeding of unknown cause.Ryeqo must not be used together with hormonal contraception.For the full list of side effects and restrictions of Ryeqo, see the package leaflet.

Why is Ryeqo authorised in the EU?

Symptoms linked to uterine fibroids can be serious and debilitating. Ryeqo was shown to be effective at reducing moderate to severe symptoms of uterine fibroids, such as heavy periods, with manageable side effects. Therefore, the European Medicines Agency decided that Ryeqo's benefits are greater than its risks and it can be authorised for use in the EU.

What measures are being taken to ensure the safe and effective use of Ryeqo?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ryeqo have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ryeqo are continuously monitored. Suspected side effects reported with Ryeqo are carefully evaluated and any necessary action taken to protect patients.

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Ryzodeg

What is Ryzodeg?

Ryzodeg is a medicine that contains the active substances insulin degludec and insulin aspart. It is available as a solution for injection in a cartridge (100 units/ml) and in a pre-filled pen (100 units/ml).

What is Ryzodeg used for?

Ryzodeg is used to treat diabetes in adults, adolescents and children from 2 years of age.The medicine can only be obtained with a prescription.

How is Ryzodeg used?

Ryzodeg is injected once or twice a day, at mealtimes. It is given as an injection under the skin in the abdominal wall (at the front of the waist), upper arm or thigh. The place for injection should be altered with each injection to reduce the risk of developing fatty lumps under the skin that can affect the amount of Ryzodeg absorbed into the blood.The dose of Ryzodeg is determined individually for each patient. In type 1 diabetes, Ryzodeg is used with rapid-acting insulin, which is injected at other mealtimes.

How does Ryzodeg work?

Diabetes is a disease in which the body does not produce enough insulin to control the level of blood sugar or when the body is unable to use insulin effectively. Ryzodeg is a replacement insulin for the insulin normally made by the body.The active substances in Ryzodeg, insulin degludec and insulin aspart, are produced by a method known as 'recombinant DNA technology': they are made by a yeast that has received a gene (DNA), which makes the yeast able to produce them.Insulin degludec and insulin aspart are slightly different from human insulin. The differences mean that insulin degludec is absorbed more slowly by the body. This means it has a long duration of action. Meanwhile, insulin aspart is absorbed faster by the body than human insulin, and therefore it starts to work as soon as it is injected and has a short duration of action.The replacement insulin acts in the same way as natural insulin, and helps glucose from the blood to enter cells. By controlling the level of blood glucose, the symptoms and complications of diabetes are reduced. Injecting Ryzodeg at a main meal provides long-acting insulin to control blood sugar until the next dose as well as short-acting insulin to help deal with the extra sugar from the meal.

How has Ryzodeg been studied?

Ryzodeg has been studied in one main study involving 548 adults with type 1 diabetes and in four main studies involving 1,866 adults with type 2 diabetes. The studies compared Ryzodeg given at mealtimes with insulin glargine or insulin detemir (long-acting insulins), or with biphasic insulin (an insulin formulation consisting of a mixture of intermediate- and rapid-acting insulin). In the studies in type 1 diabetes, patients also received injections of rapid acting insulin at other mealtimes. In the studies in type 2 diabetes, Ryzodeg was either given alone or in combination with other antidiabetes medicines.Ryzodeg has also been studied in one main study in 362 children aged between 1 and 17 years with type 1 diabetes. Ryzodeg was given once a day at mealtime with insulin aspart given at other mealtimes and this treatment was compared with treatment comprising insulin detemir given once or twice a day with insulin aspart given at all mealtimes.All of the studies measured the level of glycosylated haemoglobin (HbA1c), which is the percentage of haemoglobin in the blood attached to glucose. HbA1c gives an indication of how well the blood glucose is controlled. All the studies in adults lasted six months, but one was extended to one year. The study in children lasted 16 weeks.

What benefit has Ryzodeg shown during the studies?

The studies in adults showed that Ryzodeg was at least as effective as long-acting insulins and biphasic insulin in controlling blood glucose levels in patients with type 1 and type 2 diabetes. The reduction in HbA1c levels (in percentage points) was 0.7 in patients with type 1 diabetes and between 1 and 1.7 across the trials in patients with type 2 diabetes. In the study in children, the combined used of Ryzodeg and insulin aspart was at least as effective as insulin detemir and insulin aspart, with average HbA1c reductions of 0.27 and 0.23 percentage points respectively.

What is the risk associated with Ryzodeg?

The most frequently reported side effect during treatment with Ryzodeg is hypoglycaemia (low blood glucose levels).

Why has Ryzodeg been approved?

The CHMP concluded that Ryzodeg is effective in controlling blood glucose levels in adults, adolescents and children aged over 2 years with diabetes. Because the dose requirements in young children may not be stable and because they cannot express symptoms of hypoglycaemia, Ryzodeg is not suitable for children aged under 2 years. The Committee concluded that Ryzodeg is generally safe and its side effects are comparable to those of other insulin analogues. It also noted that in the studies with adults Ryzodeg reduces the risk of hypoglycaemia during the night in patients with type 1 and type 2diabetes. The CHMP decided that Ryzodeg's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Ryzodeg?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ryzodeg have been included in the summary of product characteristics and the package leaflet.

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