E.P.A.R s  Editing

Padcev

What is Padcev and what is it used for?

Padcev is a cancer medicine for treating adults with urothelial cancer (a cancer of the bladder and urinary tract).Padcev is for patients whose cancer is advanced or has spread and who have already had platinumbased chemotherapy and an immunotherapy.It contains the active substance enfortumab vedotin.

How is Padcev used?

It is given as an infusion (drip) into a vein over 30 minutes. The patient should have an infusion three times over the course of 28 days (on days 1, 8 and 15) and should continue treatment until the disease gets worse or the side effects become intolerable.Padcev can only be obtained with a prescription, and a doctor experienced in the use of cancer medicines should start and supervise treatment. The doctor may stop treatment or reduce the dose if the patient experiences severe side effects. For more information about using Padcev, see the package leaflet or contact your doctor or pharmacist.

How does Padcev work?

The active substance in Padcev, enfortumab vedotin, consists of an antibody (a type of protein) combined with another substance known as MMAE. The antibody first attaches to a protein on the surface of cancer cells to gain entry into the cells. Once the active substance is inside the cells, MMAE disrupts the cells' internal skeleton, causing cell death and helping to stop the cancer from getting worse or spreading.

What benefits of Padcev have been shown in studies?

Padcev was more effective than chemotherapy at prolonging patients' lives in a main study of 608 patients with advanced urothelial cancer who had already had platinum-based chemotherapy and an immunotherapy. In this study, patients treated with Padcev lived on average for around 13 months while those who had chemotherapy lived on average for 9 months.

What are the risks associated with Padcev?

The most common side effects with Padcev (which may affect more than 1 in 10 people) are hair loss, tiredness, reduced appetite, nerve damage affecting sensation of pain, temperature and touch, diarrhoea, nausea, itching, taste disturbance, anaemia (low red blood cell counts), weight loss, rash, dry skin, vomiting, increased levels of liver enzymes and high levels of blood sugar.For the full list of side effects and restrictions of Padcev, see the package leaflet.

Why is Padcev authorised in the EU?

There are few choices for patients with urothelial cancer who have had platinum-based chemotherapy and an immunotherapy. A main study showed that Padcev can help prolong life in these patients, and the side effects of the medicine were similar to those that occur after chemotherapy.The European Medicines Agency decided that Padcev'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 Padcev?

The company that markets Padcev will ensure that all healthcare professionals prescribing this medicine are given a patient information pack, which will include a patient card. The card will inform patients that treatment could cause severe skin reactions such as Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) and advise them to seek immediate medical care if they have symptoms of these reactions.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Padcev have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Padcev are continuously monitored. Suspected side effects reported with Padcev are carefully evaluated and any necessary action taken to protect patients.

---

Palforzia

What is Palforzia and what is it used for?

Palforzia is a medicine for treating peanut allergy in children from 4 to 17 years of age and patients who become adults whilst on treatment. While taking this medicine, patients continue avoiding peanuts.Palforzia contains peanut powder.

How is Palforzia used?

Palforzia is available as a powder in capsules or sachets. The patient opens the capsules or sachets and mixes the powder with a small amount of soft food (such as like fruit puree, yogurt and rice pudding).In the first phase of treatment, which takes place in the clinic, the patient receives increasing doses of Palforzia over several hours on a single day under observation of the doctor. For the second phase, the doctor prescribes increasing doses each of which the patient should take daily for two weeks if they can tolerate it. This phase of increasing doses under supervision lasts at least 22 weeks. If the patient continues to tolerate treatment, in the third phase they will then be prescribed a daily dose to maintain the effects of the medicine.Palforzia can only be obtained with a prescription. Treatment should be started by a healthcare professional qualified to treat allergic diseases. Because this medicine can cause serious allergic reactions in some patients, for the first phase of treatment, facilities must be on hand for treating such reactions. The patients should also have self-injectable adrenaline with them at all times.For more information about using Palforzia, see the package leaflet or contact your doctor or pharmacist.

How does Palforzia work?

Palforzia works in people with peanut allergy by gradually increasing the body's ability to tolerate small amounts of peanut (desensitisation). Palforzia can help reduce the severity of allergic reactions after coming into contact with peanut. It is not effective against other nut or food allergies.Palforzia does not treat the symptoms of peanut allergy and must not be taken during an allergic reaction.

What benefits of Palforzia have been shown in studies?

Two main studies involving 671 patients have shown that Palforzia can help some patients tolerate a small amount of peanuts with only mild symptoms.In one of the studies, 50% of the patients aged 4 to 17 who took Palforzia could tolerate 1000 mg of peanut protein with only mild symptoms, compared with 2% of those who received placebo (a dummy treatment). In the second study, 58% of 4- to 17-year-olds could tolerate the same dose of peanut protein with only mild symptoms compared with 2% of those who took placebo.

What are the risks associated with Palforzia?

The most common side effects with Palforzia (which may affect more than 1 in 5 people) are abdominal (belly) pain and discomfort, irritation in the throat and mouth, itchy skin, nausea, vomiting and urticaria (itchy rash).Palforzia should not be taken by patients with severe or uncontrolled asthma or those who have ever had problems with swallowing or stomach acid or severe mast cell disorder (a condition that causes allergic-like reactions). It should also not be taken by patients who have had a severe allergic reaction in the past two months.For the full list of restrictions and side effects of Palforzia, see the package leaflet.

Why is Palforzia authorised in the EU?

Studies show that Palforzia can help young patients (aged 4 to 17) with peanut allergy to tolerate peanut protein with only mild symptoms. Although there are insufficient data from patients who become adults while on treatment, these patients should be able to decide with their doctor whether or not to continue treatment.The side effects of Palforzia, including allergic reactions, can be managed by following advice for patients and healthcare professionals in the product information. The European Medicines Agency therefore concluded that Palforzia'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 Palforzia?

The company that markets Palforzia will provide patients, healthcare professionals and caregivers with information about how to take the medicine and manage its risks. Patients will also receive a patient card which they should carry at all times.Recommendations and precautions for the safe and effective use of Palforzia have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Palforzia are continuously monitored. Side effects reported with Palforzia are carefully evaluated and any necessary action taken to protect patients.

---

Palonosetron Accord

What is Palonosetron Accord and what is it used for?

Palonosetron Accord is a medicine used to prevent nausea (feeling sick) and vomiting caused by chemotherapy (medicines to treat cancer). It is used in adults and children 1 month of age or older for chemotherapy with medicines that are either a strong trigger of nausea and vomiting (such as cisplatin) or a moderate trigger (such as cyclophosphamide, doxorubicin or carboplatin).Palonosetron Accord contains the active substance palonosetron. It is a 'generic medicine'. This means that Palonosetron Accord is similar to a 'reference medicine' already authorised in the European Union (EU) called Aloxi. For more information on generic medicines, see the question-and-answer document here.

How is Palonosetron Accord used?

Palonosetron Accord should only be given before chemotherapy. It is available as a solution for injection or infusion (drip) into a vein, which should be given by a healthcare professional about 30 minutes before the start of chemotherapy. In adults, the recommended dose is 250 micrograms, injected into a vein over 30 seconds. It may be given with a corticosteroid (another type of medicine that can be used to prevent nausea and vomiting) to increase the effect. In children, the solution should be given by infusion into a vein over 15 minutes at a dose of 20 micrograms per kilogram body weight.The medicine can only be obtained with a prescription.

How does Palonosetron Accord work?

The active substance in Palonosetron Accord, palonosetron, is a '5HT3 antagonist'. This means that it stops a chemical in the body called 5-hydroxytryptamine (5HT, also known as serotonin) from attaching to 5HT3 receptors in the gut. When 5HT attaches to these receptors, it normally causes nausea and vomiting. By blocking these receptors, Palonosetron Accord prevents the nausea and vomiting that often happen after chemotherapy.

How has Palonosetron Accord been studied?

The company provided data from the published literature on palonosetron. No additional studies were needed as Palonosetron Accord is a generic medicine that is given by injection and contains the same active substance as the reference medicine, Aloxi.

What are the benefits and risks of Palonosetron Accord?

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

Why is Palonosetron Accord approved?

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

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

A risk management plan has been developed to ensure that Palonosetron Accord 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 Palonosetron Accord, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Palynziq

What is Palynziq and what is it used for?

Palynziq is a medicine that is used to treat phenylketonuria (PKU) in adults and adolescents from 16 years of age.Patients with this genetic disease cannot process the amino acid phenylalanine from dietary protein, and as a result the amino acid builds up in the blood to abnormally high levels, causing problems in the nervous system. Palynziq is used in patients whose blood levels of phenylalanine have not been adequately controlled with other treatments.Palynziq was designated an 'orphan medicine' (a medicine used in rare diseases) on 28 January 2010. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu309708.Palynziq contains the active substance pegvaliase.

How is Palynziq used?

The medicine can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in treating PKU. Phenylalanine blood levels must be measured before starting treatment. During treatment, monthly measurements are recommended. Palynziq is intended for long-term use.Palynziq is available as pre-filled syringes (2.5, 10 and 20 mg) for injection under the skin. The recommended starting dose is 2.5 mg once a week for 4 weeks. The dose and frequency of injection are then increased gradually (up to a maximum dose of 60 mg once a day) to achieve adequate control of phenylalanine blood levels. Palynziq must be used with stringent measures to manage any serious allergic reactions, especially in the first few months.For more information about using Palynziq, see the package leaflet or contact your doctor or pharmacist.

How does Palynziq work?

The active substance in Palynziq, pegvaliase, is a bacterial enzyme that can break down phenylalanine, thereby stopping phenylalanine from building up in the body and helping to relieve the symptoms of phenylketonuria. The enzyme in pegvaliase is 'pegylated' (attached to a chemical called PEG), allowing it to remain in the body and to act for longer.

What benefits of Palynziq have been shown in studies?

The main study investigating Palynziq in patients with PKU consisted of different parts. Throughout the study, patients were required to maintain a constant level of dietary protein intake, to ensure that changes in blood phenylalanine levels could be attributed to treatment rather than to changes in protein intake.During the first part, all patients were given Palynziq at a dose of 20 or 40 mg for up to 13 weeks. Eighty-six patients who responded to treatment (i.e. whose blood phenylalanine levels were reduced by at least 20%) where then either kept on the same dose of Palynziq or were given placebo (a dummy treatment). After 8 weeks of treatment, blood phenylalanine levels remained under control in patients taking Palynziq but they returned to pre-treatment levels in patients on placebo, showing that Palynziq was more effective than placebo in reducing blood phenylalanine levels and keeping them within an acceptable range.In the extension phase of the study patients received an individual optimized dose of Palynziq. It was shown that for the majority of patients continued treatment with Palynziq for 18 months was effective at keeping blood phenylalanine levels under control (below 600 micromoles per litre).

What are the risks associated with Palynziq?

The most common side effects with Palynziq (which may affect more than 7 in 10 people) are reactions at the injection site, pain in the joints and allergic reactions. The most significant allergic reactions include acute systemic allergic reaction, angioedema (swelling under the skin in areas such as the face, throat, arms and legs), and serum sickness (allergic reaction caused by animal proteins or serum). For the full list of side effects of Palynziq, see the package leaflet.Palynziq must not be used in patients who have had an allergic reaction to pegvaliase, to any of the other components of Palynziq or to any other pegylated medicine.

Why is Palynziq authorised in the EU?

Palynziq was shown to be effective at reducing levels of blood phenylalanine and keeping them under control. The safety of Palynziq is considered acceptable, and important side effects such as allergic reactions are considered manageable with additional stringent measures (see below). The European Medicines Agency therefore decided that Palynziq'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 Palynziq?

The company that markets Palynziq will provide information material for doctors and for patients and carers about the risk of allergic reactions with Palynziq, including how to identify them promptly and what to do in case such a reaction occurs.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Palynziq have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Palynziq are continuously monitored. Side effects reported with Palynziq are carefully evaluated and any necessary action taken to protect patients.

---

Pandemic Influenza Vaccine H5N1 Astrazeneca

What is Pandemic influenza vaccine H5N1 AstraZeneca and what is it used for?

Pandemic influenza vaccine H5N1 AstraZeneca is a vaccine developed to protect children aged between 12 months and 18 years against influenza (flu) during a flu pandemic.A flu pandemic occurs when a new strain of flu virus appears that can spread easily because people have no immunity (protection) against it. It can particularly affect children who have not had seasonal flu or received flu vaccines previously. A flu pandemic can affect people worldwide and cause many deaths.Pandemic influenza vaccine H5N1 AstraZeneca contains live, attenuated (weakened) influenza A virus A/Vietnam/1203/2004 (H5N1) strain.

How is Pandemic influenza vaccine H5N1 AstraZeneca used?

Pandemic influenza vaccine H5N1 AstraZeneca is available as a nasal spray. The dose is one spray (0.1 ml) into each nostril. Two doses of the vaccine are recommended and the child should receive the second dose at least 4 weeks after the first.1 Previously known as Pandemic influenza vaccine H5N1 MedImmuneThe vaccine can only be obtained with a prescription. It should be given in an officially declared pandemic and according to official guidance.

How does Pandemic influenza vaccine H5N1 AstraZeneca work?

A vaccine against a specific disease 'teaches' the immune system (the body's natural defences) to defend itself against the disease. Pandemic influenza vaccine H5N1 AstraZeneca is a pandemic preparedness vaccine. This vaccine is intended to help with the management of a future pandemic.It is not possible to prepare a vaccine for a future pandemic because the strain of the pandemic flu virus is not known in advance. Instead, a pandemic preparedness vaccine can be made to contain a bird flu virus strain that could potentially cause a future pandemic. Most people will not have come into contact with it and therefore will not have built up protection ('immunity') against it. Testing this pandemic preparedness vaccine helps to predict how people will react to the vaccine at the time of a pandemic, when the virus strain in the vaccine will be replaced by a weakened version of the actual strain causing the pandemic.When a child is given the vaccine, the immune system recognises the weakened virus in the vaccine as foreign and makes antibodies against it. The immune system will then be able to produce antibodies more quickly and in large numbers when it comes into contact with the virus again. This helps to protect against the flu that the virus causes.

What benefits of Pandemic influenza vaccine H5N1 AstraZeneca have been shown in studies?

Because a new pandemic live attenuated vaccine cannot be tested in children, the benefit of this vaccine in children was predicted from studies in adults and from studies of similar live attenuated flu vaccines in children.Three main studies involving 107 adults found that Pandemic influenza vaccine H5N1 AstraZeneca was able to prepare the immune system to defend itself against the H5N1 virus strain in individuals who had never come into contact with it. Antibodies against this type of vaccine are not easy to measure. However, a second vaccine that acts in a different way is able to make antibodies that can be measured easily. In those who received the second vaccine 3 weeks to 5 years after vaccination with Pandemic influenza vaccine H5N1 AstraZeneca, antibodies increased 4-fold in 73% (8 out of 11) of the individuals compared with 10% of the individuals who had not been previously vaccinated with Pandemic influenza vaccine H5N1 AstraZeneca. This showed that antibodies against Pandemic influenza vaccine H5N1 AstraZeneca increased substantially when vaccinated adults came into contact with the virus again. In addition, there is evidence indicating that the vaccine can protect against different strains of H5N1 virus. The results were similar to those from three other studies involving 170 adults given pandemic preparedness vaccines containing similar types of bird flu virus, such as H7N9 and H7N7, instead of H5N1.In addition, the company presented extensive supportive data from large studies and from clinical practice on how well other similar pandemic and seasonal live attenuated influenza A vaccines work in children.Further studies on the effects on the vaccine in children will need to be provided once the the flu strain causing the pandemic is included in the vaccine.Pandemic influenza vaccine H5N1 AstraZeneca0F

What are the risks associated with Pandemic influenza vaccine H5N1 AstraZeneca?

The most common side effects with Pandemic influenza vaccine H5N1 AstraZeneca (which may affect more than 1 in 10 people) are decreased appetite, headache, runny or stuffy nose, and feeling unwell. For the full list of all side effects reported with Pandemic influenza vaccine H5N1 AstraZeneca, see the package leaflet.Pandemic influenza vaccine H5N1 AstraZeneca must not generally be given to children who have had a severe allergic reaction to any of the substances in the vaccine including gelatin and gentamicin or to children who have had a severe allergic reaction to eggs or egg proteins, such as ovalbumin. However, in a pandemic, it might be appropriate to give it to children with allergies if facilities for medical treatment of severe allergic reactions are immediately available. For the full list of restrictions, see the package leaflet.

Why is Pandemic influenza vaccine H5N1 AstraZeneca approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) noted that preparing for a potential flu pandemic in children and adolescents meets an important medical need. The vaccine is expected to protect children against pandemic flu, on the basis of data obtained with this vaccine in adults. This is further supported by data in children given similar seasonal and pandemic live attenuated flu vaccines in large studies and in clinical practice. Although Pandemic influenza vaccine H5N1 AstraZeneca might increase wheezing in children aged 1 to 2 years, the risk is considered acceptable in a pandemic situation. Thus, the CHMP decided that the benefits of the medicine in children aged 1 to 18 years are greater than its risks and recommended that it be given marketing authorisation.Pandemic influenza vaccine H5N1 AstraZeneca has been given 'conditional approval'. 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 summary will be updated as necessary.

What information is still awaited for Pandemic influenza vaccine H5N1 AstraZeneca?

Since Pandemic influenza vaccine H5N1 AstraZeneca has been granted a conditional approval, the company that markets Pandemic influenza vaccine H5N1 AstraZeneca will conduct studies to gather more information on its effectiveness and side effects during its use in a pandemic as well as its shelf life.

What measures are being taken to ensure the safe and effective use of Pandemic influenza vaccine H5N1 AstraZeneca?

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pandemic influenza vaccine H5N1 AstraZeneca have been included in the summary of product characteristics and the package leaflet.

---

Pantozol Control

What is Pantozol Control?

Pantozol Control is a medicine that contains the active substance pantoprazole. It is available as gastroresistant tablets (20 mg). 'Gastroresistant' means that the tablet's contents pass through the stomach without being broken down until they reach the intestine. This prevents the active substance from being destroyed by the acid in the stomach.Pantozol Control is similar to a 'reference medicine' already authorised in the European Union (EU) called Pantozol.

What is Pantozol Control used for?

Pantozol Control is used for the short-term treatment of the symptoms of acid reflux in adults. Acid reflux is when acid produced in the stomach escapes into the gullet, causing heartburn and acid regurgitation (acid flowing up into the mouth).The medicine can be obtained without a prescription.

How is Pantozol Control used?

The recommended dose of Pantozol Control is one tablet once a day until symptoms have stopped. The patient may need to take the medicine for two to three days in a row for symptoms to improve. If there is no improvement in symptoms within two weeks of continuous treatment, patients shouldconsult their doctor. Patients should not take the medicine for longer than four weeks without consulting their doctor.The tablets should be swallowed whole with liquid before a meal and should not be chewed or crushed.

How does Pantozol Control work?

The active substance in Pantozol Control, pantoprazole, is a proton pump inhibitor. It works by blocking 'proton pumps', proteins found in specialised cells in the stomach lining that pump acid into the stomach. By blocking the pumps, pantoprazole reduces acid production, relieving the symptoms of acid reflux.Pantoprazole-containing medicines have been available in the European Union (EU) since 1994. The reference medicine, Pantozol, is only available with a prescription. It is used for long-term treatments and is also used to treat a wider range of gastrointestinal diseases (conditions affecting the gut) than Pantozol Control.

How has Pantozol Control been studied?

Because pantoprazole has been in use for many years, the applicant presented data from the scientific literature. The applicant also presented information from two main studies looking at the effects of pantoprazole 20 mg in a total of 563 adults who had symptoms of acid reflux, including at least one episode of heartburn in the three days before the studies began. The first study compared pantoprazole with placebo (a dummy treatment) in 219 adults, and the second compared it with ranitidine (another medicine used to treat acid reflux symptoms) in 344 adults. The main measure of effectiveness was the number of patients with symptoms of heartburn over the first two weeks of treatment.

What benefit has Pantozol Control shown during the studies?

Pantoprazole was more effective than placebo and ranitidine at improving the symptoms of acid reflux. In the first study, 74% of the patients taking pantoprazole (80 out of 108) and 43% of those taking placebo (48 out of 111) had no heartburn after two weeks. Pantoprazole was also more effective than placebo at reducing symptoms of acid regurgitation. In the second study, 70% of the patients taking pantoprazole (121 out of 172) and 59% of those talking ranitidine (102 out of 172) had no heartburn after two weeks of treatment.

What is the risk associated with Pantozol Control?

The most common side effects with Pantozol Control (seen in around 1 patient in 100) are diarrhoea and headache. For the full list of all side effects reported with pantoprazole, see the package leaflet.Pantozol Control must not be used in people who are hypersensitive (allergic) to pantoprazole, soya or any of the other ingredients. It must not be used with atazanavir (a medicine used to treat human immunodeficiency virus [HIV] infection).

Why has Pantozol Control been approved?

The CHMP noted that pantoprazole 20 mg was effective in the short-term treatment of reflux symptoms and that there is a long safety experience with the medicine as a prescription medicine. It was also of the opinion that, based on the experience of the use of pantoprazole, the availability ofPantozol Control without medical supervision is appropriate. The CHMP therefore decided that Pantozol Control's benefits are greater than its risks and recommended that it be given marketing authorisation.

---

Parsabiv

What is Parsabiv and what is it used for?

Parsabiv is a medicine used to reduce the levels of parathyroid hormone in adults who have high levels of this hormone because of their long-term kidney disease (secondary hyperparathyroidism). Parathyroid hormone is produced by the parathyroid glands in the neck and regulates calcium and phosphate levels. High levels of parathyroid hormone can cause loss of calcium from the bones, bone pain and fractures, and heart and circulation problems.Parsabiv is used in patients on haemodialysis (a technique for removing waste products from the blood using a blood filtration machine). It contains the active substance etelcalcetide.

How is Parsabiv used?

Parsabiv is available as a solution for injection. Treatment is started at a dose of 5 mg three times a week and the dose is then adjusted according to the patient's parathyroid hormone level or calcium level. It is given at the end of a haemodialysis session into the line that leads back from the dialysis machine to the patient's vein. In some circumstances, it can be given by injection into a vein.Parsabiv can only be obtained with a prescription. For further information, see the package leaflet.

How does Parsabiv work?

When cells in the parathyroid gland detect high levels of calcium in the blood, they reduce the amount of parathyroid hormone entering the blood. The active substance in Parsabiv, etelcalcetide, is a calcimimetic. This means that it mimics the action of calcium on these cells and in this way, it reduces the parathyroid hormone levels in the blood. Reduced parathyroid hormone decreases the levels of calcium in the blood.

What benefits of Parsabiv have been shown in studies?

Parsabiv has been investigated in three main studies involving 1,706 patients on haemodialysis who had long-term kidney disease and secondary hyperparathyroidism. The first two studies compared Parsabiv with placebo (a dummy treatment), and the third study compared it with cinacalcet, another calcimimetic medicine. In all three studies, Parsabiv was given for 26 weeks. The main measure of effectiveness was a reduction in parathyroid hormone by more than 30% after at least 20 weeks of treatment.In the first two studies, Parsabiv was effective in 75% (380 out of 509) of patients compared with 9% (46 out of 514) of patients given placebo. In the third study, Parsabiv was found to be at least as effective as cinacalcet: in 68% (232 out of 340) patients given Parsabiv compared with 58% (198 out of 343) patients given cinacalcet.

What are the risks associated with Parsabiv?

The most common side effects with Parsabiv (which may affect more than 1 in 10 people) are low calcium level in the blood, muscle spasm, diarrhoea, nausea (feeling sick) and vomiting.Parsabiv must not be started if the patient's blood calcium level is below the normal range. For the full list of Parsabiv's side effects and restrictions, see the package leaflet.

Why is Parsabiv approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Parsabiv's benefits are greater than its risks and recommended that it be approved for use in the EU. The medicine has been found effective for reducing parathyroid hormone in the blood in patients with kidney disease being treated with haemodialysis and its side effects are those expected of a calcimimetic substance.

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

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

---

Paxlovid

What is Paxlovid and what is it used for?

Paxlovid is a medicine used for treating COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.Paxlovid contains two active substances, PF-07321332 and ritonavir, in two different tablets.

How is Paxlovid used?

Paxlovid can only be obtained with a prescription. The recommended dose is two tablets, each containing 150 mg PF-07321332, plus one tablet containing 100 mg ritonavir, to be taken together by mouth twice a day for 5 days. Paxlovid should be given as soon as possible after a diagnosis of COVID19 has been made and within 5 days of the start of symptoms.For more information about using Paxlovid, see the package leaflet or contact your doctor or pharmacist.

How does Paxlovid work?

Paxlovid is an antiviral medicine that reduces the ability of SARS-CoV-2 (the virus that causes COVID19) to multiply in the body. The active substance PF-07321332 blocks the activity of an enzyme needed by the virus to multiply. Paxlovid also contains a low dose of the medicine ritonavir, which slows the breakdown of PF-07321332, enabling it to remain longer in the body at levels that affect the multiplication of the virus. Together, the active substances can help the body to overcome the virus infection, and prevent the disease becoming severe.

What benefits of Paxlovid have been shown in studies?

A main study involving patients with COVID-19 and at least one underlying condition putting them at risk of severe COVID-19 looked at the effects of Paxlovid on rate of hospitalisation or death within 28 days of treatment when compared with placebo (a dummy treatment). The analysis was done in patients who received Paxlovid within 5 days after COVID-19 symptoms began and who did not receive nor were expected to receive treatment with antibodies. Over the month following treatment, the rate of hospitalisation or death was 0.8% (8 out of 1,039) for patients who received Paxlovid, comparedwith 6.3% (66 out of 1,046) for those who received placebo. There were no deaths in the Paxlovid group and 12 deaths in the placebo group.The majority of patients in the study were infected with the Delta variant. Based on laboratory studies, Paxlovid is also expected to be active against Omicron and other variants.

What are the risks associated with Paxlovid?

The most common side effects with Paxlovid (which may affect less than 1 in 10 people) are dysgeusia (taste disturbance), diarrhoea, headache and vomiting.Paxlovid must not be used together with medicines that are harmful at high levels in the blood and whose breakdown in the body is reduced by ritonavir. Paxlovid must also not be taken by people who have just stopped these medicines as some of the medicine may still remain in the body. Paxlovid must also not be taken with medicines that may reduce its effectiveness or by patients who are taking St John's wort (a herbal preparation used to treat depression). To identify interactions with ritonavir, a drug interaction tool is available on the website of the company marketing Paxlovid which can be accessed through a QR code in the product information and outer carton.For the full list of restrictions and side effects of Paxlovid, see the package leaflet.

Why is Paxlovid authorised in the EU?

Paxlovid 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 Paxlovid was favourable and side effects were generally mild. However, the well-known effect of ritonavir on other medicines was a concern and advice is included in Paxlovid's product information. The European Medicines Agency concluded that Paxlovid's benefits are greater than its risks and it can be authorised for use in the EU.Paxlovid was originally given 'conditional authorisation' because there was more evidence to come about the medicine. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full authorisation.

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

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

---

Pazenir

What is Pazenir and what is it used for?

Pazenir is used to treat the following cancers in adults:• metastatic breast cancer, when the first treatment has stopped working and standard treatment including an anthracycline (another type of cancer medicine) is not suitable. 'Metastatic' means that the cancer has spread to other parts of the body;• metastatic adenocarcinoma of the pancreas, as a first treatment in combination with another cancer medicine, gemcitabine;• non-small cell lung cancer, as a first treatment in combination with the cancer medicine carboplatin when the patient cannot have surgery or radiotherapy.Pazenir contains the active substance paclitaxel attached to a human protein called albumin and is a 'generic medicine'. This means that Pazenir contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Abraxane. For more information on generic medicines, see the question-and-answer document here.

How is Pazenir used?

Pazenir is given as an infusion into a vein over a period of 30 minutes. The recommended dose depends on the patient's height and weight.In metastatic breast cancer, Pazenir is given on its own every three weeks.In metastatic adenocarcinoma of the pancreas, Pazenir is given in 4-week treatment cycles. The medicine is given once a day on days 1, 8 and 15 of each cycle. Immediately after giving Pazenir, gemcitabine should be given.In non-small cell lung cancer, treatment is carried out in 3-week cycles with Pazenir given on days 1, 8 and 15 of each cycle and carboplatin given on day 1 immediately after Pazenir.Pazenir should only be given under the supervision of a cancer doctor in clinics that are specialised in giving 'cytotoxic' (cell-killing) medicines. It should not be interchanged with other medicines containing paclitaxel. The medicine can only be obtained with a prescription.SendFor more information about using Pazenir, see the package leaflet or contact your doctor or pharmacist.

How does Pazenir work?

The active substance in Pazenir, paclitaxel, belongs to the group of cancer medicines known as the 'taxanes'. Paclitaxel blocks a stage of cell division in which the cell's internal 'skeleton' is dismantled to allow the cell to divide. By keeping this structure intact, the cells cannot divide and they eventually die.Pazenir also affects non-cancer cells such as blood and nerve cells, which can cause side effects.Paclitaxel has been available as a cancer medicine since 1993. In Pazenir, as in its reference medicineAbraxane, paclitaxel is attached to a human protein called albumin in tiny particles known as 'nanoparticles'. This makes it easy to prepare a suspension of paclitaxel, which can be infused into a vein.

How has Pazenir 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, Abraxane, and do not need to be repeated for Pazenir.As for every medicine, the company provided studies on the quality of Pazenir. There was no need for 'bioequivalence' studies to investigate whether Pazenir is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because Pazenir is given by infusion into a vein and the nanoparticles it contains rapidly separate into its constituent parts in the same way as Abraxane's.

What are the benefits and risks of Pazenir?

Because Pazenir 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 Pazenir authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Pazenir has been shown to be comparable to Abraxane. Therefore, the Agency's view was that, as for Abraxane, the benefits of Pazenir 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 Pazenir?

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

---

Pecfent

What is PecFent and what is it used for?

PecFent is a medicine used to treat breakthrough pain in adult patients with cancer. Breakthrough pain is when a patient experiences additional, sudden pain in spite of ongoing treatment with painkillers. PecFent is used in patients who are already using opioids (a group of painkillers that includes morphine and fentanyl) to control long-term cancer pain.PecFent is a 'hybrid medicine'. This means that it is similar to 'reference medicines' containing the same active substance, but given in a different way. While the reference medicines Effentora (buccal tablets) and Actiq (lozenges) are taken by mouth, PecFent is given as a spray into the nose.PecFent contains the active substance fentanyl.

How is PecFent used?

PecFent is available as a nasal spray (100 and 400 micrograms per spray) and can only be obtained by 'special' prescription. This means that because the medicine can be misused or cause addiction, it is used under stricter conditions than normal. Treatment with PecFent should be started by and remain under the supervision of a doctor who has experience in managing opioid treatment in cancer patients. The doctor should keep in mind the potential for PecFent to be abused.When a patient starts to take PecFent the doctor will need to work out the appropriate dose that will provide adequate pain relief with as few side effects as possible. The first trial dose should always be 100 micrograms (one spray into one nostril). The patient should be monitored carefully while the dose is increased.The doses should be given as either one spray or two sprays of the same strength. Patients should not take more than four doses a day and should leave a gap of at least four hours between treating each episode of pain.For more information about using PecFent, see the package leaflet or contact your doctor or pharmacist.

How does PecFent work?

The active substance in PecFent, fentanyl, is an opioid. It is a well-known substance, which has been used to control pain for many years. When the patient sprays PecFent into the nose, a dose of fentanyl is rapidly absorbed into the blood stream through the blood vessels in the nose. Once in the bloodstream, fentanyl acts on receptors in the brain and spinal cord to relieve pain.

What benefits of PecFent have been shown in studies?

Because PecFent is a hybrid medicine, the applicant presented data on the reference medicines in addition to results from its own studies.In one main study, PecFent was shown to be more effective than placebo (a dummy treatment) at treating breakthrough cancer pain in 83 adults who were being treated with opioids. The main measure of effectiveness was the change in the severity of pain measured by the patients ranking their pain on a scale from 0 to 10. The average reduction in pain during the first 30 minutes after use was 6.6 points in patients receiving PecFent compared with 4.5 in those receiving placebo.An additional study measured the 'acceptability' of PecFent by the patients, rating how satisfied they were with PecFent, and how easy and convenient they found it to use. In this study, patients reported that they were 'satisfied' or 'very satisfied' with PecFent treatment for around 90% of breakthrough pain episodes.

What are the risks associated with PecFent?

Typical opioid side effects are to be expected with PecFent; often these will stop or become less intense with continued use of the medicine. The most serious of these side effects are respiratory depression (inhibition of breathing), circulatory depression (slow heartbeat), hypotension (low blood pressure) and shock (a steep fall in blood pressure). Patients should be closely monitored for these side effects. For the full list of side effects reported with PecFent, see the package leaflet.PecFent must not be used in patients who are not already taking opioids to maintain pain control, who have severe respiratory depression (inhibition of breathing) or who have severe obstructive lung conditions (diseases that severely impede breathing). It must not be used to treat short-term pain other than breakthrough pain. For the full list of restrictions, see the package leaflet.

Why is PecFent authorised in the EU?

The European Medicines Agency noted that there was a need for fast-acting pain medicines for breakthrough pain in patients with cancer. Based on available data, the Agency concluded that PecFent'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 PecFent?

The company that markets PecFent will provide educational materials in each EU Member State to make sure that patients, doctors and pharmacists are aware of how PecFent should be used, the risk of accidental exposure to fentanyl and how to dispose of the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of PecFent have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of PecFent are continuously monitored. Side effects reported with PecFent are carefully evaluated and any necessary action taken to protect patients.

---

Pedea

What is Pedea?

Pedea is a solution for injection that contains the active substance ibuprofen.

What is Pedea used for?

Pedea is used to treat 'patent ductus arteriosus' in newborn premature babies who were born six or more weeks too early (less than 34 weeks gestational age). Patent ductus arteriosus is a condition where the ductus arteriosus (the blood vessel that allows blood to bypass the baby's lungs before birth) fails to close after birth. This causes heart and lung problems in the baby.The medicine can only be obtained with a prescription.

How is Pedea used?

Treatment with Pedea should only be carried out in a neonatal intensive care unit under the supervision of an experienced neonatologist (a doctor specialising in newborn babies).Pedea is given as three injections into a vein at 24-hour intervals. Each injection lasts 15 minutes. The first injection is given when the baby is at least six hours old. If the ductus arteriosus has not closed by 48 hours after the final injection, or if it re-opens, a second course of three doses of Pedea may be given. If the condition is unchanged after the second course of therapy, surgery may be necessary. Pedea should not be used before there is proof that the baby has patent ductus arteriosus.

How does Pedea work?

The active substance in Pedea, ibuprofen, has been used since the 1960s as a painkiller and an anti inflammatory medicine. It works by reducing the level of chemical messengers called prostaglandins within cells. As prostaglandins are also involved in keeping the ductus arteriosus open after birth, Pedea is thought to work by reducing the levels of prostaglandins, allowing this blood vessel to close.

How has Pedea been studied?

Because ibuprofen has been in use for a long time, the company presented information from the published literature. It also presented the results of studies, including one study looking at different doses of Pedea in 40 newborn premature babies. The main measure of effectiveness was the number of babies whose ductus arteriosus closed without the need for surgery.A further study compared the effects of Pedea and placebo (a dummy treatment) in 131 newborns who were treated before there was proof that they had patent ductus arteriosus.

What benefit has Pedea shown during the studies?

In the study looking at the treatment of patent ductus arteriosus, the approved dose of Pedea led to a closure rate of 75% in babies born 11 to 13 weeks premature (six out of eight) and 33% in babies born 14 to 16 weeks premature (two out of six).In study looking at the use of Pedea before there was proof that the babies had patent ductus arteriosus, Pedea seemed to be more effective than placebo at preventing surgery. However, the study had to be stopped early because of side effects (kidney and lung problems).

What is the risk associated with Pedea?

The cause of any side effects seen in babies receiving Pedea is difficult to assess because they may be related to the patent ductus arteriosus or to Pedea itself. The most common side effects seen in babies receiving the medicine (seen in more than 1 baby in 10) are thrombocytopenia (low blood platelet counts), neutropenia (low levels of neutrophils, a type of white blood cell), bronchopulmonary dysplasia (abnormal lung tissue, usually seen in babies born prematurely), increased blood creatinine levels (a marker of kidney function) and decreased blood sodium levels. For the full list of all side effects reported with Pedea, see the package leaflet.Pedea must not be used in babies who have a life-threatening infection, bleeding, blood clotting problems or significant kidney problems. It must also not be used in babies with congenital heart disease where an open ductus arteriosus is needed for the blood to flow, or in babies with necrotising enterocolitis (a severe bacterial infection causing death of tissue in the gut). For the full list of restrictions see the see the package leaflet.

Why has Pedea been approved?

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

---

Pedmarqsi

What is Pedmarqsi and what is it used for?

Pedmarqsi is a medicine used in children aged 1 month to less than 18 years old to reduce the risk of hearing loss caused by the cancer medicine cisplatin when used to treat solid tumours that have not spread.Pedmarqsi contains the active substance sodium thiosulfate.

How is Pedmarqsi used?

Pedmarqsi can only be obtained with a prescription and must be given in a hospital under the supervision of an appropriately qualified doctor. It is given as an infusion (drip) into a vein lasting 15 minutes, exactly 6 hours after the patient has received cisplatin.For more information about using this medicine, see the package leaflet or contact you or your child's doctor or pharmacist.

How does Pedmarqsi work?

The way Pedmarqsi works is not fully understood, but the active substance, sodium thiosulfate, is thought to act by binding to and blocking the action of cisplatin that has not been taken up by cells and preventing damage to cells caused by molecules known as 'oxygen free radicals'. These combined actions are expected to help protect the ear against hearing loss caused by cisplatin.

What benefits of Pedmarqsi have been shown in studies?

Two studies found that Pedmarqsi reduced the risk of hearing loss in children aged 1 month to 18 years who were receiving cisplatin to treat solid tumours.The first study involved 114 children with hepatoblastoma (a cancer of the liver), with an average age of about 19 months. The results showed that 35% (20 out of 57) of children who received Pedmarqsi 6 hours after each dose of cisplatin developed hearing loss compared with 67% (35 out of 52) of children who only received cisplatin.The second study involved 125 children aged 1 month to 18 years with different types of cancer, including hepatoblastoma, neuroblastoma (a cancer of immature nerve cells) and tumours of the central nervous system. The study found that hearing loss was experienced by 29% (14 out of 49) of children who received Pedmarqsi after each cisplatin dose compared with 56% (31 out of 55) of those who received only cisplatin.

What are the risks associated with Pedmarqsi?

For the full list of side effects and restrictions with Pedmarqsi, see the package leaflet.The most common side effects with Pedmarqsi (which may affect more than 1 in 10 people) include vomiting, nausea (feeling sick), hypernatraemia (high blood levels of sodium), hypophosphataemia (low blood levels of phosphate) and hypokalaemia (low blood levels of potassium).The most common serious side effects with Pedmarqsi (which may affect more than 1 in 10 people) include hypersensitivity (allergic reactions).Pedmarqsi must not be used in infants under the age of 1 month.

Why is Pedmarqsi authorised in the EU?

Hearing loss due to cisplatin is an important clinical issue for which there were no treatment options available at the time of the authorisation of Pedmarqsi. Pedmarqsi has been shown to prevent hearing loss in children and adolescents caused by cisplatin treatment for certain cancers. In addition, the safety profile of Pedmarqsi is in line with that known for sodium thiosulfate when given for other uses and is considered acceptable. The European Medicines Agency therefore decided that Pedmarqsi'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 Pedmarqsi?

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

---

Pegasys

What is Pegasys and what is it used for?

Pegasys is an antiviral medicine used to treat:• chronic (long-term) hepatitis B in adults and children from 3 years of age• chronic hepatitis C in adults and children from 5 years of age.Hepatitis B and C are diseases of the liver due to infection with the hepatitis B and C viruses, respectively. Pegasys is usually used alone for hepatitis B infection but is taken in combination with other medicines for hepatitis C. For more information about when to use this medicine in adults and children, see the summary of product characteristics (SmPC).Pegasys contains the active substance peginterferon alfa-2a.

How is Pegasys used?

Pegasys is given by injection under the skin in the abdomen (belly) or thigh - once a week for 48 weeks for hepatitis B and once a week for between 16 and 72 weeks for hepatitis C.The adult dose is usually 180 micrograms but the children's dose varies depending on their height and weight. Doses may need to be adjusted for patients who experience side effects.Pegasys can only be obtained with a prescription and treatment should be started by a doctor who has experience in the treatment of hepatitis B or C. For further information see the package leaflet.

How does Pegasys work?

The active substance in Pegasys, peginterferon alfa-2a, belongs to the group 'interferons'. Interferons are natural substances produced by the body that help it fight infections caused by viruses. The exact way alfa interferons work in viral diseases in not fully understood, but it is thought that they act as immunomodulators (substances that modify how the immune system, the body's defence system, works). Alfa interferons may also block the multiplication of viruses.Peginterferon alfa-2a is similar to interferon alfa-2a, which is widely available in the European Union (EU) as Roferon-A. In Pegasys, the interferon alfa-2a has been 'pegylated' (attached to a chemical called polyethylene glycol). This decreases the rate at which interferon is removed from the body and allows the medicine to be given less often.

What benefits of Pegasys have been shown in studies?

Studies show that Pegasys is effective at clearing signs of viral infection in adults and children with chronic hepatitis B or C.Hepatitis BPegasys was more effective than lamivudine (another antiviral medicine) at clearing the hepatitis B virus in 2 studies of 1,372 adult patients. In these studies, the proportions of patients with no signs of viral activity in their blood 6 months after treatment were 32% with Pegasys and 22% with lamivudine among HBeAg-positive patients (those with the common type of the hepatitis B virus). Among 'HBeAgnegative' patients (those infected with a virus that has mutated and can be more difficult to treat), the clearance rate was 43% with Pegasys and 29% with lamivudine.In a study of 151 children with hepatitis B aged 3 and above, 26% of those treated with Pegasys no longer had viral activity in their blood after 24 weeks, compared with 3% of those not given any treatment.Hepatitis CFor hepatitis C, Pegasys has been studied on its own and in combination with other medicines.Three studies of 1,441 adult patients showed that more patients taking Pegasys alone had no signs of hepatitis viral activity in their blood after treatment (28 to 39%) than patients taking interferon alfa-2a (8 to 19%).Another study in 1,149 adult patients showed that the combination of Pegasys with ribavirin was also more effective than Pegasys alone (45% responders at follow-up compared with 24%) and as effective as the combination of interferon alfa-2a and ribavirin (39% responders).Additional studies showed that peginterferon alfa-2a in combination with telaprevir and ribavirin or with boceprevir and ribavirin significantly increased the proportion of patients who responded to treatment compared with peginterferon alfa-2a plus ribavirin.Finally, a study in 55 children showed similar effectiveness with the combination of Pegasys and ribavirin to that seen in adults treated with Pegasys and ribavirin.

What are the risks associated with Pegasys?

The most common side effects with Pegasys (seen in more than 1 patient in 10) are loss of appetite, headache, insomnia (difficulty sleeping), irritability, gut disorders (diarrhoea, nausea, and belly ache) rash, itching, hair loss, pain in muscles and joints, flu-like illness, reactions at the site of the injection and tiredness. For the full list of all side effects reported with Pegasys, see the package leaflet.Pegasys must not be used in people who are hypersensitive (allergic) to alpha interferons or any of the other ingredients. Pegasys must also not be used in patients with certain liver, heart and other conditions. For the full list of restrictions with Pegasys, see the package leaflet.

Why is Pegasys approved?

Studies showed that Pegasys is effective at clearing signs of viral infection in adults and children with chronic hepatitis B or C. The European Medicines Agency (EMA) considered the benefits to outweigh the risks seen with this medicine and therefore recommended that it be given marketing authorisation.

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

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

---

Pelgraz

What is Pelgraz and what is it used for?

Pelgraz is a medicine used in cancer patients to help with neutropenia (low levels of neutrophils, a type of white blood cell), which is a common side effect of cancer treatment and can leave patients vulnerable to infections.It is given specifically to reduce the duration of neutropenia and prevent febrile neutropenia (when neutropenia is accompanied by fever).Pelgraz is not intended for use in patients with the blood cancer chronic myeloid leukaemia or with myelodysplastic syndromes (conditions in which large numbers of abnormal blood cells are produced, , which can develop into leukaemia).Pelgraz is a 'biosimilar medicine'. This means that Pelgraz is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Pelgraz is Neulasta. For more information on biosimilar medicines, see here.

How is Pelgraz used?

Pelgraz 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 or blood disorders. It is available as a prefilled syringe containing a solution for injection under the skin. Pelgraz is given as a single dose of 6 mg injected under the skin at least 24 hours after the end of each cycle of chemotherapy (treatment with cancer medicines). Patients can inject themselves if they have been trained appropriately.For more information about using Pelgraz, see the package leaflet or contact your doctor or pharmacist.

How does Pelgraz work?

The active substance in Pelgraz, pegfilgrastim, consists of filgrastim, which is very similar to a human protein called granulocyte-colony-stimulating factor (G-CSF). Filgrastim works by encouraging thebone marrow to produce more white blood cells, increasing white blood cell counts and so treating neutropenia.Filgrastim has been available in other medicines in the European Union (EU) for a number of years. In Pelgraz, filgrastim has been 'pegylated' (attached to a chemical called polyethylene glycol). This slows down the removal of filgrastim from the body, allowing the medicine to be given less often.

What benefits of Pelgraz have been shown in studies?

Laboratory studies comparing Pelgraz with Neulasta have shown that the active substance in Pelgraz is highly similar to that in Neulasta in terms of structure, purity and biological activity. Studies have also shown that giving Pelgraz produces similar levels of the active substance in the body to giving Neulasta.In addition, a study involving 589 patients who had chemotherapy after surgery for breast cancer showed that Pelgraz was as effective as Neulasta in reducing the duration of neutropenia. Neutropenia lasted on average 1.6 days with both medicines.Because Pelgraz is a biosimilar medicine, the studies on effectiveness and safety of pegfilgrastim carried out with Neulasta do not all need to be repeated for Pelgraz.

What are the risks associated with Pelgraz?

The most common side effect with Pelgraz (which may affect more than 1 in 10 people) is pain in the bones. Pain in muscles is also common. For the full list of side effects and restrictions with Pelgraz, see the package leaflet.

Why is Pelgraz authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Pelgraz has a highly similar structure, purity and biological activity to Neulasta and is distributed in the body in the same way. In addition, a study in breast cancer patients undergoing chemotherapy has shown that the effectiveness of Pelgraz is equivalent to that of Neulasta in reducing the duration of neutropenia.All these data were considered sufficient to conclude that Pelgraz will behave in the same way as Neulasta in terms of effectiveness and safety in its approved uses. Therefore, the Agency's view was that, as for Neulasta, the benefit of Pelgraz outweighs the identified risk and it can be authorised for use in the EU.

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

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

---

Pelmeg

What is Pelmeg and what is it used for?

Pelmeg is a medicine used in cancer patients to help with neutropenia (low levels of neutrophils, a type of white blood cell), which is a common side effect of cancer treatment and can leave patients vulnerable to infections.It is given specifically to reduce the duration of neutropenia and prevent febrile neutropenia (when neutropenia is accompanied by fever).Pelmeg is not intended for use in patients with the blood cancer chronic myeloid leukaemia or with myelodysplastic syndromes (conditions in which large numbers of abnormal blood cells are produced, which can develop into leukaemia).Pelmeg is a 'biosimilar medicine'. This means that Pelmeg is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Pelmeg is Neulasta. For more information on biosimilar medicines, see here.

How is Pelmeg used?

Pelmeg 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 or blood disorders. It is available as a prefilled syringe containing a solution for injection under the skin. Pelmeg is given as a single dose of 6 mg injected under the skin at least 24 hours after the end of each cycle of chemotherapy (treatment with cancer medicines). Patients can inject themselves if they have been trained appropriately.For more information about using Pelmeg, see the package leaflet or contact your doctor or pharmacist.

How does Pelmeg work?

The active substance in Pelmeg, pegfilgrastim, is a form of filgrastim, which is very similar to a human protein called granulocyte-colony-stimulating factor (G-CSF). Filgrastim works by encouraging thebone marrow to produce more white blood cells, increasing white blood cell counts and so treating neutropenia.Filgrastim has been available in other medicines in the European Union (EU) for a number of years. In Pelmeg, filgrastim has been 'pegylated' (attached to a chemical called polyethylene glycol). This slows down the removal of filgrastim from the body, allowing the medicine to be given less often.

What benefits of Pelmeg have been shown in studies?

Laboratory studies comparing Pelmeg with Neulasta have shown that the active substance in Pelmeg is highly similar to that in Neulasta in terms of structure, purity and biological activity. Studies have also shown that giving Pelmeg produces similar levels of the active substance in the body to giving Neulasta.Because Pelmeg is a biosimilar medicine, the studies on effectiveness and safety of pegfilgrastim carried out with Neulasta do not all need to be repeated for Pelmeg.

What are the risks associated with Pelmeg?

The safety of Pelmeg 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 Neulasta. The most common side effect with Pelmeg (which may affect more than 1 in 10 people) is pain in the bones. Pain in muscles is also common. For the full list of side effects and restrictions with Pelmeg, see the package leaflet.

Why is Pelmeg authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Pelmeg has a highly similar structure, purity and biological activity to Neulasta and is distributed in the body in the same way.All these data were considered sufficient to conclude that Pelmeg will behave in the same way as Neulasta in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Neulasta, the benefit of Pelmeg outweighs the identified risk and it can be authorised for use in the EU.

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

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

---

Pemazyre

What is Pemazyre and what is it used for?

Pemazyre is a cancer medicine used to treat adults with cholangiocarcinoma (biliary tract cancer or cancer of the bile ducts) when the cancer cells have an abnormal form of a receptor (target) called FGFR2 on their surface. Pemazyre is used when the cancer has spread to other parts of the body or cannot be removed by surgery and has worsened after previous treatment with at least one cancer medicine.Cholangiocarcinoma is rare, and Pemazyre was designated an 'orphan medicine' (a medicine used in rare diseases) on 24 August 2018. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu3182066.Pemazyre contains the active substance pemigatinib.

How is Pemazyre used?

Pemazyre is available as tablets to be taken by mouth. The medicine can only be obtained with a prescription and treatment must be started by a doctor experienced in diagnosis and treatment of the disease. It is taken in three-week cycles consisting of two weeks where Pemazyre is taken daily followed by a week without the medicine. Treatment can continue for as long as the patient benefits from it and side effects are manageable.For more information about using Pemazyre, see the package leaflet or contact your doctor or pharmacist.

How does Pemazyre work?

The active substance in Pemazyre, pemigatinib, belongs to a group of medicines called protein kinase inhibitors. It works by blocking the activity of receptors called fibroblast growth factor receptors (FGFRs). Abnormal FGFRs are found on the surface of cancer cells and are involved in the growth and spread of the cancer. By blocking their activity, Pemazyre reduces the growth and spread of the cancer.

What benefits of Pemazyre have been shown in studies?

Pemazyre was effective in reducing the size of the cancer lesions in one main study involving 108 patients with biliary tract cancer with abnormal FGFR2. Around 37% of patients had a shrinkage of their cancer that lasted on average for 8 months.

What are the risks associated with Pemazyre?

The most common side effects with Pemazyre (which may affect more than 1 in 10 people) are high or low levels of phosphate in the blood, alopecia (hair loss), diarrhoea, problems with the nails, tiredness, nausea (feeling sick), dysgeusia (taste disturbances), stomatitis (inflammation of the lining of the mouth), constipation, joint pain, dry mouth, eyes and skin, rash and numbness on the palms and soles, low levels of sodium in the blood and high levels of creatinine in the blood, which could indicate kidney problems.Pemazyre must not be taken with the herbal medicine St John's wort. For the full list of side effects and restrictions with Pemazyre, see the package leaflet.

Why is Pemazyre authorised in the EU?

Pemazyre is considered effective in patients with biliary tract cancer that progressed after at least one prior treatment and for whom there are no other authorised treatments. Patients can tolerate the side effects of the medicine when they are closely monitored and treated if needed. The European Medicines Agency therefore decided that Pemazyre's benefits are greater than its risks and it can be authorised for use in the EU.Pemazyre 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 Pemazyre?

Since Pemazyre has been given conditional authorisation, the company that markets the medicine will provide the final results of the main study on the safety and effectiveness of Pemazyre and the results of a study comparing Pemazyre with gemcitabine and cisplatin (other cancer medicines) in patients with newly diagnosed biliary tract cancer.

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

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

---

Pemetrexed Accord

What is Pemetrexed Accord and what is it used for?

Pemetrexed Accord is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed Accord is a 'generic medicine'. This means that Pemetrexed Accord is similar to a'reference medicine' already authorised in the European Union (EU) called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed Accord contains the active substance pemetrexed.

How is Pemetrexed Accord used?

Pemetrexed Accord is available as a powder that is made up into a solution for infusion (drip) into a vein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of cancer medicines.The recommended dose is 500 mg per square metre of body surface area (calculated using the patient's height and weight). It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Accord. When Pemetrexed Accord is given with cisplatin, an 'anti-emetic' medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).

How does Pemetrexed Accord work?

The active substance in Pemetrexed Accord, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed Accord been studied?

The company provided data from the published literature on pemetrexed. No additional studies were needed as Pemetrexed Accord is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Alimta.

What are the benefits and risks of Pemetrexed Accord?

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

Why is Pemetrexed Accord approved?

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

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

A risk management plan has been developed to ensure that Pemetrexed Accord 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 Pemetrexed Accord, 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.

---

Pemetrexed Baxter

What is Pemetrexed Baxter and what is it used for?

Pemetrexed Baxter is used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced or metastatic (meaning it has spread to other parts of the body) 'non-small-cell' lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed Baxter is a 'generic medicine'. This means that Pemetrexed Baxter contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed Baxter contains the active substance pemetrexed.

How is Pemetrexed Baxter used?

Pemetrexed Baxter can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.Pemetrexed Baxter is given once every three weeks as an infusion (drip) into a vein lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Baxter.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects.For more information about using Pemetrexed Baxter, see the package leaflet or contact your doctor or pharmacist.Send

How does Pemetrexed Baxter work?

The active substance in Pemetrexed Baxter, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells). In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed Baxter 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, Alimta, and do not need to be repeated for Pemetrexed Baxter.As for every medicine, the company provided studies on the quality of Pemetrexed Baxter. There was no need for 'bioequivalence' studies to investigate whether Pemetrexed Baxter is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because Pemetrexed Baxter is given by infusion into a vein, so the active substance is delivered straight into the bloodstream.

What are the benefits and risks of Pemetrexed Baxter?

Because Pemetrexed Baxter 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 Pemetrexed Baxter authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, PemetrexedBaxter has been shown to have comparable quality and to be bioequivalent to Alimta. Therefore, the Agency's view was that, as for Alimta, the benefits of Pemetrexed Baxter 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 Pemetrexed Baxter?

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

---

Pemetrexed Fresenius Kabi

What is Pemetrexed Fresenius Kabi and what is it used for?

Pemetrexed Fresenius Kabi is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed Fresenius Kabi is a 'generic medicine'. This means that Pemetrexed Fresenius Kabi is similar to a 'reference medicine' already authorised in the European Union (EU) called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed Fresenius Kabi contains the active substance pemetrexed.

How is Pemetrexed Fresenius Kabi used?

Pemetrexed Fresenius Kabi is available as a powder that is made up into a solution for infusion (drip) into a vein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.The recommended dose is calculated using the patient's height and weight. It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Fresenius Kabi. When Pemetrexed Fresenius Kabi is given with cisplatin, an 'anti-emetic' medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).

How does Pemetrexed Fresenius Kabi work?

The active substance in Pemetrexed Fresenius Kabi, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed Fresenius Kabi been studied?

The company provided data from the published literature on pemetrexed. No additional studies were needed as Pemetrexed Fresenius Kabi is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Alimta.

What are the benefits and risks of Pemetrexed Fresenius Kabi?

Because Pemetrexed Fresenius Kabi is a generic medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Pemetrexed Fresenius Kabi approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements, Pemetrexed Fresenius Kabi has been shown to be comparable to Alimta. Therefore, the CHMP's view was that, as for Alimta, the benefit outweighs the identified risk. The Committee recommended that Pemetrexed Fresenius Kabi be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Pemetrexed Fresenius Kabi?

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

---

Pemetrexed Hospira

What is Pemetrexed Hospira and what is it used for?

Pemetrexed Hospira is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed Hospira is a 'generic medicine'. This means that Pemetrexed Hospira is similar to a 'reference medicine' already authorised in the European Union (EU) called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed Hospira contains the active substance pemetrexed.

How is Pemetrexed Hospira used?

Pemetrexed Hospira is available as a powder that is made up into a solution for infusion (drip) into avein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.The recommended dose is 500 mg per square metre of body surface area (calculated using the patient's height and weight). It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Hospira. When Pemetrexed Hospira is given with cisplatin, an 'anti-emetic' medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).

How does Pemetrexed Hospira work?

The active substance in Pemetrexed Hospira, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed Hospira been studied?

The company provided data from the published literature on pemetrexed. No additional studies were needed as Pemetrexed Hospira is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Alimta.

What are the benefits and risks of Pemetrexed Hospira?

Because Pemetrexed Hospira is a generic medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Pemetrexed Hospira approved?

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

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

A risk management plan has been developed to ensure that Pemetrexed Hospira 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 Pemetrexed Hospira, 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.

---

Pemetrexed Krka

What is Pemetrexed Krka and what is it used for?

Pemetrexed Krka is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received platinum-based chemotherapy.Pemetrexed Krka contains the active substance pemetrexed. It is a 'generic medicine'. This means that Pemetrexed Krka contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Alimta. For more information on generic medicines, see the question-and-answer document here.

How is Permetrexed Krka used?

Pemetrexed Krka is available as a powder that is made up into a solution for infusion (drip) into a vein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.The recommended dose of Permetrexed Krka is 500 mg per square metre of body surface area (calculated using the patient's height and weight). It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Krka. When Pemetrexed Krka is given with cisplatin, an antiemetic medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood cell counts are low or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).For more information about using Pemetrexed Krka, see the package leaflet or contact your doctor or pharmacist.

How does Pemetrexed Krka work?

The active substance in Pemetrexed Krka, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes involved in producing nucleotides (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing. Pemetrexed is converted into its active form more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This slows down the division of cancer cells, while normal cells are only slightly affected.

How has Pemetrexed Krka 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, Alimta, and do not need to be repeated for Pemetrexed Krka.As for every medicine, the company provided studies on the quality of Pemetrexed Krka. There was no need for 'bioequivalence' studies to investigate whether Pemetrexed Krka is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because Pemetrexed Krka is given by infusion into a vein, so the active substance is delivered straight into the bloodstream.

What are the benefits and risks of Pemetrexed Krka?

Because Pemetrexed Krka 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 Pemetrexed Krka authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Pemetrexed Krka has been shown to be comparable to Alimta. Therefore, the Agency's view was that, as for Alimta, the benefit of Pemetrexed Krka outweighs the identified risk and it can be authorised for use in the EU.

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

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

---

Pemetrexed Medac

What is Pemetrexed medac and what is it used for?

Pemetrexed medac is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed medac is a 'generic medicine'. This means that Pemetrexed medac is similar to a'reference medicine' already authorised in the European Union (EU) called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed medac contains the active substance pemetrexed.

How is Pemetrexed medac used?

Pemetrexed medac is available as a powder that is made up into a solution for infusion (drip) into a vein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.The recommended dose is 500 mg per square metre of body surface area (calculated using the patient's height and weight). It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed medac. When Pemetrexed medac is given with cisplatin, an 'anti-emetic' medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).

How does Pemetrexed medac work?

The active substance in Pemetrexed medac, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed medac been studied?

The company provided data from the published literature on pemetrexed. No additional studies were needed as Pemetrexed medac is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Alimta.

What are the benefits and risks of Pemetrexed medac?

Because Pemetrexed medac is a generic medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Pemetrexed medac approved?

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

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

A risk management plan has been developed to ensure that Pemetrexed medac 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 Pemetrexed medac, 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.

---

Pemetrexed Sandoz

What is Pemetrexed Sandoz and what is it used for?

Pemetrexed Sandoz is a cancer medicine used to treat two types of lung cancer:• malignant pleural mesothelioma (a cancer of the lining of the lungs that is usually caused by exposure to asbestos), where it is used together with cisplatin in patients who have not received chemotherapy before and whose cancer cannot be removed by surgery;• advanced non-small-cell lung cancer of the kind known as 'non-squamous', where it is used either in combination with cisplatin in previously untreated patients or on its own in patients who have previously received cancer treatment. It can also be used as a maintenance treatment in patients who have received a platinum-based chemotherapy.Pemetrexed Sandoz is a 'generic medicine'. This means that Pemetrexed Sandoz is similar to a 'reference medicine' already authorised in the European Union (EU) called Alimta. For more information on generic medicines, see the question-and-answer document here.Pemetrexed Sandoz contains the active substance pemetrexed.

How is Pemetrexed Sandoz used?

Pemetrexed Sandoz is available as a powder that is made up into a solution for infusion (drip) into a vein. The medicine can only be obtained with a prescription and should only be given under the supervision of a doctor who is qualified in the use of chemotherapy.The recommended dose is 500 mg per square metre of body surface area (calculated using the patient's height and weight). It is given once every three weeks as an infusion lasting 10 minutes. To reduce side effects, patients should take a corticosteroid (a type of medicine that reduces inflammation) and folic acid (a type of vitamin), and receive injections of vitamin B12 during treatment with Pemetrexed Sandoz. When Pemetrexed Sandoz is given with cisplatin, an 'anti-emetic' medicine (to prevent vomiting) and fluids (to prevent dehydration) should also be given before or after the cisplatin dose.Treatment should be delayed or stopped, or the dose reduced, in patients whose blood counts are abnormal or who have certain other side effects. For more information, see the summary of product characteristics (also part of the EPAR).

How does Pemetrexed Sandoz work?

The active substance in Pemetrexed Sandoz, pemetrexed, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells), which belongs to the group 'antimetabolites'. In the body, pemetrexed is converted into an active form that blocks the activity of the enzymes that are involved in producing 'nucleotides' (the building blocks of DNA and RNA, the genetic material of cells). As a result, the active form of pemetrexed slows down the formation of DNA and RNA and prevents the cells from dividing and multiplying. The conversion of pemetrexed into its active form occurs more readily in cancer cells than in normal cells, leading to higher levels of the active form of the medicine and a longer duration of action in cancer cells. This results in the division of cancer cells being reduced, while normal cells are only slightly affected.

How has Pemetrexed Sandoz been studied?

The company provided data from the published literature on pemetrexed. No additional studies were needed as Pemetrexed Sandoz is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Alimta.

What are the benefits and risks of Pemetrexed Sandoz?

Because Pemetrexed Sandoz is a generic medicine, its benefits and risks are taken as being the same as the reference medicine's.

Why is Pemetrexed Sandoz approved?

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

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

A risk management plan has been developed to ensure that Pemetrexed Sandoz 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 Pemetrexed Sandoz, 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.

---

Pepaxti

What is Pepaxti and what is it used for?

Pepaxti is a medicine used to treat adults with multiple myeloma (a cancer of the bone marrow) when the cancer has not responded to previous treatments (refractory).It is used in combination with dexamethasone (an anti-inflammatory medicine) in adults who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and whose disease has worsened since the last treatment.For patients who have had an autologous stem cell transplantation (a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells from the patients themselves), Pepaxti can be used if the time from transplantation to when the cancer comes back is at least three years.Multiple myeloma is rare, and Pepaxti was designated an 'orphan medicine' (a medicine used in rare diseases) on 19 March 2015. Further information on the orphan designation can be found here: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-15-1463 Pepaxti contains the active substance melphalan flufenamide.

How is Pepaxti used?

The medicine can only be obtained with a prescription. Treatment with Pepaxti must be started and supervised by doctors experienced in the treatment of multiple myeloma.It is given by infusion (drip) into a vein over 30 minutes on day 1 of a 28-day cycle, and the dose depends on body weight. The doctor may reduce or stop the dose if the patient develops certain side effects. Treatment should continue until the patient no longer benefits from it, or the side effects become unacceptable.The recommended dose of dexamethasone given in combination with Pepaxti is 40 mg by mouth on days 1, 8, 15 and 22 of each 28-day treatment cycle. For patients 75 years of age and older the recommended dose of dexamethasone is 20 mg.For more information about using Pepaxti, see the package leaflet or contact your doctor or pharmacist.

How does Pepaxti work?

Melphalan flufenamide, the active substance in this medicine, is a type of cancer medicine known as an alkylating agent. It interferes with the normal function and repair of DNA, the genetic instructions that cells need to function and multiply. Because cancer cells tend to grow and multiply more than normal cells they are more vulnerable to the action of the medicine. By damaging the DNA of cancer cells, melphalan flufenamide can help kill them and prevent the cancer from growing and spreading.

What benefits of Pepaxti have been shown in studies?

Pepaxti taken together with dexamethasone was shown to be effective at clearing the cancer in one main study involving 157 patients with multiple myeloma whose disease stopped responding and had come back after three previous therapies. Clinically relevant results were shown for the 52 patients who have either not had a transplant or who had a transplant and whose disease progressed more than 3 years after. For those patients, around 29% had a response (which means a reduction in the signs of the cancer) with Pepaxti and dexamethasone lasting around 7.6 months.In an additional study comparing Pepaxti and dexamethasone with pomalidomide (another cancer medicine) and dexamethasone, a beneficial effect was also seen for patients who had no prior transplantation or had a transplant and whose disease progressed more than 3 years after: Patients receiving Pepaxti and dexamethasone lived for an average of 9.3 months without their disease getting worse, compared with 4.6 months for patients receiving pomalidomide and dexamethasone. Patients also lived overall with 23.6 months on Pepaxti and dexamethasone and 19.8 months with pomalidomide and dexamethasone.

What are the risks associated with Pepaxti?

The most common side effects with Pepaxti (which may affect more than 1 in 10 people) are thrombocytopenia (low blood platelet counts), neutropenia (low levels of neutrophils, a type of white blood cell), anaemia (low red blood cell counts), nausea, diarrhoea and fever. The most frequent serious side effects are pneumonia (infection of the lungs), thrombocytopenia and respiratory tract infection (infection of the airways).Pepaxti must not be used during breastfeeding.For the full list of side effects and restrictions with Pepaxti, see the package leaflet.

Why is Pepaxti authorised in the EU?

The European Medicines Agency decided that Pepaxti's benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted the unmet medical need for patients with multiple myeloma who no longer improve with the available therapies. Despite some limitations in the studies, the results were considered clinically relevant, with the exception of the subgroup of patients who had an autologous stem cell transplant and whose disease progressed within three years of transplantation.Regarding safety, although side effects, including severe effects, were seen with treatment involving Pepaxti, these were considered acceptable and manageable.

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

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

---

Pergoveris

What is Pergoveris and what is it used for?

Pergoveris is a fertility medicine used in women to stimulate the development of follicles, the structures inside the ovaries that contain an egg.Pergoveris is for adult women who have low levels of two hormones that stimulate the ovaries - follicle-stimulating hormone (FSH) and luteinising hormone (LH).The medicine contains the active substances follitropin alfa and lutropin alfa.

How is Pergoveris used?

Pergoveris is available as a solution for injection in a pre-filled pen or as a powder and solvent to be made up into a solution for injection. Pergoveris is injected under the skin once a day until the patient has developed a suitable follicle, as assessed using ultrasound scans and by measuring blood oestrogen levels. This may take up to 5 weeks. The recommended starting dose is 150 International Units (IU) of follitropin alfa and 75 IU of lutropin alfa once a day, but this should be tailored to the patient's response. Using less than the recommended starting dose may not be sufficient to stimulate development of a follicle. If necessary, the dose of follitropin alfa can be increased by adding it as a separate medicine, with 7 to 14 days between each dose increase.The first injection must be given under direct supervision of a doctor who has experience in the treatment of fertility problems, but the patient can inject herself if she wants to, provided she has been properly trained and has access to expert advice.The medicine can only be obtained with a prescription. For further information see the package leaflet.

How does Pergoveris work?

The active substances in Pergoveris, follitropin alfa and lutropin alfa, are copies of the natural hormones FSH and LH. In the body, FSH stimulates the production of eggs, and LH stimulates their release. By replacing the missing hormones, Pergoveris allows women with FSH and LH deficiency to develop a follicle, which will release an egg after an injection of the hormone human chorionic gonadotrophin (hCG). This may help these women to become pregnant.

What benefits of Pergoveris have been shown in studies?

Both active substances have already been authorised in the European Union (EU), follitropin alfa as GONAL-f and lutropin alfa as Luveris. Therefore, the company presented information from studies carried out during the development of Luveris to support the use of Pergoveris. In these studies, the combination of follitropin alfa and lutropin alfa at the same doses as in Pergoveris produced active follicles.The company also carried out bioequivalence studies to establish whether the combined injection produced the same levels of the active substances in the body as the two medicines given separately. These studies confirmed that Pergoveris produced similar blood levels of follitropin alfa and lutropin alfa as when the two medicines are given separately.

What are the risks associated with Pergoveris?

The most common side effects reported with Pergoveris (seen in more than 1 patient in 10) are headache, ovarian cysts and injection site reactions (e.g. pain, itching, redness, bruising, swelling or irritation at the site of injection). Treatment can cause overstimulation of the ovaries (known as ovarian hyperstimulation syndrome, OHSS), which can lead to serious medical problems. Mild or moderate OHSS is common, while severe OHSS is uncommon. Thromboembolism (clots in the blood vessels) may occur very rarely, usually associated with severe OHSS.Pergoveris must not be used in women who have:• tumours of the hypothalamus or pituitary gland,• enlarged ovaries or a cyst on the ovary that is not due to polycystic ovarian disease and is of unknown origin,• bleeding from the genital region whose cause is unknown,• cancer of the ovary, womb or breast.Pergoveris must not be used when a benefit cannot be obtained, such as in women with primary ovarian failure (when the ovaries stop working before the menopause). It must also not be used in women who have malformations of the sexual organs or fibroid tumours of the womb that would stop them from becoming pregnant.For the full list of all side effects and restrictions with Pergoveris, see the package leaflet.

Why is Pergoveris approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Pergoveris'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 Pergoveris?

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

---

Perjeta

What is Perjeta and what is it used for?

Perjeta is a cancer medicine for treating adults with 'HER2-positive' breast cancer (where a protein called HER2 is found on the cancer cells). Perjeta is used in the following situations:• treatment of metastatic breast cancer (cancer that has spread to other parts of the body) that has not already been treated with chemotherapy medicines or medicines designed to target HER2, or for breast cancer that has come back locally after treatment and cannot be removed by surgery. In these cases, Perjeta is used with trastuzumab and docetaxel (other cancer medicines);• treatment of locally advanced, inflammatory or early-stage breast cancer at high risk of coming back, in combination with trastuzumab and chemotherapy, before the patient undergoes surgery;• treatment of early breast cancer at high risk of coming back, in combination with trastuzumab and chemotherapy, after the patient has had surgery.Perjeta contains the active substance pertuzumab.

How is Perjeta used?

Perjeta can only be obtained with a prescription and treatment should be started under the supervision of a doctor who is experienced in using cancer medicines and in a hospital setting where resuscitation equipment is available.Perjeta is given by infusion (drip) into a vein. The recommended first dose is 840 mg given over one hour. This is followed by a dose of 420 mg every three weeks, with each dose given over half an hour to one hour. Treatment with Perjeta should be interrupted or stopped permanently if the patient gets certain side effects.For more information about using Perjeta, see the package leaflet or contact a doctor or pharmacist.

How does Perjeta work?

The active substance in Perjeta, pertuzumab, is a monoclonal antibody, a type of protein that has been designed to attach to HER2, a protein found on HER2-positive cancer cells. By attaching to HER2,pertuzumab stops HER2 producing signals that cause the cancer cells to grow. It also activates cells of the immune system (the body's natural defences), which then kill the cancer cells.

What benefits of Perjeta have been shown in studies?

Perjeta has been studied in one main study involving 808 adults with previously untreated HER2positive metastatic breast cancer. The effects of Perjeta were compared with placebo (a dummy treatment) when given together with other cancer medicines (trastuzumab and docetaxel). Patients were treated until their disease got worse or the side effects of treatment became unmanageable. The main measure of effectiveness was progression-free survival (how long the patients lived without their disease getting worse). Patients treated with Perjeta lived for 18.5 months without their disease getting worse, compared with 12.4 months for patients given placebo.Perjeta has also been studied in two main studies involving a total of 642 patients with earlier stages of breast cancer who were to undergo surgery. In these studies, Perjeta was given with trastuzumab or chemotherapy or both. The studies looked at how many patients responded to treatment (i.e. patients who had no cancer cells in the breast after surgery). In the first study, 46% of the patients treated with Perjeta plus trastuzumab and docetaxel responded to treatment, compared with 29% of patients who received trastuzumab and docetaxel alone. Response to treatment in the second study ranged from 57% to 66% where Perjeta was given with trastuzumab and chemotherapy medicines.A fourth ongoing study compared Perjeta with placebo (both given with trastuzumab and chemotherapy) in 4,805 women with early breast cancer who had had surgery to remove the cancer. Perjeta was shown to be of benefit in patients whose cancer was at a high risk of coming back: after 4 years, the disease had not spread in 90% of patients with 'node-positive' cancer treated with Perjeta compared with 87% of those receiving placebo; for those with 'hormone-receptor negative' cancer, this figure was 91% of patients treated with Perjeta, and 89% of patients given placebo.

What are the risks associated with Perjeta?

The most common side effects (affecting more than 3 in 10 people) with Perjeta when given with trastuzumab and chemotherapy are neutropenia (low levels of neutrophils, a type of white blood cell important for fighting infections), diarrhoea, nausea (feeling sick), vomiting, hair loss and tiredness. The most common severe side effect (affecting more than 1 in 10 people) is neutropenia, with or without fever.For the full list of all side effects and restrictions with Perjeta, see the package leaflet.

Why is Perjeta authorised in the EU?

HER2-positive breast cancer is an aggressive form of breast cancer which occurs in around one in five cases. The European Medicines Agency considered that Perjeta has been shown to benefit patients with metastatic cancer by extending the amount of time patients lived without their disease getting worse as well as how long they lived. It considered that this would provide an additional benefit when added to other medicines for HER2-positive cancer, notably trastuzumab. Perjeta has also been shown to improve the outcome of patients with earlier stages of breast cancer, when used with trastuzumab and chemotherapy. The Agency considered that, despite the side effects of Perjeta, the overall safety profile was acceptable.

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

The company that markets Perjeta will carry out a study to assess the effects of using Perjeta and trastuzumab together with a type of cancer medicines called taxanes, in previously untreated patients with HER2-positive metastatic or locally advanced breast cancer.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Perjeta have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Perjeta are continuously monitored. Side effects reported with Perjeta are carefully evaluated and any necessary action taken to protect patients.

---

Peyona

What is Peyona and what is it used for?

Peyona is a stimulant medicine used for treating apnoea of prematurity, a condition in which babies born prematurely stop breathing for longer than 20 seconds.Peyona contains the active substance caffeine citrate.

How is Peyona used?

Peyona can only be obtained with a prescription. A doctor with experience of treating newborn babies on intensive care should supervise the start of treatment with the medicine. Peyona should be given only in an intensive care unit for newborns that is well equipped to closely monitor the baby.The dose of Peyona is calculated using the baby's weight. The first dose (of 20 mg caffeine citrate per kilogram of bodyweight) is given by infusion (drip) into a vein over 30 minutes, using a device to closely control the rate at which the medicine is given. To continue treatment, Peyona is given in lower doses (5 mg caffeine citrate per kilogram of bodyweight) every 24 hours. These lower doses can be given either by infusion over 10 minutes or by mouth (e.g. through a tube into the stomach).Treatment usually continues until the baby can breathe well enough for at least 5 days.For more information about using Peyona, see the package leaflet or contact your doctor or pharmacist.

How does Peyona work?

Apnoea in premature babies occurs because the part of the baby's brain that controls breathing ('breathing centre') is not fully developed.Caffeine citrate, the active substance in Peyona, blocks the effect of adenosine. Adenosine is a natural substance that slows down the activity of some parts of the brain including the breathing centre. By reducing the effect of adenosine, caffeine citrate stimulates the brain to resume breathing.

What benefits of Peyona have been shown in studies?

Because caffeine citrate has been used in premature babies for a long time, the company presented information from published scientific literature.In a study involving 85 premature babies who had had several episodes of apnoea, caffeine citrate was compared with placebo (a dummy treatment) over 10 days. On 6 out of 10 days, caffeine citrate was more effective than placebo in reducing the number of apnoea episodes by at least a half. In addition, 22% of babies given caffeine citrate had at least 8 days with no apnoea compared with none of babies who received placebo.A study involving 2,006 premature babies with apnoea found that 46% of babies given placebo died or had neurological disabilities compared with 40% of babies given caffeine citrate.A review of five studies compared caffeine or theophylline (another stimulant) with placebo in 192 premature babies with apnoea. The review considered a baby to be in treatment failure if there was no halving of the number of apnoea episodes, if the baby required a machine to help with breathing or if the baby died. Fewer babies treated with caffeine or theophylline had treatment failure compared with placebo.

What are the risks associated with Peyona?

The most common side effects with Peyona (which may affect up to 1 in 10 babies) are hyperglycaemia (high blood glucose levels), tachycardia (rapid heartbeat), and phlebitis (inflammation of a vein) and inflammation at the site of infusion.For the full list of side effects and restrictions of Peyona, see the package leaflet.

Why is Peyona authorised in the EU?

The European Medicines Agency decided that Peyona's benefits are greater than its risks and it can be authorised for use in the EU. Published scientific literature has shown that Peyona is effective and its side effects are manageable.

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

The company that markets Peyona will provide a card to display in intensive care units where the medicine will be used. It will include information, warnings and precautions on the appropriate and safe use of Peyona, including how to work out and prescribe the dose.Recommendations and precautions for the safe and effective use of Peyona have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Peyona are continuously monitored. Side effects reported with Peyona are carefully evaluated and any necessary action taken to protect patients.

---

Pheburane

What is Pheburane and what is it used for?

Pheburane is a medicine that contains the active substance sodium phenylbutyrate. It is used to treat patients who have urea cycle disorders. These patients are not able to get rid of waste nitrogen from the body because they lack some enzymes that are usually found in the liver. In the body, waste nitrogen is in the form of ammonia, which is toxic when it accumulates, especially for the brain. Pheburane is used in patients who lack one or more of the following enzymes: carbamylphosphate synthetase, ornithine transcarbamylase, or argininosuccinate synthetase. It can be used in patients with the following forms of the disease:• 'early-onset' disease in patients who show a complete lack of one or more of these enzymes within the first month of life;• 'late-onset' disease in patients who show a partial lack of one or more of these enzymes after the age of one month and have had high blood ammonia levels that affected the brain's activity.Pheburane is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Pheburane granules are available at a lower strength and contain different excipients (inactive ingredients) to mask the unpleasant taste of the active substance. The reference medicine for Pheburane is Ammonaps.

How is Pheburane used?

Pheburane is available as granules (483 mg/g). It can only be obtained with a prescription and treatment should be supervised by a doctor who has experience in treating patients with urea cycle disorders.Pheburane is used with a special low-protein diet to reduce the intake of nitrogen. The daily dose of Pheburane is adjusted for each patient individually and depends on the patient's diet, height and weight. Regular blood tests are needed to find the correct daily dose.The daily dose of Pheburane should be divided into equal amounts and given with each meal. The granules can be sprinkled onto food immediately before being swallowed or placed in the mouth and swallowed immediately with a drink.Pheburane may be a life-long treatment unless the patient has a successful liver transplant.

How does Pheburane work?

Eating protein brings nitrogen into the body, which is then transformed into ammonia. Patients with urea cycle disorders cannot get rid of ammonia from the body, so it can reach high levels, leading to serious problems including disability, brain damage and death. The active substance in Pheburane, sodium phenylbutyrate, is converted into a substance called phenylacetate in the body. Phenylacetate combines with the amino acid glutamine, which contains nitrogen, to form a substance that can be removed from the body by the kidneys. This allows the levels of nitrogen in the body to decrease, reducing the amount of ammonia produced.

How has Pheburane been studied?

Studies in patients have been limited to tests to determine that Pheburane is bioequivalent to the reference medicine, Ammonaps. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Pheburane?

Because Pheburane is a hybrid 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 Pheburane approved?

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

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

Safety information has been included in the summary of product characteristics and the package leaflet for Pheburane, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Phelinun

What is Phelinun and what is it used for?

Phelinun is a cancer medicine for treating patients with:• cancers of the bone marrow (which produces blood cells) - multiple myeloma, acute lymphoblastic leukaemia and acute myeloid leukaemia;• Hodgkin and non-Hodgkin lymphomas, which are cancers that affect white blood cells called lymphocytes;• Childhood neuroblastoma, a cancer of nerve cells in different parts of the body;• ovarian cancer;• mammary adenocarcinoma, a type of breast cancer.It is used either on its own or in combination with other cancer medicines, or radiotherapy or both.Phelinun can also be used for stem cell transplantation in adults and children with blood cancers and some other blood disorders in children. It is given with other cytotoxic (cell-killing) medicines for conditioning treatment (to clear cells in the bone marrow) before the patient receives healthy stem cells from a donor to replace the diseased cells.Phelinun contains the active substance melphalan.Phelinun is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Phelinun is intended for an additional use (conditioning treatment). The reference medicine for Phelinun is Alkeran 50 mg/10 ml, which is marketed in France.

How is Phelinun used?

Phelinun can only be obtained with a prescription and it must be given under the supervision of a doctor experienced in the use of cancer medicines and conditioning treatment for stem cell transplantation.Phelinun is given by infusion (drip) into a vein and the dose depends on the condition it is being used for as well as the patient's weight and height. The dose can be split and given over 2 or 3 consecutive days.For more information about using Phelinun, see the package leaflet or contact your doctor or pharmacist.

How does Phelinun work?

Melphalan, the active substance in Phelinun is a type of cytotoxic medicine known as alkylating agent. It prevents cells from dividing by stopping the DNA (the cell's genetic material) from duplicating itself to form new cells. Melphalan's action therefore affects cells that divide rapidly, such as cancer cells and cells of the bone marrow.

What benefits of Phelinun have been shown in studies?

Studies on the benefits and risks of the active substance, melphalan, for the treatment of cancers have already been carried out with the reference medicine, Alkeran, and do not need to be repeated for Phelinun.The company also provided evidence from over 20 published studies to show that melphalan is effective for conditioning treatment in adults and children undergoing haematopoietic (blood) stem cell transplantation.As for every medicine, the company provided studies on the quality of Phelinun. There was no need for 'bioequivalence' studies to investigate whether Phelinun is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because Phelinun is given by infusion into a vein, so the active substance is delivered straight into the bloodstream.

What are the risks associated with Phelinun?

The most common side effects with Phelinun (which may affect more than 1 in 10 people) include reduced levels of blood cells and platelets (blood components involved in clotting), infections, gastrointestinal disorders (such as diarrhoea, vomiting, mouth ulcers and bleeding) and disorders of the immune system (the body's natural defences) including graft-versus-host disease (transplanted cells attacking the body).Phelinun must not be used during breast-feeding or as conditioning treatment during pregnancy.For the full list of side effects and restrictions of Phelinun, see the package leaflet.

Why is Phelinun authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Phelinun has been shown to be comparable to Alkeran for the treatment of blood cancers. Although main studies to measure the effectiveness of Phelinun for conditioning treatment in adults and children are not available, evidence from published studies shows that it is effective, and in some cases its side effects may be lower than those of other options for conditioning treatment.The European Medicines Agency therefore decided that Phelinun'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 Phelinun?

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

---

Phesgo

What is Phesgo and what is it used for?

Phesgo is a cancer medicine for treating adults with 'HER2-positive' breast cancer (where a protein called HER2 is found on the cancer cells).It is used in combination with other cancer medicines in:• patients with early breast cancer (when the cancer has not spread to other parts of the body) at high risk of coming back, after they have surgery;• patients with locally advanced, inflammatory breast cancer or with early breast cancer at high risk of coming back, before they have surgery;• patients whose cancer that has come back locally after treatment and cannot be removed by surgery;• patients with metastatic breast cancer (cancer that has spread to other parts of the body).Phesgo contains the active substances pertuzumab and trastuzumab. For more information about the use of Phesgo and the other medicines the patients will receive, see the package leaflet.

How is Phesgo used?

Phesgo can only be obtained with a prescription and treatment should be started under the supervision of a doctor who is experienced in using cancer medicines and in a hospital setting where resuscitation equipment is available.Phesgo is given as an injection under the skin. The first dose is given over 8 minutes as an injection containing pertuzumab 1200 mg and trastuzumab 600 mg. This is followed by an injection containing pertuzumab 600 mg / trastuzumab 600 mg given over 5 minutes every 3 weeks. The duration of treatment depends on whether Phesgo is given before or after surgery, and on the type of breast cancer being treated.For more information about using Phesgo, see the package leaflet or contact your doctor or pharmacist.

How does Phesgo work?

The active substances in Phesgo, pertuzumab and trastuzumab, are monoclonal antibodies (a type of protein) that have been designed to attach to HER2. HER2 is a protein on cancer cells that makes the tumour cells grow more quickly and that is present in large quantities in about a quarter of breast cancers. By attaching to HER2, pertuzumab and trastuzumab stop HER2 from producing signals that cause the cancer cells to grow. They also activate cells of the immune system (the body's natural defences), which then kill the cancer cells.Pertuzumab and trastuzumab attach to 2 different parts of HER2 and their actions have a complementary effect. These combined actions slow down cancer growth.

What benefits of Phesgo have been shown in studies?

Pertuzumab and trastuzumab given by infusion (drip) into a vein are already authorised to be used together for treating HER2-positive breast cancer. A main study in 500 patients showed that Phesgo given under the skin was as effective as this combination.The study showed that the levels of pertuzumab and trastuzumab in the blood were similar in patients who received Phesgo and those who received the combination by infusion. In addition, in both groups, about 60% of patients (150 out of 252 in the Phesgo group and 148 out of 248 in the pertuzumab plus trastuzumab group) had no signs of cancer in the breast and glands under the arm after one year of treatment.

What are the risks associated with Phesgo?

The most common side effects with Phesgo (which may affect more than 3 in 10 people) are alopecia (hair loss), diarrhoea, nausea (feeling sick), anaemia (low red blood cell counts), weakness and joint pain.The most common serious side effects with Phesgo (which may affect up to 1 in 10 people) are neutropenia (low white blood cell counts) with or without fever, heart failure (when the heart does not pump blood as well as it should), fever, infections of blood or lungs (sepsis, pneumonia) and decreased neutrophil (a type of white blood cell) count.For the full list of side effects and restrictions of Phesgo, see the package leaflet.

Why is Phesgo authorised in the EU?

Phesgo contains two active substances, pertuzumab and trastuzumab, which are already authorised for treating early and metastatic HER2-positive breast cancer and are available as infusion into a vein. Phesgo is as effective at treating breast cancer as the individual medicines given into a vein. Because it is given under the skin, it may be more convenient for patients and is less invasive and faster than being given the medicines by infusion. Apart from the reactions at the injection site, the side effects with Phesgo are similar to those seen with pertuzumab and trastuzumab medicines by infusion.The European Medicines Agency therefore decided that Phesgo'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 Phesgo?

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

---

Pifeltro

What is Pifeltro and what is it used for?

Pifeltro is an antiviral medicine used to treat adults and adolescents from 12 years of age weighing at least 35 kg who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS). Pifeltro is used together with other antiviral medicines.It is only used in patients where the virus has not developed resistance to medicines that work in the same way as Pifeltro.Pifeltro contains the active substance doravirine.

How is Pifeltro used?

Pifeltro can only be obtained with a prescription and treatment should be started by a doctor experienced in managing HIV infection.Pifeltro is available as tablets (100 mg). The recommended dose is one tablet daily.For more information about using Pifeltro, see the package leaflet or contact your doctor or pharmacist.

How does Pifeltro work?

The active substance in Pifeltro, doravirine, is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Doravirine blocks the activity of reverse transcriptase, a virus enzyme that allows HIV to reproduce itself in the cells it has infected.Pifeltro helps keep the amount of HIV in the blood at a low level. It does not cure HIV infection or AIDS but, when used in combination with other antivirals, it holds off the damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Pifeltro have been shown in studies?

Studies showed that Pifeltro taken with other antivirals was as effective at keeping HIV infection under control as standard HIV combination treatments.In a study of 766 adult patients, 83% of patients taking Pifeltro (together with either emtricitabine and tenofovir disoproxil or abacavir and lamivudine) had undetectable levels of HIV in their blood (fewer than 40 copies/ml) after 48 weeks of treatment. This compares with 79% of patients taking a standard combination of darunavir plus ritonavir (together with either emtricitabine and tenofovir disoproxil or abacavir and lamivudine).In a second study with 728 adult patients, 84% of patients treated with Pifeltro in combination with tenofovir disoproxil and lamivudine had undetectable HIV levels by 48 weeks compared with 80% of patients given a combination of efavirenz, tenofovir disoproxil and emtricitabine.A third study that included 43 adolescent patients aged 12 to 18 years who had been previously treated for HIV showed that Pifeltro (together with tenofovir disoproxil and lamivudine) was also effective at keeping viral load below 40 copies/ml in this age group; 95% (41 of 43 patients) had undetectable levels after 24 weeks, and 93% (40 of 43 patients) had undetectable levels after 48 weeks.

What are the risks associated with Pifeltro?

The most common side effects with doravirine (which may affect up to 1 in 10 people) are nausea (feeling sick) and headache.Pifeltro must not be used with certain medicines that may reduce its effectiveness. For the full list of side effects and restrictions with Pifeltro, see the package leaflet.

Why is Pifeltro authorised in the EU?

Pifeltro was shown to be effective at keeping HIV infection under control in both adults and adolescent from 12 years of age. In addition, Pifeltro's side effects are mostly mild.The European Medicines Agency therefore decided that Pifeltro'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 Pifeltro?

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

---

Pioglitazone Accord

What is Pioglitazone Accord and what is it used for?

Pioglitazone Accord is used to treat type 2 diabetes in adults (aged 18 years or over), particularly those who are overweight. It is used in addition to diet and exercise as follows:• on its own in patients for whom metformin (another diabetes medicine) is not suitable.• in combination with metformin in patients who are not satisfactorily controlled on metformin alone, or with a sulphonylurea (another type of diabetes medicine) when metformin is not suitable in patients who are not satisfactorily controlled on a sulphonylurea alone;• together with both metformin and a sulphonylurea in patients who are not satisfactorily controlled despite treatment with two medicines by mouth;• together with insulin in patients who are not satisfactorily controlled with insulin alone and cannot take metformin.Pioglitazone Accord is a 'generic medicine'. This means that Pioglitazone Accord is similar to a 'reference medicine' already authorised in the European Union (EU) called Actos. For more information on generic medicines, see the question-and-answer document here.Pioglitazone Accord contains the active substance pioglitazone.

How is Pioglitazone Accord used?

Pioglitazone Accord can only be obtained with a prescription.The medicine is available as tablets (15, 30 and 45 mg) and the recommended starting dose is 15 or 30 mg once a day. This dose may need to be increased after one or two weeks to up to 45 mg once a day if better blood glucose (sugar) control is needed.Treatment with Pioglitazone Accord should be reviewed after three to six months, and discontinued in patients who are not deriving sufficient benefit. At subsequent reviews prescribers should confirm that benefits to patients are maintained.

How does Pioglitazone 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. The active substance in Pioglitazone Accord, pioglitazone, makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces. As a consequence, the blood glucose levels are reduced and this helps to control type 2 diabetes.

How has Pioglitazone Accord been studied?

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

What are the benefits and risks of Pioglitazone Accord?

Because Pioglitazone 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 Pioglitazone Accord approved?

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

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

The company that markets Pioglitazone Accord will produce educational material for doctors prescribing the medicine, which will cover the possible risk of heart failure and bladder cancer with treatments that contain pioglitazone, the criteria for selecting patients and the need to review treatment regularly and stop treatment if patients are no longer benefiting.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pioglitazone Accord have also been included in the summary of product characteristics and the package leaflet.

---

Pioglitazone Actavis

What is Pioglitazone Actavis and what is it used for?

Pioglitazone Actavis is used to treat type 2 diabetes in adults (aged 18 years or over), particularly those who are overweight. It is used in addition to diet and exercise as follows:• on its own in patients for whom metformin (another diabetes medicine) is not suitable;• in combination with metformin in patients who are not satisfactorily controlled on metformin alone, or with a sulphonylurea (another type of diabetes medicine) when metformin is not suitable in patients who are not satisfactorily controlled on a sulphonylurea alone;• together with both metformin and a sulphonylurea in patients who are not satisfactorily controlled despite treatment with two medicines by mouth;• together with insulin in patients who are not satisfactorily controlled with insulin alone and cannot take metformin.Pioglitazone Actavis is a 'generic medicine'. This means that Pioglitazone Actavis is similar to a 'reference medicine' already authorised in the European Union (EU) called Actos. For more information on generic medicines, see the question-and-answer document here.Pioglitazone Actavis contains the active substance pioglitazone.

How is Pioglitazone Actavis used?

Pioglitazone Actavis can only be obtained with a prescription.The medicine is available as tablets (15, 30 and 45 mg) and the recommended starting dose is 15 or 30 mg once a day. This dose may need to be increased after one or two weeks to up to 45 mg once a day if better blood glucose (sugar) control is needed.Treatment with Pioglitazone Actavis should be reviewed after three to six months, and discontinued in patients who are not deriving sufficient benefit. At subsequent reviews prescribers should confirm that benefits to patients are maintained.

How does Pioglitazone Actavis 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 Pioglitazone Actavis, pioglitazone, makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces. As a consequence, the blood glucose levels are reduced and this helps to control type 2 diabetes.

How has Pioglitazone Actavis been studied?

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

What are the benefits and risks of Pioglitazone Actavis?

Because Pioglitazone 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 is Pioglitazone Actavis approved?

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

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

The company that markets Pioglitazone Actavis will produce educational material for doctors prescribing the medicine, which will cover the possible risk of heart failure and bladder cancer with treatments that contain pioglitazone, the criteria for selecting patients and the need to review treatment regularly and stop treatment if patients are no longer benefiting.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pioglitazone Actavis have also been included in the summary of product characteristics and the package leaflet.

---

Piqray

What is Piqray and what is it used for?

Piqray is a cancer medicine used to treat postmenopausal women and men with breast cancer that is locally advanced or has spread to other parts of the body.Piqray can only be used when the cancer cells have receptors for certain hormones on their surface (HR-positive) and do not have large quantities of another receptor called HER2 (HER2-negative). The cancer cells must also have been shown to have a specific mutation (change) in the gene called 'PIK3CA'. Piqray is used with the medicine fulvestrant (hormone treatment for breast cancer) after hormone treatment used alone has failed.Piqray contains the active substance alpelisib.

How is Piqray used?

Piqray can only be obtained with a prescription and should be started by a doctor experienced in using cancer medicines.Piqray is available as tablets to take by mouth immediately after food. The recommended dose is 300 mg once a day at about the same time each day, and treatment should continue for as long as the patient benefits from it. If the patient has unacceptable side effects, the doctor may stop treatment or reduce the dose.For more information about using Piqray, see the package leaflet or contact your doctor or pharmacist.

How does Piqray work?

In patients whose cancer cells have a PIK3CA mutation, an abnormal form of the enzyme PI3K is produced that stimulates cancer cells to divide and grow in an uncontrolled fashion. The active substance in Piqray, alpelisib, works by blocking the activity of the abnormal PI3K, thereby reducing the growth and spread of the cancer.

What benefits of Piqray have been shown in studies?

A main study involved 340 patients with advanced breast cancer with a PIK3CA mutation in whom hormone treatment had not worked or the cancer had come back. Patients treated with Piqray in combination with fulvestrant lived on average for 11 months without their disease getting worse compared with around 6 months for patients who received placebo (a dummy treatment) with fulvestrant.What are the risks associated with PiqrayThe most common side effects with Piqray (which may affect more than 1 in 5 people) are increased blood sugar which may require treatment (less frequently, reduced blood sugar), increased levels of creatinine (which may indicate kidney problems), stomatitis (inflammation of the lining of the mouth), nausea, vomiting, diarrhoea, decreased appetite and weight loss, abnormal blood tests for liver function, increased blood levels of lipase (which may indicate inflammation of the pancreas), rash, reduced levels of lymphocytes (a type of white blood cell), anaemia (reduced red blood cells), tiredness, hypocalcaemia (low blood levels of calcium), prolonged blood clotting time and hair loss.For the full list of side effects and restrictions of Piqray, see the package leaflet.

Why is Piqray authorised in the EU?

The European Medicines Agency decided that Piqray's benefits are greater than its risks and it can be authorised for use in the EU. Piqray used with fulvestrant increased the time before the disease got worse in patients with HR-positive and HER2-negative breast cancer that is advanced or has spread. In terms of the medicine's side effects, the main concern is high blood sugar levels which may lead to diabetes and gut problems but the Agency has recommended measures to manage this.

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

The company that markets Piqray will carry out a study to investigate its effectiveness and long-term safety. The company will also provide information on the medicine for healthcare professionals, including information on high blood sugar levels and how to manage them.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Piqray have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Piqray are continuously monitored. Side effects reported with Piqray are carefully evaluated and any necessary action taken to protect patients.

---

Pirfenidone Aet

What is Pirfenidone AET and what is it used for?

Pirfenidone AET is a medicine used to treat adults with mild to moderate idiopathic pulmonary fibrosis (IPF). IPF is a long-term disease in which fibrous scar tissue continuously forms in the lungs, causing persistent cough, frequent lung infections and severe shortness of breath. 'Idiopathic' means that the cause of the disease is unknown.Pirfenidone AET is a 'generic medicine'. This means that Pirfenidone AET contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Esbriet. For more information on generic medicines, see the question-and-answer document here.Pirfenidone AET contains the active substance pirfenidone.

How is Pirfenidone AET used?

Pirfenidone AET can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the diagnosis and treatment of IPF.The medicine is available as tablets (267, 534 and 801 mg) that are taken with food. The dose of Pirfenidone AET is increased steadily, starting with 267 mg three times a day in the first week, 534 mg three times a day in the second week and 801 mg three times a day from the third week onwards.Patients who have side effects such as stomach problems, skin reactions to light or significant changes in the levels of liver enzymes may need to take a lower dose, at least temporarily.For more information about using Pirfenidone AET, see the package leaflet or contact your doctor or pharmacist.

How does Pirfenidone AET work?

The mechanism of action of pirfenidone, the active substance in Pirfenidone AET, is not fully understood but it has been shown to reduce the production of fibroblasts and other substances involved in the formation of fibrous tissue during the body's tissue repair process, thereby slowing down the progression of the disease in IPF patients.Send

How has Pirfenidone AET been studied?

Studies on the benefits and risks of the active substance in the authorised use have already been carried out with the reference medicine, Esbriet, and do not need to be repeated for Pirfenidone AET.As for every medicine, the company provided data on the quality of Pirfenidone AET. 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 Pirfenidone AET?

Because Pirfenidone AET 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 Pirfenidone AET authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Pirfenidone AET has been shown to have comparable quality and to be bioequivalent to Esbriet. Therefore, the Agency's view was that, as for Esbriet, the benefits of Pirfenidone AET 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 Pirfenidone AET?

The company that markets Pirfenidone AET must ensure that all doctors who are expected to prescribe the medicine are provided with information material on skin reactions to light and changes in liver enzymes following use of Pirfenidone AET and how to minimise the risk.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pirfenidone AET have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Pirfenidone AET are continuously monitored. Suspected side effects reported with Pirfenidone AET are carefully evaluated and any necessary action taken to protect patients.

---

Pirfenidone Viatris

What is Pirfenidone Viatris and what is it used for?

Pirfenidone Viatris is used to treat adults with mild to moderate idiopathic pulmonary fibrosis (IPF). IPF is a long-term disease in which fibrous scar tissue continuously forms in the lungs, causing persistent cough, frequent lung infections and severe shortness of breath. 'Idiopathic' means that the cause of the disease is unknown.Pirfenidone Viatris is a 'generic medicine'. This means that it contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Esbriet. For more information on generic medicines, see the question-and-answer document here.Pirfenidone Viatris contains the active substance pirfenidone.

How is Pirfenidone Viatris used?

Pirfenidone Viatris is available as tablets (267, 534 or 801 mg) that are taken at mealtimes. The dose of Pirfenidone Viatris is increased steadily, starting with 267 mg three times a day in the first week, to 534 mg three times a day in the second week and 801 mg three times a day from the third week onwards.Patients who have side effects such as stomach problems, skin reactions to light or significant changes in the levels of liver enzymes may need to take a lower dose or have their treatment interrupted at least temporarily.Pirfenidone Viatris can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the diagnosis and treatment of IPF.For more information about using Pirfenidone Viatris, see the package leaflet or contact your doctor or pharmacist.

How does Pirfenidone Viatris work?

The mechanism of action of pirfenidone, the active substance in Pirfenidone Viatris, is not fully understood but it has been shown to reduce the production of cells and substances involved in the formation of fibrous scar tissue, thereby slowing down the progression of IPF in patients.

How has Pirfenidone Viatris been studied?

Studies on the benefits and risks of the active substance in the authorised use have already been carried out with the reference medicine, Esbriet, and do not need to be repeated for Pirfenidone Viatris.As for every medicine, the company provided studies on the quality of Pirfenidone Viatris. 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 Pirfenidone Viatris?

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

Why is Pirfenidone Viatris authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, PirfenidoneViatris has been shown to have comparable quality and to be bioequivalent to Esbriet. Therefore, the Agency's view was that, as for Esbriet, the benefits of Pirfenidone Viatris 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 Pirfenidone Viatris?

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

---

Pixuvri

What is Pixuvri?

Pixuvri is a medicine that contains the active substance pixantrone. It is available as a powder that is made up into a solution for infusion (a drip into a vein).

What is Pixuvri used for?

Pixuvri is used to treat adult patients with non-Hodgkin's B cell lymphoma. This is a cancer of the lymph tissue (part of the immune system) that affects a type of white blood cell called B lymphocytes, or B cells. Pixuvri is used when the lymphoma is aggressive and has come back or has not responded to other chemotherapy treatments (medicines to treat cancer).The medicine can only be obtained with a prescription.

How is Pixuvri used?

Pixuvri must be given by a doctor who has experience in the use of anticancer medicines and who has access to facilities for monitoring the patient.The dose of Pixuvri is based on the patient's body surface area (calculated using the patient's height and weight). The recommended dose is 50 mg/m2 given as an infusion into a vein over at least 60 minutes on days 1, 8 and 15 of a 28-day cycle. Pixuvri can be given for up to six cycles. In patients who develop side effects or who have very low blood levels of neutrophils (a type of white blood cellthat fights infection) and platelets (components that help the blood to clot), the dose may have to be reduced or treatment may have to be delayed.

How does Pixuvri work?

The active substance in Pixuvri, pixantrone, is a cytotoxic medicine (a medicine that kills cells that are dividing, such as cancer cells) that belongs to the group 'anthracyclines'. It works by interfering with the DNA within cells, preventing them from making more copies of DNA and making proteins. This means that the cancer cells in non-Hodgkin's B cell lymphoma cannot divide and eventually die.

How has Pixuvri been studied?

The effects of Pixuvri were first tested in experimental models before being studied in humans.Pixuvri was compared with other chemotherapy treatments in one main study involving 140 adults with aggressive non-Hodgkin's B cell lymphoma, who had previously received at least two other treatments, and whose cancer had come back or had not responded to treatment. Patients were given either six cycles of Pixuvri or another approved anticancer medicine chosen by their doctor.The main measure of effectiveness was the number patients who had a complete response to treatment.

What benefit has Pixuvri shown during the studies?

Pixuvri was shown to be beneficial in patients with aggressive non-Hodgkin's B cell lymphoma: 20% of patients responded completely to Pixuvri (14 out of 70 patients) compared with 5.7% of patients receiving other agents (4 out of 70 patients).

What is the risk associated with Pixuvri?

The most common side effects with Pixuvri (seen in more than 1 patient in 10) are neutropenia, leucopenia and lymphopenia (low levels of different types of white blood cells), thrombocytopenia (low levels of platelets in the blood), anaemia (low levels of red blood cells), nausea (feeling sick), vomiting, skin discolouration, hair loss, chromaturia (abnormal colouration of the urine) and asthenia (weakness). For the full list of all side effects reported with Pixuvri, see the package leaflet.Pixuvri must not be used in patients who are hypersensitive (allergic) to pixantrone or any of the other ingredients. It must not be used in patients with severe liver problems and in patients whose bone marrow produces abnormally low levels of blood cells. Patients receiving Pixuvri must not be given vaccines containing attenuated (weakened live) viruses.

Why has Pixuvri been approved?

The CHMP concluded that patients with aggressive non-Hodgkin's B cell lymphoma had a better response to treatment with Pixuvri than other cancer treatments. In addition, patients treated with Pixuvri lived for longer without their disease getting worse. The CHMP also considered the seriousness of the disease and the lack of suitable alternative treatments for patients whose non-Hodgkin's B cell lymphoma has come back or has not responded to other chemotherapy treatments. The side effects of the medicine were considered to be short term and manageable. However, the Committee noted that more data were needed on the benefits of Pixuvri in patients who have received previous treatment with rituximab (another medicine commonly used to treat lymphoma). The CHMP concluded that the benefits of Pixuvri are greater than its risks and recommended that it be given marketing authorisation.Pixuvri has been given 'conditional approval'. This means that there is more evidence to come about the medicine, in particular its benefits in patients who have previously been treated with rituximab. Every year, the European Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Pixuvri?

The company that makes Pixuvri will carry out a study to further investigate the effects of using Pixuvri in patients who had received prior treatment with rituximab.

---

Plavix

What is Plavix and what is it used for?

Plavix is a medicine used to prevent problems caused by blood clots in adults who have:• recently had a myocardial infarction (heart attack). Plavix can be started between a few days and 35 days after the attack;• recently had an ischaemic stroke (stroke caused by failure of the blood supply to part of the brain). Plavix can be started between seven days and six months after the stroke;• peripheral arterial disease (problems with blood flow in the arteries);• a condition known as 'acute coronary syndrome', when it should be given with acetylsalicylic acid (also known as aspirin). Acute coronary syndrome is a group of heart problems that includes heart attacks and unstable angina (a severe type of chest pain).Some of these patients may be undergoing percutaneous coronary intervention (a procedure that unblocks blood vessels of the heart to restore its blood supply) and may have had a stent inserted (a short tube placed in an artery to prevent it closing up). Others may benefit from thrombolytic or fibrinolytic treatment (treatments to dissolve blood clots).• atrial fibrillation (irregular rapid contractions of the upper chambers of the heart), when it should be given with acetylsalicylic acid. It is used in those patients who have at least one risk factor for vascular events such as a heart attack or stroke, cannot take vitamin K antagonists (other medicines that prevent blood clots) and are at low risk of bleeding.Plavix contains the active substance clopidogrel.

How is Plavix used?

Plavix is available as tablets and can only be obtained with a prescription.Plavix is taken once a day as a 75 mg tablet. Use of a loading dose (an initial higher dose) and the duration of treatment depend on the age of the patient and the disease being treated. For patients undergoing a percutaneous coronary intervention or eligible for thrombolytic or fibrinolytic therapy, treatment should start as early as possible after start of symptoms.For more information about using Plavix, see the package leaflet or contact your doctor or pharmacist.

How does Plavix work?

The active substance in Plavix, clopidogrel, is an inhibitor of platelet aggregation. This means that it helps to prevent blood clots from forming. Blood clots are caused by cells in the blood called platelets sticking together. Clopidogrel stops the platelets sticking together by blocking a substance called ADP from attaching to a receptor on their surface. This stops the platelets becoming 'sticky', reducing the risk of a blood clot forming and helping to prevent another heart attack or stroke.

What benefits of Plavix have been shown in studies?

Plavix was more effective than acetylsalicylic acid at preventing new ischaemic events. In a study in around 19,000 patients who had recently had a heart attack or an ischaemic stroke, or who had established peripheral artery disease, 939 patients who were given Plavix experienced a new ischemic event (heart attack, ischaemic stroke or death) over a period of one to three years, compared with 1,020 patients who were given acetylsalicylic acid. This corresponds to a relative reduction in risk of 9% compared with acetylsalicylic acid and means that fewer patients will have new ischaemic events if they receive Plavix than if they receive acetylsalicylic acid.In three studies involving over 61,000 patients with non-ST segment elevation acute coronary syndrome, 2,172 of whom had a stent inserted during the study, Plavix was given in combination with acetylsalicylic acid and compared with placebo (a dummy treatment). In these studies, which differed in duration from up to 8 days to up to one year, the overall relative risk of an event such as a blocked artery, another heart attack or death was reduced by 20% when patients were given Plavix and acetylsalicylic acid compared with placebo. There was also a reduction in the patients who had a stent inserted. In 2 studies in 49,000 patients with ST segment elevation myocardial infarction, fewer patients on Plavix had events than patients on placebo (262 against 377 in the CLARITY study, and 2,121 against 2,310 in the COMMIT study).In a study in around 7,500 patients with atrial fibrillation who had at least one risk factor for vascular events and who could not take vitamin K antagonist therapy, patients were given Plavix together with acetylsalicylic acid or placebo for an average of three years. In this study, Plavix plus acetylsalicylic acid reduced the risk of new events by 11% compared with placebo taken with acetylsalicylic acid, with the largest reduction (28%) seen for stroke.Study results published in medical journals showed that Plavix was effective for up to 12 months at reducing the occurrence of heart attack, stroke or death in patients treated for heart attack with STsegment elevation who are having a percutaneous coronary intervention.

What are the risks associated with Plavix?

Bleeding reactions are the most common side effects reported with Plavix. The most common of these (which may affect up to 1 in 10 people) are haematoma (a collection of blood under the skin), epistaxis (nosebleeds), gastrointestinal haemorrhage (bleeding in the stomach or gut), bruising and bleeding where the skin is punctured.Other side effects (which may affect up to 1 in 10 people) are diarrhoea, abdominal pain (stomach ache) and dyspepsia (heartburn).For the full list of side effects of Plavix, see the package leaflet.Plavix must not be used in people who may be hypersensitive (allergic) to clopidogrel or any of the other ingredients. It must not be used in patients who have severe liver disease or a disease that may cause bleeding such as a stomach ulcer or bleeding in the brain.

Why is Plavix authorised in the EU?

The European Medicines Agency decided that Plavix'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 Plavix?

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

---

Plegridy

What is Plegridy and what is it used for?

Plegridy is a medicine used to treat multiple sclerosis (MS), a disease in which inflammation damages the protective insulation around nerves (demyelination) as well as the nerves themselves. It is used specifically in adults with a type of MS known as relapsing-remitting MS, where the patient has flareups of symptoms (relapses) between periods of recovery (remissions).Plegridy contains the active substance peginterferon beta-1a.

How is Plegridy used?

Plegridy can only be obtained with a prescription and treatment should be started under the supervision of a doctor experienced in treating MS.Plegridy is available as an injection in pre-filled pens or pre-filled syringes, given every 2 weeks. The dose should be increased in two-week steps until the full dose is reached after 4 weeks.Plegridy is given by injection under the skin of the abdomen, the arm or the thigh, or by injection into the thigh muscle using a different type of syringe. Patients can inject Plegridy themselves, provided that they have been trained.For more information about using Plegridy, see the package leaflet or contact your doctor or pharmacist.

How does Plegridy work?

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 Plegridy works in MS is not yet known but it seems to calm down the immune system, and prevents relapses of MS.The active substance in Plegridy 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 Plegridy,this interferon has been 'pegylated' (attached to a chemical called polyethylene glycol). This decreases the rate at which the medicine is removed from the body and allows it to be given less often.

What benefits of Plegridy have been shown in studies?

Plegridy has been shown to reduce the rate of relapses in patients with relapsing-remitting MS in a main study which lasted two years and involved 1,516 patients. During the first year, patients were given Plegridy every two or four weeks, or placebo (a dummy treatment); during the second year, all patients were given Plegridy every two or four weeks. The main measure of effectiveness was the number of relapses that patients experienced over one year but the study also looked at other measures including how fast the patients' disability progressed.During the first year, patients treated with Plegridy every two or four weeks experienced fewer relapses on average than patients on placebo: 0.26 and 0.29 relapses versus 0.40, respectively. The progression of disability was reduced in patients given Plegridy every two weeks but less clearly so in those given the medicine every four weeks. Plegridy continued to produce benefit in the second year of treatment.This study was extended for two further years to investigate the long-term safety and efficacy of Plegridy, and available data from the extension phase at the time of approval were consistent with the results of the main study.

What are the risks associated with Plegridy?

The most common side effects with Plegridy (which may affect more than 1 in 10 people) are headache, muscle pain, joint pain, flu-like symptoms, pyrexia (fever), chills, asthenia (weakness), and erythema (reddening of the skin), pain or pruritus (itching) at the injection site.Plegridy 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 Plegridy, see the package leaflet.

Why is Plegridy authorised in the EU?

The European Medicines Agency decided that Plegridy's benefits are greater than its risks and it can be authorised for use in the EU. The Agency considered that Plegridy given every two weeks has been shown to produce about a 30% reduction in the number of relapses in patients with relapsing-remitting MS compared with placebo, which is comparable to the effect of other MS medicines containing nonpegylated interferon beta, and is considered clinically relevant.Also, the Agency considered Plegridy to be of greater benefit to patients when given every two weeks as compared to less frequent injections tested in the study. When Plegridy was given every four weeks its beneficial effect was smaller, and it was not possible to identify a group of patients in whom this less frequent dosing was considered appropriate.With regards to the safety profile, the most common side effects observed during treatment with Plegridy are considered to be manageable and generally consistent with those seen with non-pegylated interferon medicines.

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

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

---

Plenadren

What is Plenadren and what is it used for?

Plenadren is a medicine used to treat adrenal insufficiency in adults. Adrenal insufficiency (including primary insufficiency or Addison's disease) is a condition where the adrenal glands (located just above the kidneys) do not produce enough of a steroid hormone called cortisol (also known as the stress hormone because it is released in response to stress). Symptoms include weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin. Adrenal insufficiency can require life-long treatment to replace the missing cortisol.Because the number of patients with adrenal insufficiency is low, the disease is considered 'rare', and Plenadren was designated an 'orphan medicine' (a medicine used in rare diseases) on 22 May 2006.Plenadren contains the active substance hydrocortisone.

How is Plenadren used?

Plenadren can only be obtained with a prescription. It is available as modified-release tablets (5 mg and 20 mg).The usual daily dose ranges from 20 to 30 mg, once per day early in the morning; tablets should be swallowed whole with a glass of water at least 30 minutes before food. Treatment may need to be individually adjusted according to how the patient responds. In situations of excessive physical or mental stress or illness, patients may need further doses of hydrocortisone. This may be given as Plenadren tablets twice or three times daily or as conventional immediate-release tablets or injections, either alone or in combination with Plenadren.

How does Plenadren work?

The active substance in Plenadren, hydrocortisone, is the pharmaceutical form of cortisol, the main steroid hormone secreted by the adrenal gland. Hydrocortisone replaces the natural cortisol that is missing in patients with adrenal insufficiency. It has been used in medicines for several decades.Because it is available as a modified-release tablet, Plenadren releases hydrocortisone over a longer period of time allowing for a once-daily dosing. It is taken early in the morning to mimic the fact that in healthy people the blood level of cortisol increases early in the morning.

What benefits of Plenadren have been shown in studies?

The effects of Plenadren were investigated in one main study involving 64 patients with adrenal insufficiency. Plenadren, given once per day, was compared with conventional hydrocortisone treatment, which is given three times per day. The study looked at the levels of cortisol in the patients' blood during a 24-hour period following three months of treatment. In patients taking Plenadren the cortisol levels achieved were considered to be satisfactory for patients with adrenal insufficiency. The overall amount of cortisol absorbed into the blood was around 20% lower in patients taking Plenadren compared with patients taking conventional hydrocortisone treatment.

What are the risks associated with Plenadren?

The most common side effects with Plenadren (seen in more than 1 patient in 10) are fatigue (tiredness), diarrhoea, vertigo (feeling dizzy) and headache.For the full list of all side effects and restrictions with Plenadren, see the package leaflet.

Why is Plenadren approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) noted that Plenadren achieved satisfactory levels of cortisol during the treatment of patients with adrenal insufficiency. TheCommittee also noted that with Plenadren there is the convenience of once daily dosing. Although once daily dosing comes with a risk of cortisol levels being too low in the afternoon, this can be managed by adding further doses of hydrocortisone if needed.The CHMP concluded that the benefits of Plenadren were greater than its risks and recommended that it be granted marketing authorisation.

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

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

---

Plerixafor Accord

What is Plerixafor Accord and what is it used for?

Plerixafor Accord is a medicine used to mobilise blood stem cells from a patient's bone marrow so that they can be collected and used later for transplantation in the same patient.Plerixafor Accord is used together with the hormone granulocyte-colony stimulating factor (G-CSF) and is intended only for patients in whom collection of stem cells is difficult.The patients who are given Plerixafor Accord are:• adults with lymphoma or multiple myeloma (types of blood cancer);• children from 1 year of age who have lymphoma or solid tumours.Plerixafor Accord is a 'generic medicine'. This means that Plerixafor Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU. The reference medicine for Plerixafor Accord is Mozobil. For more information on generic medicines, see the question-and-answer document here.Plerixafor Accord contains the active substance plerixafor.

How is Plerixafor Accord used?

Plerixafor Accord is given as an injection under the skin. It can only be obtained with a prescription and treatment should only be started and supervised by a doctor who has experience in treating cancer or blood disorders. After the patient has been given Plerixafor Accord, their stem cells are extracted from the blood and stored before transplantation. Because of this, treatment should be carried out in collaboration with a specialised centre that has experience with this type of procedure and can monitor the stem cells.Plerixafor Accord is used together with G-CSF. G-CSF is used on its own for 4 days before Plerixafor Accord is started. Plerixafor Accord is given 6 to 11 hours before the patient's blood is taken and the stem cells are extracted. It can be used for up to 7 consecutive days. The dose depends on the bodyweight of the patient.For more information about using Plerixafor Accord, see the package leaflet or contact your doctor or pharmacist.Send

How does Plerixafor Accord work?

Plerixafor Accord is used to mobilise the stem cells from the bone marrow so they can be released into the blood. The active substance in Plerixafor Accord, plerixafor, works by blocking the activity of a protein called 'CXCR4 chemokine receptor'. This protein normally helps to keep stem cells within the bone marrow. By blocking its activity, Plerixafor Accord allows the stem cells to be released into the blood, so that they can be collected.

How has Plerixafor Accord been studied?

Studies on the benefits and risks of the active substance in the authorised use have already been carried out with the reference medicine, Mozobil, and do not need to be repeated for Plerixafor Accord.As for every medicine, the company provided studies on the quality of Plerixafor Accord. There was no need for 'bioequivalence' studies to investigate whether Plerixafor Accord is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because the composition of Plerixafor Accord is very similar to the reference medicine and when given by injection under the skin, the active substance in both products is expected to be absorbed in the same way.

What are the benefits and risks of Plerixafor Accord?

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

Why is Plerixafor Accord authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Plerixafor Accord has been shown to be comparable to Mozobil. Therefore, the Agency's view was that, as for Mozobil, the benefits of Plerixafor 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 Plerixafor Accord?

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

---

Pluvicto

What is Pluvicto and what is it used for?

Pluvicto is a medicine used to treat cancer of the prostate (a gland of the male reproductive system). It is used when the cancer is metastatic (spreading to other parts of the body), progressive, castration-resistant (worsens despite treatment to lower levels of the male sex hormone testosterone), and the cancer cells have a protein called prostate-specific membrane antigen (PSMA) on their surface (PSMA-positive prostate cancer).Pluvicto is used together with androgen deprivation therapy (treatment to lower male sex hormones) in adults previously treated with androgen receptor pathway inhibitors (medicines for prostate cancer), and a medicine of the group of cancer medicines known as taxanes. Androgen receptor pathway inhibitors may also be added to Pluvicto and androgen deprivation therapy.Pluvicto is a radiopharmaceutical (a medicine that gives off a small amount of radioactivity) that contains the active substance lutetium (177Lu) vipivotide tetraxetan.

How is Pluvicto used?

Because Pluvicto gives off some radioactivity, it is only used in special controlled areas and must be given to patients by healthcare professionals qualified and authorised to use radiopharmaceuticals.Before starting treatment, the doctor will check that the patient's tumours have PSMA on their cell surfaces with a positron emission tomography (PET) scan.Pluvicto is given by injection or infusion (drip) into a vein once every 6 weeks for up to a total of 6 doses.Blood tests will be done before and during treatment to detect certain side effects early. Based on the results of these tests and any side effects the patient may develop, the doctor may decide to delay, change or stop treatment with Pluvicto.For more information about Pluvicto, including precautions that should be taken to limit radioactivity exposure to patients and people around them, see the package leaflet or contact your doctor or pharmacist.

How does Pluvicto work?

Pluvicto works by attaching to the PSMA protein found on the surface of the prostate cancer cells. The radioactivity it emits kills the tumour cells it is attached to but has little effect on neighbouring cells.

What benefits of Pluvicto have been shown in studies?

Pluvicto was shown to be effective at increasing the time patients live without their cancer getting worse and the time they live overall.In a main study involving 831 patients with progressive, metastatic, castration-resistant and PSMApositive prostate cancer, 551 patients were treated with Pluvicto together with other treatments for prostate cancer (best standard of care) and 280 were given standard of care only. The study showed that patients given Pluvicto lived for 8.7 months on average without their cancer getting worse, compared with 3.4 months on average for those treated with standard of care only. In addition, on average, patients treated with Pluvicto lived 15.3 months, while those receiving standard of care lived for 11.3 months.

What are the risks associated with Pluvicto?

The most common side effects with Pluvicto (which may affect more than 1 in 10 people) are tiredness, dry mouth, nausea (feeling sick), anaemia (low levels of red blood cells), decreased appetite and constipation.The most common serious side effects (which may affect up to 1 in 20 people) are anaemia, thrombocytopenia (low levels of blood platelets), lymphopenia (low levels of lymphocytes, a type of white blood cell) and tiredness.For the full list of side effects and restrictions of Pluvicto, see the package leaflet.

Why is Pluvicto authorised in the EU?

Pluvicto has been shown to increase both the time people with progressive, metastatic, castrationresistant and PSMA-positive prostate cancer live without their disease getting worse and the time they live overall. Although treatment with Pluvicto may cause more side effects than standard of care, they are considered manageable. The European Medicines Agency also noted the limited treatment options available for patients with this type of cancer. The Agency therefore decided that Pluvicto'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 Pluvicto?

The company that markets Pluvicto will ensure that patient given this medicine have access to a patient guide containing important information on the risk of radioactivity and precautions they should take to limit exposure to themselves and people around them.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pluvicto have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Pluvicto are continuously monitored. Suspected side effects reported with Pluvicto are carefully evaluated and any necessary action taken to protect patients.

---

Polivy

What is Polivy and what is it used for?

Polivy is a cancer medicine used to treat adults with diffuse large B-cell lymphoma (DLBCL) whose cancer has returned or has stopped responding to other treatments and who cannot have a bonemarrow transplantation.It is used in combination with two other medicines, bendamustine and rituximab.DLBCL is rare, and Polivy was designated an 'orphan medicine' (a medicine used in rare diseases) on 16 April 2018. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu3182013.Polivy contains the active substance polatuzumab vedotin.

How is Polivy used?

Polivy can only be obtained with a prescription, and treatment must be given under the supervision of a healthcare professional experienced in the diagnosis and treatment of cancer.Polivy is for infusion (drip) into a vein over 90 minutes. It is given in 21-day cycles with rituximab and bendamustine. The dose of Polivy depends on the patient's bodyweight and is given for 6 cycles.Patients are given paracetamol and an antihistamine medicine before receiving Polivy to reduce the risk of reactions to the infusion. If the patient develops an infusion-related reaction, the infusion should be slowed down or interrupted. The doctor may reduce or stop the dose of Polivy if the patient develops side effects affecting blood cells.For more information about using Polivy, see the package leaflet or contact your doctor or pharmacist.

How does Polivy work?

Patients with DLBCL have cancerous B cells, which are a type of white blood cell. The active substance in Polivy, polatuzumab vedotin, is made up of a monoclonal antibody (a type of protein) combined with a substance called monomethyl auristatin E (MMAE). The monoclonal antibody attaches to a protein called CD79b on B cells, including cancerous B cells, and in doing so causes MMAE to be released inside them. MMAE then stops the B cells from dividing and causes them to die.

What benefits of Polivy have been shown in studies?

Polivy was investigated in a study involving 80 patients with DLBCL. Half of the patients received Polivy added to the standard regimen of bendamustine plus rituximab whereas the other half received bendamustine plus rituximab alone. After 6 to 8 weeks of treatment, there were no signs of the cancer (complete response) in 40% of patients receiving Polivy plus rituximab and bendamustine compared with 18% of patients receiving rituximab and bendamustine alone.

What are the risks associated with Polivy?

Polivy can affect the production of blood cells. The most common side effects with Polivy in combination with bendamustin and rituximab (which may affect more than 3 in 10 people) were anaemia (low red blood cell count), thrombocytopenia (low blood platelet count), neutropenia (low white blood cell count), tiredness, diarrhoea, nausea (feeling sick) and fever. Serious side effects (which may affect up to 1 in 10 people) include febrile neutropenia (low white blood cell count with fever), fever, and pneumonia (infection of the lungs).The medicine must not be given to patients who have a severe infection. For the full list of side effects and restrictions of Polivy, see the package leaflet.

Why is Polivy authorised in the EU?

The main study showed that Polivy is effective at treating patients whose disease was not responding to previous treatment or had returned and who could not have a transplant. Although the study included a limited number of patients and more data are needed to confirm the results, the European Medicines Agency considered that Polivy meets an unmet medical need.Serious side effects can occur; however, these are manageable if appropriate measures are in place. The Agency therefore decided that Polivy's benefits are greater than its risks and it can be authorised for use in the EU.Polivy has been given a '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 Polivy?

Since Polivy has been given conditional authorisation, the company that markets Polivy will provide further data on its effects to confirm Polivy's safety and effectiveness when used in combination with other cancer medicines in patients with DLBCL.

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

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

---

Pombiliti

What is Pombiliti and what is it used for?

Pombiliti is a medicine used to treat adults with late-onset Pompe disease (acid alpha-glucosidase [GAA] deficiency), an inherited disorder in which patients have breathing difficulties and muscle weakness. Pombiliti is used in combination with another medicine, miglustat.Pombiliti contains the active substance cipaglucosidase alfa.

How is Pombiliti used?

Pombiliti is given by infusion (drip) into a vein every other week. The infusion starts 1 hour after taking miglustat and lasts 4 hours. Pombiliti may be given at home in patients who tolerate their infusions well.The medicine can only be obtained with a prescription and treatment should be supervised by a physician experienced in the management of patients with Pompe disease or similar diseases.For more information about using Pombiliti, see the package leaflet or contact your doctor or pharmacist.

How does Pombiliti work?

Patients with Pompe disease lack an enzyme called acid alpha-glucosidase (GAA) which is important for breaking down glycogen (a complex sugar stored in the body) into glucose (a simple sugar). As a result, glycogen accumulates in the muscles, including the heart and diaphragm (the main breathing muscle under the lungs), causing heart problems, breathing difficulties and muscle weakness.The active substance in Pombiliti, cipaglucosidase alfa, is an enzyme that acts in the same way as the missing GAA enzyme (i.e. breaking down glycogen into glucose). It replaces GAA and prevents further damage caused by the build-up of glycogen. Pombiliti is given in combination with miglustat, an enzyme stabilizer which helps cipaglucosidase alfa to stay functional.

What benefits of Pombiliti have been shown in studies?

A main study involving 125 patients showed that Pombiliti in combination with miglustat improved the physical abilities of patients with late-onset Pompe disease. The study looked at changes in the distance patients were able to walk before and after treatment. On average, patients treated with Pombiliti and miglustat for 1 year were able to walk 20 more metres in 6 minutes than they could before treatment.

What are the risks associated with Pombiliti?

The most common side effects with Pombiliti (which may affect up to 1 in 10 people) are chills, dizziness, flushing, sleepiness, chest discomfort, cough, swelling at the infusion site and pain.Serious side effects (which may affect up to 1 in 50 people) are itchy rash, serious allergic reactions, fever, feeling faint, difficulty breathing, swelling in the throat, wheezing and low blood pressure.Pombiliti must not be used in people who have had life-threatening allergic reactions to the active substance or to any of the other ingredients of the medicine. It must also not be used in people who cannot have miglustat.For the full list of side effects and restrictions, see the package leaflet.

Why is Pombiliti authorised in the EU?

Pompe disease is a rare and debilitating disease, with patients having life-threatening heart and respiratory problems. Studies show that, when given in combination with miglustat, Pombiliti is effective at improving or stabilising the physical abilities of patients with late-onset Pompe disease. The side effects of Pombiliti, which are mostly mild to moderate, are considered manageable. The European Medicines Agency therefore decided that the benefits of Pombiliti 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 Pombiliti?

The company that markets Pombiliti will provide educational materials on home infusion to healthcare professionals who are expected to prescribe, dispense or use Pombiliti. They are intended to provide guidance on how Pombiliti and miglustat should be given to the patients and how to manage risks related to the infusion, such as allergic reactions. Patients will also be provided with a guide on home infusion and an infusion diary to help recognise and report infusion reactions.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pombiliti and miglustat have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Pombiliti in combination with miglustat are continuously monitored. Suspected side effects reported with Pombiliti are carefully evaluated and any necessary action taken to protect patients.

---

Ponvory

What is Ponvory and what is it used for?

Ponvory is a medicine for treating adults with relapsing active forms of multiple sclerosis.Multiple sclerosis is a disease of the brain and spinal cord in which inflammation attacks the protective covering (sheath) around nerves and damages the nerves themselves.Ponvory contains the active substance ponesimod.

How is Ponvory used?

Ponvory is available as tablets. For the first two weeks, the patient takes tablets once daily with the dose increasing from 2 mg to 10 mg. After two weeks the patient takes a single 20 mg tablet once a day.The medicine can only be obtained with a prescription. Treatment is started under the supervision of a doctor experienced in managing multiple sclerosis. For more information, including about the dosing, see the package leaflet or contact your doctor or pharmacist.

How does Ponvory work?

In multiple sclerosis, the immune system (the body's natural defences) incorrectly attacks the protective sheath around the nerves and the nerves themselves in the brain and spinal cord.The active substance in Ponvory, ponesimod, blocks T cells and B cells (two types of white blood cells involved in the immune system) inside the lymph nodes. Ponesimod does this by binding to a target (receptor), called the sphingosine-1-phosphate receptor, on the surface of T cells and B cells, which the cells need to leave the lymph nodes. By blocking these cells in the lymph nodes, Ponvory prevents them from traveling towards the brain and spinal cord, thus limiting the damage they cause in patients with multiple sclerosis.

What benefits of Ponvory have been shown in studies?

A main study involving 1,133 adults with relapsing forms of multiple sclerosis showed that Ponvory was more effective than another multiple sclerosis medicine, teriflunomide, at reducing the number ofrelapses (flare-ups). After two years of treatment, the average number of relapses a year in patients taking Ponvory was 0.2 compared with 0.3 in patients taking teriflunomide. The average number of relapses in a year was reduced by about a third in patients taking Ponvory compared with patients taking teriflunomide.

What are the risks associated with Ponvory?

The most common side effects of Ponvory (which may affect more than 1 in 10 people) are infections of the nose and throat and increased levels of liver enzymes. For the full list of side effects of Ponvory, see the package leaflet.Ponvory must not be used in patients who have recently experienced certain heart problems or stroke and in patients with problems with heart rhythm, severely weakened immune system, severe or longterm infections, cancer, or moderate or severe liver problems. It must also not be taken during pregnancy or by women who can have children and are not using effective contraception. For the full list of restrictions, see the package leaflet.

Why is Ponvory authorised in the EU?

A main study showed that Ponvory was more effective than teriflunomide at reducing the number of relapses in patients with relapsing forms of multiple sclerosis. The side effects that occur with Ponvory are similar to those seen with medicines of the same class and are considered manageable.The European Medicines Agency therefore decided that Ponvory'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 Ponvory?

The company that markets Ponvory must distribute educational material for healthcare professionals and patients with information on the use of the medicine, such as dosing, monitoring and tests to be carried out before treatment. The company will also provide information about avoiding pregnancy while taking Ponvory.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ponvory have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Ponvory are continuously monitored. Side effects reported with Ponvory are carefully evaluated and any necessary action taken to protect patients.

---

Posaconazole Accord

What is Posaconazole Accord and what is it used for?

Posaconazole Accord is an antifungal medicine used to treat adults with the following fungal diseases, when treatments with other antifungal medicines (amphotericin B, itraconazole or fluconazole) cannot be tolerated or have failed:• invasive aspergillosis (fungal infection caused by Aspergillus),• fusariosis (fungal infection caused by Fusarium),• chromoblastomycosis and mycetoma (long-term fungal infections of the skin or the tissue just below the skin, usually caused by fungal spores infecting wounds due to thorns or splinters),• coccidioidomycosis (fungal infection of the lungs caused by breathing in spores).Posaconazole Accord is also used to prevent invasive fungal infections in patients whose immune system is weakened because of treatments they are receiving for blood or bone marrow cancers or medicines used in haematopoietic stem cell transplantation (a procedure where the patient's bone marrow is replaced by stem cells from a donor to form new bone marrow).Posaconazole Accord contains the active substance posaconazole and is a 'generic medicine'. This means that Posaconazole Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Noxafil. For more information on generic medicines, see the question-and-answer document here.

How is Posaconazole Accord used?

Posaconazole Accord can only be obtained with a prescription and treatment should be started by adoctor who has experience in managing fungal infections or in treating patients at high risk of invasive fungal infections.Posaconazole Accord is available as gastro-resistant tablets (100 mg). Gastro-resistant means that the tablets pass through the stomach without being broken down until they reach the intestine.The recommended dose is 300 mg twice a day on the first day followed by 300 mg once a day thereafter; the duration of treatment depends on the severity of the disease and the patient's response.SendFor more information about using Posaconazole Accord, see the package leaflet or contact your doctor or pharmacist.

How does Posaconazole Accord work?

The active substance in Posaconazole Accord, posaconazole, is an antifungal medicine that belongs to the triazole group. It works by preventing the formation of ergosterol, which is an important part of fungal cell walls. Without ergosterol, the fungus dies or is prevented from spreading. The list of fungi Posaconazole Accord is active against can be found in the summary of product characteristics.

How has Posaconazole 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, Noxafil, and do not need to be repeated for Posaconazole Accord.As for every medicine, the company provided studies on the quality of Posaconazole 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 Posaconazole Accord?

Because Posaconazole 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 Posaconazole Accord authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, PosaconazoleAccord has been shown to have comparable quality and to be bioequivalent to Noxafil. Therefore, the Agency's view was that, as for Noxafil, the benefit of Posaconazole Accord outweighs the identified risk and it can be authorised for use in the EU.

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

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

---

Posaconazole Ahcl

What is Posaconazole AHCL and what is it used for?

Posaconazole AHCL is an antifungal medicine used to treat adults with the following fungal diseases, when treatments with other antifungal medicines (amphotericin B, itraconazole or fluconazole) cannot be tolerated or have failed:• invasive aspergillosis (fungal infection caused by Aspergillus),• fusariosis (fungal infection caused by Fusarium),• chromoblastomycosis and mycetoma (long-term fungal infections of the skin or the tissue just below the skin, usually caused by fungal spores infecting wounds due to thorns or splinters),• coccidioidomycosis (fungal infection of the lungs caused by breathing in spores).Posaconazole AHCL is also used as a first-line treatment for 'thrush', a fungal infection of the mouth and throat due to Candida. It is used in patients whose infection is severe or in patients with weakened immune systems, when medicines applied topically (directly on the thrush) are unlikely to work.Posaconazole AHCL is also used to prevent invasive fungal infections in patients whose immune system is weakened because of treatments they are receiving for blood or bone marrow cancers or medicines used in haematopoietic stem cell transplantation (a procedure where the patient's bone marrow is replaced by stem cells from a donor to form new bone marrow).Posaconazole AHCL contains the active substance posaconazole and is a 'generic medicine'. This means that Posaconazole AHCL contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Noxafil. For more information on generic medicines, see the question-and-answer document here.

How is Posaconazole AHCL used?

Posaconazole AHCL can only be obtained with a prescription and treatment should be started by adoctor who has experience in managing fungal infections or in treating patients at high risk of invasive fungal infections.Posaconazole AHCL is available as an oral suspension (40 mg/ml) which is taken with a meal or nutritional supplement.SendFor the treatment of fungal infections, with the exception of thrush, Posaconazole AHCL is taken at a dose of 400 mg (10 ml) twice a day, or 200 mg (5 ml) four times a day in patients who are not eating. The duration of treatment depends on the severity of the disease and the patient's response. For thrush, Posaconazole AHCL is taken as 200 mg (5 ml) on the first day followed by 100 mg (2.5 ml) once a day for the following 13 days. For the prevention of invasive fungal infections, Posaconazole AHCL is taken at a dose of 200 mg (5 ml) three times a day. The duration of treatment depends on the patient's condition.For more information about using Posaconazole AHCL, see the package leaflet or contact your doctor or pharmacist.

How does Posaconazole AHCL work?

The active substance in Posaconazole AHCL, posaconazole, is an antifungal medicine that belongs to the triazole group. It works by preventing the formation of ergosterol, which is an important part of fungal cell walls. Without ergosterol, the fungus dies or is prevented from spreading. The list of fungi posaconazole is active against can be found in the summary of product characteristics.

How has Posaconazole AHCL 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, Noxafil, and do not need to be repeated for Posaconazole AHCL.As for every medicine, the company provided studies on the quality of Posaconazole AHCL. 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 Posaconazole AHCL?

Because Posaconazole AHCL 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 Posaconazole AHCL authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, PosaconazoleAHCL has been shown to have comparable quality and to be bioequivalent to Noxafil. Therefore, the Agency's view was that, as for Noxafil, the benefit of Posaconazole AHCL outweighs the identified risk and it can be authorised for use in the EU.

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

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

---

Potactasol

What is Potactasol?

Potactasol is a medicine that contains the active substance topotecan. It is available as a powder to be made up into a solution for infusion (drip) into a vein.Potactasol is a 'generic medicine'. This means that Potactasol is similar to a 'reference medicine' already authorised in the European Union (EU) called Hycamtin. For more information on generic medicines, see the question-and-answer document here.

What is Potactasol used for?

Potactasol is a cancer medicine. It is used on its own to treat patients with:• metastatic cancer of the ovary (when the cancer has spread to other parts of the body). It is used after at least one other treatment has failed;• small cell lung cancer, when the cancer has relapsed (come back). It is used when giving the original treatment again is not recommended.It is also used together with cisplatin (another cancer medicine) to treat women with cancer of the cervix, when the cancer has come back after radiotherapy, or when the disease is at an advanced stage (the cancer has spread beyond the cervix).The medicine can only be obtained with a prescription.

How is Potactasol used?

Treatment with Potactasol should only be given under the supervision of a doctor experienced in the use of chemotherapy. Infusions should be carried out in a specialised cancer ward.The dose of Potactasol to be used depends on the type of cancer that it is being used to treat and the patient's weight and height. When Potactasol is used on its own for ovarian cancer, it is given by infusion over 30 minutes. For both ovarian and lung cancer, Potactasol is given every day for five days with a three-week interval between the start of each course. Treatment may continue until the disease gets worse.When used with cisplatin in cervical cancer, Potactasol is given as an infusion on days 1, 2 and 3 (with cisplatin given on day 1). This is repeated every 21 days for six courses or until the disease gets worse.Doses of Potactasol may need to be adjusted or treatment delayed, depending on side effects. For full details, see the summary of product characteristics, also part of the EPAR.

How does Potactasol work?

The active substance in Potactasol, topotecan, is a cancer medicine that belongs to the group'topoisomerase inhibitors'. It blocks an enzyme called topoisomerase I, which is involved in the division of DNA. When the enzyme is blocked, the DNA strands break. This prevents the cancer cells from dividing and they eventually die. Potactasol also affects non-cancer cells, which causes side effects.

How has Potactasol been studied?

The company has provided data from the published literature on topotecan. No additional studies were needed as Potactasol is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Hycamtin.

What are the benefits and risks of Potactasol?

Because Potactasol 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 Potactasol been approved?

The CHMP concluded that, in accordance with EU requirements, Potactasol has been shown to be comparable to Hycamtin. Therefore, the CHMP's view was that, as for Hycamtin, the benefit outweighs the identified risk. The Committee recommended that Potactasol be given marketing authorisation.

---

Poteligeo

What is Poteligeo and what is it used for?

Poteligeo is a cancer medicine used to treat mycosis fungoides and Sezary syndrome - two cancers of blood cells that affect mainly the skin. It is used in patients who have received previous treatment by mouth or injection.Both mycosis fungoides and Sezary syndrome belong to a group of rare cancers (cutaneous T-cell lymphomas), and Poteligeo was designated an 'orphan medicine' (a medicine used in rare diseases) on 14 October 2016. Further information on the orphan designation can be found here: ema.europa.eu/Find medicine/Human medicines/Rare disease designation Poteligeo contains the active substance mogamulizumab.

How is Poteligeo used?

Poteligeo can only be obtained with a prescription and treatment should be supervised by a doctor who has experience in the treatment of cancer and in a place where equipment for resuscitation is available in case of rare and severe allergic reaction to the medicine.The medicine is given as an infusion (drip) into a vein lasting at least 1 hour. The recommended dose depends on the patient's body weight and is given once a week for the first 4 weeks and then every 2 weeks. Patients should be monitored during and after the infusion for certain side effects related to the infusion. To reduce this risk, patients may be given other medicines such as an antipyretic (medicine that reduces fever) and an antihistamine (for treating allergic reactions) before or during treatment with Poteligeo.The doctor may interrupt or stop treatment, or reduce the dose, if the patient develops certain serious side effects.For more information about using Poteligeo, see the package leaflet or contact your doctor or pharmacist.

How does Poteligeo work?

The active substance in Poteligeo, mogamulizumab, is a monoclonal antibody (a type of protein) that has been designed to attach to a receptor (target) called CCR4. CCR4 is found on the surface of white blood cells, including the cancerous cells in mycosis fungoides or Sezary syndrome. By attaching to CCR4, mogamulizumab stimulates the body's immune system to attack the cancer cells, helping to control the disease.

What benefits of Poteligeo have been shown in studies?

Poteligeo was shown to be more effective than a comparator medicine, vorinostat, in a study of 372 adults with either mycosis fungoides or Sezary syndrome. In this study, patients receiving Poteligeo lived for around 8 months without their disease getting worse compared with 3 months for patients on vorinostat.In all patients the cancer did not respond to a previous treatment or had come back.

What are the risks associated with Poteligeo?

The most common side effects with Poteligeo (seen in more than 1 patient in 10) are infusion-related reactions and rash. The most commonly reported serious reactions are pneumonia (infection of the lungs), fever, infusion-related reactions and cellulitis (inflammation of the deep skin tissue).For the full list of side effects and restrictions with Poteligeo, see the package leaflet.

Why is Poteligeo authorised in the EU?

Poteligeo is effective at prolonging the time patients with mycosis fungoides or Sezary syndrome live without their disease getting worse. Effects are clinically relevant considering that patients have limited treatment options. The side effects seen with Poteligeo are considered manageable and most of them are mild or moderate. The European Medicines Agency therefore decided that Poteligeo'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 Poteligeo?

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

---

Pradaxa

What is Pradaxa and what is it used for?

Pradaxa is an anticoagulant medicine used for:• preventing the formation of blood clots in the veins in adults who have had an operation to replace a hip or knee;• preventing stroke (caused by a blood clot in the brain) and systemic embolism (a blood clot in another organ) in adults who have an abnormal heartbeat called 'non-valvular atrial fibrillation' and are considered to be at risk of stroke;• treating deep vein thrombosis (DVT, a blood clot in a deep vein, usually in the leg) and pulmonary embolism (PE, a clot in a blood vessel supplying the lungs) in adults, and preventing these conditions from occurring again.• treating blood clots in veins and preventing them from occurring again in children Pradaxa contains the active substance dabigatran etexilate.

How is Pradaxa used?

Pradaxa is taken by mouth and it is available as capsules for adults and children above 8 years of age, granules for children less than 12 years of age and a powder and solvent to be made into a solution to drink for children less than 1 year of age. Pradaxa can only be obtained with a prescription. The dose and duration of treatment depend on the condition Pradaxa is being used to treat, the patient's age and kidney function, and other medicines the patient is taking. For children the dose also depends on their weight.When changing between the different forms of the medicine, the doctor may need to alter the dose. All patients at increased risk of bleeding should be monitored closely and the doctor may reduce the dose of Pradaxa.In all patients, kidney function should also be assessed before starting treatment to exclude patients with severely reduced kidney function, and should be re-assessed during treatment if any worsening is suspected. When Pradaxa is used long term in patients with non-valvular atrial fibrillation, or when it is used in patients with DVT or PE, kidney function should be assessed at least once a year if their kidney function is mildly to moderately reduced or if they are over 75 years old.For more information about using Pradaxa, see the package leaflet or contact your doctor or pharmacist.

How does Pradaxa work?

The active substance in Pradaxa, dabigatran etexilate, is a 'prodrug' of dabigatran. This means that it is converted into dabigatran in the body. Dabigatran is an anticoagulant, meaning that it prevents the blood from coagulating (clotting). It blocks a substance called thrombin, which is central to the process of blood clotting.

What benefits of Pradaxa have been shown in studies?

Prevention of blood clots after hip or knee replacementPradaxa (220 or 150 mg a day) was as effective as enoxaparin (an anticoagulant given by injection) in preventing formation of blood clots or death in patients who had undergone hip or knee replacement in two main studies.The first study involved a total of 2,101 patients who had had a knee replacement operation. During the treatment period, blood clots were detected in 36% of the patients taking 220 mg Pradaxa (183 out of 503), compared with 38% of the patients receiving enoxaparin (193 out of 512). There was one death in each group (less than 1%).The second study involved a total of 3,494 patients who had had a hip replacement. During the treatment period, blood clots were detected in 6% of the patients taking 220 mg Pradaxa (53 out of880), compared with 7% of the patients receiving enoxaparin (60 out of 897). Three patients in the Pradaxa group died (less than 1%), but two of these deaths were unrelated to blood clots.In both studies, there was some evidence that a 220 mg dose of Pradaxa may be more effective than a 150 mg dose.Prevention of blood clots or stroke in patients at risk of strokePradaxa (110 mg or 150 mg twice a day) was as effective as warfarin (another anticoagulant given by mouth) in preventing stroke or a blood clot blocking blood vessels in other parts of the body in a study of patients with non-valvular atrial fibrillation who were considered to be at risk of stroke.In the study, around 18,000 adults were treated for one to three years. The proportion of patients who had a stroke or other problems caused by blood clots each year was around 1.5% for patients taking 110 mg Pradaxa (183 patients out of 6,015) and 1.1% for patients taking 150 mg Pradaxa (135 out of 6,076), compared with 1.7% for patients taking warfarin (203 out of 6,022).Treatment and prevention of DVT and PEPradaxa was as effective as warfarin in reducing formation of blood clots in the veins (DVT) or lungs (PE), or blood-clot-related death during treatment.Two main studies in over 5,100 adults with symptoms of DVT or PE, and who were initially treated with an injectable anticoagulant, compared Pradaxa with warfarin. Blood clots or blood-clot-related death occurred in 2.7% (68 out of 2,553) of patients treated with Pradaxa, compared with 2.4% (62 out of 2,554) of patients treated with warfarin.Another two studies looked at the prevention of VTE or PE in around 4,200 adults with symptoms of recurring blood clots and who were on long-term treatment with anticoagulants. One of these studiescompared Pradaxa with warfarin and the other compared Pradaxa with placebo (a dummy treatment). In the first study, blood clots or blood-clot-related death occurred in 1.8% (26 out of 1,430) of patients treated with Pradaxa, compared with 1.3% (18 out of 1,426) of patients treated with warfarin. In the second study, blood clots or blood-clot-related death occurred in 0.4% (3 out of 681) of patients treated with Pradaxa, compared with 5.6% (37 out of 662) of patients treated with placebo.In a study in 267 children with confirmed DVT or PE aged from birth to 18 years of age, Pradaxa was compared with standard of care. Treatment with Pradaxa resolved blood clots in 46% of patients compared with 42% of patients treated with standard of care. Blood clots did not recur in 96% of patients taking Pradaxa compared with 92% of patients treated with standard of care.

What are the risks associated with Pradaxa?

The most common side effect with Pradaxa (which may affect more than 1 in 10 people) is bleeding. Pradaxa must not be used in adults who have severely reduced kidney function, or children with moderately or severely reduced kidney function. It must also not be used in patients who are currently bleeding significantly or who have a condition putting them at significant risk of major bleeding. It must not be used in patients taking any other anticoagulant medicine, except when the anticoagulant medicine is being switched or when heparin (another anticoagulant medicine) is being used in specific medical procedures. Pradaxa must also not be used in patients with serious liver problems, in those with artificial heart valves or in patients being treated with certain medicines. For the full list of side effects and restrictions of Pradaxa, see the package leaflet.

Why is Pradaxa authorised in the EU?

The effect of Pradaxa in preventing blood clots in adults who have undergone a hip or knee replacement is comparable to that of enoxaparin. Blood clots occur rarely in children and treatment has involved injection of anticoagulant medicines. Pradaxa, which is taken by mouth, is more convenient for adults and children. Pradaxa compared well with warfarin in reducing the risk of strokes in adults with atrial fibrillation without increasing the risk of major bleeding. Since certain patients who take Pradaxa are at increased risk of bleeding, a number of precautions were included in the prescribing information.In addition, the overall benefit of Pradaxa in the treatment and prevention of DVT and PE is comparable to that of warfarin. However, the number of bleeding events was lower for Pradaxa than for warfarin. Although the studies showed a small higher risk of heart problems with Pradaxa than with warfarin, the benefits of Pradaxa were still considered to outweigh its risks. Therefore, the European Medicines Agency decided that Pradaxa'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 Pradaxa?

The company that makes Pradaxa will provide an educational pack for all doctors who are expected to prescribe the medicine, to increase awareness of the risk of bleeding and provide guidance on how to manage it. Patients will also receive an alert card summarising key safety information on the medicine. The company will also provide a training video and technical support by phone for the preparation and dosing of the solution.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pradaxa have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Pradaxa are continuously monitored. Side effects reported with Pradaxa are carefully evaluated and any necessary action taken to protect patients.

---

Praluent

What is Praluent and what is it used for?

Praluent is a medicine for lowering levels of fat in the blood.It is used to reduce fat levels in adults with primary hypercholesterolaemia (high levels of blood cholesterol without an identifiable cause, often resulting from the person's genetic makeup) and mixed dyslipidaemia (abnormal levels of different fats in the blood, including cholesterol).It is also used to reduce the risk of heart problems and strokes in patients who have atherosclerotic cardiovascular disease (heart problems such as heart attack, stroke or other problems of the circulatory system caused by fatty deposits build up in the walls of the arteries).Praluent is used in combination with a statin or a statin and other fat-lowering medicines. Praluent can also be used without a statin in patients who cannot take statins. Some patients are required to be on a low fat diet.It contains the active substance alirocumab.

How is Praluent used?

Before starting treatment with Praluent, other causes of excess cholesterol and abnormal fat levels in the blood should be excluded. The medicine can only be obtained with a prescription.Praluent is available as a solution for injection in a pre-filled syringe or pre-filled pen (75 mg, 150 mg and 300 mg). The injection is given under the skin of the abdomen, thigh or upper arm.The usual starting dose is 75 mg every two weeks, but patients requiring bigger reductions of blood fat levels may start with 150 mg every two weeks or 300 mg every 4 weeks. The dose of Praluent is adjusted based on the levels of fats in blood and response to the medicine. If the desired response is not achieved after 4 to 8 weeks of treatment, the doctor can increase or decrease the dose.Patients or their carers can inject the medicine once they have been trained by a healthcare professional. For more information about using Praluent, see the package leaflet or contact your doctor or pharmacist.

How does Praluent work?

The active substance in Praluent, alirocumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a specific enzyme called PCSK9. This enzyme attaches to cholesterol receptors on the surface of liver cells and causes these receptors to be absorbed and broken down inside the cells. These receptors control blood levels of cholesterol, especially LDLcholesterol, by removing it from the bloodstream. By attaching and blocking PCSK9, Praluent prevents the receptors from being broken down inside cells and therefore increases the number of these receptors on the cell surface, where they can attach to LDL-cholesterol and remove it from the bloodstream. This helps to reduce the amount of LDL-cholesterol in the blood. Alirocumab also helps to reduce other fatty substances from blood in patients with mixed dyslipidaemia.

What benefits of Praluent have been shown in studies?

Hypercholesterolaemia and mixed dyslipidaemiaPraluent has been studied in 10 main studies involving over 5,000 adult patients with hypercholesterolaemia (including patients with heterozygous familial disease) and mixed dyslipidaemia. Some studies looked at Praluent taken on its own, while others studied Praluent in combination with other fat-lowering medicines, including patients on the maximum recommended doses of statins. Some studies compared Praluent with placebo (a dummy treatment) and others to another medicine for hypercholesterolaemia (ezetimibe). These studies showed that when Praluent was given on top of a statin it led to a substantial reduction in blood levels of LDL-cholesterol (between 39 and 62% more than placebo) after 6 months of treatment. When given on top of standard treatment or on its own, Praluent produced a 24 to 36% greater reduction in blood levels of LDL-cholesterol than ezetimibe.Atherosclerotic heart diseaseIn a study involving over 18,000 patients who had established heart disease, less than 10% of patients given Praluent had a cardiovascular event (meaning death, heart attack, stroke, chest pain due to problems with the blood flow to the heart leading to hospitalisation) during the study compared with over 11% of patients given placebo.

What are the risks associated with Praluent?

The most common side effects with Praluent (which may affect up to 1 in 10 people) are injection site reactions such as pain and redness, problems affecting the nose and throat such as colds, and itching.The most common side effects leading to treatment discontinuation were local injection site reactions.For the full list of side effects and restrictions, see the package leaflet.

Why is Praluent authorised in the EU?

The European Medicines Agency decided that Praluent'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, including patients on maximum recommended doses of statins or those intolerant to them, treatment with Praluent led to a significant reduction in LDLcholesterol levels, which is a known risk factor for cardiovascular (affecting the heart and blood vessels) disease. Therefore, Praluent has been approved for use in patients who do not adequately respond to the maximum tolerated dose of statins or who cannot be given statins.In patients with atherosclerotic heart disease, Praluent reduced the number of cardiovascular events, in particular heart attacks and strokes. With regard to safety, the Agency noted an acceptable safety profile.

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

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

---

Pramipexole Accord

What is Pramipexole Accord?

Pramipexole Accord is a medicine that contains the active substance pramipexole. It is available as tablets (0.088, 0.18, 0.35, 0.7 and 1.1 mg).Pramipexole Accord is a 'generic medicine'. This means that Pramipexole Accord is similar to a 'reference medicine' already authorised in the European Union (EU) called Mirapexin. For more information on generic medicines, see the question-and-answer document here.

What is Pramipexole Accord used for?

Pramipexole Accord is used to treat the symptoms of Parkinson's disease, a progressive brain disorder that causes shaking, slow movement and muscle stiffness. Pramipexole Accord can be used either on its own or in combination with levodopa (another medicine for Parkinson's disease), at any stage of disease including the later stages when levodopa starts becoming less effective.The medicine can only be obtained with a prescription.

How is Pramipexole Accord used?

The starting dose is one 0.088 mg tablet three times a day. The dose should be increased every five to seven days until symptoms are controlled without causing side effects that cannot be tolerated. The maximum daily dose is three 1.1 mg tablets. Pramipexole Accord must be given less often in patients who have problems with their kidneys. If treatment is stopped for any reason, the dose should be decreased gradually.

How does Pramipexole Accord work?

The active substance in Pramipexole Accord, pramipexole, is a dopamine agonist (a substance that imitates the action of dopamine). Dopamine is a messenger substance in the parts of the brain that control movement and co-ordination. 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. Pramipexole stimulates the brain as dopamine would, so that patients can control their movement and have fewer of the signs and symptoms of Parkinson's disease, such as shaking, stiffness and slowness of movement.

How has Pramipexole Accord been studied?

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

What are the benefits and risks of Pramipexole Accord?

Because Pramipexole 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 Pramipexole Accord been approved?

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

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

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

---

Pramipexole Teva

What is Pramipexole Teva?

Pramipexole Teva is a medicine containing the active substance pramipexole base. It is available as white, round tablets (0.088, 0.18, 0.35 and 0.7 mg).Pramipexole Teva is a 'generic medicine'. This means that Pramipexole Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called Sifrol. For more information on generic medicines, see the question-and-answer document here.

What is Pramipexole Teva used for?

Pramipexole Teva is used to treat the symptoms of Parkinson's disease, a progressive brain disorder that causes shaking, slow movement and muscle stiffness. Pramipexole Teva can be used either on its own or in combination with levodopa (another medicine for Parkinson's disease), at any stage of disease including the later stages when levodopa starts becoming less effective. The medicine can only be obtained with a prescription.

How is Pramipexole Teva used?

Pramipexole Teva tablets should be swallowed with water, with or without food. The starting dose is 0.088 mg three times per day. The dose should be increased every five to seven days until symptoms are controlled without causing side effects that cannot be tolerated. The maximum daily dose is 1.1 mg three times per day. Pramipexole Teva must be given less frequently in patients who have problems with their kidneys. If treatment is stopped for any reason, the dose should be decreased gradually. For more information, see the Package Leaflet.

How does Pramipexole Teva work?

The active substance in Pramipexole Teva, pramipexole, is a dopamine agonist, which imitates the action of dopamine. Dopamine is a messenger substance in the parts of the brain that control movement and co-ordination. 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. Pramipexole stimulates the brain as dopamine would, so that patients can control their movement and have fewer of the signs and symptoms of Parkinson's disease, such as shaking, stiffness and slowness of movement.

How has Pramipexole Teva been studied?

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

What are the benefit and risk of Pramipexole Teva?

Because Pramipexole 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 Pramipexole Teva been approved?

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

---

Prandin

What is Prandin?

Prandin is a medicine that contains the active substance repaglinide. It is available as round tablets (white: 0.5 mg; yellow: 1 mg; peach: 2 mg).

What is Prandin used for?

Prandin 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. Prandin 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 Prandin used?

Prandin 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. Prandin 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.Prandin 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 Prandin 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. Prandin helps the pancreas to produce more insulin at mealtimes and is used to control type 2 diabetes.

How has Prandin been studied?

Prandin has been studied in 45 'clinical pharmacology' studies (looking at how the medicine works in the body) and 16 clinical trials (looking at its effects in treating type 2 diabetes patients). A total of 2,156 patients received Prandin in all trials combined.The main studies compared Prandin with other medicines used in type 2 diabetes (glibenclamide, glipizide or gliclazide). Another study looked at the effect of adding Prandin to metformin. The studies measured 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 Prandin shown during the studies?

In all studies, Prandin led to a decrease in the level of HbA1c, which showed that blood glucose levels had been controlled to a similar level to that seen with the comparator medicines. In the study where Prandin was added to metformin, the effects of the two medicines were at least additive (equivalent to the effects of the two medicines added together).Prandin produced a good insulin response to a meal within 30 minutes of being dosed in type 2 diabetes patients, leading to a blood glucose-lowering effect throughout the meal. The raised insulin levels returned to normal after the meal.

What is the risk associated with Prandin?

The most common side effects with Prandin (seen in between 1 and 10 patients in 100) are hypoglycaemia (low blood glucose levels), abdominal (tummy) pain and diarrhoea. For the full list of all side effects seen with Prandin, see the Package Leaflet.Prandin should not be used in people who may be hypersensitive (allergic) to repaglinide or any of the other ingredients. It should also not be used in patients with type 1 (insulin-dependent) diabetes who do not have any 'C-peptide' in their blood (a marker of type 1 diabetes). It should also not be used in patients with diabetic ketoacidosis (high levels of ketones [acids] in the blood), in patients with severe liver problems or in patients also taking gemfibrozil (a medicine used to reduce blood fat levels). Prandin doses may also need to be adjusted when given with some medicines used in heart conditions, and to treat pain, asthma and other conditions. The full list is available in the Package Leaflet.

Why has Prandin been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Prandin's benefits are greater than its risks for the treatment of type 2 diabetes. The Committee recommended that Prandin be given marketing authorisation.

---

Prasugrel Mylan

What is Prasugrel Mylan and what is it used for?

Prasugrel Mylan is taken together with aspirin to prevent atherothrombotic events (problems caused by blood clots and hardening of the arteries) in patients with acute coronary syndrome who are undergoing percutaneous coronary intervention. Acute coronary syndrome is a group of conditions in which blood supply in the vessels supplying the heart is interrupted so heart tissue cannot work properly or dies. It includes unstable angina (a severe type of chest pain) and heart attack. Percutaneous coronary intervention is a procedure used to unblock the blood vessels supplying the heart.Prasugrel Mylan contains the active substance prasugrel and is a 'generic medicine'. This means that Prasugrel Mylan contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Efient. For more information on generic medicines, see the question-and-answer document here.

How is Prasugrel Mylan used?

Prasugrel Mylan is available as tablets (5 and 10 mg) and can only be obtained with a prescription. Prasugrel Mylan treatment starts with one 60-mg dose. This is then followed by 10 mg taken once a day, except in patients weighing less than 60 kg, who should take 5 mg once a day. Patients taking Prasugrel Mylan should also take aspirin as prescribed by their doctors. It is recommended that treatment with Prasugrel Mylan and aspirin continue for up to a year.The use of Prasugrel Mylan is not recommended in patients over 75 years of age, unless the doctor has carefully considered its benefits and risks, and regards treatment with Prasugrel Mylan as necessary. In this case, the patient should take 5 mg daily following a 60-mg starting dose.For more information about using Prasugrel Mylan, see the package leaflet or contact your doctor or pharmacist.

How does Prasugrel Mylan work?

The active substance in Prasugrel Mylan, prasugrel, is an inhibitor of platelet aggregation. This means that it helps to prevent blood clots from forming. Blood clots are caused by special cells in the blood, the platelets, sticking together (aggregating). Prasugrel stops the platelets aggregating by blocking a substance called ADP from binding to a receptor (target) on their surface. This stops the platelets becoming 'sticky', reducing the risk of a blood clot forming and helping to prevent a heart attack or a stroke.

How has Prasugrel Mylan been studied?

Studies on the benefits and risks of the active substance in the authorised use have already been carried out with the reference medicine, Efient, and do not need to be repeated for Prasugrel Mylan.As for every medicine, the company provided studies on the quality of Prasugrel 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 Prasugrel Mylan?

Because Prasugrel 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 Prasugrel Mylan authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Prasugrel Mylan has been shown to have comparable quality and to be bioequivalent to Efient. Therefore, the Agency's view was that, as for Efient, the benefit of Prasugrel Mylan outweighs the identified risk and it can be authorised for use in the EU.

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

The company that markets Prasugrel Mylan will make sure that educational materials are available for doctors who will treat patients with the medicine. The materials will include information on how to prescribe the medicine safely and remind doctors that the medicine is not recommended for patients over the age of 75 years.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Prasugrel Mylan have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Prasugrel Mylan are continuously monitored. Side effects reported with Prasugrel Mylan are carefully evaluated and any necessary action taken to protect patients.

---

Pravafenix

What is Pravafenix?

Pravafenix is a medicine that contains the active substances pravastatin and fenofibrate. It is available as green and olive capsules containing 40 mg pravastatin and 160 mg fenofibrate.

What is Pravafenix used for?

Pravafenix is used in adults at high risk of heart disease whose 'low-density-lipoprotein' (LDL or 'bad') cholesterol is already being controlled with pravastatin alone but who still need to improve their cholesterol levels and to reduce their levels of triglycerides (a type of fat).The medicine can only be obtained with a prescription.

How is Pravafenix used?

Before starting treatment with Pravafenix, the doctor should first investigate all possible causes of the patient's abnormal cholesterol and triglycerides levels and place the patient on a suitable diet.The recommended dose is one capsule a day taken during the evening meal. The medicine should always be taken with food as it is less well absorbed from an empty stomach. The patient's blood should be monitored regularly to see how the medicine is working. The doctor should stop treatment if an adequate response is not seen within three months.

How does Pravafenix work?

The active substances in Pravafenix, pravastatin and fenofibrate, work in different ways and their actions have a complementary effect.Pravastatin belongs to the group called 'statins'. It reduces total blood cholesterol by blocking the action of HMG-CoA reductase, an enzyme in the liver involved in the production of cholesterol. As the liver needs cholesterol to produce bile, the reduced blood cholesterol level causes the liver cells to produce receptors that draw cholesterol from the blood, reducing its level even further. The cholesterol drawn out of the blood in this way is the LDL, or 'bad' cholesterol.Fenofibrate is a 'PPAR agonist'. It activates a type of receptor called the 'peroxisomeproliferator-activated receptor alpha', which is involved in breaking down fat from the diet, especially triglycerides. When the receptors are activated, the breakdown of fats is accelerated, and this helps clear the blood of cholesterol and triglycerides.

How has Pravafenix been studied?

Because pravastatin and fenofibrate have been used in medicines for a number of years, the company presented information from the scientific literature in addition to results from its own studies.The company carried out one main study, in which Pravafenix was compared with pravastatin alone in 248 patients at high risk of heart disease who had abnormal levels of cholesterol and triglyceride fats. The main measure of effectiveness was the reduction in the level of cholesterol after 12 weeks (excluding HDL or 'good' cholesterol).

What benefit has Pravafenix shown during the studies?

In the main study Pravafenix was shown to be more effective than pravastatin alone in reducing nonHDL-cholesterol levels. Non-HDL-cholesterol levels were reduced on average by around 14% in patients taking Pravafenix compared with 6% in patients taking pravastatin alone.

What is the risk associated with Pravafenix?

The most common side effects with Pravafenix (seen in between 1 and 10 patients in 100) are abdominal distension (bloating), abdominal pain (stomach ache), constipation, diarrhoea, dry mouth, dyspepsia (heartburn), eructation (belching), flatulence (gas), nausea (feeling sick), abdominal discomfort, vomiting and raised blood levels of liver enzymes. For the full list of all side effects reported with Pravafenix, see the package leaflet.Pravafenix should not be used in people who may be hypersensitive (allergic) to the active substances or any of the other ingredients. Pravafenix must not be used in patients aged below 18 years or in patients with severe liver problems, moderate to severe kidney problems, photo allergy or phototoxic reactions (allergic reaction or skin damage due to light exposure) during treatment with fibrates or ketoprofen. It must also not be used in patients with gall bladder disease, chronic or acute pancreatitis (inflammation of the pancreas) or a history of myopathy (muscle disorders) or rhabdomyolysis (breakdown of muscle fibres) following treatment with a statin or a fibrate. It must not be given to women who are pregnant or breastfeeding.

Why has Pravafenix been approved?

The CHMP looked at newly published data on the benefits of the combination of statins and fenofibrate. The Committee also noted that the benefits of Pravafenix were mainly in patients who had high levelsof triglyceride fats and low levels of HDL cholesterol. The Committee therefore decided that Pravafenix's benefits are greater than its risks in this group of patients and recommended that it be given marketing authorisation.

---

Praxbind

What is Praxbind and what is it used for?

Praxbind is a medicine used to neutralise the effects of dabigatran (the active substance of Pradaxa), a medicine that treats and prevents blood clots. Praxbind is used to rapidly stop the anticlotting effect of dabigatran, before emergency surgery or in case of life-threatening bleeding.Praxbind contains the active substance idarucizumab.

How is Praxbind used?

Praxbind is available as a solution for injection or infusion (drip) into a vein. The recommended dose of Praxbind is 5 g given into a vein as two injections or infusions, one after the other. A second 5-g dose may be given as two further injections or infusions, if needed.The medicine can only be obtained with a prescription and it is for use in hospital only.

How does Praxbind work?

The active substance in Praxbind, idarucizumab, is a monoclonal antibody fragment. A monoclonal antibody is a type of protein that has been designed to recognise and attach to a specific structure (called an antigen). Praxbind works by attaching firmly to dabigatran, and forming a complex in the blood. This rapidly stops dabigatran's anticlotting effect.

What benefits of Praxbind have been shown in studies?

Praxbind has been investigated in three main studies involving 141 healthy adults who previously received dabigatran. In the studies, volunteers received either Praxbind or placebo (a dummy treatment) after treatment with Pradaxa for 3.5 days. Results showed that Praxbind was able to completely neutralise Pradaxa's anticlotting effect within 5 minutes of use. In a still ongoing trial, an interim analysis showed similar results in 123 patients who had uncontrolled bleeding or required emergency surgery while using Pradaxa. Most patients in the study were taking Pradaxa to prevent stroke due to an 'abnormal heart beat' (atrial fibrillation).

What are the risks associated with Praxbind?

At the time of authorisation Praxbind has not been associated with any specific side effects.For the information on the restrictions with Praxbind, see the package leaflet.

Why is Praxbind approved?

The main studies showed that Praxbind is effective at neutralising the effects of Pradaxa, and its action is rapid, complete and sustained. The extent of Praxbind's benefit depends on the patient's overall health, the severity of bleeding and the location of bleeding. No side effects have been identified. The Agency's Committee for Medicinal Products for Human Use (CHMP) therefore decided that Praxbind'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 Praxbind?

A risk management plan has been developed to ensure that Praxbind 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 Praxbind, 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.

---

Pregabalin Accord

What is Pregabalin Accord and what is it used for?

Pregabalin Accord is a medicine used to treat adults with the following conditions:• neuropathic pain (pain due to nerve damage), including peripheral neuropathic pain, such as the pain experienced by patients with diabetes or herpes zoster (shingles), and central neuropathic pain, such as the pain experienced by patients who have had a spinal cord injury;• epilepsy, where it is used as an 'add-on' to other epilepsy treatment in patients who have partial seizures (epileptic fits starting in one specific part of the brain);• generalised anxiety disorder (long-term anxiety or nervousness about everyday matters).Pregabalin Accord contains the active substance pregabalin.Pregabalin Accord is a 'generic medicine'. This means that Pregabalin Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Lyrica. For more information on generic medicines, see the question-and-answer document here.

How is Pregabalin Accord used?

Pregabalin Accord is available as capsules (25, 50, 75, 100, 150, 200, 225 and 300 mg) and can only be obtained with a prescription. The recommended starting dose is 150 mg per day, divided into two or three doses. After one week, the dose can be increased to 300 mg per day. Doses can be increased further until the most effective dose is reached. The maximum dose is 600 mg per day. To stop treatment with Pregabalin Accord, the dose should be reduced gradually, over at least a week. Patients who have kidney problems may need to take lower doses.

How does Pregabalin Accord work?

The active substance in Pregabalin Accord, pregabalin, is similar in structure to the body's own 'neurotransmitter' gamma-amino butyric acid (GABA), but has very different biological effects. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. The exact way in which pregabalin works is not fully understood, but it is thought to affect the way that calcium enters nerve cells. This reduces the activity of some of the nerve cells in the brain and spinal cord, reducing the release of other neurotransmitters that are involved in epilepsy and anxiety.

How has Pregabalin Accord 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, Lyrica, and do not need to be repeated for Pregabalin Accord.As for every medicine, the company provided studies on the quality of Pregabalin 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 Pregabalin Accord?

Because Pregabalin 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 Pregabalin Accord approved?

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

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

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

---

Pregabalin Mylan

What is Pregabalin Mylan and what is it used for?

Pregabalin Mylan is a medicine used to treat adults with the following conditions:• neuropathic pain (pain due to nerve damage), including peripheral neuropathic pain, such as the pain experienced by patients with diabetes or herpes zoster (shingles), and central neuropathic pain, such as the pain experienced by patients who have had a spinal cord injury;• epilepsy, where it is used as an 'add-on' to other epilepsy treatment in patients who have partial seizures (epileptic fits starting in one specific part of the brain);• generalised anxiety disorder (long-term anxiety or nervousness about everyday matters).Pregabalin Mylan contains the active substance pregabalin.Pregabalin Mylan is a 'generic medicine'. This means that Pregabalin Mylan contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Lyrica. For more information on generic medicines, see the question-and-answer document here.

How is Pregabalin Mylan used?

Pregabalin Mylan is available as capsules (25, 50, 75, 100, 150, 200, 225 and 300 mg) and can only be obtained with a prescription. The recommended starting dose is 150 mg per day, divided into two or three doses. After three to seven days, the dose can be increased to 300 mg per day. Doses can be increased further until the most effective dose is reached. The maximum dose is 600 mg per day. To stop treatment with Pregabalin Mylan the dose should be reduced gradually, over at least a week. Patients who have kidney problems may need to take lower doses.

How does Pregabalin Mylan work?

The active substance in Pregabalin Mylan, pregabalin, is similar in structure to the body's own 'neurotransmitter' gamma-amino butyric acid (GABA), but has very different biological effects. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. The exact way that pregabalin works is not fully understood, but it is thought to affect the way that calcium enters nerve cells. This reduces the activity of some of the nerve cells in the brain and spinal cord, reducing the release of other neurotransmitters that are involved in epilepsy and anxiety.

How has Pregabalin 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, Lyrica, and do not need to be repeated for Pregabalin Mylan.As for every medicine, the company provided studies on the quality of Pregabalin 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 Pregabalin Mylan?

Because Pregabalin 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 Pregabalin Mylan approved?

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

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

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

---

Pregabalin Pfizer

What is Pregabalin Pfizer and what is it used for?

Pregabalin Pfizer is a medicine that contains the active substance pregabalin. It is used to treat adults with the following conditions:• neuropathic pain (pain due to nerve damage), including peripheral neuropathic pain, such as the pain experienced by patients with diabetes or herpes zoster (shingles), and central neuropathic pain, such as the pain experienced by patients who have had a spinal cord injury;• epilepsy, where it is used as an 'add-on' to existing treatment in patients who have partial seizures (epileptic fits starting in one specific part of the brain) that cannot be controlled with their current treatment;• generalised anxiety disorder (long-term anxiety or nervousness about everyday matters).This medicine is the same as Lyrica, which is already authorised in the European Union (EU). The company that makes Lyrica has agreed that its scientific data can be used for Pregabalin Pfizer ('informed consent').

How is Pregabalin Pfizer used?

The medicine can only be obtained with a prescription and is available as capsules (25, 50, 75, 100,150, 200, 225 and 300 mg). The recommended starting dose of Pregabalin Pfizer is 150 mg per day,divided into two or three doses. After three to seven days, the dose can be increased to 300 mg per day. Doses can be increased up to twice more until the most effective dose is reached. The maximum dose is 600 mg per day. Stopping treatment with Pregabalin Pfizer should also be done gradually, over at least a week.The capsules should be swallowed whole with water. Patients who have kidney problems need to take lower doses.

How does Pregabalin Pfizer work?

The active substance in Pregabalin Pfizer, pregabalin, is similar in structure to the body's own 'neurotransmitter' gamma-amino butyric acid (GABA), but has very different biological effects. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. The exact way that pregabalin works is not fully understood, but it is thought to affect the way that calcium enters nerve cells. This reduces the activity of some of the nerve cells in the brain and spinal cord, reducing the release of other neurotransmitters that are involved in pain, epilepsy and anxiety.

What benefits of Pregabalin Pfizer have been shown in studies?

Pregabalin Pfizer has been compared with placebo (a dummy treatment) in 22 studies.In neuropathic pain, the benefits of Pregabalin Pfizer were evaluated for up to 12 weeks using a standard pain questionnaire. In 10 studies involving over 3,000 patients with peripheral neuropathic pain (either diabetic pain or shingles), 35% of the patients treated with Pregabalin Pfizer had a decrease in pain scores of 50% or more, compared with 18% of the patients treated with placebo. In asmaller study involving 137 patients with central neuropathic pain due to a spinal cord injury, 22% of patients treated with Pregabalin Pfizer had a decrease in pain scores of 50% or more, compared with 8% of the patients treated with placebo.In epilepsy, the benefits of Pregabalin Pfizer were evaluated in 3 studies involving 1,000 patients that looked at how much it reduced the number of seizures patients had after 11 to 12 weeks. About 45% of the patients taking 600 mg Pregabalin Pfizer a day and about 35% of those taking 300 mg Pregabalin Pfizer a day had a reduction in seizures of 50% or more. This compared with about 10% of the patients taking placebo.Pregabalin Pfizer was more effective than placebo in generalised anxiety disorder: in 8 studies involving over 3,000 patients, 52% of the patients taking Pregabalin Pfizer had an improvement of 50% or more in their anxiety measured with a standard anxiety questionnaire, compared with 38% of the patients taking placebo.

What are the risks associated with Pregabalin Pfizer?

The most common side effects with Pregabalin Pfizer (seen in more than 1 patient in 10) are dizziness and somnolence (sleepiness). For the full list of all side effects and restrictions, see the package leaflet.

Why is Pregabalin Pfizer approved?

The CHMP decided that Pregabalin Pfizer'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 Pregabalin Pfizer?

A risk management plan has been developed to ensure that Pregabalin Pfizer 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 Pregabalin Pfizer, 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.

---

Pregabalin Sandoz

What is Pregabalin Sandoz and what is it used for?

Pregabalin Sandoz is a medicine used to treat adults with the following conditions:• neuropathic pain (pain due to nerve damage), including peripheral neuropathic pain, such as the pain experienced by patients with diabetes or herpes zoster (shingles), and central neuropathic pain, such as the pain experienced by patients who have had a spinal cord injury;• epilepsy, where it is used as an 'add-on' to existing treatment in patients who have partial seizures (epileptic fits starting in one specific part of the brain) that cannot be controlled with their current treatment;• generalised anxiety disorder (long-term anxiety or nervousness about everyday matters).Pregabalin Sandoz is a 'generic medicine'. This means that Pregabalin Sandoz is similar to a 'reference medicine' already authorised in the European Union (EU) called Lyrica. For more information on generic medicines, see the question-and-answer document here.Pregabalin Sandoz contains the active substance pregabalin.

How is Pregabalin Sandoz used?

Pregabalin Sandoz is available as capsules (25, 50, 75, 100, 150, 200, 225 and 300 mg) and can only be obtained with a prescription. The recommended starting dose is 150 mg per day, divided into two or three doses. After three to seven days, the dose can be increased to 300 mg per day. Doses can be increased up to twice more until the most effective dose is reached. The maximum dose is 600 mg per day. Stopping treatment with Pregabalin Sandoz should also be done gradually, over at least a week. Doctors may need to lower the dose in patients who have kidney problems.

How does Pregabalin Sandoz work?

The active substance in Pregabalin Sandoz, pregabalin, is similar in structure to the body's own 'neurotransmitter' gamma-amino butyric acid (GABA), but has very different biological effects. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. The exact way that pregabalin works is not fully understood, but it is thought to affect the way that calcium enters nerve cells. This reduces the activity of some of the nerve cells in the brain and spinal cord, reducing the release of other neurotransmitters that are involved in pain, epilepsy and anxiety.

How has Pregabalin Sandoz been studied?

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

What are the benefits and risks of Pregabalin Sandoz?

Because Pregabalin Sandoz 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 Pregabalin Sandoz approved?

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

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

A risk management plan has been developed to ensure that Pregabalin Sandoz 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 Pregabalin Sandoz, 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.

---

Pregabalin Zentiva

What is Pregabalin Zentiva and what is it used for?

Pregabalin Zentiva is a medicine used to treat adults with the following conditions:• epilepsy, where it is used as an 'add-on' to existing treatment in patients who have partial seizures (epileptic fits starting in one specific part of the brain) that cannot be controlled with their current treatment;• generalised anxiety disorder (long-term anxiety or nervousness about everyday matters).Pregabalin Zentiva is a 'generic medicine'. This means that Pregabalin Zentiva is similar to a 'reference medicine' already authorised in the European Union (EU) called Lyrica. For more information on generic medicines, see the question-and-answer document here.Pregabalin Zentiva contains the active substance pregabalin.

How is Pregabalin Zentiva used?

Pregabalin Zentiva is available as capsules (25, 50, 75, 100, 150, 200, 225 and 300 mg) and can only be obtained with a prescription. The recommended starting dose is 150 mg per day, divided into two or three doses. After three to seven days, the dose can be increased to 300 mg per day. Doses can be increased up to twice more until the most effective dose is reached. The maximum dose is 600 mg perday. Stopping treatment with Pregabalin Zentiva should also be done gradually, over at least a week. Doctors may need to lower the dose in patients who have kidney problems.

How does Pregabalin Zentiva work?

The active substance in Pregabalin Zentiva, pregabalin, is similar in structure to the body's own 'neurotransmitter' gamma-amino butyric acid (GABA), but has very different biological effects. Neurotransmitters are chemicals that allow nerve cells to communicate with each other. The exact way that pregabalin works is not fully understood, but it is thought to affect the way that calcium enters nerve cells. This reduces the activity of some of the nerve cells in the brain and spinal cord, reducing the release of other neurotransmitters that are involved in epilepsy and anxiety.

How has Pregabalin Zentiva been studied?

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

What are the benefits and risks of Pregabalin Zentiva?

Because Pregabalin Zentiva 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 Pregabalin Zentiva approved?

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

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

A risk management plan has been developed to ensure that Pregabalin Zentiva 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 Pregabalin Zentiva, 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.

---

Prehevbri

What is PreHevbri and what is it used for?

PreHevbri is a vaccine for adults that is used in line with official recommendations to protect against hepatitis B (an infectious disease of the liver caused by hepatitis B virus). By preventing hepatitis B, the vaccine is also expected to protect against hepatitis D (another disease of the liver, caused by the hepatitis D virus).PreHevbri contains three proteins from the outer part of the hepatitis B virus.

How is PreHevbri used?

PreHevbri is available as a suspension for injection. It can only be obtained with a prescription. The vaccination schedule consists of three doses, to be given in the muscle of the upper arm. The second and third vaccinations should be given one month and six months after the first dose.For more information about using PreHevbri, see the package leaflet or contact your doctor or pharmacist.

How does PreHevbri work?

PreHevbri is a vaccine. Vaccines work by 'teaching' the immune system (the body's natural defences) to defend itself against a disease. PreHevbri contains three different proteins that are found on the outside 'envelope' of the hepatitis B virus. These proteins (known as surface antigens) are adsorbed (fixed) to an aluminium compound to help stimulate the immune response. When a person is given the vaccine, the immune system recognizes the different parts of the surface antigen as 'foreign' and makes antibodies against them. When a person later comes into contact with hepatitis B virus, the immune system will be able to produce antibodies more quickly, and this helps to protect against hepatitis B. PreHevbri does not contain the virus itself and cannot cause hepatitis B.The virus that causes hepatitis D is a so-called incomplete virus. It cannot make copies of itself without the help of hepatitis B virus. Therefore, by protecting against hepatitis B, PreHevbri is also expected to protect against hepatitis D.

What benefits of PreHevbri have been shown in studies?

The benefits of PreHevbri were evaluated in two main studies in 4,445 adults which compared the immune response to the vaccine with that to Engerix B (another hepatitis B vaccine). The main measure of effectiveness was the percentage of people who had protective levels of antibodies four weeks after they had received their third vaccination. The results from both studies showed that PreHevbri was at least as effective as the other hepatitis B vaccine.In the first study, involving adults from 18 to over 70 years of age, 91.4% (656 out of 718) people who were given three doses of PreHevbri and 76.5% (553 out of 723) people who were given three doses of the other hepatitis B vaccine produced protective levels of antibodies. In people from 45 years of age, 89.4% of those given PreHevbri (559 out of 625) produced protective levels of antibodies compared with 73.0% of those given the other vaccine (458 out of 627). In the second study in adults aged 18 to 45 years, 1,740 out of 1,753 (99.3%) people given PreHevbri and 561 out of 592 (94.8%) people given the other vaccine were protected after they completed their vaccination course.

What are the risks associated with PreHevbri?

The most common side effects with PreHevbri (which may affect more than 1 in 10 people) are reactions such as tenderness and itching at the site of injection, muscle pain, tiredness, and headache.For the full list of side effects of PreHevbri, see the package leaflet.PreHevbri must not be used in people who are hypersensitive (allergic) to the active substance or any of the other ingredients of the vaccine, or in those who have had a severe allergic reaction after being given any other hepatitis B vaccine.

Why is PreHevbri authorised in the EU?

PreHevbri was shown to be at least as effective as another hepatitis B vaccine. Protective levels of antibodies were seen in older participants and those with chronic conditions such as diabetes (who might be expected to have a weaker immune response), as well as in younger, fitter individuals. Though local reactions seemed to be somewhat more common with PreHevbri than with the comparator vaccine, they were largely mild to moderate, and the safety profile was considered acceptable. The European Medicines Agency therefore decided that the benefits of PreHevbri 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 PreHevbri?

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

---

Pretomanid Fgk

What is Pretomanid FGK and what is it used for?

Pretomanid FGK is a medicine for treating adults with drug-resistant tuberculosis. It is used to treat tuberculosis that is:• extensively drug-resistant (resistant to at least 4 antibiotics used for treating tuberculosis, including the standard antibiotics isoniazid and rifampicin);• multi-drug resistant (resistant to isoniazid and rifampicin) and when antibiotics used for this form of tuberculosis do not work or cause unacceptable side effects.Pretomanid FGK is used together with bedaquiline and linezolid.Pretomanid FGK contains the active substance pretomanid.Tuberculosis is rare in the EU, and Pretomanid FGK was designated an 'orphan medicine' (a medicine used in rare diseases) on 29 November 2007. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu 307513.

How is Pretomanid FGK used?

The medicine can only be obtained with a prescription. Treatment should be started and monitored by a doctor experienced in managing multi-drug resistant (MDR) tuberculosis.Pretomanid FGK is available as tablets (200 mg). The recommended dose is 1 tablet with food once daily for 6 months or longer if necessary. It must be taken in combination with bedaquiline and linezolid.For more information about using Pretomanid FGK, see the package leaflet or contact your doctor or pharmacist.

How does Pretomanid FGK work?

The way the active substance in Pretomanid FGK works is not fully understood. It is thought to block the building of the cell walls of the bacteria that cause tuberculosis (Mycobacterium tuberculosis) by interfering with the production of one of the cell wall components. Pretomanid is also thought to triggerthe production of substances that are toxic for the bacteria (reactive nitrogen species). These actions are expected to kill the bacteria.

What benefits of Pretomanid FGK have been shown in studies?

A main study showed that Pretomanid FGK taken with bedaquiline and linezolid for 6 months is effective at clearing the bacteria causing tuberculosis in patients with either extensively drug-resistant tuberculosis or MDR tuberculosis when other treatments did not work or cause too many side effects.In this study, 90% of patients with extensively drug-resistant tuberculosis (63 out of 70) and 95% of patients with MDR tuberculosis (35 out of 37) were cleared of the infection and did not get re-infected in the 6 months after the end of the treatment.

What are the risks associated with Pretomanid FGK?

The most common side effects with Pretomanid FGK (which may affect more than 1 in 10 people) are nausea (feeling sick), vomiting and blood tests showing raised levels of liver enzymes (a sign of liver stress).For the full list of side effects and restrictions of Pretomanid FGK, see the package leaflet.

Why is Pretomanid FGK authorised in the EU?

Pretomanid FGK used with bedaquiline and linezolid has been shown to be effective at treating difficultto-treat tuberculosis. Although the number of patients included in the main study was small and the effects of the combination were not compared with those of other treatments, the European Medicines Agency considered that the high cure rate in the study, the shorter treatment duration and simplification of treatment compared to existing therapies are significant benefits. Treatment options are limited for these patients with difficult-to-treat, life-threatening infections.The safety profile of the combination regimen is considered acceptable and the side effects manageable, provided that close monitoring and surveillance of the patients during and after treatment are in place.The European Medicines Agency decided that Pretomanid FGK's benefits are greater than its risks and it can be authorised for use in the EU.Pretomanid FGK 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 Pretomanid FGK?

Since Pretomanid FGK has been given conditional authorisation, the company that markets Pretomanid FGK will provide the final results of ongoing studies looking at the safety and effectiveness of various doses and treatment durations.

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

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

---

Prevenar 13

What is Prevenar 13?

Prevenar 13 is a vaccine. It is available as a suspension for injection that contains parts from 13 different types of the bacterium Streptococcus pneumoniae (S. pneumoniae).

What is Prevenar 13 used for?

Prevenar 13 is used to protect children aged between six weeks and 17 years against invasive disease, pneumonia (infection of the lungs) and acute otitis media (infection of the middle ear) caused by S. pneumoniae. It is also used to protect adults and the elderly against invasive disease and pneumonia caused by S. pneumoniae. Invasive disease occurs when the bacterium spreads through the body causing serious infections such as septicaemia (blood infection) and meningitis (infection of the membranes around the brain and spine).When prescribing Prevenar 13, consideration should be given to the risk of invasive disease and pneumonia in the different age groups, other diseases the vaccinees may have and the type of bacteria in the different geographical areas.The vaccine can only be obtained with a prescription.

How is Prevenar 13 used?

Adults and children aged two years and above should receive one single dose of Prevenar 13 into the shoulder muscle.In children below two years of age, the vaccine is given by injection into the thigh muscle. The vaccination schedule depends on the age of the child and should be based on official recommendations:• children aged between six weeks and six months are normally given four doses. The first three doses are given with an interval of one month between each dose. The fourth dose, the booster, is given between 11 and 15 months of age. Alternatively, when Prevenar 13 is given as part of a routine immunisation programme, two doses can be given at the ages of two and four months, followed by a booster at 11 to 15 months of age;• children aged between seven months and 11 months should first receive two doses with an interval of at least one month followed by a third dose in the second year;• children between 12 and 23 months of age should receive two doses with an interval of at least two months;• children between two and 17 years of age should receive a single dose.Prevenar 13 can be used in children who have started vaccination with Prevenar (another vaccine authorised in the European Union for S. pneumoniae, which contains parts of seven of the 13 types of S. pneumoniae included in Prevenar 13).Further information on the use of Prevenar 13 in people at increased risk of pneumococcal infections (such as patients with HIV or people who have received a haematopoietic stem cell transplant) and on how to switch from Prevenar to Prevenar 13 can be found in the summary of product characteristics (also part of the EPAR).

How does Prevenar 13 work?

Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend itself against a disease. When a person is given the vaccine, the immune system recognises the parts of the bacterium contained in the vaccine as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies more quickly when it is exposed to the bacterium. This helps to protect against the disease.Prevenar 13 contains small amounts of polysaccharides (a type of sugar) extracted from the 'capsule' that surrounds the S. pneumoniae bacterium. These polysaccharides have been purified, then 'conjugated' (attached) to a carrier to help them to be recognised by the immune system. The vaccine is also 'adsorbed' (fixed) onto an aluminium compound to enhance the immune response.Prevenar 13 contains the polysaccharides from 13 different types of S. pneumoniae (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F). In Europe, it is estimated that these are responsible for between 73 and 100% of the cases of invasive disease in children under the age of five years, and at least 50 - 76% of the cases of invasive disease in adults, depending on the country. Prevenar 13 is very similar to Prevenar but contains six additional polysaccharides from serotypes which are responsible for between 16 and 60% of the cases.

How has Prevenar 13 been studied?

In children, the ability of Prevenar 13 to trigger the production of antibodies (immunogenicity) was assessed in two main studies involving 1,266 healthy children who were vaccinated between the ages of two and 15 months and in a third study involving 598 children aged between five and 17 years old who had previously been vaccinated with Prevenar or who had never been vaccinated for invasive pneumococcal disease. Prevenar 13 was compared with Prevenar. The studies compared the immune response for Prevenar 13 with that for Prevenar against the seven polysaccharides that they share in common. In the first two studies they were compared directly, and in the third study the results for Prevenar 13 were compared to those obtained for Prevenar in a previous study. The immune response to the additional six polysaccharides in Prevenar 13 was compared with the lowest immune response to any of the polysaccharides in Prevenar. Additional studies in children looked at the effects of giving booster vaccinations, switching from Prevenar to Prevenar 13 and using Prevenar 13 alongside other vaccines routinely given to children.In adults, Prevenar 13 was investigated in four main studies. The first study involved 835 adults aged50 to 64 years who had not previously been vaccinated against invasive disease caused byS. pneumoniae. The second study involved 938 adults aged 70 years or older who had already been vaccinated against invasive disease caused by S. pneumoniae at least five years earlier. In both studies, Prevenar 13 was compared with a similar vaccine containing the polysaccharides from 23 different types of S. pneumoniae (23-valent polysaccharide vaccine). The studies compared the immune responses one month after vaccination with the two vaccines. A third study, which involved 900 adults aged 18 to 49, compared the immune response to Prevenar 13 with the response in adults aged 60 to 64. A fourth study involved approximately 85,000 adults over 65 year of age who had not previously been vaccinated with the 23-valent polysaccharide vaccine, and compared Prevenar 13 with placebo (a dummy treatment). The main measure of effectiveness was based on the number of subjects who developed a first episode of pneumonia caused by a type of S. pneumoniae covered by Prevenar 13.

What benefit has Prevenar 13 shown during the studies?

In children under five years of age, Prevenar 13 produced a response that was at least as good as Prevenar for six of the seven S. pneumoniae polysaccharides they share in common in the first main study, and for five of the seven in the second. Where the response to Prevenar 13 was lower than the comparator, the differences were considered to be small. All six of the additional polysaccharides in Prevenar 13 produced a response at least as good as the lowest response seen with Prevenar in the first main study. This was true for five of the six additional polysaccharides in the second study.In children aged between five and 17 years old, Prevenar 13 produced a response that was at least as good as Prevenar for all seven S. pneumoniae polysaccharides they share in common. All six of the additional polysaccharides in Prevenar 13 produced a response that was similar to the response seen with Prevenar against the seven polysaccharides.The additional studies showed that Prevenar 13 led to an increase in antibody production following booster vaccinations and supported a switch to Prevenar 13 in children who had started vaccination with Prevenar. Prevenar 13 was not shown to affect the immunogenicity of other vaccines routinely given to children.In adults aged 50 and older, in the first two main studies Prevenar 13 produced an immune response that was at least as good as the 23-valent polysaccharide vaccine for all 12 of the S. pneumoniae polysaccharides they share in common, and for several of these serotypes the immune response was better with Prevenar 13. Adults aged 18 to 49 had an immune response with Prevenar 13 which was as good as the response in adults aged 60 to 64.The fourth study in adults over 65 years of age showed that Prevenar 13 reduced the incidence of pneumonia by almost half: 49 out of 42,240 (around 0.1%) subjects fell ill with pneumonia caused byS. pneumoniae in the vaccine group, compared with 90 out of 42,256 (around 0.2%) subjects in the placebo group.

What is the risk associated with Prevenar 13?

The most common side effects with Prevenar 13 (seen in more than 1 patient in 10) in children are decreased appetite, fever (only very common in children aged 6 weeks to 5 years), irritability, reactions at the site of injection (reddening or hardening of the skin, swelling, pain or tenderness), somnolence (sleepiness) and poor quality sleep. In adults and the elderly, the most common side effects (seen in more than 1 patient in 10) are decreased appetite, headaches, diarrhoea, fever (only very common in adults aged 18 to 29 years), vomiting (only very common in adults aged 18 to 49 years), rash, reactions at the site of injection, limitation of arm movement, arthralgia and myalgia (joint and muscle pain), chills and fatigue. For the full list of all side effects reported with Prevenar 13, see the package leaflet.Prevenar 13 must not be used in people who are hypersensitive (allergic) to the active substances, to any of the other ingredients or to diphtheria toxoid (a weakened toxin from the bacterium that causes diphtheria). People who have a severe fever should not receive the vaccine until they have recovered, but they can still be given the vaccine if they have a mild infection such as a cold.

Why has Prevenar 13 been approved?

The CHMP decided that Prevenar 13's benefits are greater than its risks and recommended that it be granted marketing authorisation. The CHMP noted that in children the immune system's response to Prevenar 13 was comparable to that of Prevenar, which is already authorised for the protection of children against S. pneumoniae in the EU. The Committee also noted that Prevenar 13 contains additional polysaccharides from the types of S. pneumoniae that are responsible for causing disease in children in Europe.In adults and the elderly, the Committee noted that community-acquired pneumonia and invasive pneumococcal disease may be an important health problem and that the benefit in terms of protection outweighed the risk of adverse reactions. For the prevention of pneumonia, although the use of Prevenar 13 was only investigated in adults over 65 years of age, the CHMP considered that the results could also be applied to younger adults as studies have shown that their immune response is similar or higher than that among adults older than 65.

What measures are being taken to ensure the safe and effective use of Prevenar 13?

A risk management plan has been developed to ensure that Prevenar 13 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 Prevenar 13, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Prevymis

What is Prevymis and what is it used for?

Prevymis is an antiviral medicine used to prevent illness caused by cytomegalovirus (CMV) in adults having an allogeneic haematopoietic stem cell transplant to replace their bone marrow. Allogeneic haematopoietic stem cell transplantation involves using stem cells from a donor to replace the recipient's bone marrow cells to form new bone marrow that produces healthy blood cells.Many people have CMV in their body but it is usually inactive and it does not cause harm. However, CMV can become active in patients whose immune system is weakened such as those having stem cell transplants.Because the number of patients with CMV disease is low, the disease is considered 'rare', and Prevymis was designated an 'orphan medicine' (a medicine used in rare diseases) on 15 April 2011.Prevymis contains the active substance letermovir.

How is Prevymis used?

Prevymis can only be obtained with a prescription, and treatment should be started by a doctor experienced in managing patients who have had an allogeneic haematopoietic stem cell transplant. Doctors should consider official guidance on the use of antiviral medicines when using Prevymis.Prevymis is available as tablets to be taken by mouth and as a concentrate that is made up into a solution for infusion (drip) into a vein and given over about an hour. The usual recommended dose by mouth or as an infusion is 480 mg once daily. If ciclosporin (a medicine that prevents rejection of the transplant) is used at the same time, the Prevymis dose is reduced to 240 mg once daily. Treatment with Prevymis is started on the day of the transplant or on any day up to 28 days afterwards and it is continued for 100 days after the transplantation; longer treatment may be considered in some patients. For further information, see the package leaflet.

How does Prevymis work?

For CMV to multiply, its genetic material (DNA) needs to be copied and packaged into protein shells to produce more viruses that can then infect other cells. Letermovir, the active substance in Prevymis, blocks a virus enzyme called 'terminase'. Terminase is involved in packaging the DNA in the protein shells of the virus. By blocking the enzyme, the medicine prevents viruses from developing properly, so that CMV cannot multiply and infect other cells. This is expected to prevent CMV disease in transplant recipients who already have CMV in their body.

What benefits of Prevymis have been shown in studies?

A main study involving 570 adults found Prevymis was more effective than placebo (a dummy treatment) in preventing CMV infection after allogeneic haematopoietic stem cell transplantation. Of the patients receiving Prevymis, about 38% (122 out of 325) had signs of CMV becoming active 24 weeks after the stem cell transplant compared with 61% of the patients (103 out of 170) receiving placebo.All patients in this study were CMV seropositive, meaning they had come into contact with the virus before and were likely to be carrying it in an inactive form.

What are the risks associated with Prevymis?

The most common side effects with Prevymis (which may affect up to 1 in 10 people) are nausea (feeling sick), diarrhoea and vomiting. For the full list of side effects reported with Prevymis, see the package leaflet.Prevymis must not be used together with the medicine pimozide, or ergot medicines such as ergotamine and dihydroergotamine. The combination of Prevymis and ciclosporin must not be used with dabigatran, atorvastatin, pitavastatin, rosuvastatin and simvastatin. For the full list of restrictions, see the package leaflet.

Why is Prevymis approved?

Prevymis is effective in preventing CMV from becoming active and causing disease in adult recipients of a stem cell transplantation to replace the bone marrow. It has few side effects unlike other medicines used for the treatment of CMV disease which can damage bone marrow and affect blood cells. The European Medicines Agency therefore decided that Prevymis'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 Prevymis?

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

---

Prezista

What is Prezista and what is it used for?

Prezista is used together with low-dose ritonavir and other HIV medicines to treat patients from 3 years of age (weighing at least 15 kg) who are infected with human immunodeficiency virus type 1 (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).In adults and adolescents (12 years of age or more and weighing at least 40 kg), Prezista is also used with another medicine, cobicistat, in combination with other HIV medicines to treat HIV-1 infection.Prezista contains the active substance darunavir.

How is Prezista used?

Prezista can only be obtained with a prescription and treatment should be started by a healthcare professional who has experience in managing HIV infection.Prezista is taken by mouth with or soon after a meal and it is available as tablets, or as a liquid (oral suspension) for patients unable to swallow tablets. The medicine is always taken with cobicistat (in adults or adolescents) or with low-dose ritonavir (in adults and children) plus other HIV medicines. If used with cobicistat the medicine is taken once daily; if used with ritonavir it is taken once or twice daily.The dose of Prezista depends on previous HIV treatment, whether the virus has any resistance to the medicine, and the patient's age, weight and overall health. For more information about using Prezista, see the package leaflet or contact your doctor or pharmacist.

How does Prezista work?

The active substance in Prezista, darunavir, is a protease inhibitor. It blocks an enzyme called protease, which is involved in the reproduction of HIV. When the enzyme is blocked, the virus does not reproduce normally slowing down its multiplication in the body. Either ritonavir or cobicistat is used with Prezista as a 'booster'. These booster medicines slow darunavir's breakdown, increasing the levels of darunavir in the blood. This allows a lower dose of darunavir to be used for the same antiviral effect.Prezista, taken in combination with other HIV medicines, reduces the amount of HIV-1 in the blood and keeps it at a low level. Prezista does not cure HIV-1 infection, but it holds off damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Prezista have been shown in studies?

Six main studies in adults found that Prezista was effective at keeping HIV infection under control. In all of the studies, the patients also took other HIV medicines. The main measures of effectiveness were changes in the levels of HIV in the blood (viral load).• One study compared ritonavir-boosted Prezista with ritonavir-boosted lopinavir (another protease inhibitor) in 691 adults who had not been treated for HIV before. After 48 weeks, 84% of the patients taking ritonavir-boosted Prezista had viral loads below 50 copies/ml (287 out of 343) compared with 78% of those taking ritonavir-boosted lopinavir (271 out of 346).• Three studies involved adults who had been treated before who received 600 mg Prezista twice a day. One study compared ritonavir-boosted Prezista with ritonavir-boosted lopinavir in 604 patients who had taken some anti-HIV medicines in the past. 77% of those taking ritonavirboosted Prezista had viral loads below 400 copies/ml after 48 weeks (211 of 274), compared with 68% of those taking ritonavir-boosted lopinavir (189 out of 280). The other two studies compared ritonavir-boosted Prezista with other protease inhibitors chosen on the basis of the patient's previous treatments and predicted response, in a total of 628 patients who had taken many anti-HIV medicines in the past. 70% of those taking the approved dose of ritonavir-boosted Prezista (92 out of 131) had at least a 90% reduction in viral load after 24 weeks, compared with 21% of those taking the comparator protease inhibitors (26 out of 124).• The fifth study involving 590 adults who had been treated before found that Prezista 800 mg once a day was as effective as Prezista 600 mg twice a day: after 48 weeks, 72% of the patients taking Prezista 800 mg once day had viral loads below 50 copies/ml (212 out of 294) compared with 71% of those taking Prezista 600 mg twice a day (210 out of 296).• Prezista in combination with the booster cobicistat was evaluated in a study in 313 adult patients all of whom received 800 mg Prezista and 150 mg cobicistat once a day, in addition to two other HIV medicines. The study included both previously treated patients and those who had not received HIV medicines before. Around 81% (253 out of 313) of patients had viral loads below 50 copies/ml after 48 weeks.Ritonavir-boosted Prezista has also been studied in 101 previously treated children aged between 3 and 18 years and 12 previously untreated children aged between 12 to 18 years who weighed at least 40 kg.• Prezista was effective at keeping HIV infection under control in previously treated children: 74% of children aged above 6 years (59 out of 80) had at least a 90% reduction in viral loads after 24 weeks of treatment; 81% of those aged between 3 and 6 (17 out of 21) had viral loads below 50 copies/ml after 48 weeks.• In the study of previously untreated children, 83% (10 out of 12) had viral loads below 50 copies/ml after 48 weeks of treatment.Blood levels of cobicistat-boosted Prezista were found to be similar in adults and adolescents and its effectiveness is therefore expected to be similar. In an ongoing study involving previously treated children and adolescents, of 7 patients aged 12 to 16 years and weighing at least 40 kg who were given cobicistat and Prezista, 6 had viral loads below 50 copies/ml after 48 weeks of treatment.

What are the risks associated with Prezista?

In adults, the most common side effects with Prezista (which may affect more than 1 in 10 people) are diarrhoea, nausea (feeling sick) and vomiting, headache and rash. For the full list of all side effects reported with Prezista, see the package leaflet.Prezista must not be taken by patients who have severely reduced liver function, or who are taking medicines which may decrease its effect, or cause serious side effects if given with Prezista combinations. For the full list of these medicines, see the package leaflet.

Why is Prezista authorised in the EU?

The European Medicines Agency decided that Prezista'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 Prezista?

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

---

Prialt

What is Prialt?

Prialt is a solution for infusion that contains the active substance ziconotide.

What is Prialt used for?

Prialt is used to treat severe, long-term pain in adults who need a painkiller by intrathecal injection (injection into the space that surrounds the spinal cord and the brain).Because the number of patients who have long-term pain that requires painkillers to be injected directly into the spine is low, the disease is considered 'rare', and Prialt was designated an 'orphan medicine' (a medicine used in rare diseases) on 9 July 2001.The medicine can only be obtained with a prescription.

How is Prialt used?

Treatment with Prialt should only be carried out by a doctor who has experience in the intrathecal dosing of medicines.Prialt must be given as a very slow continuous infusion through an intrathecal catheter (a tube inserted into the spinal canal) using an infusion pump capable of delivering an accurate amount of the medicine. Prialt may need to be diluted before use, especially with the lower doses needed at the start of treatment. The starting dose of Prialt is 2.4 micrograms per day. The dose should be gradually increased, preferably every two days or more, to obtain the best balance between pain relief andpossible side effects. The dose must not be increased more than once in any 24 hour period. Most patients need doses lower than 9.6 micrograms per day. The maximum dose is 21.6 micrograms per day.

How does Prialt work?

The active substance in Prialt, ziconotide, is a copy of a natural substance called omega-conopeptide, which is found in the venom of a type of sea snail. Ziconotide acts by blocking special pores called calcium channels on the surface of the nerve cells that transmit the pain signals. By blocking the flow of calcium into the nerve cells, ziconotide interferes with the transmission of pain signals within the spine. This helps to bring relief from pain.

How has Prialt been studied?

Prialt has been compared with placebo (a dummy treatment) in 589 patients with severe long-term pain in three main studies. Two of the studies were short-term, lasting five or six days: one in pain due to cancer or AIDS, and one in pain due to other causes such as nerve damage. The third study looked at the use of the medicine over three weeks. In all of the studies, the main measure of effectiveness was the change in the Visual Analog Scale of Pain Intensity (VASPI). This is a score given by the patients of their pain on a scale from 0 mm (no pain) to 100 mm (maximum pain).

What benefit has Prialt shown during the studies?

Prialt was more effective than placebo in the first two studies. Before treatment, patients with cancer or AIDS pain had an average VASPI score of 74 mm, and those with other types of pain had a score of80 mm. After treatment, the scores in patients receiving Prialt decreased to 35 and 54 mm, respectively, while scores in patients receiving placebo were 61 and 72 mm.In the third study, there was a trend for Prialt to be more effective than placebo, with the VASPI score changing from 81 mm before treatment to 68 mm in patients receiving Prialt and to 74 mm in patients receiving placebo.

What is the risk associated with Prialt?

The most common side effects with Prialt (seen in more than 1 patient in 10) are confusion, dizziness, nystagmus (uncontrolled eye movement), impaired memory (forgetfulness), headache, somnolence (sleepiness), blurred vision, nausea (feeling sick), vomiting, abnormal gait (difficulty walking) and asthenia (weakness).Prialt must not be used in patients at the same time as intrathecal chemotherapy (medicines to treat cancer that are injected into the spinal canal). For the full list of all side effects and restrictions with Prialt, see the package leaflet.

Why has Prialt been approved?

The Committee for Medicinal Products for Human Use (CHMP) concluded that Prialt provides an alternative to other intrathecal painkillers, such as opioids. It decided that Prialt's benefits are greater than its risks and recommended that it be given marketing authorisation.Prialt 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 17 January 2014.Prialt

What information is still awaited for Prialt?

The company that makes Prialt is carrying out a study looking at the long-term use of the medicine, looking in particular at the possibility of development of tolerance to treatment (when doses of a medicine that used to be effective become less effective over time).

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

A risk management plan has been developed to ensure that Prialt 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 Prialt, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Pritor

What is Pritor?

Pritor is a medicine that contains the active substance telmisartan. It is available as tablets (20, 40 and 80 mg).

What is Pritor used for?

Pritor is used to treat essential hypertension (high blood pressure) in adults. 'Essential' means that the hypertension has no obvious cause.Pritor is also used to prevent cardiovascular problems (problems with the heart and blood vessels) such as heart attacks or strokes. It is used in patients who have had problems due to blood clots in the past (such as heart disease, a stroke or artery disease) or who have type 2 diabetes that has damaged an organ (such as the eyes, heart or kidneys).The medicine can only be obtained with a prescription.

How is Pritor used?

For the treatment of essential hypertension, the usual recommended dose of Pritor is 40 mg once a day, but some patients may benefit from using 20 mg once a day. If the target blood pressure is not reached, the dose can be increased to 80 mg, or another medicine for hypertension can be added, such as hydrochlorothiazide.For the prevention of cardiovascular problems, the recommended dose is 80 mg once a day. The doctor should monitor the patient's blood pressure closely when starting Pritor, and may decide to adjust the patient's blood pressure-lowering medication. Patients with severely reduced kidney function should receive a lower starting dose of 20 mg once a day. Patients with mild or moderately reduced liver function should not receive doses higher than 40 mg a day.

How does Pritor work?

The active substance in Pritor, telmisartan, is an 'angiotensin II receptor antagonist', which means that it blocks the action of a hormone in the body called angiotensin II. Angiotensin II is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the receptors to which angiotensin II normally attaches, telmisartan stops the hormone having an effect, allowing the blood pressure to drop, reducing the risks associated with high blood pressure, such as having a heart attack or stroke. It also allows the heart to pump blood more easily, which can help to reduce the risk of future cardiovascular problems.

How has Pritor been studied?

For the treatment of essential hypertension, Pritor has been studied in 2,647 patients who took Pritor either alone or in combination with hydrochlorothiazide. Various doses of Pritor were compared with placebo (a dummy treatment) and with other medicines for hypertension (atenolol, lisinopril, enalapril and amlodipine). The main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats).For the prevention of cardiovascular problems, 80 mg Pritor once a day has been studied in one main study involving almost 26,000 patients aged 55 years or over who had heart or artery disease, had had a stroke, or had diabetes and were at high risk of cardiovascular problems. Pritor was compared with ramipril (another medicine to prevent cardiovascular problems), and with the combination of both medicines. The main measure of effectiveness was the reduction in the number of patients who died or were admitted to hospital, or who had a heart attack or stroke. The patients were followed up for an average of four and a half years.

What benefit has Pritor shown during the studies?

In the treatment of essential hypertension, Pritor was more effective than placebo at reducing diastolic blood pressure and had similar effects to the other medicines for hypertension.In the prevention of cardiovascular problems, Pritor had a similar effect to ramipril, with around 17% of patients dying, being admitted to hospital because of cardiovascular problems, or having a heart attack or stroke. The combination of the two medicines was no more effective than either medicine taken alone and was linked to an increased risk of side effects.

What is the risk associated with Pritor?

Side effects with Pritor are not common. However, the following side effects are seen in between 1 and 10 patients in 1,000: upper respiratory tract infection (colds) including inflammation of the throat and sinuses, urinary tract infection (infection of the structures that carry urine) including bladder infection, anaemia (low red blood cell counts), hyperkalaemia (high blood potassium levels), depression, insomnia (difficulty sleeping), syncope (fainting), vertigo (a spinning sensation), bradycardia (slow heart rate), hypotension (low blood pressure), dyspnoea (difficulty breathing), cough, abdominal pain (stomach ache), diarrhoea, dyspepsia (heartburn), flatulence (gas), vomiting, hyperhidrosis (excessive sweating), pruritus (itching), rash, myalgia (muscle pain), back pain, muscle spasms, renal impairment (reduced kidney function) including sudden kidney failure, chest pain, asthenia (weakness) and increased blood levels of creatinine (a marker of muscle breakdown). Hypotension may be more common in patients receiving Pritor to prevent cardiovascular problems. For the full list of all side effects reported with Pritor, see the package leaflet.Pritor must not be used in women who are more than three months pregnant. Its use during the first three months of pregnancy is not recommended. Pritor must not be used in people who have severe liver problems or bile problems. In patients with type 2 diabetes or in patients with moderate or severe kidney impairment, Pritor must also not be used in combination with aliskiren-containing medicines (also used to treat essential hypertension). For the full list of restrictions, see the package leaflet.

Why has Pritor been approved?

The CHMP decided that Pritor'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 Pritor?

A risk management plan has been developed to ensure that Pritor 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 Pritor, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Pritorplus

What is PritorPlus?

PritorPlus is a medicine that contains two active substances, telmisartan and hydrochlorothiazide. It is available as tablets (40 or 80 mg telmisartan and 12.5 mg hydrochlorothiazide; 80 mg telmisartan and 25 mg hydrochlorothiazide).

What is PritorPlus used for?

PritorPlus is used in adult patients who have essential hypertension (high blood pressure) that is not adequately controlled by telmisartan alone. 'Essential' means that the hypertension has no obvious cause.The medicine can only be obtained with a prescription.

How is PritorPlus used?

PritorPlus is taken by mouth once a day with liquid, with or without food. The dose of PritorPlus to be used depends on the dose of telmisartan that the patient was taking before: patients who were receiving 40 mg telmisartan should take the 40/12.5 mg tablets, and patients who were receiving 80 mg telmisartan should take the 80/12.5 mg tablets. The 80/25 mg tablets are used in patients whose blood pressure is not controlled using the 80/12.5 mg tablets or who have been stabilised using the two active substances taken separately before switching to PritorPlus.

How does PritorPlus work?

PritorPlus contains two active substances, telmisartan and hydrochlorothiazide.Telmisartan is an 'angiotensin II receptor antagonist', which means that it blocks the action of a hormone in the body called angiotensin II. Angiotensin II is a powerful vasoconstrictor (a substance that narrows blood vessels). By blocking the receptors to which angiotensin II normally attaches, telmisartan stops the hormone having an effect, allowing the blood vessels to widen.Hydrochlorothiazide is a diuretic, which is another type of treatment for hypertension. It works by increasing urine output, reducing the amount of fluid in the blood and reducing blood pressure.The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

How has PritorPlus been studied?

PritorPlus has been studied in five main studies involving a total of 2,985 patients with mild to moderate hypertension. In four of these studies, PritorPlus was compared with placebo (a dummy treatment) and with telmisartan taken alone in a total of 2,272 patients. The fifth study compared the effects of remaining on the 80/12.5 mg tablet with switching to the 80/25 mg tablet in 713 patients who had not responded to the 80/12.5 mg tablet. In all studies, the main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats).

What benefit has PritorPlus shown during the studies?

PritorPlus was more effective at reducing diastolic blood pressure than telmisartan taken alone and than placebo. In patients who were not controlled on the 80/12.5 mg tablet, switching to the 80/25 mg tablet was more effective in reducing diastolic blood pressure than remaining on the lower dose.

What is the risk associated with PritorPlus?

The most common side effect with PritorPlus (seen in between 1 and 10 patients in 100) is dizziness. For the full list of all side effects reported with PritorPlus, see the package leaflet.PritorPlus must not be used in women who are more than three months pregnant. Its use during the first three months of pregnancy is not recommended. PritorPlus must also not be used in people who have severe liver, kidney or bile problems, blood potassium levels that are too low, or blood calcium levels that are too high. In patients with type 2 diabetes or in patients with moderate or severe kidney impairment, PritorPlus must also not be used in combination with aliskiren-containing medicines (also used to treat essential hypertension). For the full list of restrictions, see the package leaflet.Care must be taken when using PritorPlus with other medicines that have an effect on blood potassium levels. The full list of these medicines is given in the package leaflet.

Why has PritorPlus been approved?

The CHMP decided that PritorPlus's benefits are greater than its risks for the treatment of essential hypertension in patients whose blood pressure is not adequately controlled on telmisartan alone. The Committee recommended that PritorPlus be given marketing authorisation.

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

A risk management plan has been developed to ensure that PritorPlus 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 PritorPlus, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Privigen

What is Privigen and what is it used for?

Privigen is a medicine used to support the immune system (the body's natural defences) in two main groups of patients:• Patients who are at risk of infection because they do not have enough antibodies (also called immunoglobulins, proteins in the blood that help the body to fight disease). These can be people who are born with a lack of antibodies (primary immunodeficiency syndrome, PID). These also include people who have developed a lack of antibodies after birth (secondary immunodeficiency syndrome, SID), who have low levels of certain antibodies (called IgG) and who suffer from infections that are severe, keep coming back, and are not cured by medicines used to treat infections.• Patients with certain immune disorders. These comprise patients with primary immune thrombocytopenia (ITP), who do not have enough platelets (components in the blood that help it to clot) and who are at high risk of bleeding; patients with Guillain-Barrι syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP), inflammatory disorders of the nerves that result in muscle weakness and numbness; patients with Kawasaki disease, a disease mainly seen in children which causes inflammation of blood vessels; and patients with multifocal motor neuropathy (MMN), nerve damage which causes weakness of the arms and legs.The medicine contains the active substance human normal immunoglobulin.

How is Privigen used?

Privigen can only be obtained with a prescription and treatment for patients with a lack of antibodies should be started and monitored by a doctor experienced in treating such conditions. The medicine is available as a solution for infusion (drip) into a vein.The dose and frequency of infusions (how often it is given) depend on the disease being treated. The dose may need to be adjusted for patients depending on their response.For more information about using Privigen, see the package leaflet or contact your doctor or pharmacist.

How does Privigen work?

The active substance in Privigen, human normal immunoglobulin, is a highly purified protein extracted from human plasma (part of the blood). It contains immunoglobulin G (IgG), which is a type of antibody. IgG has been used as a medicine since the 1980s and has a wide range of activity against organisms that can cause infection. Privigen works by restoring abnormally low IgG levels to their normal range in the blood. At higher doses, it can help to adjust an abnormal immune system and modulate the immune response.

What benefits of Privigen have been shown in studies?

As human normal immunoglobulin has been used to treat these diseases for a long time, and in accordance with current guidelines, only three small studies were needed to establish the effectiveness and safety of Privigen in patients. Privigen was not compared to other treatments in the studies.In the first study, Privigen was used in 80 patients with PID, with the medicine being infused every three or four weeks. The main measure of effectiveness was the number of serious bacterial infections over a year's treatment. The patients had an average of 0.08 serious infections per year. Since this is below the predefined threshold of one serious infection per year, this indicates that the medicine is effective as replacement therapy.The second study looked at using Privigen in 57 patients with ITP. Privigen was given on two consecutive days. The main measure of effectiveness was the highest blood platelet level that was achieved in the week after Privigen was given. In this study, 46 (81%) of the 57 patients had a platelet count above 50 million platelets per millilitre at least once during the study. This confirmed that Privigen is effective in immunomodulation.A third study examined the use of Privigen for immunomodulation in 28 patients with CIDP who were given Privigen every three weeks over a period of 24 weeks. The main measure of effectiveness was the number of patients who showed improvement of their disability, measured by a decrease on a 10point scale of disability in their arms and legs. In this third study, 17 (61%) of the 28 patients responded to treatment with an improvement of at least one point on the disability scale. The average improvement was about 1.4 points.

What are the risks associated with Privigen?

The most common side effects with Privigen (seen in more than 1 patient in 10) are headache, nausea, pain (including in the back, neck, limbs, joints and face), fever, chills and a flu-like illness.Some side effects are more likely with a high rate of infusion, in patients with low immunoglobulin levels, or in patients who have not received human normal immunoglobulin before or for a long time. For the full list of all side effects with Privigen, see the package leaflet.Privigen must not be used in people who are hypersensitive (allergic) to normal human immunoglobulin or any of the other ingredients, or in patients who are allergic to other types of immunoglobulins, especially where they have deficiency (very low levels) of immunoglobulin A (IgA) and they have antibodies against IgA. Privigen must not be used in patients with hyperprolinaemia type I or II (a genetic disorder causing high levels of the amino acid proline in the blood).

Why is Privigen authorised in the EU?

The European Medicines Agency concluded that Privigen'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 Privigen?

Haemolysis (breakdown of red blood cells) is an uncommon side effect in patients given human normal immunoglobulin (occurring with less than 1 dose in 100). Severe haemolysis has previously been reported to be slightly more frequent with Privigen than with some other products containing the same active substance. The company that markets Privigen has made some changes in the way it is produced to reduce this risk and is performing a study to monitor the effect of the changes.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Privigen have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Privigen are continuously monitored. Side effects reported with Privigen are carefully evaluated and any necessary action taken to protect patients.

---

Procoralan

What is Procoralan and what is it used for?

Procoralan is a heart medicine used to treat the symptoms of long-term stable angina (pains to the chest, jaw and back, brought on by physical effort) in adults with coronary artery disease (disease of the heart caused by the obstruction of the blood vessels that supply blood to the heart muscle).The medicine is used in patients who have a normal heart rhythm, and whose heart rate is at least 70 beats per minute. It is used in those who cannot be treated with beta blockers (another type of medicine to treat angina) or in combination with a beta blocker in patients whose disease is not controlled by beta blockers alone.Procoralan is also used in patients with long-term heart failure (when the heart cannot pump enough blood to the rest of the body) who have a normal heart rhythm and whose heart rate is at least 75 beats per minute. It is used in combination with standard therapy including beta blockers, or in patients who cannot be treated with beta blockers.Procoralan contains the active substance ivabradine.

How is Procoralan used?

Procoralan is available as tablets (5 and 7.5 mg) and it can only be obtained with a prescription.The recommended starting dose is 5 mg twice a day with meals, which the doctor may increase to 7.5 mg twice a day or decrease to 2.5 mg (half a 5-mg tablet) twice a day depending on the patient's heart rate and symptoms. In patients over 75 years old, a lower starting dose of 2.5 mg twice a day can be used. Treatment must be stopped if the heart rate is persistently below 50 beats per minute or if symptoms of bradycardia (slow heart rate) continue despite dose reduction. When used for angina, treatment should be stopped if symptoms do not improve after 3 months. Also, the doctor should consider stopping treatment if the medicine has only a limited effect on reducing angina symptoms or reducing the heart rate within 3 months.For more information about using Procoralan, see the package leaflet or contact your doctor or pharmacist.

How does Procoralan work?

The symptoms of angina are caused by the heart not receiving enough oxygenated blood. In stable angina, these symptoms appear during physical effort. The active substance in Procoralan, ivabradine, works by blocking the 'If currents' in the sinus node, the 'pacemaker' for the heart that controls the heart's contractions and regulates the heart rate. When these currents are blocked, the heart rate is lowered, so that the heart has less work to do and needs less oxygenated blood. Procoralan therefore reduces or prevents the symptoms of angina.The symptoms of heart failure are caused by the heart not pumping enough blood around the body. By lowering the heart rate, Procoralan reduces the stress on the heart, thereby slowing the progression of heart failure and improving symptoms.

What benefits of Procoralan have been shown in studies?

AnginaProcoralan was compared with placebo (a dummy treatment) and other treatments in five main studies involving over 4,000 adults with long-term stable angina. The main measure of effectiveness was how long patients could exercise on a bicycle or a treadmill, which was measured at the start and the end of each study. Each study lasted three to four months.Results showed that the medicine was more effective than placebo in one of the studies in 360 patients. It was as effective as atenolol (a beta blocker) in a study of 939 patients and as effective as amlodipine (another medicine used to treat angina) in a study of 1,195 patients. In a fourth study in 889 patients, Procoralan was more effective than placebo, when both were added to atenolol. However, a fifth study in 728 patients showed that adding Procoralan to amlodipine did not provide an additional benefit.A sixth study compared Procoralan with placebo in 19,102 patients with coronary artery disease and without clinical heart failure. The main measure of effectiveness was a reduction in the risk of death due to heart problems and non-fatal heart attack.In this study, a specific subgroup of patients who had symptomatic angina had a small but significant increase in the combined risk of cardiovascular death or non-fatal heart attack with Procoralan compared with placebo (3.4% vs 2.9% yearly incidence rates). However it should be noted that patients in this study were given doses higher than the recommended dose (up to 10 mg twice a day). Heart failureProcoralan was compared with placebo in one main study involving over 6,500 patients with long-term moderate to severe heart failure. Results showed that Procoralan was more effective than placebo at preventing death due to disease of the heart or blood vessels or hospitalisation due to worsening heart failure: 24.5% (793 out of 3,241) of patients treated with Procoralan died or were hospitalised due to worsening heart failure, compared with 28.7% (937 out of 3,264) of patients receiving placebo.

What are the risks associated with Procoralan?

The most common side effect with Procoralan (which may affect more than 1 in 10 people) is luminous phenomena or 'phosphenes' (a temporary brightness in the field of vision). Bradycardia (slow heart rate) is common (it may affect up to 1 in 10 people). For the full list of all side effects reported with Procoralan, see the package leaflet.Procoralan must not be used in patients who have a resting heart rate below 70 beats per minute, very low blood pressure, various types of heart disorder (including cardiogenic shock, rhythm disorders, heart attack, unstable or acute (sudden) heart failure and unstable angina) or severe liver problems. It must not be used in women who are pregnant, breast-feeding or by women who could become pregnant and who are not using appropriate contraceptives. Procoralan must not be taken with a number of other medicines.For the full list of restrictions with Procoralan, see the package leaflet.

Why is Procoralan authorised in the EU?

The European Medicines Agency concluded that Procoralan was shown to be effective in long-term angina with an acceptable safety profile for it to provide an alternative treatment for patients who cannot take beta blockers or whose disease is not controlled with them. It also concluded that Procoralan was effective in long-term heart failure with an acceptable safety profile. The Agency decided that Procoralan's benefits are greater than its risks and it can be authorised for use in the EU.For the treatment of angina, Procoralan was originally authorised for patients whose heart rate is at least 60 beats per minute. However, the use was later restricted to patients whose heart rate is at least 70 beats per minute.1

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

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

---

Procysbi

What is Procysbi and what is it used for?

Procysbi is a medicine that contains the active substance mercaptamine (also known as cysteamine). It is used in patients with nephropathic (kidney) cystinosis. Cystinosis is an inherited disease in which excess amounts of cystine, an amino acid naturally found in the body, build up within cells, especially in the kidneys and the eyes, damaging them.Because the number of patients with cystinosis is low, the disease is considered 'rare', and Procysbi was designated an 'orphan medicine' (a medicine used in rare diseases) on 20 September 2010.Procysbi is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Procysbi is available in a formulation that allows for a delayed release of the active substance in the body. The reference medicine for Procysbi is Cystagon.

How is Procysbi used?

Procysbi 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 cystinosis.Procysbi is available as gastroresistant capsules (25 and 75 mg). Gastroresistant means that the capsules' contents pass through the stomach without being broken down until they reach the intestine. The recommended daily dose is calculated according to body surface area, as 1.30 g per m2 dividedinto 2 doses given every 12 hours. Cystine levels in white blood cells (which are measured as nmol hemicystine per mg white blood cell protein), or alternatively mercaptamine concentration in the blood, should be monitored and used to adjust the dose, which should never exceed 1.95 g per m2 per day.For further information, see the package leaflet.

How does Procysbi work?

The active substance in Procysbi, mercaptamine, reacts with cystine to form another amino acid, called cysteine, and a compound called a cysteine-cysteamine salt. The body is able to remove this salt from the cells. The amount of cystine in the organs is therefore reduced, and this limits the damage to these organs.

What benefits of Procysbi have been shown in studies?

Procysbi given every 12 hours has been shown to be at least as effective as Cystagon given every 6 hours at maintaining the amount of cystine in white blood cells at acceptable levels (less than 1 nmol hemicystine per mg of white blood cell protein). In a main study involving 43 patients with nephropathic cystinosis, there was no meaningful difference between the average levels of cystine in white blood cells during a 3-week treatment with the two medicines. Levels were 0.51 nmol/mg with Procysbi, compared with 0.44 nmol/mg with Cystagon.

What are the risks associated with Procysbi?

The most common side effects with Procysbi (which may affect more than 1 in 10 people) are loss of appetite, vomiting, nausea (feeling sick), diarrhoea, lethargy (lack of energy) and pyrexia (fever). For the full list of all side effects reported with Procysbi, see the package leaflet.Procysbi must not be used in people who are hypersensitive (allergic) to any form of mercaptamine or any of the other ingredients, or to penicillamine. It must also not be used in women who are breastfeeding.

Why is Procysbi approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Procysbi's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that Procysbi was shown to be at least as effective as Cystagon at maintaining the amount of cystine in white blood cells at acceptable levels. The Committee also considered that the gastroresistant formulation, due to its less frequent administration, is expected to increase compliance with treatment and the quality of life of patients with cystinosis. Regarding its safety, the CHMP considered that the safety profile of mercaptamine is well established and the safety of Procysbi is expected to be similar to that of the reference medicine.

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

A risk management plan has been developed to ensure that Procysbi 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 Procysbi, including the appropriate precautions to be followed by healthcare professionals and patients.ProcysbiIn addition, the company that markets Procysbi will provide educational material to all doctors expected to prescribe the medicine, containing important safety information including the risk that the medicine may be harmful to the unborn child.

---

Prolia

What is Prolia and what is it used for?

Prolia is a medicine used to treat the following conditions:• osteoporosis (a disease that makes bones fragile) in women who have been through the menopause and in men who have an increased risk of fracture (broken bones). In women who have been through the menopause Prolia reduces the risk of fractures in the spine and elsewhere in the body, including in the hip;• bone loss in men receiving treatment for prostate cancer that increases their risk of fracture. Prolia reduces the risk of fractures in the spine;• bone loss in adults at increased risk of fractures who are treated long term with corticosteroid medicines given by mouth or injection.The medicine contains the active substance denosumab.

How is Prolia used?

Prolia is available as a solution for injection in prefilled syringes, each containing 60 mg denosumab.Prolia is given once every 6 months as a 60 mg injection under the skin in the thigh, abdomen (belly) or back of the arm. During treatment with Prolia, the doctor should ensure that the patient is receiving calcium and vitamin D supplements. Prolia can be given by someone who has been trained in how to give injections appropriately.The medicine can only be obtained with a prescription. For more information about using Prolia, see the package leaflet or contact your doctor or pharmacist.

How does Prolia work?

The active substance in Prolia, denosumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a specific structure in the body called RANKL. RANKL is involved in activating osteoclasts, the cells in the body that are involved in breaking down bone tissue. By attaching to and blocking RANKL, denosumab reduces the formation and activity of the osteoclasts. This reduces the loss of bone and maintains bone strength, making fractures less likely to happen.

What benefits of Prolia have been shown in studies?

Osteoporosis in womenProlia has been shown to be more effective than placebo (a dummy treatment) at reducing fractures in two main studies involving a total of over 8,000 women with osteoporosis who had been through the menopause. In the first of these studies, 2% of the women receiving Prolia had a new spine fracture after 3 years of treatment compared with 7% of the women receiving placebo. Prolia was also more effective at reducing the number of women who had fractures elsewhere in the body, including in the hip.In the second study, the women were receiving treatment for breast cancer and were considered to be at high risk of fracture. Women who took Prolia had higher bone density (a measure of how strong the bones are) in the lumbar (lower) spine after 1 year of treatment than women on placebo.Osteoporosis in menProlia has been compared with placebo in one main study involving 242 men with osteoporosis. In men who took Prolia bone density increased by 5.7% after 1 year of treatment compared with a 0.9% increase in men who took placebo.Bone loss in men receiving treatment for prostate cancerProlia has been shown to be more effective than placebo at treating bone loss in one main study involving 1,468 men receiving treatment for prostate cancer who were at an increased risk of fracture.After 2 years, men who received Prolia had an increase in bone density in the lumbar spine that was 7% higher than in those who received placebo. In addition, after 3 years the risk of new spine fractures was lower in patients who received Prolia.Bone loss in adults receiving long-term corticosteroid therapyProlia has been shown to be more effective than risedronate (a bisphosphonate medicine) at increasing bone density in one main study involving 795 adults treated with corticosteroid medicines. In patients who had been treated with corticosteroids for up to 3 months before the study, bone density in the lumbar spine increased by 3.1% after 1 year of treatment with Prolia compared with a 0.8% increase with risedronate. In patients who had been treated with corticosteroids for more than 3 months before the study, lumbar spine bone density increased by 3.6% after 1 year of treatment with Prolia compared with a 2.0% increase with risedronate.

What are the risks associated with Prolia?

The most common side effects with Prolia (seen in more than 1 patient in 10) are pain in the arms or legs, and bone, joint and muscle pain. Uncommon or rare cases of cellulitis (inflammation of deep skin tissue), hypocalcaemia (low blood calcium), hypersensitivity (allergy), osteonecrosis of the jaw (damage to the bones of the jaw, which could lead to pain, sores in the mouth or loosening of teeth) and unusual fractures of the thigh bone have been seen in patients taking Prolia.Prolia must not be used in people with hypocalcaemia (low blood calcium levels).For the full list of side effects and restrictions with Prolia, see the package leaflet.

Why is Prolia authorised in the EU?

The European Medicines Agency decided that Prolia'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 Prolia?

The company that markets Prolia will provide a card to inform patients about the risk of osteonecrosis of the jaw and to instruct them to contact their doctor if they experience symptoms.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Prolia have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Prolia are continuously monitored. Side effects reported with Prolia are carefully evaluated and any necessary action taken to protect patients.

---

Prometax

What is Prometax?

Prometax is a medicine containing the active substance rivastigmine. It is available as capsules (1.5, 3,4.5 and 6 mg), as an oral solution (2 mg/ml), and as transdermal patches, which release either 4.6 , 9.5 or 13.3 mg rivastigmine across the skin over 24 hours.

What is Prometax used for?

Prometax 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.The capsules and oral solution 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 Prometax used?

Treatment with Prometax 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 give and monitor the use of Prometax 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.Prometax capsules or oral solution 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.If the transdermal patches are used, the 4.6 mg per 24 hours patch should be used first, with the dose increased to the 9.5 mg/24 h patch after at least four weeks if the lower dose is well tolerated. The 9.5 mg/24 h patch should be used for as long as the patient benefits from it. After six months of treatment with 9.5 mg/24 hours, the doctor may increase the dose to 13.3 mg/24 hours if the patient's condition has worsened. The patches are applied to clean, dry, hairless, intact skin on the back, upper arm or chest, and are replaced every 24 hours. They should not be placed on irritated or red skin, on the thigh or abdomen (tummy), or in places where they will be rubbed by tight clothing. The patches can be worn during bathing and hot weather. The patches should not be cut into pieces. Patients can be switched from the capsules or oral solution to the patches. See the summary of product characteristics (also part of the EPAR) for detailed information.

How does Prometax work?

The active substance in Prometax, 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 substance 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, Prometax allows levels of acetylcholine to be increased in the brain, helping to reduce the symptoms of Alzheimer's dementia and dementia associated with Parkinson's disease.

How has Prometax been studied?

Prometax has been studied in mild to moderately severe Alzheimer's disease. The capsules have been studied in 2,126 patients in three main studies, and the transdermal patches in one main study involving 1,195 patients. Prometax capsules have also been studied in 541 patients with dementia due to Parkinson's disease. All of the studies lasted six months and compared the effects of Prometax 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 Prometax capsules and oral solution produced similar levels of the active substance in the blood.

What benefit has Prometax shown during the studies?

Prometax was more effective than placebo at controlling symptoms. In the three studies of Prometax capsules in patients with Alzheimer's dementia, patients taking doses of Prometax 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 Prometax capsules had in increase in symptoms of 4.1 points, compared with 4.4 in those taking placebo. The Prometax transdermal patches were also more effective than placebo in preventing dementia from getting worse.The patients with dementia due to Parkinson's disease taking Prometax 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 Prometax.

What is the risk associated with Prometax?

The types of side effects seen with Prometax depend on the type of dementia it is being used to treat and whether the capsules, oral solution or transdermal patches are used. Overall, the most common side effects (seen in more than 1 patient in 10) include nausea (feeling sick) and vomiting, particularly during the phase when the dose of Prometax is being increased. For the transdermal patch application site reactions are the most commonly seen side effects. For the full list of all side effects reported with Prometax, see the package leaflet.Prometax must not be used in people who are hypersensitive (allergic) to rivastigmine, other carbamate derivatives or any of the other ingredients. Prometax must also not be used in patients who are suspected to have had in the past a severe allergic reaction called 'allergic contact dermatitis' to Prometax patch.

Why has Prometax been approved?

The CHMP concluded that Prometax has a modest effectiveness in treating the symptoms ofAlzheimer'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, Prometax'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 Prometax's benefits are greater than its risks and recommended that it be given marketing authorisation.

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

The company that makes Prometax must ensure that all doctors who intend to prescribe Prometax transdermal patch receive an information pack containing instructions to be given to patients and caregivers on how to use the patch safely as well as a reminder card for patients and caregivers that contains key information on how to use the patch and allows them to record the application and removal of patches.

---

Proquad

What is ProQuad an what is it used for?

ProQuad is a vaccine against measles, mumps, rubella, and varicella (chickenpox).ProQuad is given to children from 12 months of age to help protect them against measles, mumps, rubella, and chickenpox. ProQuad may also be given to children from 9 months of age in certain situations, for example as part of a national vaccination programme, during an outbreak or for travel to a region where measles is common.

ProQuad contains attenuated (weakened) viruses for the diseases. How is ProQuad used?

ProQuad is injected into a muscle or under the skin, preferably in the thigh in younger children and in the upper arm in older children and adults. Rarely, in a child with a bleeding disorder, the vaccine is injected under the skin to prevent excessive bleeding.For children above 12 months of age, one ProQuad injection is sufficient for protection against measles, mumps and rubella. To protect against chickenpox, a second injection needs to be given 1 to 3 months after the first one; this can be done either by giving a second dose of ProQuad or by giving a vaccine that only protects against chickenpox.Children between 9 and 12 months of age should receive a second dose at least 3 months after the first dose for adequate protection against measles and chickenpox.ProQuad can only be obtained with a prescription. It is used according to official recommendations, including recommendations about the number of doses and the interval between them.

How does ProQuad work?

ProQuad contains weakened forms of the viruses that cause measles, mumps, rubella and chickenpox.When a person receives the vaccine, it triggers an immune response against the weakened viruses. Later, when the person comes into contact with the actual viruses, the immune system recognises them and is already prepared to attack the viruses and so protects the person from the disease.An agency of the European

What benefits of ProQuad have been shown in studies??

Because ProQuad contains well known weakened viruses, which are used in other vaccines, the company presented data from vaccines that are already on the market. Five main studies were carried out in 6,987 healthy children (aged 12 to 23 months). In these studies, after one dose, the response rates in children (measuring how well the immune system had responded to the viruses) were: 98% for measles, 96 to 99% for mumps, 99% for rubella and 91% for chickenpox. After the second dose, the rates were around 99% for measles, 100% for mumps, 98% for rubella, and 99% for chickenpox.Another study in 1,620 children from 9 to 12 months of age showed that, after two doses of ProQuad given 3 months apart, the immune response against mumps, rubella and chickenpox in children who received the first dose at 9 months of age was comparable with those who received the first dose at 12 months of age. However, children who received the first dose at 9 months of age had a lower immune response against measles.

What are the risks associated with ProQuad?

The most common side effects with ProQuad (which may affect more than 1 in 10 people) are fever, and pain and erythema (redness) at the site of injection. For the full list of side effects of ProQuad, see the package leaflet.ProQuad must not be used in children who are hypersensitive (allergic) to any chickenpox vaccine or measles, mumps or rubella vaccine, or to any of the other ingredients including neomycin. It must not be used in children who have severely weakened immune systems. It must also not be used in a pregnant woman. For the full list of restrictions, see the package leaflet.

Why has ProQuad been approved?

The European Medicines Agency decided that ProQuad's benefits are greater than its risks and it can be authorised for use in the EU in children above 12 months of age and in certain situations from 9 months of age, noting that a second vaccination against chickenpox should be given for full protection against the disease.The Agency also recommended that the vaccine be authorised in children from 9 to 12 months of age only in certain situations, for example as part of a national vaccination programme, during an outbreak or for travel to a region where measles is common.

---

Protaphane

What is Protaphane?

Protaphane is a suspension for injection that contains the active substance human insulin. It is available as vials, cartridges (Penfill), or pre-filled pens (InnoLet or FlexPen).

What is Protaphane used for?

Protaphane is used to treat diabetes.The medicine can only be obtained with a prescription.

How is Protaphane used?

Protaphane is given by injection under the skin, usually in the thigh, the abdominal wall (at the front of the waist), the gluteal region (buttocks) or the deltoid region (shoulder). The injection site should be changed for each injection. The patient's blood glucose (sugar) should be tested regularly to find the lowest effective dose.Protaphane is a long-acting insulin. It can be given once or twice a day, with or without a fast-acting insulin (given at meal times), according to the doctor's recommendation. The usual dose is between 0.3 and 1.0 international units (IU) per kilogram body weight per day.

How does Protaphane work?

Diabetes is a disease in which the body does not produce enough insulin to control the blood glucose or when the body is unable to use insulin effectively. Protaphane is a replacement insulin which is very similar to the insulin made by the pancreas. The active substance in Protaphane, human insulin, is produced by a method known as 'recombinant technology': it is made by yeast cells into which a gene (DNA) has been introduced which makes them able to produce insulin.Protaphane contains insulin mixed with another substance, protamine, in an 'isophane' form which is absorbed much more slowly during the day. This gives Protaphane a longer duration of action. The replacement insulin acts in same way as naturally produced insulin and helps glucose enter cells from the blood. By controlling the blood glucose, the symptoms and complications of diabetes are reduced.

How has Protaphane been studied?

Protaphane has been studied in four main clinical trials, which included a total of 557 patients with type 1 diabetes, when the pancreas cannot produce insulin (two studies involving 81 patients), or type 2 diabetes, when the body is unable to use insulin effectively (two studies involving 476 patients).In most patients, Protaphane was compared with other types of human insulin or insulin analogues. The studies measured the level of fasting blood glucose or glycosylated haemoglobin (HbA1c, the haemoglobin in the blood that has glucose attached). HbA1c gives an indication of how well the blood glucose is controlled. Further studies were also carried out in 225 patients comparing injecting Protaphane using a syringe, or using a pre-filled pen (InnoLet or FlexPen).

What benefit has Protaphane shown during the studies?

Protaphane led to a decrease in the level of HbA1c, indicating that blood sugar levels had been controlled to a similar level to that seen with other human insulin. Protaphane was effective for both type 1 and type 2 diabetes, and when using a standard injection or one of the pre-filled pens.

What is the risk associated with Protaphane?

The most common side effect with Protaphane (seen in more than 1 patient in 10) is hypoglycaemia (low blood glucose levels). For the full list of all side effects and restrictions, see the package leaflet.

Why has Protaphane been approved?

The CHMP decided that Protaphane'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 Protaphane?

A risk management plan has been developed to ensure that Protaphane 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 Protaphane, including the appropriate precautions to be followed by healthcare professionals and patients.

---

Protopic

What is Protopic?

Protopic is an ointment that contains the active substance tacrolimus (0.1% and 0.03%).

What is Protopic used for?

Protopic is used to treat 'flare-ups' (recurrence or worsening) of moderate to severe atopic dermatitis (eczema, an itchy red rash of the skin). 'Atopic' means that the dermatitis is linked to an allergy. Protopic is used in patients aged two years and above who do not respond well to or do not tolerate conventional treatments such as locally applied corticosteroids.Protopic can also be used to prevent flare-ups of the disease or prolong the time that patients are free from flare-ups. In maintenance treatment, it is used in patients who usually have four or more flareups per year and who have had a response to an initial course of Protopic used twice a day for up to six weeks.While Protopic 0.03% can be used in all patients over two years of age, Protopic 0.1% is only used in adults and adolescents over 16 years of age.The medicine can only be obtained with a prescription.

How is Protopic used?

Protopic should be prescribed by a doctor with experience in the diagnosis and treatment of atopic dermatitis. The ointment should be applied as a thin layer to the skin.When used for flare-ups, Protopic can be used for short-term and intermittent long-term treatment, but it should not be used continuously on a long-term basis. Protopic treatment should begin as soon as symptoms appear. Each affected area is treated twice a day with Protopic until the skin is clear. Generally, improvement is seen within one week of starting treatment. If there is no improvement after two weeks, the doctor should consider other treatment options. Children should use Protopic 0.03% twice a day for up to three weeks before reducing the frequency to once a day. Adults should start treatment with Protopic 0.1% twice a day but should switch to less frequent application or use of the lower strength (0.03%) as the condition improves.When used as maintenance treatment, Protopic should be applied twice a week to areas of the skin commonly affected by the disease. If there are signs of a flare-up, treatment should revert to twice a day as above. The doctor should review the need to continue maintenance treatment after a year. In children, this should include suspension of treatment to allow the doctor to assess whether continued treatment for the disease is necessary.

How does Protopic work?

The way in which Protopic works in atopic dermatitis is not fully understood. The active substance in Protopic, tacrolimus, is an immunomodulator. This means that it works on the immune system (the body's natural defences). Tacrolimus has been used since the mid-1990s to help prevent rejection in transplant patients (when the immune system attacks the transplanted organ). In atopic dermatitis, an over-reaction of the skin's immune system causes skin inflammation (itchiness, redness and dryness). Tacrolimus reduces the activity of the immune system, helping to relieve the skin inflammation and the itching.

How has Protopic been studied?

The use of Protopic in the treatment of flare-ups has been studied in six main studies involving 1,202 patients over the age of 16 years, and 1,535 aged from two to 16 years. Protopic was compared either with placebo (a dummy treatment) or with hydrocortisone (a corticosteroid often used for eczema). The main measure of effectiveness was the improvement in the eczema seen at the end of the studies, after three or 12 weeks, using a scoring system that looks at all of the symptoms of atopic dermatitis.Another study looked at the repeated use of Protopic for up to four years in about 800 patients.Maintenance treatment with Protopic has been studied in two main studies involving 224 patients aged 16 years or over, and 250 aged from two to 15 years. All of the patients had atopic dermatitis that had responded to a maximum of six weeks of previous treatment with Protopic. The studies compared twice-weekly Protopic with placebo, although both groups of patients could use Protopic whenever they had a flare-up of the disease. The main measure of effectiveness was the number of flare-ups the patients had over a year.

What benefit has Protopic shown during the studies?

In the treatment of flare-ups of atopic dermatitis, Protopic was more effective than hydrocortisone at producing improvements in symptoms, although it also produced more burning than hydrocortisone. In the longer study, Protopic could be used repeatedly without losing its effectiveness.In maintenance treatment, Protopic was more effective than placebo at reducing the number of flare-ups. In both studies, the patients with moderate to severe disease who were using Protopic had an average of one flare-up over a year, compared with three in those using placebo.

What is the risk associated with Protopic?

The most common side effects with Protopic (seen in more than 1 patient in 10) are a burning sensation and itching at the application site. For the full list of all the side effects reported with Protopic, see the package leaflet.Protopic should not be used in people who may be hypersensitive (allergic) to tacrolimus, any of the other ingredients or macrolides.

Why has Protopic been approved?

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

---

Puregon

What is Puregon?

Puregon is a powder and solvent to be made up into a solution for injection. It is also available as a solution for injection in a vial or a cartridge. Puregon contains the active substance follitropin beta.

What is Puregon used for?

Puregon is used to treat infertility in women in the following situations:• women who are anovulatory (do not produce eggs) and do not respond to treatment with clomiphene citrate (another medicine that stimulates ovulation).• women who are undergoing fertility treatment (assisted reproductive techniques, such as in vitro fertilisation). Puregon is administered to stimulate the ovaries to produce more than one egg at atimePuregon can also be used to stimulate sperm production in men who have hypogonadotrophic hypogonadism (a rare hormone deficiency disease).Puregon can only be obtained with a prescription.

How is Puregon used?

Treatment with Puregon should be carried out by a doctor who has experience in the treatment of fertility problems. Puregon is given as a 'subcutaneous' injection (under the skin) or into a muscle. The powder should be mixed with the solvent provided just before use. The patient or their partner may carry out the injections. Puregon should only be administered by people who have been trained by the doctor and have access to expert advice. The dose and frequency of administration of Puregon depend on its use (see above) and the patient's response to treatment. For a full description of the doses, please see the Package Leaflet.

How does Puregon work?

The active substance in Puregon, follitropin beta, is a copy of the natural hormone follicle stimulating hormone (FSH). In the body, FSH regulates the reproductive function: in women, it stimulates the production of eggs, and in men, it stimulates the production of sperm by the testicles. Previously, the FSH used as a medicine was extracted from urine. The follitropin beta in Puregon 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 FSH.

How has Puregon been studied?

Puregon's use in women undergoing fertility treatment has been studied in 981 patients. The number of eggs recovered and the ongoing pregnancy rate were the main measures of effectiveness. Puregon was studied in 172 anovulatory women, measuring how many cycles of treatment were needed for these women to ovulate. In men, Puregon was studied to see its effect on sperm production in 49 patients. In all of the studies, Puregon was compared to the natural FSH hormone that was extracted from urine.

What benefit has Puregon shown during the studies?

Puregon was as effective as the comparator in all of the studies. Puregon was as effective as urinary FSH as a fertility treatment, in producing ovulation and in producing sperm.

What is the risk associated with Puregon?

The most common side effects reported are a reaction and pain at the injection site. In 4 % of the women treated with Puregon in clinical studies, signs and symptoms related to ovarian hyperstimulation syndrome (e.g. feeling sick, weight gain, and diarrhoea) have been reported. Ovarian hyperstimulation syndrome occurs when the ovaries over-respond to treatment. Doctors and patients must be aware of this possibility. For a full list of all side effects reported with Puregon, see the Package Leaflet.Puregon should not be used in people who may be hypersensitive (allergic) to follitropin beta or any of the other ingredients. Puregon must not be used in patients with tumours of the ovary, breast, womb, testicle, pituitary gland or hypothalamus. It must not be used in men with testicular failure. In women, it must not be used when there is ovarian failure, ovarian enlargement or the presence of cysts that are not due to polycystic ovarian disease, or vaginal bleeding. For the full list of restrictions, see the Package Leaflet.

Why has Puregon been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Puregon's benefits are greater than its risks in the female for the treatment of infertility, and in the male for deficient spermatogenesis due to hypogonadotrophic hypogonadism. The Committee recommended that Puregon be given marketing authorisation.

---

Pylclari

What is Pylclari and what is it used for?

Pylclari is a diagnostic medicine used in adults with prostate cancer to detect prostate cancer cells with a protein called prostate-specific membrane antigen (PSMA), using the body scan known as positronemission tomography (PET).It is used:• to find out whether prostate cancer has spread to lymph nodes and other tissues outside the prostate before treatment is started;• to find out whether prostate cancer has returned in patients whose blood levels of prostate specific antigen (PSA) are increasing after previous treatment.Pylclari contains the active substance piflufolastat (18F).

How is Pylclari used?

The medicine can only be given in a designated nuclear medicine facility by trained healthcare professionals with technical expertise in using and handling nuclear medicine imaging agents.Pylclari is given as an injection into a vein and a PET scan is done after the injection.For more information about using Pylclari, see the package leaflet or contact your doctor or pharmacist.

How does Pylclari work?

The active substance of Pylclari, piflufolastat (18F), binds to PSMA, which is found in large numbers on the surface of most prostate cancer cells. When this diagnostic medicine is given to a patient, it binds to PSMA and is taken up by the cells. Because it contains radioactive fluorine (18F) it gives off radiation, which can be detected during a PET scan. Doctors can then see where in the body the cancer cells are.Pylclari does not treat prostate cancer.

What benefits of Pylclari have been shown in studies?

The benefits of Pylclari were shown in three main studies.In the first study in 385 men with prostate cancer, all patients received Pylclari and underwent a PET scan to check the location of cancer cells. After three different doctors had looked at the scan, patients with high-risk cancer then had surgery to remove their prostate.Among the 252 patients whose prostate was removed, the results of the PET scan correctly showed the absence of cancer cells in parts of their prostate in over 96% of patients.The second study included 208 men with suspected prostate cancer that had come back after treatment and that could not be confirmed using a standard scan. In this study, all patients received Pylclari and underwent a PET scan. The results of the PET scan showed at least one cancer lesion in 59 to 66% of patients, depending on the doctor analysing the results of the scan, and the scan correctly identified the location of the lesion in 85 to 87% of them.The third study included 215 men with suspected prostate cancer that had returned after treatment. These patients received either Pylclari or 18F-fluorocholine (another diagnostic medicine used for imaging) before they had a PET scan, and then received the other diagnostic medicine and had another PET scan up to 12 days later. The PET scans revealed prostate cancer in 58% of these patients after they were given Pylclari, compared with 40% after patients had received the other diagnostic medicine.

What are the risks associated with Pylclari?

For the full list of side effects and restrictions with Pylclari, see the package leaflet.The most common side effects with Pylclari (which may affect more than 1 in 100 people) include headache and loss of taste (dysgeusia).

Why is Pylclari authorised in the EU?

The European Medicines Agency considered that the use of Pylclari offered improvements over existing methods for detecting prostate cancer that has not yet been treated or has returned, and for screening patients who may benefit from PSMA-targeted treatment. Pylclari's side effects were usually mild and its safety profile was considered acceptable. The Agency therefore decided that Pylclari'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 Pylclari?

The company that markets Pylclari will provide medical practitioners who are expected to use this diagnostic medicine with educational materials to support interpretation of PET scans.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Pylclari have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Pylclari are continuously monitored. Suspected side effects reported with Pylclari are carefully evaluated and any necessary action taken to protect patients.

---

Pylobactell

What is Pylobactell?

Pylobactell is a diagnostic test. It is available as a kit that includes a white soluble tablet containing 100 mg of the active substance 13C-urea.

What is Pylobactell used for?

Pylobactell is used to diagnose Helicobacter pylori (H. pylori) infection in the stomach and duodenum (the part of the gut just below the stomach). H. pylori is a bacterium that is a factor in diseases such as dyspepsia (heartburn, bloating and nausea), gastritis (inflammation of the stomach) and peptic ulcer disease (ulcers in the stomach or the duodenum). The medicine can only be obtained with a prescription.

How is Pylobactell used?

Pylobactell is a breath test: breath samples are collected in the tubes provided in the kit. These samples are then sent for analysis at a specialised laboratory.To carry out the test, the patient must collect six breath samples, three before taking the Pylobactell tablet and three after taking it. The patient should fast for four hours before the test so that it is done on an empty stomach. If the patient has eaten a heavy meal then they should fast for six hours before the test.First, the patient takes a 'test meal' (such as 200 ml of pure undiluted orange juice). Five minutes later, the patient collects three breath samples. After a further five minutes, the patient takes the Pylobactell tablet dissolved in water. Finally, 30 minutes later (40 minutes after the test meal), the patient collects a further three breath samples. For full information on how the test is carried out, see the Package Leaflet.Pylobactell is not recommended for use in patients below 18 years of age because there is insufficient information on its effectiveness in this group.

How does Pylobactell work?

The active substance in Pylobactell, 13C-urea, is the natural chemical urea that has been labelled with carbon-13 (13C). This means that it contains 13C, a rare form of the carbon atom, instead of carbon-12 (12C), the form that is the most common in nature.H. pylori produces enzymes called ureases that break down urea into ammonia and carbon dioxide.The carbon dioxide is then removed from the body in the breath. If the patient has , the 13C-ureacontained in the Pylobactell tablet is broken down and the carbon dioxide in the breath also contains 13C. This 13C-labelled carbon dioxide can be measured by specialised laboratories using a technique called mass spectrometry. If there is an increased level of labelled carbon dioxide in the breath sample after 30 minutes (a positive test), the patient may have H. pylori in the stomach or duodenum. If there is no increased level of labelled carbon dioxide in the breath, the patient might not have H. pylori in the stomach or duodenum.

How has Pylobactell been studied?

The data to support the use of Pylobactell comes from two main studies of the use of antibiotics to treat H. pylori infection, where it was used as a test. A total of 366 patients underwent both a Pylobactell test and a standard biopsy test (where a sample from the stomach is analysed to see if it is infected). The results obtained were compared to see if they agreed.

What benefit has Pylobactell shown during the studies?

Pylobactell was more than 95% sensitive in detecting infection with H. pylori.

What is the risk associated with Pylobactell?

There are no known side effects of the test.Pylobactell should not be used in people who may be hypersensitive (allergic) to 13C-urea or any of the other ingredients in the tablet. Pylobactell should not be used in patients who have, or may have gastric (stomach) infection, which might interfere with the breath test.

Why has Pylobactell been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Pylobactell's benefits are greater than its risks for the in vivo diagnosis of gastroduodenal H. pylori infection. The Committee recommended that Pylobactell be given marketing authorisation.

---

Pyrukynd

What is Pyrukynd and what is it used for?

Pyrukynd is a medicine used to treat adults with pyruvate kinase deficiency (PKD), an inherited disease that causes red blood cells to break down faster than normal.PKD is rare, and Pyrukynd was designated an 'orphan medicine' (a medicine used in rare diseases) on 22 April 2020. Further information on the orphan designation can be found here: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-20-2270.Pyrukynd contains the active substance mitapivat.

How is Pyrukynd used?

Pyrukynd can only be obtained with a prescription. It is available as tablets to be taken by mouth. The recommended starting dose is one 5 mg tablet taken twice a day. The dose can be increased every four weeks, based on the patient's haemoglobin (the protein in red blood cells that carries oxygen around the body) levels and their need for a transfusion in the previous 8 weeks. The maximum recommended dose of Pyrukynd is 50 mg twice a day.If treatment needs to be interrupted or stopped completely, the dose of Pyrukynd should be gradually reduced over a period of 1 to 2 weeks.For more information about using Pyrukynd, see the package leaflet or contact your doctor or pharmacist.

How does Pyrukynd work?

Patients with PKD have a defective form of pyruvate kinase, a protein in red blood cells which converts glucose into energy. As a result, their red blood cells cannot make enough energy to hold their shape, causing them to break down before the body has time to replace them. This excessive breakdown of red blood cells is known as haemolytic anaemia.The active substance in Pyrukynd, mitapivat, attaches to and activates pyruvate kinase, causing it to work more effectively and thereby preventing the red blood cells of these patients from being broken down too fast.

What benefits of Pyrukynd have been shown in studies?

The benefits of Pyrukynd were evaluated in two main studies. In the first study, involving 80 patients with PKD who were not regularly receiving blood transfusions, Pyrukynd was compared with placebo (dummy treatment). In this study, 40% of patients treated with Pyrukynd had an increase of their haemoglobin levels of 1.5 g/dL, which was maintained at 2 or more check-ups carried out after 16, 20 and 24 weeks of treatment, compared with none of the patients treated with placebo.In the second study, involving 27 patients who were regularly receiving blood transfusions, Pyrukynd was not compared with placebo or any other medicines. In this study, the volume of red blood cells received in transfusions was reduced by more than a third in 37% of patients.

What are the risks associated with Pyrukynd?

The most common side effects with Pyrukynd (which may affect more than 1 in 10 people) are insomnia (difficulty sleeping), nausea (feeling sick) and decreased levels of the hormone oestrone seen in blood tests in male patients.For the full list of side effects and restrictions of Pyrukynd, see the package leaflet.

Why is Pyrukynd authorised in the EU?

There are limited treatment options for patients with PKD as management of the disease is restricted to supportive treatments to improve the symptoms and complications associated with haemolytic anaemia. Although there were some limitations associated with the main studies, Pyrukynd has been shown to provide clinically meaningful benefits to some patients with PKD, by increasing haemoglobin levels and reducing the need for transfusions. It was therefore considered that Pyrukynd addressed an unmet medical need in these patients.Furthermore, the side effects of Pyrukynd are considered manageable. The European Medicines Agency therefore decided that Pyrukynd'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 Pyrukynd?

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

---