E.P.A.R s  Editing

Iasibon

What is Iasibon?

Iasibon is a medicine that contains the active substance ibandronic acid. It is available as a concentrate that is made up into a solution for infusion (drip into a vein) and as tablets (50 mg).Iasibon is a 'generic medicine'. This means that Iasibon is similar to a 'reference medicine' already authorised in the European Union (EU) called Bondronat. For more information on generic medicines, see the question-and-answer document here.

What is Iasibon used for?

Iasibon is used in the following ways:• as an infusion or as a tablet to prevent 'skeletal events' (fractures [broken bones] or bone complications requiring treatment) in patients with breast cancer and bone metastases (when the cancer has spread to the bone);• as an infusion to treat hypercalcaemia (high levels of calcium in the blood) caused by tumours.The medicine can only be obtained with a prescription.

How is Iasibon used?

Iasibon treatment should only be started by a doctor who has experience in the treatment of cancer.In the prevention of skeletal events, Iasibon is either given as a 6-mg infusion lasting at least 15 minutes every three to four weeks, or as one tablet once a day. The tablets must always be taken after the patient has not eaten anything for at least six hours overnight and at least 30 minutes before thefirst food or drink of the day. They must be taken with a full glass of plain water (in areas with hard water, where tap water contains a lot of dissolved calcium, bottled water with a low mineral content should be used). The tablet should be taken while standing or sitting up, and it should not be chewed, sucked or crushed. The patient must not lie down for one hour after taking the tablet. Patients with moderate or severe kidney problems should receive Iasibon infusions at a lower dose over an hour, or the tablets every two days or every week.In the treatment of hypercalcaemia caused by tumours, Iasibon is given over 2 hours as an infusion of either 2 or 4 mg, depending on how severe the hypercalcaemia is. The infusion will normally bring the blood calcium level down to normal levels within a week.

How does Iasibon work?

The active substance in Iasibon, ibandronic acid, is a bisphosphonate. It stops the action of the osteoclasts, the cells in the body that are involved in breaking down the bone tissue. This leads to less bone loss. The reduction of bone loss helps to make bones less likely to break, which is useful in preventing fractures in cancer patients with bone metastases.Patients with tumours can have high levels of calcium in their blood, released from the bones. By preventing the breakdown of bones, Iasibon also helps to reduce the amount of calcium released into the blood.

How has Iasibon been studied?

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

What are the benefits and risks of Iasibon?

Because Iasibon 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 Iasibon been approved?

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

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

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

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Ibandronic Acid Accord

What is Ibandronic acid Accord and what is it used for?

Ibandronic acid Accord is a medicine used to treat certain conditions affecting bones and blood calcium.Ibandronic acid Accord solution for injection is used to treat osteoporosis (a disease that makes bones fragile) in women who have been through the menopause and are at risk of developing bone fractures (breaks). Its effect in reducing the risk of spine fractures has been shown in studies, but its effect on the risk of fractures of the neck of the femur (the top of the thighbone) has not been established. Ibandronic acid Accord concentrate for solution for infusion (drip) is used in adults to:• prevent 'skeletal events' (fractures or bone complications requiring treatment) in patients with breast cancer and bone metastases (when the cancer has spread to the bone);• treat hypercalcaemia (high levels of calcium in the blood) caused by tumours.Ibandronic acid Accord contains the active substance ibandronic acid and is a 'generic medicine'. This means that Ibandronic acid Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU). The reference medicines for Ibandronic acid Accord are Bondronat and Bonviva. For more information on generic medicines, see the question-and-answer document here.

How is Ibandronic acid Accord used?

Ibandronic acid Accord is available as a solution for injection (3 mg) in a pre-filled syringe and as a concentrate (2 mg and 6 mg) to be made up into a solution for infusion (drip) into a vein. It can only be obtained with a prescription.For the prevention of skeletal events or the treatment of hypercalcaemia in cancer patients, treatment with this medicine should only be started by a doctor who has experience in the treatment of cancer.In the prevention of skeletal events in patients with breast cancer and bone metastases, Ibandronic acid Accord is given into a vein as a 6 mg infusion lasting at least 15 minutes every three to four weeks. Patients with moderate or severe kidney problems should receive Ibandronic acid Accord infusions at a lower dose over an hour.In the treatment of hypercalcaemia caused by tumours, Ibandronic acid Accord is given into a vein as an infusion of 2 or 4 mg, depending on how severe the hypercalcaemia is. The infusion lasts 2 hours. This will normally bring the blood calcium level down to normal levels within a week.For the treatment of osteoporosis, Ibandronic acid Accord is given as an injection into a vein once every three months. Patients should also take vitamin D and calcium supplements.

How does Ibandronic acid Accord work?

The active substance in Ibandronic acid Accord, ibandronic acid, is a bisphosphonate. It stops the action of osteoclasts, the cells in the body that are involved in breaking down the bone tissue. This reduces bone loss. The reduction of bone loss helps to make bones less likely to break in cancer patients with bone metastases and in women with osteoporosis.Patients with tumours can have high levels of calcium in their blood, released from the bones. By preventing the breakdown of bones, Ibandronic acid Accord also helps to reduce the amount of calcium released into the blood.

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

What are the benefits and risks of Ibandronic acid Accord?

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

Why is Ibandronic acid Accord approved?

The European Medicines Agency concluded that, in accordance with EU requirements, Ibandronic acid Accord has been shown to be comparable to Bondronat and Bonviva. Therefore, the Agency's view was that, as for Bondronat and Bonviva, the benefit outweighs the identified risk. The Agency recommended that Ibandronic acid Accord be approved for use in the EU.

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

The company that markets Ibandronic acid Accord will provide a card to inform patients receiving Ibandronic acid Accord infusion about the risk of osteonecrosis of the jaw and to instruct them to contact their doctor if they get symptoms. Osteonecrosis of the jaw is a condition affecting the bones of the jaw, which could lead to pain, sores in the mouth or loose teeth.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ibandronic acid Accord have also been included in the summary of product characteristics and the package leaflet.

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Ibandronic Acid Sandoz

What is Ibandronic Acid Sandoz?

Ibandronic Acid Sandoz is a medicine that contains the active substance ibandronic acid. It is available as tablets (50 mg).Ibandronic Acid Sandoz is a 'generic medicine'. This means that Ibandronic Acid Sandoz is similar to a'reference medicine' already authorised in the European Union (EU). The reference medicine for Ibandronic Acid Sandoz is Bondronat. For more information on generic medicines, see the questionand-answer document here.

What is Ibandronic Acid Sandoz used for?

Ibandronic Acid Sandoz is used to prevent 'skeletal events' (fractures [broken bones] or bone complications requiring treatment) in patients with breast cancer and bone metastases (when the cancer has spread to the bone).The medicine can only be obtained with a prescription.

How is Ibandronic Acid Sandoz used?

The recommended dose is one tablet taken once a day. The tablets must always be taken after the patient has fasted overnight for at least six hours and at least 30 minutes before the first food or drink of the day.Ibandronic Acid Sandoz must be taken with a full glass of plain water (but not mineral water) while standing or sitting up, and the tablets should not be chewed, sucked or crushed. The patient must also not lie down for one hour after taking the tablets.

How does Ibandronic Acid Sandoz work?

The active substance in Ibandronic Acid Sandoz, ibandronic acid, is a bisphosphonate. It stops the action of osteoclasts, the cells in the body that are involved in breaking down the bone tissue. This leads to less bone loss. The reduction of bone loss helps to make bones less likely to break, which is useful in preventing fractures in cancer patients with bone metastases.

How has Ibandronic Acid Sandoz been studied?

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

What are the benefits and risks of Ibandronic Acid Sandoz?

Because Ibandronic Acid 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 has Ibandronic Acid Sandoz been approved?

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

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

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

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Ibandronic Acid Teva

What is Ibandronic Acid Teva?

Ibandronic Acid Teva is a medicine that contains the active substance ibandronic acid. It is available as tablets (50 and 150 mg).Ibandronic Acid Teva is a 'generic medicine'. This means that Ibandronic Acid Teva is similar to a 'reference medicine' already authorised in the European Union (EU). The reference medicines for Ibandronic Acid Teva are Bondronat and Bonviva. For more information on generic medicines, see the question-and-answer document here.

What is Ibandronic Acid Teva used for?

Ibandronic Acid Teva 50 mg is used to prevent 'skeletal events' (fractures [broken bones] or bone complications requiring treatment) in patients with breast cancer and bone metastases (when the cancer has spread to the bone).Ibandronic Acid Teva 150 mg is used to treat osteoporosis (a disease that makes bones fragile) in women who have been through the menopause and are at risk of developing bone fractures. Its effect in reducing the risk of spine fractures has been shown in studies, but its effect on the risk of fractures of the neck of the femur (the top of the thighbone) has not been established.The medicine can only be obtained with a prescription.

How is Ibandronic Acid Teva used?

For the prevention of skeletal events, one 50-mg tablet is taken once a day. The tablets must always be taken after the patient has fasted overnight for at least six hours and at least 30 minutes before the first food or drink of the day.For treating osteoporosis, one 150-mg tablet is taken once a month. The tablet must always be taken after an overnight fast, one hour before any food or drink except for water. Patients should also take vitamin D and calcium supplements if they do not get enough from their diet.Ibandronic Acid Teva must be taken with a full glass of plain water (but not mineral water) while standing or sitting up, and the tablets should not be chewed, sucked or crushed. The patient must also not lie down for one hour after taking the tablets.

How does Ibandronic Acid Teva work?

The active substance in Ibandronic Acid Teva, ibandronic acid, is a bisphosphonate. It stops the action of osteoclasts, the cells in the body that are involved in breaking down the bone tissue. This leads to less bone loss. The reduction of bone loss helps to make bones less likely to break, which is useful in preventing fractures in cancer patients with bone metastases and in women with osteoporosis.

How has Ibandronic Acid Teva been studied?

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

What are the benefits and risks of Ibandronic Acid Teva?

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

Why has Ibandronic Acid Teva been approved?

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

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Ibrance

What is Ibrance and what is it used for?

Ibrance is a cancer medicine used to treat breast cancer when the cancer is locally advanced (has spread nearby) or metastatic (has spread to other parts of the body). Ibrance can only be used when the cancer cells have receptors (targets) for certain hormones on their surface (HR-positive) and do not produce abnormally large quantities of a receptor called HER2 (HER [human epidermal growth factor] negative). Ibrance is used in the following ways:• together with an aromatase inhibitor (a hormonal medicine for cancer);• together with fulvestrant (another hormonal medicine for cancer) in patients who have previously been treated with a hormonal medicine.In women who have not yet reached menopause, a medicine called a luteinising hormone-releasing hormone agonist should also be given.Ibrance contains the active substance palbociclib.

How is Ibrance used?

Ibrance can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the use of cancer medicines.Ibrance is available as capsules and tablets (75 mg, 100 mg and 125 mg). The recommended dose is 125 mg once a day for 21 consecutive days, followed by a 7-day break to complete a 28-day treatment cycle. Treatment should be taken at around the same time each day. The capsules should be taken with food while the tablets can be taken with or without food. Treatment should continue for as long as the patient is benefitting from it and side effects are tolerable. If the patient experiences certain side effects, treatment may need to be interrupted or stopped, or the dose reduced.For more information about using Ibrance, see the package leaflet or contact your doctor or pharmacist.

How does Ibrance work?

The active substance in Ibrance, palbociclib, blocks the activity of enzymes known as cyclin-dependent kinases (CDK) 4 and 6, which play a key role in regulating the way cells grow and divide. In some cancers, including HR-positive breast cancer, the activity of CDK 4 and 6 is increased, which helps the cancer cells to multiply uncontrollably. By blocking CDK4 and CDK6, Ibrance slows the growth of HRpositive breast cancer cells.

What benefits of Ibrance have been shown in studies?

Ibrance has been studied in two main studies of women with HR-positive, HER2-negative breast cancer. In both studies, the main measure of effectiveness was how long patients lived without their disease getting worse (progression-free survival).The first study involved 521 women with metastatic breast cancer that had got worse after treatment with a hormonal medicine. They received either Ibrance and fulvestrant or a placebo (dummy medicine) and fulvestrant. Women taking Ibrance and fulvestrant lived on average 11.2 months without their disease getting worse compared with 4.6 months for women taking placebo and fulvestrant.The second study involved 666 women who had been through the menopause and whose breast cancer had started to spread and who had not yet received cancer treatment. They received either Ibrance and letrozole (an aromatase inhibitor) or placebo and letrozole. Women taking Ibrance and letrozole lived on average 24.8 months without their disease getting worse compared with 14.5 months for women taking placebo and letrozole.

What are the risks associated with Ibrance?

The most common side effects with Ibrance (which may affect more than 1 in 5 people) are neutropenia (low blood levels of neutrophils, a type of white blood cell that fights infection), infections, leucopenia (low white blood cell counts), tiredness, nausea (feeling sick), stomatitis (inflammation of the lining of the mouth), anaemia (low red blood cell counts), diarrhoea, alopecia (hair loss) and thrombocytopenia (low blood platelet counts).The most common severe side effects with Ibrance (which may affect up to 1 in 50 people) are neutropenia, leucopenia, infections, anaemia, tiredness and increased blood levels of liver enzymes (aspartate and alanine transaminases).For the full list of side effects of Ibrance, see the package leaflet.Ibrance must not be used by patients who are taking St John's wort (a herbal preparation used to treat depression). For the full list of restrictions, see the package leaflet.

Why is Ibrance authorised in the EU?

Ibrance has been shown to prolong the time patients live without their disease getting worse by an average of 6 to 10 months, which is considered of clear clinical value. Regarding safety, the main risk is neutropenia, which is a well-known risk of many cancer medicines and is considered manageable.The European Medicines Agency therefore decided that Ibrance'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 Ibrance?

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

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Icandra

What is Icandra and what is it used for?

Icandra is a diabetes medicine that is used together with diet and exercise to control the blood glucose (sugar) in adults with type 2 diabetes. It is used:• in patients whose blood glucose is insufficiently controlled with metformin taken alone;• in patients who are already taking the combination of vildagliptin and metformin as separate tablets;• together with other diabetes medicines, including insulin, when these medicines do not provide adequate control of the blood glucose.Icandra contains the active substances vildagliptin and metformin hydrochloride. This medicine is the same as Eucreas, which is already authorised in the EU. The company that makes Eucreas has agreed that its scientific data can be used for Icandra (informed consent).

How is Icandra used?

Icandra is available as tablets (50 mg/850 mg and 50 mg/1,000 mg), and the recommended dose is one tablet twice a day (one in the morning and one in the evening). The starting tablet strength depends on the patient's current treatment and the expected effects of Icandra. Taking Icandra with or just after food may reduce any stomach problems caused by metformin.The doctor should carry out tests to check the patient's kidney and liver function before treatment with Icandra and at regular intervals during treatment.The medicine can only be obtained with a prescription. For more information about using Icandra, see the package leaflet or contact your doctor or pharmacist.

How does Icandra work?

Type 2 diabetes is a disease in which the pancreas does not make enough insulin to control the glucose level in the blood or the body is unable to use insulin effectively. Icandra contains two active substances, each with a different mode of action.Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that works by blocking the breakdown of incretin hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By blocking the breakdown of incretin hormones in the blood, vildagliptin prolongs their action, stimulating the pancreas to produce more insulin when blood glucose levels are high. Vildagliptin does not work when the blood glucose is low. Vildagliptin also reduces the amount of glucose made by the liver, by increasing insulin levels and decreasing the levels of the hormone glucagon.Metformin works mainly by inhibiting glucose production and reducing its absorption in the gut. As a result of the action of both substances, the blood glucose is reduced, which helps to control type 2diabetes.

What benefits of Icandra have been shown in studies?

Vildagliptin on its own is approved for use in the EU under the name Galvus, and metformin has been available in the EU since 1959. Vildagliptin can be used with metformin in type 2 diabetes patients who are not satisfactorily controlled on metformin alone.Studies with Galvus as an add-on to metformin, metformin and a sulphonylurea, or metformin and insulin have been used to support the use of Icandra in the same indications. The studies compared Galvus with placebo (a dummy treatment) and measured the levels of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.Vildagliptin has been shown to be more effective than placebo at reducing HbA1c levels when it was added to metformin. Patients adding vildagliptin had falls in HbA1c levels of 0.88 percentage points after 24 weeks from a starting level of 8.38%. In contrast, patients adding placebo had smaller changes in HbA1c levels, with a rise of 0.23 percentage points from a starting level of 8.3%. In other studies, vildagliptin in combination with metformin has been shown to be more effective than placebo when used with a sulphonylurea or insulin.The applicant also presented the results of two studies showing that the active substances in the two strengths of Icandra were absorbed in the body in the same way as when they were taken as separate tablets.

What are the risks associated with Icandra?

The most common side effects with Icandra (seen in more than 1 patient in 10) are nausea (feeling sick), vomiting, diarrhoea, abdominal (belly) pain and loss of appetite. For the full list of all side effects reported with Icandra, see the package leaflet.Icandra must not be used in people who are hypersensitive (allergic) to vildagliptin, metformin or any of the other ingredients. Icandra must also not be used in patients with certain kidney, liver or heart problems or those who could develop metabolic acidosis (build-up of acid in the blood). It must also not be used in patients who consume excessive amounts of alcohol or who have alcoholism, or in women who are breastfeeding. For the full list of restrictions, see the package leaflet.

Why is Icandra authorised in the EU?

Studies have shown that vildagliptin taken with metformin is effective in reducing blood glucose levels and that the combination of vildagliptin and metformin was effective as an add-on to a sulphonylurea or insulin. The combination of the two active substances vildagliptin and metformin in one tablet mayIcandra (vildagliptin Icandra0F (vildagliptin / metformin hydrochloride)help patients to stick to their treatment. The European Medicines Agency therefore decided that Icandra' 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 Icandra?

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

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Icatibant Accord

What is Icatibant Accord and what is it used for?

Icatibant Accord is a medicine used to treat the symptoms of hereditary angioedema in patients aged 2 years and over.Patients with angioedema have rapid swelling that can occur anywhere in the body, such as in the face or limbs, or around the gut, causing discomfort and pain. Attacks of hereditary angioedema can be life threatening when the swelling around the throat presses against the airway. Icatibant Accord is used in patients whose angioedema is linked to naturally low levels of a protein called 'C1 esterase inhibitor'.Icatibant Accord contains the active substance icatibant and is a 'generic medicine'. This means that Icatibant Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Firazyr. For more information on generic medicines, see the question-and-answer document here.

How is Icatibant Accord used?

Treatment with Icatibant Accord should be started under the supervision of a healthcare professional. Icatibant Accord is available as a solution in a pre-filled syringe to be injected slowly under the skin, preferably in the abdomen (belly). The doctor may decide that the patient or their caregiver can inject the medicine themselves, after they have been trained by a healthcare professional.The recommended dose of Icatibant Accord in adults is one single injection. If symptoms continue or come back, a second injection can be given after 6 hours. If needed, treatment can be repeated for a third time after an additional 6 hours. No more than three injections should be given in any 24-hour period. The dose for adolescents and children depends on their body weight.The medicine can only be obtained with a prescription.For more information about using Icatibant Accord, see the package leaflet or contact your doctor or pharmacist.Send

How does Icatibant Accord work?

Patients with hereditary angioedema have high levels of a substance called 'bradykinin', which is involved in causing inflammation and swelling. The active substance in Icatibant Accord, icatibant, blocks the receptors that bradykinin normally attaches to. This blocks the activity of bradykinin, helping to relieve the symptoms of the disease.

How has Icatibant 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, Firazyr, and do not need to be repeated for Icatibant Accord.As for every medicine, the company provided data on the quality of Icatibant Accord. There was no need for 'bioequivalence' studies to investigate whether Icatibant 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 Icatibant 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 Icatibant Accord?

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

Why is Icatibant Accord authorised in the EU?

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

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

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Iclusig

What is Iclusig and what is it used for?

Iclusig is a cancer medicine that contains the active substance ponatinib. It is used to treat adults with the following types of leukaemia (cancer of the white blood cells):• chronic myeloid leukaemia (CML) in its different stages known as chronic, accelerated and blast phases;• acute lymphoblastic leukaemia (ALL) in patients who are 'Philadelphia-chromosome positive' (Ph+). Ph+ means that some of the patient's genes have rearranged themselves to form a special chromosome called the Philadelphia chromosome that leads to the development of leukaemia. The Philadelphia-chromosome is found in some ALL patients and is present in most patients with CML.Iclusig is used in patients who cannot tolerate or do not respond to dasatinib (patients with CML or ALL) or nilotinib (patients with CML), which are other cancer medicines of the same class, and for whom subsequent treatment with imatinib (a third such medicine) is not considered appropriate. It is also used in patients who have a genetic mutation called 'T315I mutation' which makes them resistant to treatment with imatinib, dasatinib or nilotinib.These diseases are rare, and Iclusig was designated an 'orphan medicine' (a medicine used in rare diseases) on 2 February 2010. Further information on the orphan designations can be found here: ema.europa.eu/Find medicine/Human medicines/Rare disease designation (CML; ALL).

How is Iclusig used?

Iclusig can only be obtained with a prescription and treatment should be started by a doctor who is experienced in the diagnosis and treatment of leukaemia.Iclusig is available as tablets (15 mg, 30 mg and 45 mg). The recommended starting dose is 45 mg once per day. Treatment is continued for as long as the patient benefits. If a patient develops certain severe side effects, the doctor may decide to reduce subsequent doses or delay or stop treatment. The doctor should consider stopping treatment if the level of white cells in the blood does not return to normal within three months.Iclusig can lead to clots or blockages in arteries and veins and patients should have the condition of their heart and circulation considered before starting and during treatment, and be treatedappropriately for any problems. The dose may need to be reduced or interrupted if the patient experiences certain side effects; it should be interrupted immediately if a blockage develops in an artery or vein.For more information about using Iclusig, see the package leaflet or contact your doctor or pharmacist.

How does Iclusig work?

The active substance in Iclusig, ponatinib, belongs to a group of medicines called 'tyrosine kinase inhibitors'. These compounds act by blocking enzymes known as tyrosine kinases. Ponatinib acts by blocking a tyrosine kinase called Bcr-Abl. This enzyme is found on the surface of leukaemia cells where it is involved in stimulating the cells to divide uncontrollably. By blocking Bcr-Abl, Iclusig helps to control the growth and spread of leukaemia cells.

What benefits of Iclusig have been shown in studies?

Iclusig has been investigated in one main study involving 449 patients with CML or Ph+ ALL and who were intolerant or resistant to treatment with dasatinib or nilotinib, or had the T315I mutation. In the study, Iclusig was not compared with another treatment. The response to treatment was assessed by measuring the proportion of patients who had a 'major haematological response' (when the number of white blood cells returns to normal or there is no evidence of leukaemia) or a 'major cytogenetic response' (when the proportion of white blood cells containing the Philadelphia chromosome falls to below 35%).The results of the study showed that treatment with Iclusig led to clinically relevant responses in all groups of patients:• among the patients with CML in the chronic phase, around 54% (144 out of 267) had a major cytogenetic response;• among the patients with CML in the accelerated phase, around 58% (48 out of 83) had a major haematological response;• among the patients with CML in the blast phase, around 31% (19 out of 62) had a major haematological response;• among the patients with Ph+ ALL, around 41% (13 out of 32) had a major haematological response.

What are the risks associated with Iclusig?

The most common serious side effects with Iclusig (which may affect more than 2 in 100 people) are pneumonia (infection of the lungs), pancreatitis (inflammation of the pancreas), pyrexia (fever), abdominal pain (stomach ache), myocardial infarction (heart attack), atrial fibrillation (irregular rapid contractions of the upper chambers of the heart), peripheral arterial occlusive disease (problem with blood flow in the arteries), anaemia (low red blood cell counts), angina pectoris (pains to the chest, jaw and back due to problems with blood flow to the heart), decreased blood levels of platelets (components that help the blood to clot), febrile neutropenia (low white blood cell counts with fever), hypertension (high blood pressure), coronary artery disease (heart disease caused by the obstruction of the blood vessels that supply the heart muscle), cardiac failure (when the heart does not work as well as it should), cerebrovascular accident (stroke), sepsis (blood poisoning), cellulitis (inflammationof the deep skin tissue), acute kidney injury (kidney damage), urinary tract infection (infection of the structures that carry urine) and increased levels of lipase (an enzyme).Arterial occlusive adverse events (clots or blockages in the arteries) occurred in 25% of patients, with serious adverse events occurring in 20% of patients. Serious venous occlusive adverse events (clots or blockages in the veins) occurred in 5% of patients. Venous thromboembolic reactions (problems due to blood clots in the veins) occurred in 6% of patients.For the full list of side effects and restrictions with Iclusig, see the package leaflet.

Why is Iclusig authorised in the EU?

The European Medicines Agency decided that Iclusig's benefits are greater than its risks and it can be authorised for use in the EU. Iclusig was shown to be an effective treatment for those patients with CML or Ph+ ALL who have limited treatment options. Regarding its safety, the side effects with Iclusig were largely similar to those of other tyrosine kinase inhibitors and mostly manageable with dose reduction or dose delay. The risk of problems (including heart attacks and strokes) resulting from blood clots or blockages in arteries or veins could be reduced by checking for and treating contributory conditions such as high blood pressure and raised cholesterol both before and during treatment.

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

The company that markets Iclusig will provide educational material for all doctors who are expected to prescribe this medicine highlighting important risks for which monitoring and dose adjustments are recommended. Also, the company will conduct a study in order to determine the best starting dose of Iclusig and to assess the safety and effectiveness of Iclusig following dose reduction in patients with chronic phase CML who achieve major cytogenetic response.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Iclusig have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Iclusig are continuously monitored. Side effects reported with Iclusig are carefully evaluated and any necessary action taken to protect patients.

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Idacio

What is Idacio and what is it used for?

Idacio is a medicine that acts on the immune system (the body's natural defences) and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin);• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints);• rheumatoid arthritis (a disease causing inflammation of the joints);• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when there are clear signs of inflammation but X-ray does not show disease;• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints);• Crohn's disease (a disease causing inflammation of the gut);• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut);• hidradenitis suppurativa (also known as acne inversa, a long-term skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin);• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Idacio is mostly used in adults when their condition is severe, moderately severe or getting worse, or when patients cannot use other treatments. For more information on the use of Idacio in all conditions, including when it can be used in children, see the package leaflet or contact your doctor or pharmacist.Idacio contains the active substance adalimumab and is a 'biosimilar medicine'. This means that Idacio is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Idacio is Humira. For more information on biosimilar medicines, see here.

How is Idacio used?

Idacio is available as a solution for injection under the skin in a vial or pre-filled syringe or pen, and is usually given every 2 weeks. The dose and frequency of injection depend on the condition to be treated and the dose for a child is usually calculated according to the child's weight. After training, patients or their carers may inject Idacio if their doctor considers it appropriate.Idacio can only be obtained with a prescription and treatment must be started and supervised by a doctor who has experience in the treatment of the diseases for which Idacio is used. Eye specialists treating uveitis should also take advice from doctors who have experience of using adalimumab.For more information about using Idacio, see the package leaflet or contact your doctor or pharmacist.

How does Idacio work?

The active substance in Idacio, adalimumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a substance in the body called tumour necrosis factor (TNF). TNF is involved in causing inflammation and is found at high levels in patients with the diseases that Idacio is used to treat. By attaching to TNF, adalimumab blocks its activity, thereby reducing inflammation and other symptoms of the diseases.

What benefits of Idacio have been shown in studies?

Laboratory studies comparing Idacio with the reference medicine Humira have shown that the active substance in Idacio is highly similar to that in Humira in terms of structure, purity and biological activity. Studies have also shown that giving Idacio produces similar levels of the active substance in the body to giving Humira.In addition, a study involving 443 patients with plaque psoriasis has shown that Idacio is as effective as Humira in controlling the disease. The study compared injections of the two medicines given under the skin every 2 weeks: after 16 weeks, 90% of those treated with Idacio and 92% of those treated with Humira had at least a 75% reduction in signs and symptoms of psoriasis.Because Idacio is a biosimilar medicine, the studies on effectiveness and safety of adalimumab carried out with Humira do not all need to be repeated for Idacio.

What are the risks associated with Idacio?

The safety of Idacio 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 Humira. The most common side effects with adalimumab (which may affect more than 1 in 10 people) are infections (including in the nose, throat and sinuses), injection site reactions (redness, itching, bleeding, pain or swelling), headache and muscle and bone pain.Like other medicines of its class, Idacio may affect the ability of the immune system to fight off infections and cancer, and there have been some cases of serious infections and blood cancers in patients using adalimumab.Other rare serious side effects of adalimumab (which may affect up to 1 in 1,000 people) include failure of the bone marrow to produce blood cells, disorder of the nerves, lupus and lupus-like conditions (where the immune system attacks the patient's own tissues, causing inflammation and organ damage), and Stevens-Johnson syndrome (life-threatening reaction with flu-like symptoms and painful rash affecting the skin, mouth, eyes and genitals).Idacio must not be used in patients with active tuberculosis or other severe infections, or in patients with moderate to severe heart failure (an inability of the heart to pump enough blood around the body).For the full list of side effects and restrictions with Idacio, see the package leaflet.

Why is Idacio authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Idacio has a highly similar structure, purity and biological activity to Humira and is distributed in the body in the same way. In addition, studies in psoriasis have shown that the effectiveness of Idacio is equivalent to that of Humira.All these data were considered sufficient to conclude that Idacio will behave in the same way as Humira in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Humira, the benefits of Idacio 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 Idacio?

The company that markets Idacio must provide educational packs for doctors who prescribe the medicine. These packs will include information on the safety of the medicine. An alert card will also be given to patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Idacio have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Idacio are continuously monitored. Side effects reported with Idacio are carefully evaluated and any necessary action taken to protect patients.

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Idefirix

What is Idefirix and what is it used for?

Idefirix is a medicine used to prevent the body from rejecting a newly transplanted kidney.Idefirix is used before transplantation in adults who have antibodies against the donor kidney and are considered 'highly sensitised' based on a positive crossmatch test. It should be reserved for patients who are unlikely to obtain a transplant under the available kidney allocation system.Graft organ rejection following solid organ transplantation is rare, and Idefirix was designated an 'orphan medicine' (a medicine used in rare diseases) on 12 January 2017. Further information on the orphan designation can be found here: https://www.ema.europa.eu/en/medicines/human/orphandesignations/eu3161826.Idefirix contains the active substance imlifidase.

How is Idefirix used?

Idefirix is for hospital use only and can only be obtained with a prescription. Idefirix treatment should only be prescribed and supervised by a doctor experienced in the use of immunosuppressive medicines (medicines that reduce the activity of the immune system, the body's natural defences) and in the management of sensitised kidney transplant patients.Idefirix is given as an infusion (drip) into a vein. The medicine is given as a single dose in the 24 hours before transplantation. If necessary, a second dose can be given within 24 hours after the first dose.Patients treated with Idefirix still require standard immunosuppressive therapy after kidney transplantation.For more information about using Idefirix, see the package leaflet or contact your doctor or pharmacist.

How does Idefirix work?

Highly sensitised patients have high levels of antibodies (proteins in the blood that fight infections and other foreign cells) against the donor's tissue, including immunoglobulin G (IgG) antibodies. This makes their body more likely to reject the donor organ. The active substance in Idefirix, imlifidase, isan enzyme (a protein) that breaks down the IgG antibodies, thereby reducing the likelihood of the body rejecting the donor kidney.

What benefits of Idefirix have been shown in studies?

Idefirix was investigated in one main study of 19 patients with end-stage kidney disease who were highly sensitised to the donor kidney based on a positive crossmatch test. Within 24 hours of receiving Idefirix, 17 of the patients became crossmatch-negative and one was borderline crossmatch-positive, making all 18 eligible for kidney transplantation. A total of 16 patients had a functioning kidney 6 months after transplantation.Additional data on the benefits of Idefirix came from three supportive studies. Analyses of the data from all four studies showed that 43 out of a total of 46 patients had a functioning kidney 6 months after transplantation.

What are the risks associated with Idefirix?

The most common side effects with Idefirix (which may affect more than 1 in 10 people) are infections, including pneumonia (infection of the lungs), urinary tract infection and sepsis (blood poisoning). Other common side effects (which may affect up to 1 in 10 people) are pain and reactions around the infusion site, increased blood levels of certain liver enzymes, muscle pain, headache and flushing.The most common serious side effects with Idefirix (which may affect up to 1 in 10 people) are pneumonia and sepsis.Idefirix should not be used in people with a serious infection or thrombotic thrombocytopenic purpura.For the full list of side effects and restrictions, see the package leaflet.

Why is Idefirix authorised in the EU?

The European Medicines Agency decided that Idefirix's benefits are greater than its risks and it can be authorised for use in the EU.Antibodies against the donor's graft are a major obstacle to successful transplantation in patients with kidney failure. Patients who are highly sensitised therefore usually remain on dialysis with shorter life expectancy and poor quality of life. In light of this unmet medical need and despite the need for further data, the Agency considered that the available evidence suggests that Idefirix is effective at reducing antibody levels in highly sensitised adults, allowing them to receive a kidney transplant. The safety profile of Idefirix is considered manageable.Idefirix 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 Idefirix?

Since Idefirix has been given conditional authorisation, the company that markets Idefirix will provide additional data from an ongoing study into the long-term graft functioning and survival in patients who have undergone kidney transplantation after Idefirix treatment. The company will also provide data from a new study to confirm the long-term effectiveness and safety of Idefirix.

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

The company that markets Idefirix will provide results of a long-term study of Idefirix to confirm its effectiveness.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Idefirix have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Idefirix are continuously monitored. Side effects reported with Idefirix are carefully evaluated and any necessary action taken to protect patients.

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Idelvion

What is Idelvion and what is it used for?

Idelvion is a medicine used to prevent and treat bleeding in patients with haemophilia B, an inherited bleeding disorder caused by lack of a clotting protein called factor IX. It can be used in patients of all ages.Because the number of patients with haemophilia B is low, the disease is considered 'rare', and Idelvion was designated an 'orphan medicine' (a medicine used in rare diseases) on 4 February 2010.Idelvion contains the active substance albutrepenonacog alfa.

How is Idelvion used?

Idelvion can only be obtained with a prescription, and treatment should be supervised by a doctor with experience in treating haemophilia.Idelvion is available as powder and solvent that are mixed together to make a solution for injection into a vein. The dose and the frequency of the injections depend on the patient's bodyweight and whether Idelvion is used to treat or prevent bleeding, as well as the severity of the patient's factor IX deficiency, the extent and location of the bleeding and the patient's age and health. For further information on how to use this medicine, see the summary of product characteristics (also part of the EPAR).

How does Idelvion work?

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

What benefits of Idelvion have been shown in studies?

In a study in 80 adults and adolescents and another study in 27 children aged less than 12 years, Idelvion was effective at preventing bleeding, with most patients experiencing no bleeding while on preventive treatment. Furthermore, Idelvion was effective in treating bleeding episodes when they did occur; around 93% of the bleeding episodes resolved with one Idelvion injection.

What are the risks associated with Idelvion?

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

Why is Idelvion approved?

Studies show that Idelvion is effective at preventing and treating bleeding episodes in patients with haemophilia B, and its safety is comparable to that of other factor IX products. The Agency'sCommittee for Medicinal Products for Human Use (CHMP) therefore decided that Idelvion'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 Idelvion?

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

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Ifirmacombi

What is Ifirmacombi?

Ifirmacombi is a medicine that contains two active substances, irbesartan and hydrochlorothiazide. It is available as tablets (150 mg irbesartan and 12.5 mg hydrochlorothiazide; 300 mg irbesartan and 25 mg hydrochlorothiazide; 300 mg irbesartan and 12.5 mg hydrochlorothiazide).Ifirmacombi is a 'generic medicine'. This means that Ifirmacombi is similar to a 'reference medicine' already authorised in the European Union (EU) called CoAprovel. For more information on generic medicines, see the question-and-answer document here.

What is Ifirmacombi used for?

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

How is Ifirmacombi used?

The dose of Ifirmacombi to be used depends on the dose of irbesartan or hydrochlorothiazide that the patient was taking before. Doses higher than 300 mg irbesartan and 25 mg hydrochlorothiazide once a day are not recommended. Ifirmacombi may be added to other treatments for hypertension.

How does Ifirmacombi work?

Ifirmacombi contains two active substances, irbesartan and hydrochlorothiazide.Irbesartan 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, irbesartan 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 lowering the blood pressure.The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

How has Ifirmacombi been studied?

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

What are the benefits and risks of Ifirmacombi?

Because Ifirmacombi 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 Ifirmacombi been approved?

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

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Ifirmasta

What is Ifirmasta?

Ifirmasta is a medicine that contains the active substance irbesartan. It is available as tablets (75, 150 and 300 mg).Ifirmasta is a 'generic medicine'. This means that Ifirmasta is similar to a 'reference medicine' already authorised in the European Union (EU) called Aprovel. For more information on generic medicines, see the question-and-answer document here.

What is Ifirmasta used for?

Ifirmasta is used in adults who have essential hypertension (high blood pressure). 'Essential' means that the hypertension has no obvious cause. Ifirmasta is also used to treat kidney disease in adults with hypertension and type 2 diabetes.The medicine can only be obtained with a prescription.

How is Ifirmasta used?

The usual recommended dose of Ifirmasta is 150 mg once a day. If the blood pressure is not sufficiently controlled, the dose can be increased to 300 mg a day or other medicines for hypertension can be added, such as hydrochlorothiazide. A starting dose of 75 mg can be used in patients receiving haemodialysis (a blood clearance technique) or in patients over 75 years of age.1 Previously known as Irbesartan Krka.In patients with hypertension and type 2 diabetes, Ifirmasta is added to some other treatments for hypertension. Treatment is started at 150 mg once a day and is usually increased to 300 mg once a day.

How does Ifirmasta work?

The active substance in Ifirmasta, irbesartan, 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, irbesartan stops the hormone having an effect, allowing the blood vessels to widen. This allows the blood pressure to drop, reducing the risk caused by high blood pressure, such as having a stroke.

How has Ifirmasta been studied?

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

What are the benefit and risk of Ifirmasta?

Because Ifirmasta 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 Ifirmasta been approved?

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

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Ikervis

What is Ikervis and what is it used for?

Ikervis is a medicine used to treat severe keratitis, an inflammation of the cornea (the transparent layer covering the front of the eye) in adult patients with dry eye disease. It is used when treatment with artificial tears (tear substitutes) is insufficient to improve the condition.Ikervis contains the active substance ciclosporin.

How is Ikervis used?

Ikervis can only be obtained with a prescription and treatment should only be started by a healthcare professional trained in ophthalmology (eye medicine).The medicine is available as single-dose eye drops and the recommended dose is one drop in each affected eye daily at bedtime. The doctor should confirm the need for continuing treatment at least every 6 months. If other eye drops are used, the different medicines must be given at least 15 minutes apart. Ikervis should be given last.For further information, see the package leaflet.

How does Ikervis work?

In patients with dry eye disease, either not enough tear fluid is produced to create the protective film of moisture that normally coats the surface of the eye, or abnormalities in the tear fluid cause it to dry out too quickly. Without sufficient protection from the tear fluid, the cornea can get damaged and become inflamed (keratitis), which can eventually lead to ulceration, infection and reduced vision.The active substance in Ikervis, ciclosporin, acts on cells of the immune system (the body's natural defences) that are involved in the processes that cause inflammation. Applying it directly to the eye reduces inflammation and damage there but limits its effects elsewhere in the body.

What benefits of Ikervis have been shown in studies?

The benefits of Ikervis have been shown in one main study involving 246 patients with severe dry eye disease, where Ikervis was compared with the vehicle (the same eye drop formula but without any active substance). The main measure of effectiveness was the proportion of patients whose condition responded to treatment after six months, as measured by a combination of damage to the cornea and a score for the level of symptoms, including discomfort and pain. About 29% (44 of 154) of those given Ikervis responded, compared with 23% (21 of 91) given the vehicle. The proportion of patients who responded to treatment was therefore similar in the two groups, but when only the damage to the cornea was considered, Ikervis was significantly better than the vehicle at reducing it. Levels of HLADR (a measure of inflammation in eye cells) were also reduced in patients using Ikervis compared with the dummy treatment.

What are the risks associated with Ikervis?

The most common side effects with Ikervis (which may affect more than 1 in 10 people) are pain and irritation in the eye; other common side effects are lacrimation (excessive tears), ocular hyperaemia (red eye), and erythema (redness) of the eyelid. These symptoms are usually short lasting and occur at the time the eye drops are used. For the full list of all side effects reported with Ikervis, see the package leaflet.The medicine must not be used in patients who have or are suspected to have an infection of the eye or the tissues around the eye. For the full list of restrictions, see the package leaflet.

Why is Ikervis approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Ikervis's benefits are greater than its risks and recommended that it be approved for use in the EU. Although Ikervis had not been shown to be any better than the vehicle in improving symptoms such as discomfort and pain, there was evidence that it could reduce the inflammation and damage to the cornea associated with keratitis. The CHMP considered that this was clinically meaningful, since none of the available medicines for the condition have been shown to reduce damage to the surface of the eye, which might help prevent the progression of the disease. Regarding safety, the medicine was well tolerated, with mainly short-lasting effects on the eye at the time the eye drops are used; the risk of effects on the body as a whole was considered to be low.

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

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

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Ilaris

What is Ilaris and what is it used for?

Ilaris is a medicine for treating the following inflammatory conditions:• 4 types of periodic fever syndromes (diseases marked by recurring inflammation and fever) in adults and children aged 2 and above:-• Still's disease, a rare disease causing inflammation of joints as well as rash and fever (in adults and children aged 2 and above);• Gouty arthritis, painful inflammation of the joints caused by deposit of urate crystals (in adults).Ilaris contains the active substance canakinumab.

How is Ilaris used?

Ilaris is given as a single injection under the skin every 8 weeks for CAPs and every 4 weeks for the other periodic fever syndromes (TRAPS, HIDS/MKD and FMF) and Still's disease. In patients with gouty arthritis, a single injection is given on-demand to treat gouty arthritis attacks.Injections are usually given in the upper thigh, upper arm, abdomen or buttocks. After proper training, patients or their caregivers may inject Ilaris themselves if the doctor deems it appropriate (for gouty arthritis the medicine should always be given by a healthcare professional). For information on doses and dose adjustments, see the summary of product characteristics (also part of the EPAR).Ilaris can only be obtained with a prescription.

How does Ilaris work?

The active substance in Ilaris, canakinumab, is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a messenger molecule or 'cytokine' in the body called interleukin-1 beta. This messenger is involved in causing inflammation and is found in high levels in patients with periodic fever syndromes, Still's disease and gouty arthritis. By attaching to interleukin-1 beta, canakinumab blocks its activity, helping to reduce inflammation thereby relieving the symptoms of the diseases.

What benefits of Ilaris have been shown in studies?

Periodic fever syndromesThree studies involving 220 adults and children 2 years and older showed that Illaris was effective at reducing relapses of CAPS symptoms after a 24-week treatment period. In one of the studies, none of the patients with CAPS who received Ilaris during the 24-week treatment period had a relapse, compared with 81% of patients who received placebo (a dummy treatment). In the two other CAPS studies, which did not compare Ilaris with any other treatment, 85% of patients on Ilaris had no relapses at all. The proportion of patients with no relapse was lower (around 57%) for children aged 2 to 4 years.A fourth study in 181 patients with other periodic fever syndromes found that Ilaris was more effective than placebo in achieving a response (symptoms resolved with no new flare ups). The response rates with Ilaris and placebo were 46% and 8%, respectively in patients with TRAPS, 35% and 6% in patients with HIDS/MKD, and 61% and 6% in patients with FMF.Still's diseaseA study in 84 patients with childhood Still's disease (also known as systemic juvenile idiopathic arthritis, SJIA) found that Ilaris was more effective than placebo at reducing symptoms of arthritis: around 84% of patients who received Ilaris achieved the required reduction in symptoms, compared with about 10% of patients who received placebo. In a second study in childhood Still's disease (177 patients), the risk of experiencing a disease flare was reduced by 64% with Ilaris, compared with placebo. Ilaris treatment also allowed patients to reduce the amount of steroids they take to control inflammation.Because of the similarities between childhood Still's disease and the adult form (adult-onset Still's disease, AOSD), Ilaris is expected to have similar benefits in adults.IlarisGouty arthritisTwo studies involving 454 patients with gouty arthritis showed that Ilaris was more effective than another anti-inflammatory medicine triamcinolone acetonide at reducing pain. In patients taking Ilaris, after 3 days, the pain level was reduced from 74 to 25 (on a standard rating scale from 0 to 100), whereas in patients taking the comparator the pain level was reduced from 74 to 35. The risk of developing a new gouty arthritis attack was also reduced with Ilaris (17% with Ilaris versus 37% with triamcinolone acetonide).

What are the risks associated with Ilaris?

Serious infections have been observed in patients taking Ilaris. The most common infections were of the nose and throat. Some infections were unusual or opportunistic infections due to reduced white blood cell levels. For the full list of all side effects reported with Ilaris, see the package leaflet.Ilaris must not be used in patients with active or severe infection. For the full list of restrictions, see the package leaflet.

Why is Ilaris approved?

Studies have shown that Ilaris is effective at reducing symptoms or relapses in patients with periodic fever syndromes, Still's disease and gouty arthritis. The main risk with this medicine is infection, mostly affecting the nose and throat. The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that the benefits seen with Ilaris outweigh its risks and recommended that it be authorised in the EU.Ilaris was originally authorised under 'exceptional circumstances', because, for scientific reasons, limited information was available at the time of approval. As the company had supplied the additional information requested, the 'exceptional circumstances' ended on 22 March 2017

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

The company that markets Ilaris will provide doctors who will use Ilaris with educational material containing the prescribing information, the patient reminder card and information for doctors containing important safety information about Ilaris, including precautions to be taken when using the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Ilaris have also been included in the summary of product characteristics and the package leaflet.

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Ilumetri

What is Ilumetri and what is it used for?

Ilumetri is a medicine that acts on the immune system and is used to treat plaque psoriasis, a disease causing red, scaly patches on the skin. It is used in adults with moderate to severe disease for whom treatments applied to the skin are not suitable.Ilumetri contains the active substance tildrakizumab.

How is Ilumetri used?

Ilumetri can only be obtained with a prescription and should be used under the supervision of a doctor experienced in diagnosing and treating plaque psoriasis.Ilumetri is available as a solution in pre-filled syringes for injection under the skin. The recommended dose is one 100 mg injection, followed by a further dose after 4 weeks and then an injection every 12 weeks. The dose may be increased to 200 mg in certain patients, for example patients badly affected by the disease or with bodyweight over 90 kg. The doctor may decide to stop treatment if the condition does not improve after 28 weeks.After training, patients may inject Ilumetri themselves if the doctor considers it appropriate.For more information about using Ilumetri, see the package leaflet or contact your doctor or pharmacist.

How does Ilumetri work?

The active substance in Ilumetri, tildrakizumab, is a monoclonal antibody (a type of protein) which is designed to attach to interleukin 23 and block its activity. Interleukin 23 is a substance that controls the growth and maturation of some types of T cells. These T cells, which are part of the immune system (the body's natural defences), are involved in causing inflammation that is linked to the development of plaque psoriasis. By blocking the action of interleukin 23, Ilumetri reduces inflammation and symptoms associated with the disease.

What benefits of Ilumetri have been shown in studies?

Two main studies involving adults found Ilumetri effective for treating moderate to severe plaque psoriasis in patients for whom treatments applied to the skin did not work well enough.The first study involving 771 patients compared Ilumetri with placebo (a dummy treatment). After 12 weeks, 64% and 62% of patients given 100 mg and 200 mg Ilumetri respectively had at least a 75% improvement in disease severity compared with 6% of those given placebo. Additionally, 58% of those given 100 mg and 59% of those given 200 mg had almost complete skin clearance compared with 7% given placebo.The second study involving 1,090 patients compared Ilumetri with placebo and with etanercept(another psoriasis medicine). After 12 weeks, 61% and 66% of patients given 100 mg and 200 mg Ilumetri respectively had at least 75% improvement in severity compared with 48% of those given etanercept and 6% given placebo. Of those given Ilumetri, 55% (for 100 mg) and 59% (for 200 mg) had almost complete skin clearance compared with 48% given etanercept and 5% given placebo.

What are the risks associated with Ilumetri?

The most common side effects with Ilumetri are upper respiratory tract (nose and throat) infections (which may affect more than 1 in 10 people). Headache, gastroenteritis (diarrhoea and vomiting), nausea (feeling sick), diarrhoea, pain at the site of the injection and back pain may affect up to 1 in 10 people.Ilumetri must not be used in patients who have a serious ongoing infection such as tuberculosis. For the full list of side effects and restrictions with Ilumetri, see the package leaflet.

Why is Ilumetri authorised in the EU?

Ilumetri is effective in treating psoriasis and some patients can experience total clearing of their psoriasis. Patients do not experience many side effects. Information on the use of Ilumetri in the long term is limited and studies are ongoing. The European Medicines Agency decided that Ilumetri'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 Ilumetri?

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

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Imatinib Accord

What is Imatinib Accord and what is it used for?

Imatinib Accord is a cancer medicine used to treat the following diseases:• chronic myeloid leukaemia (CML), a cancer of the white blood cells in which granulocytes (a type of white blood cell) start growing out of control. Imatinib Accord is used when the patients are 'Philadelphia chromosome positive' (Ph+). This means that some of their genes have re-arranged themselves to form a special chromosome called the Philadelphia chromosome. Imatinib Accord is used in adults and children who have been newly diagnosed with Ph+ CML and who are not eligible for bone marrow transplantation. It is also used in adults and children in the 'chronic phase' of the disease if it is not responding to interferon alfa (another cancer medicine), and in more advanced phases of the disease ('accelerated phase' and 'blast crisis');• Ph+ acute lymphoblastic leukaemia (ALL), a type of cancer in which lymphocytes (another type of white blood cell) multiply too quickly. Imatinib Accord is used in combination with other cancer medicines in adults and children who have been newly diagnosed with Ph+ ALL. It is also used alone in adults to treat Ph+ ALL that has returned following previous treatment, or is not responding to other medicines;• myelodysplastic or myeloproliferative diseases (MD/MPD), a group of diseases in which the body produces large numbers of abnormal blood cells. Imatinib Accord is used to treat adults with MD/MPD who have re-arrangements of the gene for platelet-derived growth factor receptor (PDGFR);• advanced hypereosinophilic syndrome (HES) or chronic eosinophilic leukaemia (CEL), diseases in which eosinophils (another type of white blood cell) start growing out of control. Imatinib Accord is used to treat adults with HES or CEL who have a specific re-arrangement of two genes calledFIP1L1 and PDGFRα;• dermatofibrosarcoma protuberans (DFSP), a type of cancer (sarcoma) in which cells in the tissue beneath the skin divide uncontrollably. Imatinib Accord is used to treat adults with DFSP that cannot be removed with surgery, and in adults who are not eligible for surgery when the cancer has returned after treatment or has spread to other parts of the body.Imatinib Accord contains the active substance imatinib. It is a 'generic medicine'. This means that Imatinib Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Glivec. For more information on generic medicines, see the question-and-answer document here.

How is Imatinib Accord used?

Imatinib Accord is available as tablets (100 and 400 mg). It can only be obtained with a prescription and treatment should be started by a doctor who has experience in the treatment of patients with cancers of the blood or solid tumours. Imatinib Accord is given by mouth with a meal and a large glass of water to reduce the risk of irritation of the stomach and gut. The dose depends on the disease being treated, the age and condition of the patient, and the response to treatment, but it should not exceed 800 mg a day. For more information, see the package leaflet.

How does Imatinib Accord work?

The active substance in Imatinib Accord, imatinib, is a protein-tyrosine kinase inhibitor. This means that it blocks some specific enzymes known as tyrosine kinases. These enzymes can be found in some receptors on the surface of cancer cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these receptors, Imatinib Accord helps to control cell division.

How has Imatinib 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, Glivec, and do not need to be repeated for Imatinib Accord.As for every medicine, the company provided studies on the quality of Imatinib Accord. The company also carried out studies that showed that it is 'bioequivalent' to the reference medicine, Glivec. 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 Imatinib Accord?

Because Imatinib 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 Imatinib Accord approved?

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

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

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

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Imatinib Teva

What is Imatinib Teva and what is it used for?

Imatinib Teva is a cancer medicine. It is used to treat the following diseases:• chronic myeloid leukaemia (CML), a cancer of the white blood cells in which granulocytes (a type of white blood cell) start growing out of control. Imatinib Teva is used when the patients are 'Philadelphia chromosome positive' (Ph+). This means that some of their genes have re-arranged themselves to form a special chromosome called the Philadelphia chromosome. Imatinib Teva is used in adults and children who have been newly diagnosed with Ph+ CML and who are not eligible for a bone marrow transplant. It is also used in adults and children in the 'chronic phase' of the disease if it is not responding to interferon alpha (another cancer medicine), and in more advanced phases of the disease ('accelerated phase' and 'blast crisis');• Ph+ acute lymphoblastic leukaemia (ALL), a type of cancer in which lymphocytes (another type of white blood cell) multiply too quickly. Imatinib Teva is used in combination with other cancer medicines in adults and children who have been newly diagnosed with Ph+ ALL. It is also used alone in adults to treat Ph+ ALL that has returned following previous treatment, or is not responding to other medicines;• myelodysplastic or myeloproliferative diseases (MD/MPD), a group of diseases in which the body produces large numbers of abnormal blood cells. Imatinib Teva is used to treat adults with MD/MPD who have re-arrangements of the gene for platelet-derived growth factor receptor (PDGFR);• advanced hypereosinophilic syndrome (HES) or chronic eosinophilic leukaemia (CEL), diseases in which eosinophils (another type of white blood cell) start growing out of control. Imatinib Teva is used to treat adults with HES or CEL who have a specific re-arrangement of two genes calledFIP1L1 and PDGFRα;• dermatofibrosarcoma protuberans (DFSP), a type of cancer (sarcoma) in which cells in the tissue beneath the skin divide uncontrollably. Imatinib Teva is used to treat adults with DFSP that cannot be removed with surgery, and in adults who are not eligible for surgery when the cancer has returned after treatment or has spread to other parts of the body.Imatinib Teva contains the active substance imatinib. It is a 'generic medicine'. This means thatImatinib Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called Glivec. For more information on generic medicines, see the question-and-answer document here.

How is Imatinib Teva used?

Imatinib Teva can only be obtained with a prescription and treatment should be started by a doctor who has experience in the treatment of patients with cancers of the blood. It is available as capsules (100 and 400 mg) and tablets (100 and 400 mg) and is given by mouth with a meal and a large glass of water to reduce the risk of irritation of the stomach and gut. The dose depends on the age and condition of the patient, and the response to treatment, but it should not exceed 800 mg a day. For more information, see the package leaflet.

How does Imatinib Teva work?

The active substance in Imatinib Teva, imatinib, is a protein-tyrosine kinase inhibitor. This means that it blocks some specific enzymes known as tyrosine kinases. These enzymes can be found in certain receptors in cancer cells, including the receptors that are involved in stimulating the cells to divide uncontrollably. By blocking these receptors, Imatinib Teva helps to control cell division.

How has Imatinib Teva been studied?

Because Imatinib Teva is a generic medicine, studies in patients have been limited to tests to determine that the tablets and capsules are bioequivalent to the reference medicine, Glivec. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the benefits and risks of Imatinib Teva?

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

Why is Imatinib Teva approved?

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

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

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

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Imbruvica

What is Imbruvica and what is it used for?

Imbruvica is a medicine for treating adult patients with the following blood cancers:• mantle cell lymphoma (MCL) in patients whose disease does not respond to or has come back after previous treatment;• chronic lymphocytic leukaemia (CLL) in both previously treated and untreated patients;• Waldenstrφm's macroglobulinaemia (also known as lymphoplasmacytic lymphoma).For the treatment of MCL, Imbruvica is taken on its own. For CLL, Imbruvica can be taken on its own but can also be taken with bendamustine and rituximab, or with either obinutuzumab, rituximab or venetoclax. For patients with Waldenstrφm's macroglobulinaemia, Imbruvica is taken on its own or with rituximab.Imbruvica contains the active substance ibrutinib.

How is Imbruvica used?

Imbruvica can only be obtained with a prescription, and treatment should be started and supervised by a doctor experienced in using cancer medicines.Imbruvica is available as capsules (140 mg) and tablets (140, 280, 420 and 560 mg). For patients with mantle cell lymphoma the dose is 560 mg once a day, and for patients with CLL or Waldenstrφm's macroglobulinaemia the usual dose of Imbruvica is 420 mg once a day. When used with venetoclax in patients with CLL, Imbruvica is given on its own for three cycles (1 cycle lasts 28 days), followed by 12 cycles of Imbruvica plus venetoclax.Treatment with Imbruvica should continue for as long as the disease improves or remains stable and the side effects are tolerable.If the patient is taking other medicines that may interact with Imbruvica or gets severe side effects, the doctor may lower the dose may or interrupt treatment. For more information about using Imbruvica, see the package leaflet or contact your doctor or pharmacist.

How does Imbruvica work?

The active substance in Imbruvica, ibrutinib, works against cancerous B lymphocytes, a type of white blood cells. It does this by blocking an enzyme called Bruton's tyrosine kinase (Btk), which promotes survival of B lymphocytes and their migration to the organs where these cells normally divide. By blocking Btk, ibrutinib decreases survival and migration of B lymphocytes, thereby delaying progression of the cancer.

What benefits of Imbruvica have been shown in studies?

Chronic lymphocytic leukaemiaIn one study in 391 patients whose disease did not respond to or had come back after previous treatment, 66% of patients receiving Imbruvica were still alive after one year with their disease not having progressed compared with around 6% of patients receiving another cancer medicine, ofatumumab.In a study involving 269 patients who had not been treated before, around 90% of patients receiving Imbruvica were still alive with their disease not having progressed after 1.5 years of treatment compared with around 52% of patients receiving a cancer medicine called chlorambucil.In a study in 578 patients whose disease had not responded to or had come back after previous treatment, death or signs that the cancer was progressing occurred in 19% of patients who took Imbruvica together with the cancer medicines bendamustine and rituximab compared with 63% in those who took bendamustine and rituximab without Imbruvica.In a study in 229 previously untreated patients, after 31 months, 79% of patients treated with Imbruvica and obinutuzumab were alive with their disease not having progressed compared with 36% of patients who took chlorambucil and obinutuzumab.In another study of 529 previously untreated patients, after 3 years around 12% treated with Imbruvica and rituximab had a worsening of their disease or died compared with 25% of patients treated with chemotherapy plus rituximab.In a study involving 211 previously untreated patients, after 28 months, death or signs that the cancer was progressing occurred in 21% of patients who took Imbruvica with venetoclax compared with 64% of patients who took chlorambucil and obinutuzumab.Another study involving 159 previously untreated patients showed that 55% of patients treated with Imbruvica plus venetoclax had a complete response (i.e. disappearance of all signs of cancer).Mantle cell lymphomaIn a study in 111 patients with mantle cell lymphoma that did not respond to or had come back after previous treatment, 21% of patients taking Imbruvica had complete response and 47% had partial response (i.e. the patient improved but some signs of the disease remained). The average duration of response to treatment was 17.5 months.A second study in 280 such patients compared Imbruvica with another cancer medicine, temsirolimus. The average time before patients died or the disease got worse was 15 months with Imbruvica versus 6 months with temsirolimus.Waldenstrφm's macroglobulinaemiaIn one main study involving 63 patients who had previously received another treatment for Waldenstrφm's macroglobulinaemia, the disease responded to treatment with Imbruvica in 87% of patients. Response to treatment was measured as a reduction in the blood levels of the protein IgM, which is present in high levels in patients with Waldenstrφm's disease.In a study involving 150 patients with Waldenstrφm's macroglobulinaemia, after 26 months, death or signs that the cancer was progressing occurred in 19% of patients who took Imbruvica together with rituximab compared with 56% of patients who took only rituximab.

What are the risks associated with Imbruvica?

The most common side effects with Imbruvica (which may affect more than 1 in 5 people) are diarrhoea, neutropenia (low levels of neutrophils, a type of white blood cell), pain in muscles and bones, haemorrhage (bleeding), rash, nausea (feeling sick), joint pain, nose and throat infections, and thrombocytopenia (low blood platelet counts).The most serious side effects (which may affect more than 1 in 20 people) are neutropenia, thrombocytopenia, lymphocytosis (high levels of white blood cells known as lymphocytes), high blood pressure and pneumonia (lung infection). For the full list of side effects of Imbruvica, see the package leaflet.St. John's wort (a herbal remedy used for depression and anxiety) must not be used in patients treated with Imbruvica. For the full list of restrictions, see the package leaflet.

Why is Imbruvica authorised in the EU?

Imbruvica was shown to be effective at delaying progression of chronic lymphocytic leukaemia, both in untreated patients and in those who had received treatment previously. In addition, Imbruvica was effective in patients with mantle cell lymphoma that did not respond to or had come back after previous treatment, a group of patients with poor prognosis and few other treatment options. In addition, Imbruvica was shown to be effective in patients with Waldenstrφm's macroglobulinaemia. The side effects of the medicine were considered acceptable.The European Medicines Agency decided that Imbruvica'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 Imbruvica?

The company that markets Imbruvica needs to provide further data on the benefits of Imbruvica in the treatment of chronic lymphocytic leukaemia from follow-up of previously treated patients.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Imbruvica have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Imbruvica are continuously monitored. Side effects reported with Imbruvica are carefully evaluated and any necessary action taken to protect patients.

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Imcivree

What is Imcivree and what is it used for?

Imcivree is a medicine used to treat obesity and help control hunger caused by certain genetic conditions that affect how the brain controls feelings of hunger. It is used in adults and children aged 6 years and older with Bardet Biedl syndrome (BBS), and in those who have pro-opiomelanocortin (POMC) deficiency or leptin receptor (LEPR) deficiency resulting from changes (mutations) in both copies of the genes responsible for making POMC or LEPR.Bardet Biedl syndrome, pro-opiomelanocortin deficiency and leptin receptor deficiency are rare, and Imcivree was designated an 'orphan medicine' (a medicine used in rare diseases). Further information on the orphan designations can be found on the European Medicines Agency's website (proopiomelanocortin deficiency: 14 July 2016; leptin receptor deficiency: 19 November 2018; Bardet Biedl syndrome: 21 August 2019).Imcivree contains the active substance setmelanotide.

How is Imcivree used?

Imcivree can only be obtained with a prescription and treatment should be prescribed and supervised by a doctor with expertise in treating obesity caused by genetic conditions.Imcivree is given once a day as an injection under the skin. The dose depends on the condition being treated, the effect of the treatment and how well it is tolerated. After being trained, patients or carers can inject the medicine themselves.For more information about using Imcivree, see the package leaflet or contact your healthcare provider.

How does Imcivree work?

People with POMC deficiency have low levels of pro-opiomelanocortin, a substance that is converted into several hormones, including melanocyte-stimulating hormone (MSH). Low levels of MSH lead to loss of feeling of fullness after eating. In people with LEPR deficiency and BBS, the receptor (target) for the hormone leptin does not work properly so signals to the nerves that make the body feel full andcontrol feelings of hunger cannot be sent. People with POMC, LEPR deficiency and BBS feel continuously hungry and quickly put on weight.The active substance in Imcivree, setmelanotide, attaches to and activates a receptor called melanocortin receptor 4, which is normally activated through leptin and MSH, promoting a feeling of fullness after eating. By attaching to this receptor directly, Imcivree is expected to reduce excessive food intake and obesity.

What benefits of Imcivree have been shown in studies?

In 2 main studies, Imcivree was shown to be effective at reducing body weight by at least 10% in people with POMC and LEPR deficiency.The first study was carried out in 10 patients with obesity due to POMC deficiency resulting from mutations in both copies of the genes for either POMC or PCSK1. After one year of treatment, 8 out of 10 people achieved at least a 10% reduction in body weight.In the second study carried out in 11 patients with obesity due to LEPR deficiency caused by mutations in both copies of the gene for LEPR, 5 people out of 11 achieved at least a 10% reduction in body weight after one year.The studies also looked at the effects of Imcivree on the feeling of hunger as measured using a questionnaire: the percentage of patients who achieved at least a 25% reduction in hunger scores was 50% in the first study, and 73% in the second study.In a study that included 28 patients aged 12 years or older with BBS, around 36% of the patients achieved at least a 10% reduction in body weight after one year of treatment.Imcivree was not compared to another medicine in these studies.

What are the risks associated with Imcivree?

The most common side effects with Imcivree (which may affect more than 1 in 10 people) are hyperpigmentation (coloration of the skin), injection site reaction, nausea (feeling sick), and headache.For the full list of side effects and restrictions of Imcivree, see the package leaflet.

Why is Imcivree authorised in the EU?

The number of people with BBS, POMC or LEPR deficiency is extremely small, so the number of people included in the studies was very limited. However, the studies showed that Imcivree helps to reduce bodyweight and feelings of hunger in these patients. These benefits are considered significant considering that there are no other medicines for these patients. Imcivree's side effects are manageable and long-term safety is monitored in a dedicated study after authorisation.The European Medicines Agency therefore decided that Imcivree'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 Imcivree?

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

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Imfinzi

What is Imfinzi and what is it used for?

Imfinzi is a medicine used to treat lung cancer. It is for use in adults with:• non-small cell lung cancer (NSCLC) that is locally advanced (meaning it has spread into tissues around the lungs, but not to other parts of the body) and cannot be removed by surgery and is not getting worse after radiation treatment and platinum-based chemotherapy (medicines to treat cancer). Imfinzi is used on its own and only when the cancer produces a protein known as PD-L1;• NSCLC that has metastasised (spread) outside the lungs. Imfinzi is given together with tremelimumab (another cancer medicine) and platinum-based chemotherapy, and is used when the cancer has no mutations (changes) in the so-called EGFR and ALK genes;• small cell lung cancer (SCLC) that has spread within the lungs or to other parts of the body (extensive-stage SCLC) and has not been treated previously. Imfinzi is given together with etoposide and either carboplatin or cisplatin (chemotherapy medicines);• biliary tract cancer (BTC), a cancer of the bile ducts (tubes that carry bile from the liver and gallbladder to the gut). It is used in combination with gemcitabine and cisplatin (other cancer medicines) in patients who have not been treated previously, when the cancer cannot be removed by surgery or has metastasised;• hepatocellular carcinoma (HCC, a type of liver cancer) in patients who have not been treated before and whose disease is advanced or cannot be removed by surgery. It is used in combination with tremelimumab.Imfinzi contains the active substance durvalumab.

How is Imfinzi used?

Imfinzi can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in treating cancer. It is given by infusion (drip) into a vein.The dose of Imfinzi and how often it is given depends on the type of cancer being treated. Treatment can continue for as long as the patient benefits from it or for up to 1 year for locally advanced NSCLC.Treatment may be paused or stopped permanently if the patient gets severe side effects.For more information about using Imfinzi, see the package leaflet or contact your doctor or pharmacist.

How does Imfinzi work?

The active substance in Imfinzi, durvalumab, is a monoclonal antibody, a type of protein designed to attach to a protein called PD-L1, which is present on the surface of many cancer cells.PD-L1 acts to switch off immune cells that would otherwise attack the cancer cells. By attaching to PDL1 and blocking its effects, Imfinzi increases the ability of the immune system to attack the cancer cells and thereby slows down the progression of the disease.

What benefits of Imfinzi have been shown in studies?

Non-small cell lung cancerIn one main study of 713 patients with locally advanced non-small cell lung cancer, patients given Imfinzi lived on average for around 17 months without their disease getting worse, compared with 6 months for those given placebo (a dummy treatment). Preliminary results also indicated that patients given Imfinzi lived longer overall compared with patients on placebo.In another main study of patients with metastatic NSCLC, 338 patients given Imfinzi in combination with tremelimumab and chemotherapy lived on average for 14 months, compared with 12 months for 337 patients given only chemotherapy. They also lived longer without their disease getting worse: around 6 months on average, compared with 5 months for patients who only received chemotherapy.Small cell lung cancerIn another main study of 805 patients with extensive-stage small cell lung cancer, patients given Imfinzi together with chemotherapy lived on average for 13 months compared with 10 months for those given chemotherapy alone.Biliary tract cancerIn a study with 685 patients with advanced biliary tract cancer, patients who received Imfinzi plus gemcitabine and cisplatin lived on average for 12.8 months, compared with 11.5 for those who received placebo plus gemcitabine and cisplatin.Hepatocellular carcinomaIn a main study in patients with advanced hepatocellular cancer who had not been treated before, Imfinzi in combination with tremelimumab increased the time patients lived overall compared with standard treatment (sorafenib): patients who received Imfinzi plus tremelimumab (393 patients) lived on average 16.4 months compared with 13.8 months for those who received sorafenib (389 patients). In about 20% of patients who received this regimen, the tumour shrank or disappeared, and this response lasted about 22 months on average. About 5% of patients who received sorafenib had a response to treatment and their response lasted on average 18 months.

What are the risks associated with Imfinzi?

When Imfinzi is given alone, the most common side effects (which may affect more than 1 in 10 people) are cough, nose and throat infections, fever, diarrhoea, abdominal (belly) pain, rash, itching and hypothyroidism (an underactive thyroid gland).When Imfinzi is given together with chemotherapy, the most common side effects (which may affect more than 1 in 10 people) are leucopenia (low levels of white blood cells, including neutrophils which fight infections), anaemia (low levels of red blood cells), nausea (feeling sick), tiredness, thrombocytopenia (low levels of platelets in the blood), constipation, decreased appetite, abdominal pain, hair loss, vomiting, diarrhoea, fever, rash, itching, increased level of liver enzymes and cough.When Imfinzi is given with tremelimumab and chemotherapy for non-small cell lung cancer, the most common side effects (which may affect more than 2 in 10 people) are anaemia, nausea, neutropenia(low levels of neutrophils, a type of white blood cell that fights infection), tiredness, rash, thrombocytopenia and diarrhoea. The most common serious side effects (which may affect more than 1 in 5 people) are neutropenia and anaemia. Other serious side effects (which may affect up to 1 in 10 people) are pneumonia (infection of the lungs), thrombocytopenia, leucopenia, tiredness, neutropenia with fever, colitis (inflammation of the large intestine) and increased levels of liver enzymes and lipase (an enzyme that helps digest fat, mainly made in the pancreas).When Imfinzi is given with tremelimumab for hepatocellular cancer, the most common side effects (which may affect more than 1 in 10 people) are peripheral oedema (swelling especially of the ankles and feet) and increased level of lipase.For the full list of side effects and restrictions of Imfinzi, see the package leaflet.

Why is Imfinzi authorised in the EU?

Imfinzi was shown to increase the time patients with locally advanced non-small cell lung cancer lived without their disease getting worse and the time patients with extensive small cell lung cancer or with biliary tract cancer lived overall. In combination with tremelimumab, Imfinzi had beneficial effects in patients with NSCLC and in those with hepatocellular carcinoma. The use of Imfinzi in patients with locally advanced NSCLC is restricted to those whose cancer produces PD-L1, since a clear benefit was only shown in this group of patients. Side effects with Imfinzi were considered manageable, and its safety profile acceptable and in line with that of similar medicines.The European Medicines Agency therefore decided that Imfinzi'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 Imfinzi?

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

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Imjudo

What is Imjudo and what is it used for?

Imjudo is a cancer medicine. It is used to treat:• hepatocellular carcinoma (a type of liver cancer) in adult patients who have not been treated before and whose disease is advanced or unresectable (cannot be removed by surgery). It is used in combination with durvalumab, another cancer medicine;• non-small cell lung cancer (NSCLC) that has metastasised (spread to other parts of the body) in adult patients who have not been treated before. It is given together with durvalumab and platinum-based chemotherapy and is used when the cancer has shown no mutations (changes) in the so-called EGFR and ALK genes.Imjudo contains the active substance tremelimumab.

How is Imjudo used?

Imjudo can only be obtained with a prescription and treatment must be started and supervised by a doctor with experience in treating cancer.Imjudo is given as an infusion (drip) into a vein which lasts about an hour.For the treatment of hepatocellular carcinoma, Imjudo is given once, in combination with durvalumab. After that, treatment with durvalumab is given every four weeks on its own until the disease gets worse or side effects become unacceptable.For the treatment of NSCLC, Imjudo is given in combination with durvalumab and chemotherapy until the disease gets worse or side effects become unacceptable, for up to a maximum of 5 doses.For more information about using Imjudo, see the package leaflet or contact your doctor or pharmacist.

How does Imjudo work?

The active substance in Imjudo, tremelimumab, is a monoclonal antibody (a type of protein). It is designed to attach to and block CTLA-4, a protein that controls the activity of T cells which are part of the immune system (the body's natural defences). By blocking CTLA-4, the medicine increases thenumber and activity of T cells, which can then kill cancer cells. This is expected to slow down the spread of the cancer.

What benefits of Imjudo have been shown in studies?

In a main study in patients with advanced hepatocellular carcinoma who had not been treated before and whose cancer cannot be removed by surgery, Imjudo in combination with durvalumab increased the time patients lived overall compared with standard treatment (sorafenib): patients who received Imjudo plus durvalumab (393 patients) lived on average 16.4 months compared with 13.8 months for those who received sorafenib (389 patients). In about 20% of patients who received Imjudo and durvalumab the tumour shrank or disappeared, and this response lasted about 22 months on average. About 5% of patients who received sorafenib had a response to treatment and their response lasted on average 18 months.In a main study in patients with metastatic NSCLC, 338 patients given Imjudo in combination with durvalumab and chemotherapy lived on average for 14 months, compared with 12 months for 337 patients given only chemotherapy. They also lived longer without their disease getting worse: around 6 months on average, compared with 5 months for patients who only received chemotherapy.

What are the risks associated with Imjudo?

For the full list of side effects and restrictions of Imjudo, see the package leaflet.The most common side effects with Imjudo in combination with durvalumab (which may affect more than 1 in 10 people) include rash, pruritus (itching), diarrhoea, abdominal (belly) pain, increased levels of liver enzymes, fever, hypothyroidism (an underactive thyroid gland), cough and peripheral oedema (swelling especially of the ankles and feet).The most common serious side effects (which may affect up to 1 in 10 people) include colitis (inflammation in the large bowel), diarrhoea and pneumonia (infection of the lungs).The most common side effects with Imjudo in combination with durvalumab and platinum-based chemotherapy (which may affect more than 1 in 10 people) include anaemia (low levels of red blood cells), nausea (feeling sick), neutropenia (low levels of neutrophils, a type of white blood cell that fights infection), tiredness, decreased appetite, rash, thrombocytopenia (low levels of blood platelets), diarrhoea, leukopenia (low levels of white blood cells), constipation, vomiting, increased levels of liver enzymes, fever, upper respiratory tract (nose and throat) infections, pneumonia, hypothyroidism, joint pain, cough and pruritus.The most common serious side effects (which may affect up to 1 in 10 people) include pneumonia, anaemia, thrombocytopenia, colitis, diarrhoea, fever and neutropenia with fever.Imjudo is commonly associated with side effects related to the activity of the immune system on body organs, such as immune-mediated colitis, hepatitis (inflammation of the liver) and hypothyroidism.

Why is Imjudo authorised in the EU?

The European Medicines Agency decided that Imjudo's benefits are greater than its risks and it can be authorised for use in the EU.Imjudo, given in combination with durvalumab to treat hepatocellular carcinoma or with durvalumab and chemotherapy to treat metastatic NSCLC, can increase the time patients live compared to treatment with standard therapy. When treating hepatocellular carcinoma, the side effects with Imjudo given in combination with durvalumab can be serious, but they are not more serious than those of thestandard therapy. For the treatment of NSCLC, the addition of Imjudo and durvalumab to chemotherapy, in particular concerning immune-related side effects, can be serious, and warrant precaution when treating frail or elderly patients.

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

The company that markets Imjudo must provide healthcare professionals prescribing the medicine with educational materials on the potential risk of immune-related side effects. Patients will also receive an alert card from their doctor summarising key safety information for the medicine.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Imjudo have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Imjudo are continuously monitored. Suspected side effects reported with Imjudo are carefully evaluated and any necessary action taken to protect patients.

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Imlygic

What is Imlygic and what is it used for?

Imlygic is a cancer medicine used to treat adults with melanoma (a type of skin cancer) that cannot be surgically removed and that has spread to other parts of the body (but not to bone, lung, brain and other internal organs).Imlygic is a type of advanced therapy medicine called a 'gene therapy product'. This is a type of medicine that works by delivering genes into the cells of the body. It contains the active substance talimogene laherparepvec.

How is Imlygic used?

Treatment with Imlygic should be started and given under the supervision of a doctor with expertise in the treatment of cancer.Imlygic is available as a solution for injection in two different strengths. It is given as an injection into melanoma tumours. The first dose is given using the lower strength of Imlygic, but subsequent doses use the higher strength. The second dose is given three weeks after the first dose and treatment is continued every two weeks for at least six months, unless the doctor considers that the patient is not benefiting from the medicine. The volume to be injected depends on the size of the tumour and thenumber of tumours to be injected. For more information, see the summary of product characteristics (also part of the EPAR).

How does Imlygic work?

The active substance in Imlygic, talimogene laherparepvec, is a type of gene therapy called 'oncolytic virus'. It is derived from a weakened herpes simplex virus 1 (the cold sore virus). This virus has been modified so it can infect and multiply inside melanoma cells. Imlygic uses the melanoma cells' own machinery to multiply, eventually overwhelming melanoma cells and killing them. Although Imlygic can enter healthy cells, it is not designed to multiply inside them.In addition, Imlygic makes the infected melanoma cells produce a protein called GM-CSF. This protein stimulates the patient's immune system (the body's natural defences) to recognise and destroy melanoma cells.

What benefits of Imlygic have been shown in studies?

Imlygic has been studied in one main study involving 436 patients with inoperable melanoma that had spread to other parts of the body (but not to bone and brain). The study, which lasted 24 months, compared Imlygic with GM-CSF injected under the skin. The main measure of effectiveness was the proportion of patients who responded to treatment and for whom the response lasted for at least six months before the patients' health declined or they required another therapy. Response to treatment was defined as reduction by at least 50% in the signs of melanoma.When looking at the subset of patients in the study (249 patients) whose disease had not spread to the lung or other internal organs, 25% (41 out of 163) of patients treated with Imlygic had a sustained response to treatment, compared with around 1% (1 out of 86) of patients treated with GM-CSF.

What are the risks associated with Imlygic?

The most common side effects with Imlygic (which may affect more than 1 in 4 people) are tiredness, chills, pyrexia (fever), nausea (feeling sick), flu-like illness and pain at the injection site. Most of these side effects were mild or moderate in severity. The most common serious side effect (affecting around 2 in 100 people) was cellulitis (infection of the upper layers of the skin). Because Imlygic contains a herpes virus, it may reactivate at a later time causing herpes infections such as cold sores. In patients whose immune system is weak (e.g. patients with HIV), Imlygic may cause more widespread disease. Imlygic must not be used in patients with a severely impaired immune system because if the virus gets reactivated, the herpes infection could spread to other parts of the body. For the full list of all side effects and restrictions reported with Imlygic, see the package leaflet.

Why is Imlygic approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) noted that Imlygic is a therapy with a novel mechanism of action which can be a valuable addition to existing therapies for advanced inoperable melanoma, an area of unmet medical need. Patients with inoperable melanoma which had spread to other parts of the body (but not to bone, brain or lung) showed a prolonged reduction in their melanoma tumours when treated with Imlygic, although it is still not known whether this will translate into longer survival. Regarding safety, Imlygic was relatively well tolerated and most side effects were mild or moderate in severity. Thus, CHMP decided that Imlygic'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 Imlygic?

A risk management plan has been developed to ensure that Imlygic 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 Imlygic, including the appropriate precautions to be followed by healthcare professionals and patients.The company has put in place a controlled distribution programme to qualified centres to ensure that the cold storage and handling requirements are observed and to control the distribution to the patients. As part of this programme, the medicine will only be supplied to doctors who have received appropriate educational materials on the risk of herpes infection, particularly in patients with an impaired immune system, on the risk of transmission of the virus to healthcare professionals or other close contacts of the patient (accidental exposure), and on the necessary precautions to be taken when administering and disposing of the product. Patients will also be provided with educational materials and a patient alert card informing on the risks with the medicine and how to avoid accidental exposure to Imlygic.The company will also carry out three studies to further characterise the benefits and risks of Imlygic, including a study of Imlygic in patients with advanced melanoma that can be surgically removed.Further information can be found in the summary of the risk management plan.

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Imnovid

What is Imnovid and what is it used for?

Imnovid is a cancer medicine used to treat multiple myeloma (a cancer of the bone marrow). It is used in combination with bortezomib (another cancer medicine) and dexamethasone (an anti-inflammatory medicine) in adults who have received at least one treatment including lenalidomide (another cancer medicine).It is also used in combination with dexamethasone in adults who have received at least two prior therapies, including both lenalidomide and bortezomib, and whose disease has worsened.Imnovid contains the active substance pomalidomide.Multiple myeloma is rare, and Imnovid was designated an 'orphan medicine' (a medicine used in rare diseases) on 8 October 2009. Further information on the orphan designation can be found on ema.europa.eu/medicines/human/orphan-designations/EU309672.

How is Imnovid used?

Treatment with Imnovid must be started and supervised by a doctor experienced in treating multiple myeloma. The medicine can only be obtained with a prescription.Imnovid is available as capsules (1, 2, 3 and 4 mg). It is taken in the first 2 weeks of 3-week treatment cycles, when given in combination with bortezomib and dexamethasone, and in the first 3 weeks of 4-week treatment cycles when given in combination with dexamethasone only. The recommended starting dose is 4 mg once a day, taken at the same time each day.Treatment with Imnovid may need to be interrupted or stopped, or the dose reduced, if the disease gets worse or certain side effects occur. For more information about using Imnovid, see the package leaflet or contact your doctor or pharmacist.1 Previously known as Pomalidomide Celgene.

How does Imnovid work?

The active substance in Imnovid, pomalidomide, is an immunomodulating agent. This means that it affects the activity of the immune system (the body's natural defences). Pomalidomide works in a number of ways in multiple myeloma, similarly to other immunomodulating medicines such as lenalidomide and thalidomide: it blocks the development of tumour cells, prevents the growth of blood vessels within tumours and also stimulates some specialised cells of the immune system to attack the tumour cells.

What benefits of Imnovid have been shown in studies?

Imnovid has been studied in one main study involving 455 adults with multiple myeloma whose disease did not get better or came back after previous treatments. Imnovid plus low-dose dexamethasone was more effective than high-dose dexamethasone alone at delaying the worsening of multiple myeloma. The disease worsened after 16 weeks on average in patients taking Imnovid plus low-dose dexamethasone, compared with 8 weeks in those taking high-dose dexamethasone.A further study included 559 patients with multiple myeloma who had received at least one treatment including lenalidomide, and whose disease got worse during or after their last treatment. Patients treated with Imnovid, bortezomib and low-dose dexamethasone lived on average 11.2 months before their disease got worse, compared with 7.1 months for patients treated with bortezomib and low dose dexamethasone.

What are the risks associated with Imnovid?

The most common side effects with Imnovid (which affect more than 1 in 10 patients), some of which can be serious, include anaemia (low red blood cell counts), neutropenia (low white blood cell count), tiredness, thrombocytopenia (low platelet counts), fever, peripheral oedema (swelling of the limbs due to fluid retention), peripheral neuropathy (nerve damage causing tingling, pain and numbness in the hands and feet) and infections including pneumonia (infection of the lungs). Serious side effects, which affect up to 1 in 10 patients, include blood disorders (such as neutropenia, anaemia and thrombocytopenia), lower respiratory tract infection (such as bronchitis or pneumonia), pulmonary embolism (clot in a blood vessel in the lungs), flu, and acute kidney injury.Pomalidomide is expected to be harmful to the unborn child, causing severe and life-threatening birth defects. Therefore, Imnovid must not be used in women who are pregnant. It must not be used in women who could become pregnant, unless they take all the necessary steps to ensure that they are not pregnant before treatment and that they do not become pregnant during or soon after treatment. As the medicine can pass into semen, the medicine must also not be used in men who are unable to comply with the required contraceptive measures.For the full list of side effects and restrictions with Imnovid, see the package leaflet.

Why is Imnovid authorised in the EU?

The European Medicines Agency decided that Imnovid's benefits are greater than its risks and it can be authorised for use in the EU. The Agency concluded that Imnovid is effective at delaying the progression of multiple myeloma in patients whose disease has not got better or has come back after previous treatment, who have very limited treatment options. The Agency also noted that Imnovid's side effects were acceptable for these patients, with side effects similar to those of other medicines of this type.Imnovid0F (pomalidomide)Page 2/3

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

The company that makes Imnovid will set up a pregnancy-prevention programme in each MemberState. It will provide a letter and educational kits for healthcare workers, and brochures for patients, explaining that the medicine is expected to be harmful to the unborn child and detailing the steps needed to use the medicine safely. It will also supply cards for patients to ensure that all appropriate safety measures have been taken by each patient. Each Member State will also ensure that educational materials and patient cards are provided to prescribers and patients.The company will also set up a registry of patients treated with Imnovid to monitor the side effects reported and whether the medicine is used for its approved indication and in compliance with the pregnancy-prevention programme. The medicine packs containing Imnovid capsules will carry a warning on the risk of severe birth defects.The company will also provide final results from a study with Imnovid in combination with bortezomib and dexamethasone in patients with multiple myeloma who had received at least one treatment including lenalidomide, to confirm the medicine's effect on overall survival.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Imnovid have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Imnovid are continuously monitored. Side effects reported with Imnovid are carefully evaluated and any necessary action taken to protect patients.

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Imraldi

What is Imraldi and what is it used for?

Imraldi is a medicine that acts on the immune system and is used to treat the following conditions:• plaque psoriasis (a disease causing red, scaly patches on the skin)• psoriatic arthritis (a disease causing red, scaly patches on the skin with inflammation of the joints)• rheumatoid arthritis (a disease causing inflammation of the joints)• axial spondyloarthritis (inflammation of the spine causing back pain), including ankylosing spondylitis and when there is no damage on X-ray but clear signs of inflammation• Crohn's disease (a disease causing inflammation of the gut)• ulcerative colitis (a disease causing inflammation and ulcers in the lining of the gut)• polyarticular juvenile idiopathic arthritis and active enthesitis-related arthritis (both rare diseases causing inflammation in the joints)• hidradenitis suppurativa (acne inversa), a chronic skin disease that causes lumps, abscesses (collections of pus) and scarring on the skin• non-infectious uveitis (inflammation of the layer beneath the white of the eyeball).Imraldi is mostly used in adults when their conditions are severe, moderately severe or getting worse, or when patients cannot use other treatments. For detailed information on the use of Imraldi in all conditions, including when it can be used in children, see the summary of product characteristics (also part of the EPAR).Imraldi contains the active substance adalimumab and is a 'biosimilar medicine'. This means that Imraldi is highly similar to a biological medicine (also known as the 'reference medicine') that is already authorised in the European Union (EU). The reference medicine for Imraldi is Humira. For more information on biosimilar medicines, see the question-and-answer document here.

How is Imraldi used?

Imraldi can only be obtained with a prescription and treatment should be started and supervised by specialist doctors experienced in the diagnosis and treatment of the conditions for which it is authorised. Eye specialists treating uveitis with Imraldi should also take advice from doctors who have experience of using the medicine.The medicine is available as a solution for injection under the skin in a pre-filled syringe. The dose depends on the condition to be treated and in children is usually calculated according to the child's weight and height. After the starting dose, Imraldi is most often given every two weeks, but it may be given every week in certain situations. After training, patients or their carers may inject Imraldi if their doctor considers it appropriate. Patients may be given other medicines during treatment with Imraldi, such as methotrexate or corticosteroids (other anti-inflammatory medicines).

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Imvanex

What is Imvanex and what is it used for?

Imvanex is a vaccine used to protect against smallpox in adults. It contains an attenuated (weakened) form of the vaccinia virus called 'modified vaccinia virus Ankara', which is related to the smallpox virus.Smallpox was officially declared eradicated in 1980, with the last known case of the disease occurring in 1977. This vaccine will be used when it is considered necessary to protect against smallpox in accordance with official recommendations.Imvanex can also be used to protect adults from monkeypox and disease caused by the vaccinia virus.

How is Imvanex used?

Imvanex is given by injection under the skin, preferably in the upper arm. People who have not been previously vaccinated against smallpox, monkeypox or the disease caused by the vaccinia virus should receive two 0.5 ml doses, with the second dose given at least 28 days after the first.If a booster dose is considered necessary in people previously vaccinated, a single 0.5 ml dose should be given. People with a weakened immune system (the body's natural defences) who require a booster should receive two doses, with the second dose given at least 28 days after the first.The vaccine can only be obtained with a prescription. For more information about using Imvanex, see the package leaflet or contact your doctor or pharmacist.

How does Imvanex work?

Vaccines work by preparing the body to defend itself against a disease. When a person is given the vaccine, the immune system recognises the virus in the vaccine as 'foreign' and makes antibodies against it. When the person comes into contact again with similar viruses, these antibodies together with other components of the immune system will be able to kill the viruses and help protect against disease.Imvanex prepares the body to defend itself against infection with the variola (smallpox), monkeypox and vaccinia viruses. It contains a weakened form of the vaccinia virus called 'modified vaccinia virus Ankara', a virus that is closely related to the smallpox and monkeypox viruses but does not cause disease in humans and cannot reproduce in human cells. Because of the similarity between the virus inImvanex and these viruses, antibodies produced against it are expected to protect against monkeypox, smallpox and vaccinia.

What benefits of Imvanex have been shown in studies?

Imvanex was shown in studies to be effective at triggering the production of antibodies to a level expected to provide protection against smallpox.Five main studies were carried out. The studies involved over 2,000 adults, including patients with HIV and atopic dermatitis (an itchy skin condition caused by an overactive immune system) and people who had been vaccinated against smallpox in the past. Two of the studies specifically looked at the effectiveness of Imvanex as a booster. A subsequent study in 433 people who had not been vaccinated before found that the level of protective antibodies after vaccination with Imvanex was at least as high as with a conventional smallpox vaccine. It is not yet known how long the protection will last.Data from several animal studies showed protection against monkeypox in non-human primates vaccinated with Imvanex and then exposed to the monkeypox virus.Imvanex is also expected to protect against the disease caused by vaccinia virus, since the vaccine is based on a modified version of vaccinia virus.

What are the risks associated with Imvanex?

The most common side effects with Imvanex (which may affect more than 1 in 10 people) are headache, nausea, myalgia (muscle pain), tiredness and injection site reactions (pain, redness, swelling, hardening and itching).Imvanex must not be used in patients who are hypersensitive (allergic) to the active substance or any of the substances found at trace levels, such as chicken protein, benzonase and gentamicin.For the full list of side effects and restrictions, see the package leaflet.

Why is Imvanex authorised in the EU?

The European Medicines Agency considered that Imvanex is effective at triggering the production of antibodies against smallpox to a level that provides protection at least as high as that from conventional smallpox vaccines. The vaccinia virus in Imvanex cannot replicate in human cells and hence is less likely to cause side effects than conventional smallpox vaccines. Imvanex would therefore be beneficial for people who cannot be given vaccines containing replicating viruses, such as patients with a weakened immune system.For the prevention of monkeypox, the Agency considered that the effectiveness of Imvanex could be inferred from animal studies. In addition, because of the similarity between the virus in Imvanex ('modified vaccinia virus Ankara') and the variola (smallpox), monkeypox and vaccinia viruses, antibodies produced against it are expected to protect against monkeypox, smallpox as well as the disease caused by vaccinia. The safety profile of Imvanex is considered favourable, with vaccinated people experiencing mild to moderate side effects. The Agency therefore decided that Imvanex's benefits are greater than its risks and it can be authorised for use in the EU.Imvanex has been authorised under 'exceptional circumstances'. This is because it has not been possible to obtain complete information about Imvanex due to the rarity of the diseases. Every year, the Agency will review any new information that becomes available and this overview will be updated as necessary.Imvanex Imvanex (live modified vaccinia Ankara virus)

What information is still awaited for Imvanex?

Since Imvanex has been authorised under exceptional circumstances, the company that markets Imvanex will provide data on the vaccine's benefits and risks from an observational study in people who are given the vaccine, if ever there is an outbreak of smallpox in the future.The company will also collect data from an observational study that will be carried out during the ongoing monkeypox outbreak in Europe to confirm the effectiveness of the vaccine in protecting against monkeypox.

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

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

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Inbrija

What is Inbrija and what is it used for?

Inbrija is a medicine used to treat adults with Parkinson's disease (a progressive brain disease that causes shaking and muscle stiffness and slows movement).Inbrija is used to treat symptoms during 'off' periods (times when the patient has more difficulty moving about) that occur while the patient is taking their usual treatment of a combination of levodopa and an inhibitor of dopa-decarboxylase.Inbrija contains the active substance levodopa.

How is Inbrija used?

Inbrija is available as capsules containing a powder for inhalation and can only be obtained with a prescription.Inbrija should be inhaled using the Inbrija inhaler device when the patient recognises the symptoms of an 'off' period. The recommended dose is 2 capsules in each 'off' period up to a maximum of 10 capsules per day.For more information about using Inbrija, see the package leaflet or contact your doctor or pharmacist.

How does Inbrija work?

In patients with Parkinson's disease, the cells in the brain that produce dopamine, a neurotransmitter important for controlling movement, begin to die and the amount of dopamine in the brain decreases.Inbrija contains levodopa which converts into dopamine in the brain and helps to restore dopamine levels, thereby improving the symptoms of the condition. Because Inbrija is inhaled, it can supply extra levodopa (and hence dopamine) quickly when needed during an 'off' period.

What benefits of Inbrija have been shown in studies?

Two main studies have shown that Inbrija is effective at improving patients' symptoms during 'off' periods. Effects were measured using a standard symptom scale known as the unified Parkinson's disease rating scale, UPDRS, part III.The first study involved 226 patients who had 12 weeks of standard treatment with levodopa and a dopa-decarboxylase inhibitor. In this study, patients who took Inbrija during their 'off' periods had an average improvement of 10 points on the scale 30 minutes later, compared with 6 points for patients taking placebo (a dummy treatment). Of patients treated with Inbrija, 71% reported that their symptoms were improved, compared with 46% of patients on placebo.In the second study involving 77 patients who had 4 weeks of standard treatment, patients who took Inbrija during 'off' periods had an average improvement of 10 points on the scale 10 to 60 minutes later, compared with 3 points for patients taking placebo.

What are the risks associated with Inbrija?

The most common side effect with Inbrija is cough (which may affect more than 1 in 10 people). Other common side effects, which may affect up to 1 in 10 people, are falls, upper respiratory tract infection (nose and throat infection), dyskinesia (difficulty controlling movement) and discoloured sputum (phlegm).Allergic oedema (swelling) and gastrointestinal haemorrhage (bleeding in the gut) have been reported for other medicines containing levodopa. Medicines containing levodopa and a dopa-decarboxylase inhibitor have shown side effects of symptoms like neuroleptic malignant syndrome (a nervous disorder) and rhabdomyolysis (breakdown of muscle fibres).Inbrija must not be used in patients with narrow angle glaucoma (an eye disorder) or pheochromocytoma (a tumour of the adrenal glands). It must also not be used in patients taking medicines known as non-selective monoamine oxidase (MAO) inhibitors or in patients with a history of neuroleptic malignant syndrome or rhabdomyolysis. For the full list of side effects and restrictions, see the package leaflet.

Why is Inbrija authorised in the EU?

Studies show that Inbrija is effective at reducing symptoms during 'off' periods in patients with Parkinson's disease on levodopa/dopa-decarboxylase-inhibitor treatment. The safety of the medicine is in line with other similar medicines. Because it is inhaled, Inbrija provides rapid relief of symptoms, which improves patients' quality of life. The European Medicines Agency therefore decided that Inbrija'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 Inbrija?

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

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Increlex

What is Increlex?

Increlex is a solution for injection that contains the active substance mecasermin.

What is Increlex used for?

Increlex is used for the long-term treatment of patients aged two to 18 years who are short for their age due to a condition known as 'severe primary insulin-like growth factor-1 deficiency'. Patients with this condition have low levels of the hormone insulin-like growth factor-1 or IGF-1, which is required for normal growth.Because the number of patients with primary IGF-1 deficiency is low, the disease is considered 'rare', and Increlex was designated an 'orphan medicine' (a medicine used in rare diseases) on 22 May 2006.The medicine can only be obtained with a prescription.

How is Increlex used?

Treatment with Increlex should be supervised by doctors who have experience in the diagnosis and treatment of patients with growth disorders.The recommended starting dose is 0.04 mg per kilogram body weight twice a day. The dose should be tailored for each patient according to the speed of growth and side effects. The maximum dose is 0.12 mg per kilogram twice a day. Increlex is given by injection under the skin, and the injection site should be changed with each injection. It should never be injected into a vein. The injection should be carriedout shortly before or after a meal or snack. Treatment should be interrupted if the patient cannot eat for any reason. For more information, see the summary of product characteristics.

How does Increlex work?

The active substance in Increlex, mecasermin, is a copy of the hormone IGF-1. IGF-1 is important in determining how tall a child grows. It does this by stimulating cells to divide and grow and to absorb nutrients, supporting the growth of body tissues. Increlex works in the same way as natural IGF-1, replacing the missing hormone and helping the child to grow taller.

How has Increlex been studied?

Increlex has been studied in five studies involving a total of 76 children aged between one and 15 years with severe primary IGF-1 deficiency, nine of whom had received another type of recombinant IGF-1 before joining these studies. Because the disease is rare, many of the children were included in more than one of the studies. One study compared Increlex with placebo (a dummy treatment) in eight patients, but the others did not compare Increlex with any other treatments. The studies lasted between 15 months and eight years, and the main measure of effectiveness was the speed of growth.

What benefit has Increlex shown during the studies?

Increlex caused the speed of growth to increase. When the results of the studies were looked at together, the average growth rate was 2.8 cm per year before treatment. This increased to 8.0 cm in the first year of treatment and 5.8 cm in the second. The growth rate stabilised at around 4.7 cm per year from the fourth year of treatment.Some of the studies also included children who had defects in the gene for growth hormone (GH) and who had developed antibodies against GH. The company applied for an authorisation to use Increlex in these children, but withdrew its application after the end of the medicine's assessment, as this disease is not listed in the medicine's 'orphan' designation.

What is the risk associated with Increlex?

The most common side effects with Increlex (seen in more than 1 patient in 10) are headache, hypoglycaemia (low blood sugar levels), vomiting (being sick), injection site hypertrophy (lumps at the site of injection) and otitis media (infection of the middle ear).Increlex must not be used in patients who have, or are thought to have active neoplasia (abnormal cell growth). Treatment with Increlex should be stopped if neoplasia develops. Increlex must not be used in premature babies or newborns. For the full list of all side effects and restrictions with Increlex, see the package leaflet.

Why has Increlex been approved?

The CHMP decided that Increlex's benefits are greater than its risks and recommended that it be given marketing authorisation.Increlex has been authorised under 'Exceptional Circumstances'. This means that because the disease is rare, it has not been possible to obtain complete information about Increlex. Every year, theIncrelexEuropean 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 Increlex?

The company that makes Increlex will carry out a long-term study looking at the safety of the medicine, when treatment is started in young children and continued into adulthood.

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

A risk management plan has been developed to ensure that Increlex 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 Increlex, including the appropriate precautions to be followed by healthcare professionals and patients.Additionally, the company that markets Increlex will supply information packs to doctors and patients explaining how the medicine is used and its side effects. The company will also supply dose calculators to help doctors and patients (or their carers) to work out the appropriate dose.

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Incresync

What is Incresync and what is it used for?

Incresync is a diabetes medicine containing the active substances alogliptin and pioglitazone. It is used as an addition to diet and exercise in adults with type 2 diabetes to improve the control of glucose (sugar) levels in the blood:• in patients who are not satisfactorily controlled with pioglitazone alone, and who cannot be treated with metformin (another diabetes medicine);• together with metformin in patients who are not satisfactorily controlled with a combination of pioglitazone and metformin.Incresync can also be used to replace separate alogliptin and pioglitazone tablets in adults who are already being treated with this combination.

How is Incresync used?

Incresync is available as tablets and can only be obtained with a prescription. It is taken by mouth once daily. The recommended dose depends on the patient's current treatment for diabetes. For more information about using Incresync, see the package leaflet or contact your doctor or pharmacist.

How does Incresync 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 in which the body is unable to use insulin effectively. The active substances in Incresync, alogliptin and pioglitazone, work in different ways to help correct this.Alogliptin is a dipeptidyl-peptidase-4 (DPP-4) inhibitor. It works by blocking the breakdown of incretin hormones in the body. These hormones are released after a meal and stimulate the pancreas to produce insulin. By blocking the breakdown of incretin hormones in the blood, alogliptin prolongs their action in stimulating the pancreas to produce more insulin when blood glucose levels are high. Alogliptin does not work when the blood glucose is low. Alogliptin also reduces the amount of glucose made by the liver by increasing insulin levels and decreasing the levels of the hormone glucagon. Together, these processes reduce blood glucose levels and help to control type 2 diabetes. Alogliptin is licensed in the EU as Vipidia.Pioglitazone makes cells (fat, muscle and liver) more sensitive to insulin, which means that the body makes better use of the insulin it produces. Pioglitazone is authorised in the EU as Actos and associated names.As a result of the action of both active substances, glucose levels in the blood are reduced, which helps to control type 2 diabetes.

What benefits of Incresync have been shown in studies?

Incresync has been investigated in two main studies involving 1,296 patients with type 2 diabetes that was not well controlled by previous treatment. One of the studies compared the effects of alogliptin with placebo (a dummy treatment) when used as an add-on to existing treatment with pioglitazone, with or without metformin or another diabetes medicine. In the other study, the effects of adding alogliptin to existing treatment with pioglitazone and metformin were compared with increasing the doses of pioglitazone. In both studies, the main measure of effectiveness was the change in the level of glycosylated haemoglobin (HbA1c), which is the percentage of haemoglobin in the blood that has glucose attached. HbA1c levels give an indication of how well the blood glucose is controlled. HbA1c levels were measured after 26 weeks in the first study and 52 weeks in the second study.Both studies showed that the combination of the active substances in Incresync could produce a small but clinically relevant improvement in HbA1c. When alogliptin was added to pioglitazone, the improvement was a reduction of HbA1c of 0.47% at an alogliptin dose of 12.5 mg and 0.61% at an alogliptin dose of 25 mg. Incresync was at least as effective as pioglitazone and metformin in reducing HbA1c.

What are the risks associated with Incresync?

The most common side effects with Incresync (which may affect up to 1 in 10 people) are upper respiratory tract infections (nose and throat infections), sinusitis (inflammation of the sinuses), headache, nausea (feeling sick), dyspepsia (heartburn), abdominal pain (tummy ache), pruritus (itching), myalgia (muscle pain), peripheral oedema (swelling in arms and legs) and weight gain. For the full list of side effects of Incresync, see the package leaflet.Incresync must not be used in patients who are hypersensitive (allergic) to the active substances or any of the ingredients or who have had serious allergic reactions to any dipeptidyl-peptidase-4 (DPP-4) inhibitor. It must also not be used in patients who have or have ever had heart failure or bladder cancer, those with reduced liver function, diabetic ketoacidosis (a serious condition that can occur in diabetes), or blood in the urine that has not been properly investigated. For the full list of restrictions, see the package leaflet.

Why is Incresync authorised in the EU?

The European Medicines Agency decided that Incresync's benefits are greater than its risks and it can be authorised for use in the EU. The Agency considered that adding alogliptin to existing treatment with pioglitazone with or without metformin had shown to produce modest but clinically relevant improvements in HbA1c. The Agency therefore considered that the combination of alogliptin and pioglitazone in Incresync is of benefit to patients. Incresync's safety profile was consistent with that seen with the individual components.(alogliptin/pioglitazone)

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

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

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Incruse Ellipta

What is Incruse Ellipta and what is it used for?

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

How is Incruse Ellipta used?

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

How does Incruse Ellipta work?

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

What benefits of Incruse Ellipta have been shown in studies?

Incruse Ellipta was investigated in four main studies involving over 4,000 patients. Three studies compared Incruse Ellipta with placebo (a dummy treatment), while one study compared Incruse Ellipta with tiotropium (another medicine for COPD). The main measure of effectiveness was based on changes in the patients' forced expiratory volumes (FEV1, the maximum volume of air a person can breathe out in one second).1 Previously known as Incruse.Results showed that Incruse Ellipta improved lung function by an average FEV1 of 127 ml more than placebo after 12 weeks of treatment and by 115 ml more than placebo after 24 weeks of treatment. A double dose of Incruse Ellipta only showed small improvements compared with a single dose, which were not considered relevant. In the study comparing Incruse Ellipta with tiotropium, FEV1 improvements over 24 weeks were similar for both medicines.The studies also showed an improvement in symptoms such as breathlessness and wheezing.

What are the risks associated with Incruse Ellipta?

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

Why is Incruse Ellipta authorised in the EU?

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

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

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

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Inductos

What is Inductos?

Inductos is a kit for implant. The kit consists of a powder containing the active substance, dibotermin alfa, a solvent and a matrix (collagen sponge).

What is Inductos used for?

Inductos is used to help new bone develop. It can be used in the following situations:• lower back spine fusion surgery. This is a type of surgery used to relieve back pain due to a damaged disc where the disc between two vertebrae (the bones in the spine) is removed and the vertebrae are fused (joined) together. Inductos is used together with approved medical devices that correct the position of the spine. In this type of surgery, Inductos can be used instead of an autogenous bone graft (bone taken from one part of a person's body and placed in another part of the body). Inductos is used in adults who have been treated for at least six months for back pain due to a damaged disc but have not had an operation.• surgery to heal fractures (breaks) of the tibia (shin bone). Inductos is used in addition to standard treatment and care. It is only used when the nail to fix the bone does not need 'reaming' (drilling to make room for nail placement).The medicine can only be obtained with a prescription.

How is Inductos used?

Inductos should be used by a qualified surgeon. Inductos is made up into a solution before use, applied to the matrix and left for at least 15 minutes (but no more than two hours). The matrix is then cut, ifneeded, to the correct size before use. Generally one kit is sufficient. For lower back spine fusion, the damaged disc between the vertebrae is removed and replaced with one or more medical devices and Inductos. The medical devices fix the position of the vertebrae, and Inductos encourages bone to grow between the two vertebrae to join them permanently in the correct position. For a fractured tibia, Inductos is placed around the broken bone to aid healing.

How does Inductos work?

The active substance in Inductos, dibotermin alfa, acts on the bone structure. It is a copy of a protein called bone morphogenetic protein 2 (BMP-2), which is produced naturally by the body and helps with the formation of new bone tissue. When implanted, dibotermin alfa stimulates the bone tissue around the matrix to make new bone. The newly formed bone grows into the matrix, which then degrades. Dibotermin alfa is produced by a method known as 'recombinant DNA technology': it is made by cells that have received a gene (DNA) which makes them able to produce dibotermin alfa. The replacement dibotermin alfa acts in same way as BMP-2 produced naturally by the body.

How has Inductos been studied?

Inductos has been studied in 279 patients having lower back spine fusion. Spinal fusion using Inductos was compared with fusion using a bone graft removed from the hip during surgery. The main measure of effectiveness was fusion of the vertebrae confirmed by X-ray, and improvement in the pain and disability reported by the patient, measured two years after surgery.Inductos has been studied in 450 patients with a fractured tibia. Inductos was compared with standard care. The main measure of effectiveness was the number of patients who did not need further treatment for their fractured tibia (such as a bone graft or changes to the nail used to fix the bones together) in the year following surgery.

What benefit has Inductos shown during the studies?

In spinal fusion, Inductos was as effective as bone grafts. After two years, 57% of the patients treated with Inductos (69 out of 122) had responded to treatment, compared with 59% of the patients treated with a bone graft (78 out of 133).Additional studies and analysis of data from the published literature showed that Inductos was more effective than bone graft at inducing fusion of the lower back vertebrae, irrespective of the surgical technique or the type of approved medical device used to hold the bone in position.In patients with a fractured tibia, using Inductos in addition to standard care was more effective than standard care alone in reducing the risk of treatment failure. Of the patients in the standard care group, 46% needed a further intervention within a year to repair their fracture, while the proportion was 26% for those also receiving Inductos.

What is the risk associated with Inductos?

The most common side effects with Inductos (seen in more than 1 patient in 10) are radiculopathic events (problems occurring at or near the root of the nerve, along the spine, resulting in pain, weakness, numbness, or difficulty controlling specific muscles) when used in spine surgery, and localised infection when used in tibia fracture surgery. The most severe side effect is localised oedema (swelling at the surgery site) when used in upper spine (neck) surgery. For the full list of all side effects reported with Inductos, see the package leaflet.Inductos must not be used in the following situations:• patients who are still growing;• patients diagnosed with or being treated for cancer;• patients with an active infection at the surgery site;• patients with an inadequate blood supply at the fracture site;• treating a fracture that is related to a disease such as Paget's disease or cancer.For the full list of restrictions with Inductos, see the package leaflet.

Why has Inductos been approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that the benefits of Inductos are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered that Inductos is effective in single-level lumbar spine fusion as a substitute for autogenous bone graft and for the treatment of acute tibia fractures in adults, as an adjunct to standard care. Patients undergoing treatment with Inductos may be at risk of heterotopic ossification (the growth of bone in abnormal places like soft tissue); this risk is considered to be manageable with the proposed risk minimisation measures.

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

A risk management plan has been developed to ensure that Inductos 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 Inductos, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Inductos will make sure that educational material is available in all Member States for all healthcare professionals expected to use the medicine. This material will include information on the risk of heterotopic ossification and the potential risk of medication errors and incorrect use of Inductos.

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Infanrix Hexa

What is Infanrix hexa and what is it used for?

Infanrix hexa is a vaccine used to protect babies and toddlers against diphtheria, tetanus, pertussis (whooping cough), hepatitis B, poliomyelitis (polio) and diseases such as bacterial meningitis caused by the bacterium Haemophilus influenzae type b (Hib). Infanrix hexa contains the following active substances:• toxoids (chemically weakened toxins) from diphtheria and tetanus;• parts of Bordetella pertussis (B. pertussis, a bacterium that causes whooping cough);• parts of the hepatitis B virus;• inactivated polioviruses;• polysaccharides (sugars) from Haemophilus influenzae type b.

How is Infanrix hexa used?

Infanrix hexa is available as a powder and suspension that are made up into a suspension for injection. The vaccination schedule for Infanrix hexa is a course of 2 or 3 doses, given at least 1 month apart, according to official recommendations, usually in the first 6 months of life. Infanrix hexa is given by deep injection into a muscle. Subsequent injections should be given in different areas.A booster dose of Infanrix hexa or a similar vaccine must be given at least 6 months after the last dose of the initial course. The choice of booster vaccine depends on official recommendations.The vaccine can only be obtained with a prescription. For more information, see the package leaflet.

How does Infanrix hexa work?

Infanrix hexa is a vaccine that protects against a range of infections. Vaccines work by 'teaching' the immune system (the body's natural defences) to defend the body against the infections.When a child is given the vaccine, the immune system recognises the parts of the bacteria and viruses in the vaccine as 'foreign' and makes antibodies against them. The immune system will then be able to produce antibodies more quickly when the person comes into contact with the bacteria or viruses. This helps to protect against the diseases that these bacteria and viruses cause.The vaccine is 'adsorbed'. This means that the active substances are fixed onto aluminium compounds, to stimulate a better response.

What benefits of Infanrix hexa have been shown in studies?

Infanrix hexa has been studied in nine studies, involving a total of almost 5,000 children aged between 6 weeks and 2 years. Over 3,000 of the children received a course of vaccination with Infanrix hexa. The effects of Infanrix hexa were compared with those of separate vaccines containing the same active substances. The main measure of effectiveness was the production of protective antibodies.Results of the studies taken together showed that a course of injections with Infanrix hexa was as effective at producing protective levels of antibodies as giving separate vaccines containing the same active substances. Overall, between 95 and 100% of the children had antibodies to diphtheria, tetanus, pertussis, hepatitis B virus, polioviruses, and Hib, 1 month after the vaccination course.An additional five studies looked at the effects of a booster vaccination with Infanrix hexa. These studies showed that booster vaccinations with Infanrix hexa were as effective as giving separate vaccines containing the same active substances 1 month after the booster vaccination.

What is the risk associated with Infanrix hexa?

The most common side effects with Infanrix hexa (seen in more than 1 in 10 doses of the vaccine) are swelling, pain and redness at the injection site, loss of appetite, fever of 38ΊC or more, tiredness, abnormal crying, irritability and restlessness. For the full list of side effects reported with Infanrix hexa, see the package leaflet.Infanrix hexa must not be used in infants who are hypersensitive (allergic) to any of the active substances, to any of the other ingredients of the vaccine, or to neomycin and polymyxin (antibiotics) and formaldehyde. It must not be used in infants who have had an allergic reaction to a vaccine containing diphtheria, tetanus, pertussis, hepatitis B, polio or Hib. Infanrix hexa must not be used in infants who have had encephalopathy (brain disease) of unknown cause within 7 days of receiving a pertussis vaccine. Infanrix hexa should be postponed in infants with a severe sudden fever.

Why is Infanrix hexa approved?

Infanrix hexa has been shown to be effective at producing protective levels of antibodies against diphtheria, tetanus, pertussis, hepatitis B virus, polioviruses, and Hib. The safety of Infanrix hexa issimilar to other vaccines used to prevent these conditions. The European Medicines Agency therefore decided that Infanrix hexa'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 Infanrix hexa?

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

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Inflectra

What is Inflectra and what is it used for?

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

How is Inflectra used?

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

How does Inflectra work?

The active substance in Inflectra, infliximab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Infliximab has been designed to attach to a chemical messenger in the body called tumour necrosis factor-alpha (TNF-alpha). This messenger is involved in causing inflammation and is found at high levels in patients with the diseases that Inflectra is used to treat. By blocking TNF-alpha, infliximab improves the inflammation and other symptoms of the diseases.Inflectra is produced by a method known as 'recombinant DNA technology'. The infliximab is made by cells that have received a gene (DNA), which makes them able to produce it.

What benefits of Inflectra have been shown in studies?

Inflectra was studied to show that it is comparable to the reference medicine, Remicade. Inflectra was compared with Remicade in one main study involving 606 adult patients with rheumatoid arthritis. Patients received either Inflectra or Remicade in addition to methotrexate for 30 weeks. The main measure of effectiveness was the change in symptoms. After 30 weeks of treatment Inflectra was as effective as Remicade with around 60 % of patients responding to treatment with either medicine.An additional study was also carried involving 250 patients with ankylosing spondylitis out to show that Inflectra produces levels of the active substance in the body that are comparable to the reference medicine, Remicade.

What are the risks associated with Inflectra?

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

Why is Inflectra approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that, in accordance with EU requirements, Inflectra has been shown to have a comparable quality, safety and efficacy profile to Remicade. Therefore, the CHMP's view was that, as for Remicade, the benefit outweighs the identified risks. The Committee recommended that Inflectra be approved for use in the EU.

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

A risk management plan has been developed to ensure that Inflectra 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 Inflectra, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Inflectra will provide educational material to doctors who are expected to prescribe the medicine in adults and children including information on the safety of the medicine and an alert card to be given to patients. The company will also carry out studies to confirm the long-term safety of the medicine.

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Inhixa

What is Inhixa and what is it used for?

Inhixa is an anticoagulant medicine (a medicine that prevents blood clots) used in adults for:• preventing venous thromboembolism (blood clots that form inside the veins, obstructing blood flow), especially in patients who are having surgery or who are at greater risk of clots because they are bedridden due to illness;• treating deep vein thrombosis (DVT, where the clot develops in a deep vein, usually in the leg) and pulmonary embolism (PE, a clot in a blood vessels supplying the lungs);• treating DVT and PE in patients with active cancers, and preventing these clotting problems from occurring again;• treating unstable angina (a severe type of chest pain caused by problems with the blood flow to the heart);• treating certain types of myocardial infarction (heart attack);• preventing clots forming when blood is circulated through a haemodialysis machine to remove toxic substances.In the treatment of unstable angina and heart attack Inhixa is given with aspirin (acetylsalicylic acid).Inhixa contains the active substance enoxaparin sodium and is a 'biosimilar medicine'. This means that Inhixa is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Inhixa is Clexane. For more information on biosimilar medicines, see here.

How is Inhixa used?

Inhixa is usually given as an injection under the skin although in the treatment of a type of heart attack called acute ST-segment elevation myocardial infarction (STEMI) it is first given as an injection into a vein, and to prevent clots in haemodialysis machines it is injected directly into the tube carrying the blood. The dose and how long the medicine is given for, as well as whether it is given with othermedicines, depend on the condition to be prevented or treated. Doses must be adjusted in patients with severely reduced kidney function.The medicine can only be obtained with a prescription. For more information about using Inhixa, see the package leaflet or contact your doctor or pharmacist.

How does Inhixa work?

When blood clots develop inside blood vessels they may restrict the blood flow to the organs, including the heart. The active substance in Inhixa, enoxaparin, is one of a group of anticoagulant medicines called low-molecular weight heparins. Enoxaparin increases the effect of antithrombin III, a natural substance that controls the blood's clotting factors and helps prevent blood from clotting inside the body. This helps to stop the formation of new blood clots and control existing ones.

What benefits of Inhixa have been shown in studies?

Laboratory studies comparing Inhixa with Clexane have shown that the active substance in Inhixa is highly similar to that in Clexane in terms of structure, purity and biological activity.In addition, a study in 20 healthy subjects has shown that the same doses of the two products given by injection under the skin produced similar effects on blood clotting factors, using various measures that reflect the way the medicine works in the body.The company also provided information from published studies showing the benefits of enoxaparin in preventing and treating blood clots.Because Inhixa is a biosimilar medicine, the studies on effectiveness and safety of enoxaparin carried out with Clexane do not all need to be repeated for Inhixa.

What are the risks associated with Inhixa?

The safety of Inhixa 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 Clexane.The most common side effect with Inhixa (which may affect more than 1 in 10 people) is haemorrhage (bleeding); serious bleeding may occur in around 4 in 100 people given Inhixa to prevent blood clots during surgery. In addition, increased levels of liver enzymes in the blood (a sign of possible liver problems) are very common (may affect more than 1 in 10 people).For the full list of side effects reported with Inhixa, see the package leaflet.Inhixa must not be used in patients with existing major bleeding, severe disorders of blood clotting, or with conditions that increase the risk of, or from, bleeding, such as stomach ulcers or stroke. For the full list of restrictions, see the package leaflet.

Why is Inhixa authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Inhixa has a highly similar structure, purity and biological activity to Clexane, and has the same effect on blood clotting factors. The safety profiles of the two medicines were also considered similar, based on laboratory testing.All these data were considered sufficient to conclude that Inhixa will behave in the same way asClexane in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view wasthat, as for Clexane, the benefits of Inhixa 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 Inhixa?

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

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Inlyta

What is Inlyta?

Inlyta is a medicine that contains the active substance axitinib. It is available as tablets (1, 3, 5 and 7 mg).

What is Inlyta used for?

Inlyta is used to treat adults with advanced renal cell carcinoma, a type of kidney cancer. 'Advanced' means that the cancer has started to spread. Inlyta is used when treatment with Sutent (sunitinib) or 'cytokines' (other cancer medicines) has failed.The medicine can only be obtained with a prescription.

How is Inlyta used?

Treatment with Inlyta should be started by doctors who have experience in using cancer medicines.The recommended starting dose is 5 mg twice a day, taken approximately 12 hours apart. The dose can be adjusted according to the patient's response. In patients who tolerate the 5 mg dose well, who do not have high blood pressure and are not taking blood pressure medicines, the dose may be increased first to 7 mg then to a maximum of 10 mg twice a day. It may be necessary to reduce the dose or interrupt treatment to manage certain side effects. In patients taking certain other medicines, the doctor may need to adjust the dose of Inlyta.Patients with moderately reduced liver function should receive a starting dose of 2 mg twice a day. Inlyta should not be used in patients with severely reduced liver function.

How does Inlyta work?

The active substance in Inlyta, axitinib, works by blocking some enzymes known as tyrosine kinases that are found in 'vascular endothelial growth factor' (VEGF) receptors on the surface of cancer cells. VEGF receptors are involved in the growth and spread of cancer cells and in the development of blood vessels that supply the tumours. By blocking these receptors, Inlyta helps to reduce the growth and spread of the cancer and cut off the blood supply that keeps the cancer cells growing.

How has Inlyta been studied?

Inlyta has been compared with sorafenib (another cancer medicine) in one main study involving 723 patients with advanced renal cell carcinoma whose previous treatment with other cancer medicines such as sunitinib or cytokines had failed. The main measure of effectiveness was how long the patients lived without their tumour getting worse.

What benefit has Inlyta shown during the studies?

Inlyta was more effective than sorafenib in treating advanced renal cell carcinoma. Patients taking Inlyta lived for an average of 6.7 months without the disease getting worse, compared with 4.7 months in the patients taking sorafenib. Effects were better for those patients who were previously treated with cytokines rather than sunitinib.

What is the risk associated with Inlyta?

The most common side effects with Inlyta (seen in more than 20% of patients) are diarrhoea, hypertension (high blood pressure), fatigue (tiredness), dysphonia (speech disturbance), nausea (feeling sick), vomiting, decreased appetite, weight loss, palmar-plantar erythrodysaesthesia syndrome (rash and numbness on the palms of the hands and soles of the feet), haemorrhage (bleeding), hypothyroidism (an underactive thyroid gland), protein in urine, cough and constipation.For the full list of all side effects and restrictions with Inlyta, see the package leaflet.

Why has Inlyta been approved?

The CHMP concluded that the effectiveness of Inlyta in treating patients with advanced renal cell carcinoma for whom treatment with Sutent or a cytokine failed has been demonstrated. Regarding its safety, the side effects of the medicine are similar to other medicines in the same class and are considered to be acceptable and manageable. The CHMP therefore decided that Inlyta'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 Inlyta?

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

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Inomax

What is INOmax?

INOmax is a gas for inhalation that contains the active substance nitric oxide diluted in nitrogen gas at 400 or 800 parts per million (ppm).

What is INOmax used for?

INOmax is used in combination with artificial ventilation and other medicines to help improve blood oxygen levels in the following groups of patients:• newborn babies (born after 34 weeks of gestation) with breathing problems associated with pulmonary hypertension (high blood pressure in the lungs). INOmax is used in these babies to improve oxygen supply levels and to reduce the need for extracorporeal membrane oxygenation (ECMO, a technique to oxygenate the blood outside the body using a device similar to a heart-lung machine).• patients of all ages who are undergoing or have undergone heart surgery and develop pulmonary hypertension. In these patients INOmax is used to help improve heart function and reduce blood pressure in the lungs.The medicine can only be obtained with a prescription.

How is INOmax used?

INOmax treatment should be supervised by a doctor who has experience in intensive care or neonatal intensive care if the patient is a newborn baby. INOmax should only be used in units where staff have been trained in the use of a nitric oxide delivery system.INOmax is used in patients who are undergoing artificial ventilation, once the ventilation is optimised. INOmax is given after being diluted in an oxygen/air mixture supplied to the patient through the ventilator.The maximum starting dose of INOmax is 20 ppm for children up to 18 years of age, and 40 ppm for adults. This should then be reduced to 5 ppm, provided the blood in the arteries contains enough oxygen. In newborn babies with breathing problems, treatment can be continued at this dose until there is improvement in oxygen levels, for a maximum of four days. In children and adults undergoing heart surgery, treatment usually lasts for 24 to 48 hours. Treatment should not be stopped abruptly.For more information, see the summary of product characteristics.

How does INOmax work?

The active substance in INOmax, nitric oxide, is a naturally-occurring chemical in the body, which causes the muscles in the lining of the blood vessels to relax. When inhaled, it causes the vessels in the lungs to dilate (widen); this allows blood to flow more easily in the lungs to supply oxygen to the rest of the body and remove carbon dioxide, reducing pulmonary hypertension. It also helps to decrease inflammation in the lungs.

How has INOmax been studied?

Because nitric oxide is a well-known chemical, the company used data from the published literature to support INOmax's use in newborn babies with pulmonary hypertension, and in adults and children undergoing heart surgery.INOmax has also been studied in 421 neonates from 34 weeks gestation with pulmonary hypertension in two main studies. In the first study, 235 neonates with respiratory failure received either INOmax or placebo (a dummy treatment). The main measure of effectiveness was the proportion of neonates who died or needed ECMO over the first 120 days in hospital. In the second study, 186 neonates with respiratory failure received either INOmax or placebo. The main measure of effectiveness was the proportion of neonates who needed ECMO.

What benefit has INOmax shown during the studies?

In the two main studies in newborn babies with breathing problems, INOmax was more effective than placebo at reducing the need of ECMO. In the first main study, 52 (46%) of the 114 neonates receiving INOmax died or needed ECMO, compared with 77 (64%) of the 121 receiving placebo. This was mainly due to a reduction in the need for ECMO, rather than a reduction in death rates. In the second main study, 30 (31%) of the neonates receiving INOmax needed ECMO, compared with 51 (57%) of the 89 receiving placebo.In the published literature, INOmax treatment was shown to reduce the blood pressure in the lungs and improve heart function when used during or after heart surgery.

What is the risk associated with INOmax?

The most common side effect with INOmax (seen in more than 1 patient in 10) are thrombocytopenia (low blood platelet counts), hypokalaemia (low blood potassium levels), hypotension (low blood pressure), atelectasis (collapse of the whole, or part of a, lung), and hyperbilirubinaemia (high blood levels of bilirubin). For the full list of all side effects reported with INOmax, see the package leaflet.INOmax should not be used in babies who may be hypersensitive (allergic) to nitric oxide or the other ingredient (nitrogen). It must not be used in babies who have right-to-left or significant left-to-right shunting of blood (abnormal circulation of blood in the heart).

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

The company must put in place an educational programme to ensure that doctors who are going to use INOmax for the treatment of patients undergoing heart surgery are aware of the risks and the precautions necessary when using the medicine.

Why has INOmax been approved?

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

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Inovelon

What is Inovelon and what is it used for?

Inovelon is an epilepsy medicine used to treat patients aged one year or older who have LennoxGastaut syndrome, a rare type of epilepsy that usually affects children but which can continue into adulthood. Lennox-Gastaut syndrome is one of the most severe forms of epilepsy in children. Its symptoms include multiple types of seizure (fits), abnormal electrical activity in the brain, learning disability and behavioural problems. Inovelon is used as an add-on to other anti-epileptic medicines.Lennox-Gastaut syndrome is rare, and Inovelon was designated an 'orphan medicine' (a medicine used in rare diseases) on 20 October 2004. Further information on the orphan designation can be found here: ema.europa.eu/Find medicine/Human medicines/Rare disease designation.Inovelon contains the active substance rufinamide.

How is Inovelon used?

Inovelon can only be obtained with a prescription and treatment should be started by a paediatrician (a doctor specialised in treating children) or a neurologist (a doctor who treats brain disorders) experienced in the treatment of epilepsy.The dose of Inovelon depends on the patient's age and weight and whether the patient is also taking valproate (another anti-epileptic medicine). Treatment in children less than 4 years of age generally starts with a daily dose of 10 mg per kilogram body weight. In older patients, treatment usually starts with a dose of 200 or 400 mg daily. The dose is then adjusted every other day according to the patient's response to treatment.Inovelon should be taken with water and food. The daily dose is divided into two halves, taken morning and evening about 12 hours apart.The medicine should not be used in patients who have severe problems with their liver. For more information about using Inovelon, see the package leaflet or contact your doctor or pharmacist.

How does Inovelon work?

The active substance in Inovelon, rufinamide, acts by attaching to special channels (sodium channels) on brain cells that control their electrical activity. By attaching to the channels, rufinamide preventsthem switching from an inactive state to an active state. This dampens down the activity of the brain cells and prevents abnormal electrical activity from spreading through the brain. This reduces the likelihood of a seizure occurring.

What benefits of Inovelon have been shown in studies?

In a main study involving 139 patients aged between 4 and 30 years (three quarters of them below 17 years old) Inovelon caused a reduction in the number and severity of seizures. All of the patients had Lennox-Gastaut syndrome that was not controlled despite continuous treatment for at least four weeks with up to three other anti-epileptic medicines. The study compared the effects of adding Inovelon tablets or adding placebo (a dummy treatment) to the other medicines the patients were taking. The main measures of effectiveness were the change in the number of seizures in the four weeks after Inovelon or placebo was added, compared with the four weeks before it was added, as well as the change in severity of seizures assessed on a 7-point scale by the patient's parent or guardian.Patients taking Inovelon had a 35.8% reduction in the total number of seizures, falling from an average of 290 seizures in the four-week period before Inovelon was started. There was a 1.6% reduction in the patients who added placebo to their existing treatment.Patients adding Inovelon also had a 42.5% reduction in the number of 'tonic-atonic' seizures (a common type of fit in patients with Lennox-Gastaut syndrome that often involves the patient dropping to the floor), compared with a 1.9% increase in those adding placebo.An improvement in the severity of seizures was reported for about half of the patients adding Inovelon, compared with a third of those adding placebo.A study involving 37 children aged 1 to 4 years was inconclusive because of its small size and because it was not designed to show benefit. However, other analyses showed that doses based on body weight in children aged 1 to 4 years produced similar levels of the medicine in the body to those seen with standard doses in older patients. Given that the disease behaves the same way in both age groups, Inovelon could therefore be expected to act similarly in children aged 1 to 4 years.The company also presented the results of a study showing that the oral suspension produced the same levels of the active substance in the blood as the tablets.

What are the risks associated with Inovelon?

The most common side effects with Inovelon (seen in more than 1 in 10 patients) are sleepiness, headache, dizziness, vomiting, and tiredness. For the full list of side effects of Inovelon, see the package leaflet.Inovelon must not be used in patients who are hypersensitive (allergic) to rufinamide, triazole derivatives (such as some medicines used to treat fungal infections) or any of the other ingredients.

Why is Inovelon authorised in the EU?

The European Medicines Agency decided that Inovelon'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 Inovelon?

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

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Inrebic

What is Inrebic and what is it used for?

Inrebic is a medicine used to treat adults with myelofibrosis (a rare form of blood cancer) who have enlarged spleen or other symptoms related to the disease.Inrebic can be used in three types of the disease: primary myelofibrosis (also known as chronic idiopathic myelofibrosis, where the cause is unknown), post-polycythaemia vera myelofibrosis (where the disease is linked to an overproduction of red blood cells) and post-essential thrombocythaemia myelofibrosis (where the disease is linked to an overproduction of platelets, components that help the blood to clot).Inrebic is used both in patients who have not been treated with medicines known as Janus kinase (JAK) inhibitors before and in those who have been treated with the JAK inhibitor ruxolitinib.These diseases are rare, and Inrebic was designated an 'orphan medicine' (a medicine used in rare diseases). Further information on the orphan designations can be found on the European Medicines Agency's website (primary myelofibrosis: 1 October 2010; post-polycythaemia vera myelofibrosis: 26 November 2010; post-essential thrombocythaemia myelofibrosis: 26 November 2010).Inrebic contains the active substance fedratinib.

How is Inrebic used?

The medicine can only be obtained with a prescription. Treatment with Inrebic should be started and supervised by doctors experienced in the use of cancer medicines.Inrebic is available as capsules; the recommended dose is 400 mg once daily. Patients may also be given other medicines to stop them feeling sick or vomiting.Treatment should continue for as long as the patient benefits from it. The doctor may reduce the dose, interrupt treatment or stop it altogether if the patient has certain side effects.For more information about using Inrebic, see the package leaflet or contact your doctor or pharmacist.

How does Inrebic work?

The active substance in Inrebic, fedratinib, works by blocking an enzyme known as JAK2, which is involved in the production and growth of blood cells. In myelofibrosis, there is too much JAK activity, leading to the abnormal production of blood cells. These blood cells migrate to organs, including the spleen, causing them to become enlarged. By blocking JAK2, Inrebic reduces the abnormal production of blood cells, thereby reducing symptoms of the disease.

What benefits of Inrebic have been shown in studies?

In 2 main studies in patients with myelofibrosis, Inrebic was effective at reducing the size of patients' spleen.In the first study, in patients with myelofibrosis who had not been treated with a JAK inhibitor before, 36% of patients (35 out of 97) given Inrebic had at least a 35% reduction in spleen size measured by a scan, compared with 1% (1 out of 96) of patients who received placebo. In this study, 40% of patients (36 out of 89) given Inrebic had at least 50% reduction in symptoms, measured using a myelofibrosis symptom rating scale, compared with 9% (7 out of 81) of patients who received placebo.A second study involved patients with myelofibrosis who had already been treated with the JAK inhibitor ruxolitinib; for most of them, ruxolitinib treatment had not worked or could not be continued due to side effects, or the disease had come back. In this study, about 23% of patients (22 out of 97) receiving Inrebic 400 mg once daily had at least 35% reduction in spleen size.

What are the risks associated with Inrebic?

The most common side effects with Inrebic (which may affect more than 1 in 10 people) are diarrhoea, nausea (feeling sick), vomiting, anaemia (low red blood cell counts) and thrombocytopenia (low blood platelet counts). The most common serious side effects (which may affect up to 1 in 10 people) are anaemia and diarrhoea.Inrebic must not be used by pregnant women. For the full list of side effects and restrictions of Inrebic, see the package leaflet.

Why is Inrebic authorised in the EU?

Inrebic has been shown to reduce spleen size in patients with myelofibrosis who had not been treated with JAK inhibitors before and in those who had previously been treated with ruxolitinib. Reduction in spleen size and associated symptoms is considered of major clinical relevance for patients with myelofibrosis. In terms of safety, side effects of Inrebic are considered manageable.The European Medicines Agency therefore decided that Inrebic'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 Inrebic?

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

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Instanyl

What is Instanyl and what is it used for?

Instanyl is a medicine used to treat breakthrough pain in adults with cancer. Breakthrough pain is when a patient experiences additional, sudden pain in spite of ongoing treatment with painkillers. Instanyl is used in patients who are already using opioids (a group of painkillers that includes morphine and fentanyl) to control long-term cancer pain. Instanyl contains the active substance fentanyl.

How is Instanyl used?

Instanyl is available as a nasal spray (50, 100 and 200 micrograms per dose). It is available in singledose containers and in multidose containers.The medicine 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 Instanyl should be started by and remain under the supervision of a doctor who has experience in the management of opioid treatment in cancer patients. The doctor should keep in mind the potential for Instanyl to be abused.Before starting treatment with Instanyl, the patient's long-term pain should be well controlled by opioid pain killers and they should have no more than 4 episodes of breakthrough pain a day.The first dose of Instanyl is 50 micrograms (one spray of the lowest strength) in one nostril; this is increased as necessary until reaching the dose that gives the patient adequate pain relief. If there has been insufficient pain relief, the same dose can be given again at the earliest after 10 minutes.The patient should be given Instanyl for a maximum of 4 episodes of breakthrough pain a day.For more information about using Instanyl, see the package leaflet or contact your doctor or pharmacist.

How does Instanyl work?

The active substance in Instanyl, fentanyl, is an opioid. It is a well-known substance, which has been used to control pain for many years. In Instanyl, fentanyl is contained inside a nasal spray. When the patient sprays Instanyl into the nose, a dose of fentanyl is 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 Instanyl have been showed in studies?

Because fentanyl has been in use for many years, the company presented data from the scientific literature, as well as from studies that it had carried out, which showed that Instanyl was more effective than placebo (a dummy treatment) at treating breakthrough pain in cancer patients.In one main study, 178 adult cancer patients with breakthrough pain took one spray of either Instanyl (50, 100 or 200 microgram) or placebo when they experienced breakthrough pain. The reduction in pain intensity after 10 minutes was between 1.8 and 2.7 points on an 11-point pain scale for patients who took Instanyl, compared with 1.4 for patients who took placebo. The number of patients who responded to treatment was also higher in the Instanyl group than in the placebo group. A patient's breakthrough pain was considered to have responded to treatment if there was a reduction of at least 2 points.In another main study, 128 patients were given increasing doses of Instanyl until the adequate dose for pain relief was reached. The highest dose was 200 microgram given as one spray in one nostril and the patients were allowed to take a second spray after 10 minutes if there had been insufficient pain relief. Each patient then used the identified dose of Instanyl or placebo to treat breakthrough pain. The change in pain intensity after 10 minutes was between 2.0 and 2.7 points after receiving doses of Instanyl compared with 1.3 after receiving placebo. The number of breakthrough pain episodes that responded to treatment was also higher among patients who received Instanyl than those who received placebo.In a third study, which involved 139 patients and compared Instanyl with 'transmucosal' fentanyl (absorbed through the lining of the mouth), patients who received Instanyl had faster pain relief than patients who received transmucosal fentanyl . Patients taking Instanyl were allowed to take a second spray 10 minutes after the first dose if there had been insufficient pain relief.

What are the risks associated with Instanyl?

The most common side effects with Instanyl (which may affect up to 1 in 10 people) are somnolence (sleepiness), dizziness, headache, vertigo (a spinning sensation), flushing (reddening of the skin), hot flushes, throat irritation, nausea (feeling sick), vomiting and hyperhidrosis (excessive sweating). For the full list of side effects with Instanyl, see the package leaflet.Instanyl 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. It must also not be used in patients who have had facial radiotherapy (treatment with radiation to the face) or who have recurrent episodes of epistaxis (nosebleeds). ItPage 2/3must not be used in patients treated with medicines containing sodium oxybate (used to treat narcolepsy, a sleep disorder). For the full list of restrictions, see the package leaflet.

Why is Instanyl authorised in the EU?

Instanyl has been shown to provide rapid relief of pain in patients with cancer. Side effects are similar to those of other medicines containing fentanyl, and measures have been put in place to minimise the risk of misuse and overdose. The European Medicines Agency decided that Instanyl'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 Instanyl?

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

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Insulatard

What is Insulatard?

Insulatard 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 Insulatard used for?

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

How is Insulatard used?

Insulatard is given by injection under the skin 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.Insulatard 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 Insulatard 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. Insulatard is a replacement insulin which is very similar to the insulin made by the pancreas. The active substance in Insulatard, human insulin, is produced by a method known as 'recombinant technology': the insulin is made by yeast cells into which a gene (DNA) has been introduced, which makes them able to produce insulin.Insulatard contains insulin mixed with another substance, protamine, in an 'isophane' form which is absorbed much more slowly during the day. This gives Insulatard 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 Insulatard been studied?

Insulatard 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, Insulatard was compared with other types of human insulin or insulin analogues. The studies measured the levels 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 Insulatard using a syringe, or using a pre-filled pen (InnoLet or FlexPen).

What benefit has Insulatard shown during the studies?

Insulatard 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 insulins. Insulatard 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 Insulatard?

The most common side effect with Insulatard (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 Insulatard been approved?

The CHMP decided that Insulatard'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 Insulatard?

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

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Insulin Aspart Sanofi

What is Insulin aspart Sanofi and what is it used for?

Insulin aspart Sanofi is a medicine used to control blood glucose (sugar) levels in patients from one year of age who have diabetes.Insulin aspart Sanofi is a 'biosimilar medicine'. This means that Insulin aspart Sanofi is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Insulin aspart Sanofi is NovoRapid. For more information on biosimilar medicines, see here.Insulin aspart Sanofi contains the active substance insulin aspart, a rapid-acting insulin.

How is Insulin aspart Sanofi used?

Insulin aspart Sanofi can only be obtained with a prescription. It is given as an injection under the skin in the upper arm, thigh, buttock or belly. Because Insulin aspart Sanofi is a fast-acting insulin, it is usually given shortly before a meal or if more appropriate, soon after a meal. Insulin aspart Sanofi is normally used in combination with a longer-acting insulin. The dose is worked out for each patient and depends on the patient's weight and blood glucose level.A healthcare professional should explain to the patient how to use the medicine properly.For more information about using Insulin aspart Sanofi, see the package leaflet or contact your doctor or pharmacist.

How does Insulin aspart Sanofi work?

In diabetes, patients have high levels of blood glucose either because the body does not produce enough insulin or the body is unable to use insulin effectively.The active substance in Insulin aspart Sanofi is a form of insulin which is absorbed more quickly by the body than regular insulin, and can therefore act faster. It helps control blood glucose levels, thereby alleviating symptoms of diabetes and reducing the risk of complications.

What benefits of Insulin aspart Sanofi have been shown in studies?

Laboratory studies comparing Insulin aspart Sanofi with NovoRapid have shown that the active substance in Insulin aspart Sanofi is highly similar to that in NovoRapid in terms of structure, purity and biological activity. Studies have also shown that giving Insulin aspart Sanofi produces similar levels of the active substance in the body to giving NovoRapid.In addition, a study involving 597 patients already being treated with insulin for diabetes showed that 6-months' treatment using Insulin aspart Sanofi plus a longer-acting insulin (insulin glargine) was as effective in controlling blood sugar as a combination including NovoRapid and insulin glargine. The average HbA1c (a measurement that gives an indication of how well blood glucose levels are controlled over time) was 8.00% at the start in those treated with Insulin aspart Sanofi and 7.94% in those given NovoRapid; after 6 months it was 7.62% and 7.64% respectively.Because Insulin aspart Sanofi is a biosimilar medicine, the studies on effectiveness and safety of insulin aspart carried out with NovoRapid do not all need to be repeated for Insulin aspart Sanofi.

What are the risks associated with Insulin aspart Sanofi?

The safety of Insulin aspart Sanofi 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 NovoRapid.The most common side effect with Insulin aspart Sanofi (which may affect more than 1 in 10 people) is hypoglycaemia (low blood glucose levels) and the medicine must not be given to people whose blood glucose level is already low.For the full list of side effects and restrictions with Insulin aspart Sanofi, see the package leaflet.

Why is Insulin aspart Sanofi authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Insulin aspart Sanofi has a highly similar structure, purity and biological activity toNovoRapid and is distributed in the body in the same way. In addition, studies in patients with diabetes have shown that the safety and effectiveness of Insulin aspart Sanofi is equivalent to that of NovoRapid.All these data were considered sufficient to conclude that Insulin aspart Sanofi will behave in the same way as NovoRapid in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for NovoRapid, the benefits of Insulin aspart Sanofi 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 Insulin aspart Sanofi?

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

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Insulin Lispro Sanofi

What is Insulin lispro Sanofi and what is it used for?

Insulin lispro Sanofi is a medicine used to control blood glucose (sugar) levels in adults and children with diabetes who need insulin. It contains the active substance insulin lispro.Insulin lispro Sanofi is a 'biosimilar medicine'. This means that it is highly similar to a biological medicine (also known as the 'reference medicine') that is already authorised in the European Union (EU). The reference medicine for Insulin lispro Sanofi is Humalog 100 U/ml solution. For more information on biosimilar medicines, see here.

How is Insulin lispro Sanofi used?

Insulin lispro Sanofi is given as an injection under the skin in the upper arm, thigh, buttock or belly. It can also be given with an infusion pump. In some circumstances, such as when blood acid levels are dangerously high (ketoacidosis), the medicine may be given into a vein.Because Insulin lispro Sanofi is a fast-acting insulin, it is usually given shortly before a meal and, when necessary, soon after a meal. The dose of Insulin lispro Sanofi is worked out for each patient and depends on the patient's blood glucose level. The doctor should instruct the patient on how to use the medicine properly.The medicine can only be obtained with a prescription. For further information, see the package leaflet.

How does Insulin lispro Sanofi work?

In diabetes, patients have high levels of blood glucose either because the body does not produce enough insulin or the body is unable to use insulin effectively.The active substance in Insulin lispro Sanofi is a form of insulin which is absorbed more quickly by the body than human regular insulin, and can therefore act faster. It helps control blood glucose levels, thereby alleviating symptoms and reducing the risk of complications of diabetes.

What benefits of Insulin lispro Sanofi have been shown in studies?

Laboratory studies comparing Insulin lispro Sanofi with the reference medicine Humalog have shown that the active substance in Insulin lispro Sanofi is highly similar in terms of structure, purity and biological activity to that of Humalog. In addition, studies have shown that both medicines produce similar levels of the active substance in the body.Two further studies in a total of 1,012 patients compared Insulin lispro Sanofi with Humalog and found them to be similarly effective at reducing blood levels of a substance called glycosylated haemoglobin (HbA1c), which gives an indication of how well blood glucose levels are controlled over time. In one study, in patients with type 1 diabetes, HbA1c reduced by 0.44 and 0.46 percentage points with Insulin lispro Sanofi and Humalog respectively after 26 weeks; in the second study, in patients with type 2 diabetes, the corresponding figures were 0.93 versus 0.88 percentage points.

What are the risks associated with Insulin lispro Sanofi?

Insulin lispro Sanofi may cause hypoglycaemia (low blood glucose levels) and must not be given to patients whose blood glucose is already low. Severe hypoglycaemia can lead to loss of consciousness and, in very extreme cases, to death. Hypoglycaemia may be due to the medicine itself or other factors such as diet and exercise.For the full list of all side effects and restrictions with Insulin lispro Sanofi, see the package leaflet.

Why is Insulin lispro Sanofi approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) concluded that, in accordance with EU requirements for biosimilar medicines, Insulin lispro Sanofi has a highly similar structure, purity and biological activity to Humalog and is distributed in the body in the same way. In addition, studies show that both medicines have similar effects in reducing blood glucose levels and similar side effects. Therefore, the CHMP's view was that, as for Humalog, the benefits of Insulin lispro Sanofi outweigh its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe and effective use of Insulin lispro Sanofi?

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

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Insuman

What is Insuman?

Insuman is a range of insulin-containing solutions and suspensions for injection. It is supplied in vials, cartridges, or pre-filled disposable pens. The Insuman range is comprised of:• Insuman Rapid, Insuman Infusat and Insuman Implantable, which are fast-acting insulin solutions containing soluble insulin;• Insuman Basal, an intermediate-acting insulin suspension containing isophane insulin;• Insuman Comb, which is available in various combinations of fast- and intermediate-acting insulins.

What is Insuman used for?

Insuman is used in patients with diabetes (type 1 and 2) who need treatment with insulin.Insuman Rapid can also be used for the treatment of hyperglycaemic coma (coma caused by too much blood glucose [sugar]) and ketoacidosis (high levels of ketones [acids] in the blood), and to control blood glucose before, during or after an operation.Insuman Implantable is used in adult patients with type 1 diabetes that cannot be controlled with insulin given under the skin and who often have episodes of, otherwise unexplained, hyper- or hypoglycaemia (high or low blood glucose levels).The medicine can only be obtained with a prescription.

How is Insuman used?

Insuman Rapid, Infusat, Basal and Comb are given by injection under the skin, generally in the abdominal wall (tummy) or the thigh, according to the doctor's recommendations. The injection site is changed for each injection. The desired blood glucose levels, the type of Insuman to be used, and the dose and timing of injections are determined by the doctor for each patient individually, and are adjusted to suit the patient's diet, physical activity and lifestyle. The patient's blood glucose should be tested regularly to find the lowest effective dose. Insuman should be given before meals. See the package leaflet for exact timings.Insuman Rapid may also be given into a vein, but only in an intensive care unit or similar setting where the patient can be closely monitored. Insuman Infusat is specially prepared ready to be used as a continuous infusion under the skin using an external portable infusion pump.Insuman Implantable is given only by infusion into the abdominal cavity using a pump (Medtronic MiniMed implantable pump) that is implanted under the skin of the abdomen. Insuman Implantable must not be used in any other way and can only be used in centres where staff have received adequate training in the use of the implantable pump.Further information on the way Insuman is given can be found in the Summary of Product Characteristics (also part of the EPAR).

How does Insuman work?

Diabetes is a disease in which the body does not produce enough insulin to control the level of blood glucose (type 1 diabetes) or when the body is unable to use insulin effectively (type 2 diabetes). Insuman is a replacement insulin that is similar to the insulin made by the body.The active substance in Insuman, human insulin, is produced by a method known as 'recombinant DNA technology': it is made by bacteria into which a gene (DNA) has been introduced that makes the bacteria able to produce insulin. Insuman contains insulin in various forms: the soluble form, which acts quickly (within 30 minutes of injection), and the isophane and crystalline-protamine forms, which are absorbed much more slowly during the day, giving them a longer duration of action.The replacement insulin acts in the same way as naturally produced insulin and helps glucose enter cells from the blood. By controlling the level of blood glucose, the symptoms and complications of diabetes are reduced.

How has Insuman been studied?

Insuman has been studied in three trials in 780 patients with either type 1 diabetes or type 2 diabetes. In one of the studies, Insuman was given to patients with type 1 diabetes using an external insulin pump. In another study, Insuman Comb 25 was compared with semi-synthetic human insulin in patients with type 1 and type 2 diabetes. In addition, Insuman Implantable was studied in adult patients with type 1 diabetes. These patients received Insuman Implantable as a continuous infusion into the peritoneal cavity.The main measure of effectiveness in all studies was the change in the level of glycosylated haemoglobin (HbA1c), which is the percentage of haemoglobin in the blood that has glucose attached. HbA1c levels give an indication of how well the blood glucose is controlled.

What benefit has Insuman shown during the studies?

Insuman led to a decrease in the level of HbA1c, indicating that blood glucose levels had been controlled to a similar level to that seen with semi-synthetic human insulin. Insuman was effective for both type 1 and type 2 diabetes.

What is the risk associated with Insuman?

Insuman may cause hypoglycaemia. For the full list of all side effects reported with Insuman, see the Package Leaflet.Insuman must not be used in people who are hypersensitive (allergic) to human insulin or any of the other ingredients. In addition, Insuman Implantable must not be used any other way than as a continuous infusion using the Medtronic MiniMed Implantable Pump. It must also not be used in patients who are hypersensitive to titanium alloy, polysulfone or silicone material used in the components of the implanted pump. No other insulins must be used with the pump and the pump must not be used in children who have not yet reached adult size. The pump must not be implanted in people who reside permanently at elevations above at elevations above 2,439 metres (8000 feet).

Why has Insuman been approved?

The CHMP decided that Insuman's benefits are greater than its risks for the treatment of type 1 and type 2 diabetes. The Committee recommended that Insuman be given marketing authorisation.

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Integrilin

What is Integrilin?

Integrilin is a medicine that contains the active substance eptifibatide. It is available as a solution for infusion (drip into a vein) and a solution for injection.

What is Integrilin used for?

Integrilin is used to prevent a myocardial infarction (heart attack) in adults. It is used in the following groups:• patients who have unstable angina (a severe type of chest pain that varies in intensity);• patients who have already had a non-Q-wave myocardial infarction (a type of heart attack), with chest pain in the last 24 hours and with abnormalities on the electrocardiogram (ECG) or signs of heart problems in the blood.Integrilin is given with aspirin and unfractionated heparin (other medicines that prevent blood clots). The patients most likely to benefit from a treatment with Integrilin are those at high risk of myocardial infarction in the three to four days after the start of acute (sudden) angina. This includes patients who are having percutaneous transluminal coronary angiography (PTCA, a type of surgery to clear the arteries supplying the heart).The medicine can only be obtained with a prescription.

How is Integrilin used?

Integrilin should be given into a vein by a doctor who has experience in the management of heart conditions.The recommended dose is a single injection of 180 micrograms per kilogram body weight given as soon as possible after diagnosis. This is followed by a continuous infusion of 2.0 microgram/kg per minute which is continued for up to 72 hours, until the start of surgery, or until discharge from the hospital, whichever occurs first.Patients who have moderate problems with their kidneys should receive a lower dose during the infusion. Integrilin must not be used in patients with severe kidney problems. If the patient undergoes a percutaneous coronary intervention (PCI or angioplasty, a surgical procedure that is used to unblock narrowed coronary arteries), the treatment can be continued for up to 24 hours after surgery, with a maximum treatment duration of 96 hours.

How does Integrilin work?

Integrilin is an inhibitor of platelet aggregation. This means that it helps to prevent blood clots from forming. When the blood clots, this is due to special cells in the blood called platelets sticking together (aggregating). The active substance in Integrilin, eptifibatide, stops the platelets aggregating by blocking a protein called glycoprotein IIb/III on their surface that helps make them sticky. Integrilin greatly reduces the risk of a blood clot forming and helps prevent another heart attack.

How has Integrilin been studied?

Integrilin has been compared with placebo (dummy treatment) in a study involving 11,000 patients who were in hospital and had signs that they may soon develop a heart attack, or who had already had a small heart attack.An additional study compared Integrilin with placebo in 2,000 patients who were having PTCA to remove a blood clot from the coronary arteries and insert a stent (a short tube that remains in the artery to stop it closing).In both studies, patients also received other medicines to prevent the blood clotting. The main measure of effectiveness was the number of patients who had a heart attack or who died within 30 days of treatment.

What benefit has Integrilin shown during the studies?

In the first study, Integrilin was more effective than placebo in preventing death or a heart attack during the 30 days after it was given. A similar benefit was seen in the second study. The main benefit was in the reduction in further heart attacks.

What is the risk associated with Integrilin?

The most common side effect with Integrilin (seen in more than 1 patient in 10) is bleeding, which may be severe. For the full list of all side effects reported with Integrilin, see the Package Leaflet. Integrilin should not be used in people who may be hypersensitive (allergic) to eptifibatide or any of the other ingredients. It must not be used in patients who have bleeding problems or have a disease that may cause bleeding (such as stroke or severe high blood pressure), or in patients with severe liver or kidney problems. For the full list of restrictions, see the Package Leaflet.

Why has Integrilin been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Integrilin's benefits are greater than its risks when used to prevent early myocardial infarction. The Committee recommended that Integrilin be given marketing authorisation.

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Intelence

What is Intelence and what is it used for?

Intelence is a medicine for treating human immunodeficiency virus type 1 (HIV-1) in adults and children from 2 years of age. HIV-1 causes acquired immune deficiency syndrome (AIDS).Intelence is only used in patients who have been treated for their HIV infection before and it must be used together with other HIV medicines that include a 'boosted protease inhibitor'.It contains the active substance etravirine.

How is Intelence used?

Intelence can only be obtained with a prescription and treatment should be started by a doctor who has experience in the treatment of HIV infection.It is available as tablets (25, 100 and 200 mg) to be swallowed whole with a glass of water. Patients who cannot swallow can disperse the tablets in a glass of water and then drink the solution immediately.In adults, the recommended dose of Intelence is 200 mg twice a day after a meal, while in children the dose depends on body weight and ranges from 100 to 200 mg twice a day.For further information about using Intelence, see the package leaflet or contact your doctor or pharmacist.

How does Intelence work?

The active substance in Intelence, etravirine, is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It blocks the activity of reverse transcriptase, an enzyme produced by HIV that allows the virus to make more copies of itself in the cells it has infected and so spread in the body. By blocking this enzyme, Intelence, taken in combination with other HIV medicines, reduces the amount of HIV in the blood and keeps it at a low level. Intelence does not cure HIV infection, but it holds off damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Intelence have been shown in studies?

Studies have shown that Intelence, in combination with other medicines, could reduce the HIV-level(viral load) to low (below 400 copies/ml) or undetectable levels (below 50 copies/ml) in many patientswith HIV-1 infection. This was considered to show that the virus was no longer able to make new copies of itself in the body (a viral load above 1000 copies/ml indicated that the virus was actively reproducing).In two main studies in a total of 1,203 adults whose infection had not responded fully to previous treatment, the average viral load was 70,000 copies/ml at the start of treatment. After 24 weeks, 59% of the patients taking Intelence together with other HIV medicines had undetectable levels of HIV, compared with 41% of those taking placebo (a dummy treatment) plus the other HIV medicines. These findings were maintained at 48 weeks.In a main study of 101 children aged between 6 and 17 years, about half the children had undetectable levels of HIV after 24 weeks of taking Intelence in combination with other medicines, and the proportion of children with undetectable levels of HIV increased slightly after 48 weeks.Another study involved 20 children aged between 2 and 5 years whose HIV infection had not responded fully to previous treatment. The average viral load was more than 1,000 copies/ml at the start of treatment. After 48 weeks of taking Intelence together with other HIV medicines, 80% of the children had a viral load below 400 copies/ml.

What are the risks associated with Intelence?

The most common side effects with Intelence (which may affect more than 1 in 10 people) are rash, diarrhoea, nausea (feeling sick) and headache.Intelence must not be used together with elbasvir/grazoprevir, a medicine to treat hepatitis C. For the full list of side effects and restrictions with Intelence, see the package leaflet.

Why is Intelence authorised in the EU?

The European Medicines Agency decided that the benefits of Intelence are greater than its risks and that it can be authorised for use in the EU.The Agency concluded that Intelence is effective at reducing viral load to very low or undetectable levels in both adults and children and that its side effects are considered manageable.

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

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

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Intrarosa

What is Intrarosa and what is it used for?

Intrarosa is a medicine used to treat postmenopausal women with moderate to severe symptoms of vulvar and vaginal atrophy. In women with vulvar and vaginal atrophy, the wall of the vagina and surrounding tissues become thinner and can cause symptoms such as dryness, irritation and soreness around the genital area, and painful sexual intercourse.Intrarosa contains the active substance prasterone, also known as dehydroepiandrosterone (DHEA).

How is Intrarosa used?

Intrarosa is available as a 6.5 mg pessary. Women should insert the pessary into their vagina, once daily, at bedtime.The medicine can only be obtained with a prescription. For further information, see the package leaflet.

How does Intrarosa work?

In women who have been through the menopause, the thinning of the tissues in and around the vagina is caused by a fall in levels of the sex hormone oestrogen.The active substance of Intrarosa, prasterone, is converted into the sex hormones oestrogens and androgens when inserted into the vagina. As a result of increasing oestrogen levels, the number of superficial cells in the tissues in and around the vagina increases thus relieving the symptoms of vaginal atrophy.

What benefits of Intrarosa have been shown in studies?

Two studies involving 813 post-menopausal women with vulvar and vaginal atrophy found that treatment with Intrarosa was more effective than placebo (a dummy treatment) at reducing signs of thinning (atrophy) of vaginal tissues.In both studies, 6.5 mg Intrarosa was given once a day for 12 weeks. Results showed that the number of superficial cells (which normally falls with atrophy) increased by 6% and 10% with Intrarosa compared with about 1% and 2% with placebo. There was also a decrease in the number of parabasal cells (which normally increase with atrophy) of 42% and 47% with Intrarosa compared with 2% and 12% with placebo.In addition, Intrarosa treatment was better at increasing acidity in the vagina (which normally becomes less acidic with atrophy), with pH values reducing by 0.9 and 1.0 with Intrarosa and by 0.2 and 0.3 with placebo.Patients taking Intrarosa had a modest reduction in pain during sexual intercourse, which was similar or better to the effect seen in patients taking placebo. Pain during sexual intercourse was self-assessed by patients using a standard scale ranging from 0 (no pain) to 3 (severe pain). The pain reduced by 1.3 and 1.4 points with Intrarosa compared with 0.9 and 1.1 points with placebo. The effect seen in the placebo group was explained by the lubricant effect of the excipient.

What are the risks associated with Intrarosa?

The most common side effect with Intrarosa (which may affect up to 1 in 10 people) is vaginal discharge. For the full list of side effects reported with Intrarosa, see the package leaflet.Intrarosa must not be used in patients with the following conditions: genital bleeding where the cause has not been diagnosed, known or suspected breast cancer or oestrogen-dependent cancer, previous breast cancer, untreated endometrial hyperplasia (thickening of the lining of the womb), acute (shortterm) liver disease, previous liver disease where liver function tests are still abnormal, previous or current venous thromboembolism (formation of blood clots in the veins), thrombophilic disorders (abnormal blood clotting), active or recent arterial thromboembolic disease (disease caused by blood clots in the arteries), porphyria (inability to break down chemicals called porphyrins). For the full list of restrictions, see the package leaflet.

Why is Intrarosa approved?

Intrarosa has been shown to improve the structure of the vaginal tissues and to have a modest effect on pain during sexual intercourse. The medicine has an acceptable safety profile.The European Medicines Agency therefore considered that Intrarosa'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 Intrarosa?

The company that markets Intrarosa is required to conduct a study on how the medicine is used in clinical practice, including whether it is used according to the authorised product information.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Intrarosa have also been included in the summary of product characteristics and the package leaflet.

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Intuniv

What is Intuniv and what is it used for?

Intuniv is used to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents aged 6 to 17 years when stimulant medicines are not appropriate or do not control their symptoms well enough.Intuniv is used as part of a comprehensive treatment programme that typically involves psychological, educational and other interventions.The active substance in Intuniv is guanfacine.

How is Intuniv used?

Intuniv treatment must be started by a doctor specialised in childhood or adolescent behavioural problems. Before starting treatment, the doctor should carry out checks to see whether the patient is at risk of side effects of the medicine (particularly sleepiness, effects on heart rate and blood pressure, and weight gain).The dose of Intuniv requires careful adjustments, taking account side effects and benefits seen in the patient. Weekly monitoring is required at the start of treatment and the patient should continue to be monitored at least every 3 months for the first year.The medicine is available as tablets (1, 2, 3 and 4 mg). The recommended starting dose for all patients is 1 mg taken by mouth once a day. For information on dose adjustments and checks to be carried out by the doctor, see the summary of product characteristics (SmPC).The medicine can only be obtained with a prescription

How does Intuniv work?

The way Intuniv works in ADHD is not established. It is thought that the active substance, guanfacine, might influence the way signals are transmitted between cells in areas of the brain called the prefrontal cortex and basal ganglia by attaching to certain receptors that are heavily concentrated in these areas.

What benefits of Intuniv have been shown in studies?

Several studies have shown Intuniv improving ADHD symptom scores (ADHD-RS-IV) in children and adolescents.In a study of 337 children aged 6 to 17 years, the reduction in ADHD symptoms with Intuniv treatment after 10 to 13 weeks was 24 points compared with a reduction of 15 points seen with placebo (a dummy treatment) and 19 points seen with atomoxetine (an ADHD medicine). In another study of 312 adolescents aged 13 to 17, the reduction in ADHD scores at 13 weeks was 25 points with Intuniv and 19 points with placebo. Two other short-term studies involving 631 patients also showed Intuniv at various doses improving ADHD scores more than placebo.Intuniv was also evaluated in terms of treatment failures (based either on worsening of ADHD symptoms or patients stopping treatment). In a long-term maintenance study in 301 children and adolescents aged 6 to 17 years treatment failures occurred in 49% of patients taking Intuniv compared with 65% of those taking placebo.

What are the risks associated with Intuniv?

The most common side effects with Intuniv are sleepiness (in nearly half of all patients), headache (in more than a quarter), tiredness (in about 1 patient in 5), and upper abdominal pain and sedation (both in around 1 in 10). Sleepiness usually begins at the start of treatment and lasts for 2 to 3 weeks.More serious side effects are less common and include: low blood pressure and weight gain (both in around 1 patient in 30), slow heart rate (1 in 60) and fainting (in less than 1 in 100).For the full list of all side effects and restrictions, see the package leaflet.

Why is Intuniv approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) noted that stimulant medicines are first line treatments for ADHD and that these medicines provide a larger and more consistent improvement in ADHD symptoms as part of a comprehensive treatment programme. However, given the benefits seen with Intuniv, the Committee concluded that the medicine can be used as an alternative in patients who cannot take stimulants or in patients in whom stimulants do not control their symptoms well enough.The most important safety risks are slow heart rate, low blood pressure, fainting, sleepiness and sedation. The CHMP has recommended several measures, including regular monitoring to manage these risks.The CHMP therefore concluded that the benefits of Intuniv outweigh the risks recommended that it be approved for authorisation in the EU.

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

A risk management plan has been developed to ensure that Intuniv 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 Intuniv, including the appropriate precautions to be followed by healthcare professionals and patients.The company that markets Intuniv must also provide nationally agreed educational material for healthcare professionals before launching the medicine on the market. The education material should include information on side effects, a checklist to identify children at risk, and a checklist and chart for monitoring children during treatment.Further information can be found in the summary of the risk management plan.

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Invanz

What is Invanz and what is it used for?

Invanz is an antibiotic. It is used in adults and children aged over 3 months to treat the following infections:• infections within the abdomen;• community-acquired pneumonia (infection of the lungs caught away from hospital);• gynaecological infections;• foot infections in diabetes patients.Invanz is also used in adults to prevent infection after colorectal surgery (surgery in the lower part of the bowel, including the rectum).Invanz is used when the bacteria that cause the infection are likely to be killed by the antibiotic. Before using Invanz, doctors should consider official guidance on the appropriate use of antibiotics.Invanz contains the active substance ertapenem.

How is Invanz used?

Invanz is available as a vial containing a powder which is dissolved before use to make up a solution for infusion (drip) into a vein. It is infused over 30 minutes. The medicine can only be obtained with a prescription.Invanz is given at a dose of 1 g once a day in adults and adolescents. For younger patients (3 months to 12 years), a dose of 15 mg per kilogram body weight is given twice a day, up to a total of 1 g per day. Treatment with Invanz lasts between 3 and 14 days, depending on the type and the severity of the infection. Once the infection has improved, treatment can be switched to an antibiotic that can be given by mouth.For preventing infection after colorectal surgery in adults, a single dose of Invanz is given within 1 hour before the operation.

How does Invanz work?

The active substance in Invanz, ertapenem, belongs to the group of antibiotics known as'carbapenems'. It attaches to certain proteins on the bacteria cells. This upsets the essential functions that keep the cells alive, and so kills the bacteria. Invanz can work on a range of different bacteria, which are listed in the summary of product characteristics (also part of the EPAR).

What benefits of Invanz have been shown in studies?

Treatment of infectionsInvanz was compared with ceftriaxone (another antibiotic) for the treatment of adults with communityacquired pneumonia (866 patients) and urinary tract infections (592 patients), and with a combination of piperacillin and tazobactam for the treatment of abdominal infections (655 patients), gynaecological infections (412 patients), skin and soft tissue infections (infections of the skin and the tissues just beneath the skin, 540 patients); and foot infections in diabetes patients (576 patients). In studies in children, Invanz was compared with ceftriaxone (for community-acquired pneumonia, 389 children) and with ticarcillin/clavulanate (for intra-abdominal infections, 105 children). The studies examined if the infection was cured after 7 to 28 days of treatment, depending on the type of infection.Invanz was as effective as ceftriaxone or piperacillin/tazobactam for the treatment of abdominal infections, community-acquired pneumonia, gynaecological infections and foot infections in diabetes patients: Invanz was effective for 87 to 94% of patients compared with 83 to 92% for the comparator antibiotics. However, the data were not sufficient to support the use of Invanz in the treatment of urinary tract infections and skin and soft tissue infections, except foot ulcers in diabetes patients. In children, Invanz was as effective as the comparator antibiotics and had similar effectiveness to that in adults.Prevention of infections after colorectal surgeryInvanz was compared with cefotetan for preventing infection after colorectal surgery. Effectiveness was measured as absence of infection 4 weeks after treatment, which involved 952 adults. Infection was absent in about 60% patients given Invanz compared with 49% of patients given cefotetan.

What are the risks associated with Invanz?

The most common side effects with Invanz (which may affect up to 1 in 10 people) are headache, diarrhoea, nausea (feeling sick), vomiting, rash (including nappy rash in children), itching, and problems around the area where the medicine is infused (including pain and inflammation of the vein). Invanz also has an effect on some blood tests. For the full list of all side effects reported with Invanz, see the package leaflet.Invanz must not be used in people who are hypersensitive (allergic) to ertapenem or to other antibiotics of the same group (carbapenems). It must also not be used in patients who are severely allergic to other types of antibiotics, such as penicillins and cephalosporins. For the full list of restrictions see the package leaflet.

Why is Invanz approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Invanz's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that Invanz was shown to be effective, albeit with a limited number of severe cases treated during the studies for abdominal infections, community-acquired pneumonia, gynaecological infections and diabetic foot infections. The Committee concluded that it was also effective for treatment of infection in children and for preventing infection after colorectal surgery in adults.

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

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

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Invega

What is Invega and what is it used for?

Invega is an antipsychotic medicine used in adults and adolescents from 15 years of age to treat schizophrenia, a mental illness with symptoms such as disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (false beliefs).Invega is also used to treat adults with schizoaffective disorder. This is a condition in which the patient has episodes of elevated mood (mania) or low mood (depression) in addition to symptoms of schizophrenia.Invega contains the active substance paliperidone.

How is Invega used?

Invega can only be obtained with a prescription. It is available as prolonged-release tablets (3, 6, 9 and 12 mg). 'Prolonged release' means that paliperidone is released slowly from the tablet over a few hours.The recommended starting dose of Invega in adults is 6 mg once a day, taken in the morning; the starting dose in adolescents is 3 mg daily. Patients can take Invega either with food or between meals, but should not switch between taking it with food on one day and between meals on another. After assessing the symptoms, the doctor may adjust the dose to between 3 and 12 mg once a day in adults with schizophrenia and to between 6 and 12 mg once a day in patients with schizoaffective disorder. Inadolescents with schizophrenia the maximum daily dose depends on the patient's body weight and should not be more than 6 mg in those who weigh less than 51 kg. For more information on the use of Invega, including the adjustment of doses in those with kidney disease and the elderly, see the summary of product characteristics (also part of the EPAR).

How does Invega work?

The active substance in Invega, paliperidone, is known as an 'atypical' antipsychotic because it is different from the older antipsychotic medicines that have been available since the 1950s. Paliperidone is an active breakdown product (metabolite) of risperidone, another atypical antipsychotic medicine that has been used in the treatment of schizophrenia since the 1990s. In the brain, paliperidone attaches to several different receptors (targets) on nerve cells. This disrupts signals sent between brain cells by 'neurotransmitters', substances that nerve cells use to communicate with neighbouring cells. Paliperidone acts mainly by blocking the receptors for the neurotransmitters dopamine and 5-hydroxytryptamine (also called serotonin), which are involved in schizophrenia. By blocking these receptors, paliperidone helps to normalise the activity of the brain and reduce symptoms.

What benefits of Invega have been shown in studies?

SchizophreniaThree short-term studies innvolving 1,692 adults showed that Invega is more effective than placebo (a dummy treatment) and as effective as another antipsychotic medicine olanzapine at reducing symptoms of schizophrenia (as measured by a standard rating scale). In one of these studies, average symptom scores fell by between 17.9 and 23.3 points after 6 weeks in those taking Invega compared with a fall of 4.1 points with placebo. Symptom scores fell by 19.9 points in those taking olanzapine. Similar results were seen in the other two short-term studies, with higher doses of Invega being more effective than lower doses.In an additional longer-term study involving 207 adults with schizophrenia who had initially been treated over 14 weeks, Invega was more effective than placebo in preventing new symptoms for up to 35 weeks.Studies in adolescents have shown similar results with Invega to those seen in adults.Schizoaffective disorderStudies have shown that Invega can reduce symptoms scores and prevent symptoms in patients with schizoaffective disorder.In one study, patients who were given Invega had a fall in their symptom score for mania of between 27.4 and 30.6 after 6 weeks compared with 21.7 in patients who were given placebo. In another study, the fall in symptom score for mania after 6 weeks was 20.0 in the Invega group and 10.8 in the placebo group. The two studies together involved a total of 614 patients.In a third study of 334 previously treated patients, symptoms of depression came back in 15% (25 out of 164) of patients given paliperidone compared with 34% (57 out of 170) of patients given placebo.

What are the risks associated with Invega?

The most frequent side effects with Invega in adults are headache, insomnia (difficulty sleeping), sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness andslow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, increased weight, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhoea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough. Side effects in adolescents are similar to those in adults, although some side effects may occur more frequently. For the full list of all side effects reported with Invega, see the package leaflet.Invega must not be taken by people who are hypersensitive (allergic) to paliperidone or any of the other ingredients, or to risperidone.

Why is Invega approved?

The European Medicines Agency decided that Invega'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 Invega?

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

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Invokana

What is Invokana and what is it used for?

Invokana is a diabetes medicine that contains the active substance canagliflozin. It is used in adults with type 2 diabetes to control their blood glucose (sugar) level.Invokana can be used on its own in patients whose blood glucose levels are not satisfactorily controlled on diet and exercise alone and who cannot take metformin (another diabetes medicine).Invokana can also be used as an 'add-on' to other diabetes medicines, including insulin, when these medicines together with exercise and diet are not providing adequate control of the diabetes.

How is Invokana used?

Invokana is available as tablets (100 and 300 mg) and can only be obtained with a prescription. The tablets are taken once a day, preferably before the first meal of the day. The recommended starting dose is 100 mg once a day. If appropriate, the dose can be increased to 300 mg once a day.As the effects of Invokana are dependent on kidney function, the effectiveness and tolerability of the medicine are reduced in patients with reduced kidney function. The use of Invokana is therefore not recommended in patients with severely reduced kidney function. In patients with moderately reduced kidney function the dose should be limited to 100 mg once a day.For further information, see the package leaflet.

How does Invokana 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. This leads to high levels of glucose in the blood.The active substance in Invokana, canagliflozin, works by blocking a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2). SGLT2 is a protein that absorbs glucose from the urine back into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, Invokana causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood.

What benefits of Invokana have been shown in studies?

Invokana has been evaluated in 9 main studies involving a total of around 10,000 patients with type 2 diabetes. One of the studies compared Invokana with placebo (a dummy treatment) when used alone in patients whose blood glucose levels were not satisfactorily controlled on diet and exercise alone. Three studies looked at Invokana when used as add-on to one other diabetes medicine (metformin or insulin), and three further studies looked at Invokana when used as add-on to two other diabetes medicines (including metformin), when these medicines together with exercise and diet were not providing adequate control of the diabetes. A study was also performed in patients with moderately reduced kidney function, and one in older patients aged between 55 and 80 years. In all of the studies, the main measure of effectiveness was the level of a substance in the blood called glycosylated haemoglobin (HbA1c), which gives an indication of how well the blood glucose is controlled.Invokana was shown to be more effective than placebo, and at least as effective as comparator medicines, at reducing the levels of HbA1c when used alone and in combination with other diabetes medicines:• When Invokana was used on its own at a dose of 100 mg, it decreased HbA1c levels by 0.91% more than placebo after 26 weeks, while the 300 mg dose led to a reduction of 1.16% more than placebo.• Across the studies that looked at Invokana when used as add-on to one or two other diabetes medicines, the reductions in HbA1c levels after 26 weeks compared with placebo ranged from 0.76% to 0.92% with the 300 mg dose, and from 0.62% to 0.74% with the 100 mg dose.• When Invokana was used as add-on to insulin at a dose of 300 mg, it decreased HbA1c levels by 0.73% more than placebo after 18 weeks, while the 100 mg dose led to a reduction of 0.65% more than placebo.• Invokana was also shown to be at least as effective as the diabetes medicines glimepiride and sitagliptin after 52 weeks of treatment.• The study in patients with moderately reduced kidney function showed that the effects of Invokana were reduced in these patients, but still clinically relevant: the reduction of HbA1c levels compared with placebo was 0.30% with the 100 mg dose.• The study in older patients showed that Invokana had clinically relevant effects also in patients above 75 years of age with HbA1c reductions compared with placebo of 0.70% and 0.57% with the 300 mg and 100 mg doses, respectively.

What are the risks associated with Invokana?

The most common side effects with Invokana are hypoglycaemia (low blood glucose levels) when used together with insulin or a sulphonylurea, vulvovaginal candidiasis (thrush, a fungal infection of the female genital area caused by Candida) urinary tract infection (infection of the structure that carries the urine) and polyuria (abnormally large production of urine) or pollakiuria (abnormally frequent urination).For the full list of all side effects reported with Invokana, see the package leaflet.

Why is Invokana approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Invokana's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP concluded that Invokana was shown to be effective at controlling blood glucose levels. Invokana treatment also led to weight loss and reductions in blood pressure, effects that are considered beneficial in patients with diabetes. Regarding its safety, this was considered similar to other medicines of the same class (SGLT2 inhibitors). Important side effects identified included dehydration and urinary tract infection, but these were considered to be manageable.

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

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

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Irbesartan Hydrochlorothiazide Zentiva

What is Irbesartan Hydrochlorothiazide Zentiva?

Irbesartan Hydrochlorothiazide Zentiva is a medicine that contains two active substances, irbesartan and hydrochlorothiazide. It is available as tablets (150 mg or 300 mg irbesartan and 12.5 mg hydrochlorothiazide; 300 mg irbesartan and 25 mg hydrochlorothiazide).This medicine is the same as CoAprovel, which is already authorised in the European Union (EU). The company that makes CoAprovel has agreed that its scientific data can be used for Irbesartan Hydrochlorothiazide Zentiva.

What is Irbesartan Hydrochlorothiazide Zentiva used for?

Irbesartan Hydrochlorothiazide Zentiva is used in adults who have essential hypertension (high blood pressure) that is not adequately controlled by irbesartan or hydrochlorothiazide alone. 'Essential' means that the hypertension has no obvious cause.The medicine can only be obtained with a prescription.

How is Irbesartan Hydrochlorothiazide Zentiva used?

The dose of Irbesartan Hydrochlorothiazide Zentiva to be used depends on the dose of irbesartan or hydrochlorothiazide that the patient was taking before. Doses higher than 300 mg irbesartan and1 Previously known as Irbesartan Hydrochlorothiazide Winthrop.25 mg hydrochlorothiazide once a day are not recommended. Irbesartan Hydrochlorothiazide Zentiva may be added to some other treatments for hypertension.

How does Irbesartan Hydrochlorothiazide Zentiva work?

Irbesartan Hydrochlorothiazide Zentiva contains two active substances, irbesartan and hydrochlorothiazide.Irbesartan 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, irbesartan 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 lowering the blood pressure.The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

How has Irbesartan Hydrochlorothiazide Zentiva been studied?

Irbesartan on its own has been approved in the EU since 1997 under the names Karvea and Aprovel. It can be used with hydrochlorothiazide to treat hypertension. The studies of Karvea/Aprovel used with hydrochlorothiazide as separate tablets were used to support the use of Irbesartan Hydrochlorothiazide Zentiva. Further studies were also carried out with doses of 300 mg irbesartan in combination with 25 mg hydrochlorothiazide. The main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats).

What benefit has Irbesartan Hydrochlorothiazide Zentiva shown during the studies?

Irbesartan Hydrochlorothiazide Zentiva was more effective than placebo (a dummy treatment) and than hydrochlorothiazide alone in reducing diastolic blood pressure. Increasing the dose to 300 mg irbesartan and 25 mg hydrochlorothiazide may give a further decrease in blood pressure.

What is the risk associated with Irbesartan Hydrochlorothiazide Zentiva?

The most common side effects with Irbesartan Hydrochlorothiazide Zentiva (seen in between 1 and 10 patients in 100) are dizziness, nausea (feeling sick) or vomiting, abnormal urination, fatigue(tiredness), and increases in blood urea nitrogen (BUN, a breakdown product of protein), creatinine (a breakdown product of muscle) and creatine kinase (an enzyme found in muscles). For the full list of all side effects reported with Irbesartan Hydrochlorothiazide Zentiva, see the package leaflet.Irbesartan Hydrochlorothiazide Zentiva must not be used in people who are hypersensitive (allergic) to irbesartan, hydrochlorothiazide, sulfonamides, or any of the other ingredients. It 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. Irbesartan Hydrochlorothiazide Zentiva must also not be used in patients who have severe liver, kidney or bile problems, blood potassium levels that are too low or blood calcium levels that are too high.Irbesartan Hydrochlorothiazide Zentiva in combination with aliskiren-containing medicines (used to treat essential hypertension) must not be used in patients with diabetes, or moderate or severe kidneyimpairment. Care must be taken when using Irbesartan Hydrochlorothiazide Zentiva 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 Irbesartan Hydrochlorothiazide Zentiva been approved?

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

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Irbesartan Teva

What is Irbesartan Teva?

Irbesartan Teva is a medicine that contains the active substance irbesartan. It is available as white tablets (75, 150 and 300 mg).Irbesartan Teva is a 'generic medicine'. This means that Irbesartan Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called Aprovel. For more information on generic medicines, see the question-and-answer document here.

What is Irbesartan Teva used for?

Irbesartan Teva is used in patients who have essential hypertension (high blood pressure). 'Essential' means that the hypertension has no obvious cause. Irbesartan Teva is also used to treat kidney disease in patients with hypertension and type 2 diabetes (non-insulin-dependent diabetes). Irbesartan Teva is not recommended for use in patients below 18 years of age, because of a lack of information on safety and effectiveness in this age group.The medicine can only be obtained with a prescription.

How is Irbesartan Teva used?

Irbesartan Teva is taken by mouth, with or without food. The usual recommended dose is 150 mg once a day. If the blood pressure is not sufficiently controlled, the dose can be increased to 300 mg a day or other medicines for hypertension can be added, such as hydrochlorothiazide. A starting dose of 75 mg can be used in patients receiving haemodialysis (a blood clearance technique) or in patients over 75 years of age.In patients with hypertension and type 2 diabetes, Irbesartan Teva is added to other treatments for hypertension. Treatment is started at 150 mg once a day and is usually increased to 300 mg once a day.

How does Irbesartan Teva work?

The active substance in Irbesartan Teva, irbesartan, 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, irbesartan stops the hormone having an effect, allowing the blood vessels to widen. This allows the blood pressure to drop, reducing the risks associated with high blood pressure, such as having a stroke.

How has Irbesartan Teva been studied?

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

What are the benefit and risk of Irbesartan Teva?

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

Why has Irbesartan Teva been approved?

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

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Irbesartan Zentiva

What is Irbesartan Zentiva?

Irbesartan Zentiva is a medicine that contains the active substance irbesartan. It is available as tablets (75, 150 and 300 mg).This medicine is the same as Aprovel, which is already authorised in the European Union (EU). The company that makes Aprovel has agreed that its scientific data can be used for Irbesartan Zentiva.

What is Irbesartan Zentiva used for?

Irbesartan Zentiva is used in adults who have essential hypertension (high blood pressure). 'Essential' means that the hypertension has no obvious cause. Irbesartan Zentiva is also used to treat kidney disease in adults with hypertension and type 2 diabetes.The medicine can only be obtained with a prescription.

How is Irbesartan Zentiva used?

The usual recommended dose of Irbesartan Zentiva is 150 mg once a day. If the blood pressure is not sufficiently controlled, the dose can be increased to 300 mg a day or other medicines for hypertension can be added, such as hydrochlorothiazide. A starting dose of 75 mg can be used in patients receiving haemodialysis (a blood clearance technique) or in patients over 75 years of age.1 Previously known as Irbesartan Winthrop.In patients with hypertension and type 2 diabetes, Irbesartan Zentiva is added to some other treatments for hypertension. Treatment is started at 150 mg once a day and is usually increased to 300 mg once a day.

How does Irbesartan Zentiva work?

The active substance in Irbesartan Zentiva, irbesartan, 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, irbesartan stops the hormone having an effect, allowing the blood vessels to widen. This allows the blood pressure to drop, reducing the risks associated with high blood pressure, such as having a stroke.

How has Irbesartan Zentiva been studied?

Irbesartan Zentiva was originally studied in 11 trials for its effects on blood pressure. Irbesartan Zentiva was compared with placebo (a dummy treatment) in 712 patients and with other medicines for hypertension (atenolol, enalapril or amlodipine) in 823 patients. Its use in combination with hydrochlorothiazide was also examined in 1,736 patients. The main measure of effectiveness was the reduction in diastolic blood pressure (the blood pressure measured between two heartbeats).For the treatment of kidney disease, Irbesartan Zentiva was studied in two large studies involving a total of 2,326 patients with type 2 diabetes. Irbesartan Zentiva was used for two years or more. One study looked at markers of kidney damage by measuring whether the kidneys were releasing the protein albumin into the urine. The second study looked at whether Irbesartan Zentiva increased the time taken until the patients' blood creatinine levels had doubled (a marker of kidney disease), until they needed a kidney transplant or dialysis, or until they died. In this study, Irbesartan Zentiva was compared with placebo and with amlodipine.

What benefit has Irbesartan Zentiva shown during the studies?

In the blood pressure studies, Irbesartan Zentiva was more effective than placebo at reducing diastolic blood pressure and had similar effects to the other medicines for hypertension. When used with hydrochlorothiazide, the effects of the two medicines were additive.In the first kidney disease study, Irbesartan Zentiva was more effective than placebo at reducing the risk of developing kidney damage as measured by protein excretion. In the second kidney disease study, Irbesartan Zentiva reduced the relative risk of a doubling of blood creatinine levels, needing a kidney transplant or dialysis, or death during the study by 20% in comparison with placebo. There was a 23% relative risk reduction compared with amlodipine. The main benefit was on the effect on blood creatinine levels.

What is the risk associated with Irbesartan Zentiva?

The most common side effect with Irbesartan Zentiva (seen in more than 1 patient in 10) is dizziness, hyperkalaemia (high blood potassium levels). For the full description of all side effects reported with Irbesartan Zentiva, see the package leaflet.Irbesartan Zentiva must not be used in people who are hypersensitive (allergic) to irbesartan or any of the other ingredients. It 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. Irbesartan Zentiva in combinationwith aliskiren-containing medicines (used to treat essential hypertension) must not be used in patients with diabetes, or moderate or severe kidney impairment.

Why has Irbesartan Zentiva been approved?

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

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Irbesartan/Hydrochlorothiazide Teva

What is Irbesartan/Hydrochlorothiazide Teva?

Irbesartan/Hydrochlorothiazide Teva is a medicine that contains two active substances, irbesartan and hydrochlorothiazide. It is available as tablets (150 mg or 300 mg irbesartan and 12.5 mg hydrochlorothiazide; and 300 mg irbesartan and 25 mg hydrochlorothiazide).Irbesartan/Hydrochlorothiazide Teva is a 'generic medicine'. This means thatIrbesartan/Hydrochlorothiazide Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called CoAprovel. For more information on generic medicines, see the questionand-answer document here.

What is Irbesartan/Hydrochlorothiazide Teva used for?

Irbesartan/Hydrochlorothiazide Teva is used in adults who have essential hypertension (high blood pressure) that is not adequately controlled by irbesartan or hydrochlorothiazide alone. 'Essential' means that the hypertension has no obvious cause.The medicine can only be obtained with a prescription.

How is Irbesartan/Hydrochlorothiazide Teva used?

Irbesartan/Hydrochlorothiazide Teva is taken by mouth. The dose of Irbesartan/HydrochlorothiazideTeva to be used depends on the dose of irbesartan or hydrochlorothiazide that the patient was takingbefore. Doses higher than 300 mg irbesartan and 25 mg hydrochlorothiazide once a day are not recommended. Irbesartan/Hydrochlorothiazide Teva may be added to other treatments for hypertension.

How does Irbesartan/Hydrochlorothiazide Teva work?

Irbesartan/Hydrochlorothiazide Teva contains two active substances, irbesartan and hydrochlorothiazide.Irbesartan 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, irbesartan 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 lowering the blood pressure.The combination of the two active substances has an additive effect, reducing the blood pressure more than either medicine alone. By lowering the blood pressure, the risks associated with high blood pressure, such as having a stroke, are reduced.

How has Irbesartan/Hydrochlorothiazide Teva been studied?

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

What are the benefits and risks of Irbesartan/Hydrochlorothiazide Teva?

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

Why has Irbesartan/Hydrochlorothiazide Teva been approved?

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

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Iressa

What is Iressa?

Iressa is a medicine that contains the active substance gefitinib. It is available as brown tablets (250 mg).

What is Iressa used for?

Iressa is used to treat adults who have non-small cell lung cancer that is locally advanced or metastatic (when cancer cells have spread from the original site to other parts of the body). It is used in patients whose cancer cells have a mutation in the genes that make a protein called epidermal growth factor receptor (EGFR).

How is Iressa used?

Treatment with Iressa should be started and supervised by a doctor who has experience with anticancer treatments. The recommended dose is one tablet once a day. The tablet can be dispersed in water for patients who have difficulty swallowing.

How does Iressa work?

The active substance in Iressa, gefitinib, is a protein tyrosine kinase inhibitor. This means that it blocks specific enzymes known as tyrosine kinases. These enzymes can be found on the surface of cancer cells, such as EGFR on the surface of non-small cell lung cancer cells. EGFR is involved in the growth and spread of cancer cells. By blocking EGFR, Iressa helps to slow down the growth and spread of the cancer. Iressa works only in non-small cell lung cancer cells that have a mutation in their EGFR.

How has Iressa been studied?

The effects of Iressa were first tested in experimental models before being studied in humans. In one main study involving 1,217 adult patients with locally advanced or metastatic non-small cell lung cancer, Iressa was compared with a combination of carboplatin and paclitaxel (other anticancer medicines). The main measure of effectiveness was how long the patients lived without the disease getting worse.In a second main study involving 1,466 patients with locally advanced or metastatic non-small cell lung cancer, Iressa was compared with docetaxel (another anticancer medicine). The main measure of effectiveness was survival (how long the patients lived). Both studies included patients with and without the EGFR mutation.

What benefit has Iressa shown during the studies?

In the first main study, Iressa was more effective at preventing the cancer from worsening than the combination. Among patients with the EGFR mutation, those who took Iressa lived for an average of nine and a half months without the disease getting worse, compared with about six months for those who took the combination therapy. In the second main study, patient survival among all patients who took Iressa was similar to those who took docetaxel.

What is the risk associated with Iressa?

The most common side effects with Iressa (seen in more than 1 patient in 10) are loss of appetite, diarrhoea, vomiting, nausea (feeling sick), stomatitis (inflammation of the lining of the mouth), increased level of alanine aminotransferase (a liver enzyme) in the blood, skin reactions such as pustular rash, and asthenia (weakness). There is also a risk of interstitial lung disease in patients taking Iressa. For the full list of all side effects reported with Iressa, see the Package Leaflet.Iressa should not be used in people who may be hypersensitive (allergic) to gefitinib or any of the other ingredients. It must not be used in mothers who are breastfeeding.

Why has Iressa been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Iressa's benefits are greater than its risks for the treatment of adults with locally advanced or metastatic non-small cell lung cancer with activating mutations of EGFR. The Committee recommended that Iressa be given marketing authorisation.

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Iscover

What is Iscover and what is it used for?

Iscover is a medicine used to prevent problems caused by blood clots in adults who have:• recently had a myocardial infarction (heart attack). Iscover 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). Iscover 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 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.Iscover contains the active substance clopidogrel.

How is Iscover used?

Iscover is available as tablets and can only be obtained with a prescription.Iscover 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 Iscover, see the package leaflet or contact your doctor or pharmacist.

How does Iscover work?

The active substance in Iscover, 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 Iscover have been shown in studies?

Iscover 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 Iscover 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 Iscover 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, Iscover 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 Iscover and acetylsalicylic acid compared with placebo. There was also a reduction in the patients who had astent inserted. In 2 studies in 49,000 patients with ST segment elevation myocardial infarction, fewer patients on Iscover 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 Iscover together with acetylsalicylic acid or placebo for an average of three years. In this study, Iscover 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 Iscover 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 Iscover?

Bleeding reactions are the most common side effects reported with Iscover. 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 Iscover, see the package leaflet.Iscover 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 Iscover authorised in the EU?

The European Medicines Agency decided that Iscover'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 Iscover?

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

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Isentress

What is Isentress and what is it used for?

Isentress is an HIV medicine that is used in combination with other HIV medicines to treat patients who are infected with human immunodeficiency virus (HIV-1), a virus that causes acquired immune deficiency syndrome (AIDS).Isentress contains the active substance raltegravir.

How is Isentress used?

Isentress can only be obtained with a prescription and treatment should be started by a doctor who has experience in the management of HIV infection.The medicine is available as tablets to be swallowed (400 and 600 mg), chewable tablets (25 and 100 mg) and sachets containing granules for an oral suspension (each sachet containing 100 mg). The granules are to make a mixture for babies and children to drink, the chewable tablets are for bigger children, and the 400- and 600-mg tablets are for different dose regimens in older children and adults, as recommended by the doctor. Equivalent doses of these different forms do not all produce the same levels of raltegravir in the body, so they must not be used interchangeably.For more information about using Isentress see the package leaflet or contact your doctor or pharmacist.

How does Isentress work?

The active substance in Isentress, raltegravir, is an integrase inhibitor. It blocks an enzyme called integrase, which is involved in a step in the reproduction of HIV. When the enzyme is blocked, the virus cannot reproduce normally, slowing down the spread of infection. Isentress, taken in combination with other HIV medicines, reduces the amount of HIV in the blood and keeps it at a low level. Isentress does not cure HIV infection or AIDS, but it may hold off the damage to the immune system and the development of infections and diseases associated with AIDS.

What benefits of Isentress have been shown in studies?

Isentress has been studied in six main studies.• Two studies involved a total of 699 'treatment-experienced' patients who were already receiving treatment for HIV infection that was not working. The studies compared Isentress with placebo (a dummy treatment), which were added to 'optimised background therapy' (a combination of other HIV medicines chosen for each patient as it had the best chances of reducing the levels of HIV in the blood). The main measure of effectiveness was the reduction in the levels of HIV in the blood (viral load) after 16 weeks; 77% of the patients who took Isentress had viral loads below 400 copies/ml after 16 weeks, compared with 42% of those who took placebo. The response was sustained for at least 48 weeks;• A third study involved 566 patients who had not taken HIV treatment before and compared Isentress with efavirenz (another HIV medicine). All of the patients also took tenofovir and emtricitabine (other HIV medicines). The main measure of effectiveness was the number of patients who had 'undetectable' viral loads (below 50 copies per millilitre of blood) after 48 weeks. Isentress was as effective as efavirenz. After 48 weeks, 86% of the patients taking Isentress had viral loads below 50 copies/ml (241 out of 281), compared with 82% of those taking efavirenz (230 out of 282);• A fourth study in 802 patients who had not taken HIV treatment before showed that giving Isentress as a single dose of 1,200 mg once daily was as effective as giving 400 mg twice daily. Patients also received the medicine Truvada (emtricitabine with tenofovir disoproxil). After 48 weeks, 89% (472 of 531) of those on the once daily dose and 88% (235 of 266) of those taking Isentress twice daily had viral loads less than 40 copies/ml;• Isentress has also been studied in a fifth study involving 126 HIV-1 infected children between 2 and 18 years whose existing treatment for HIV infection was not working. The study showed that Isentress, given as tablets to be swallowed or chewable tablets, was safe in children and levels of the medicine obtained in the blood in children were similar to those obtained in adults. Therefore, the effectiveness observed in adults is also expected in children.• A sixth study included 26 children aged 4 weeks to 2 years who were given Isentress oral granules made into a suspension. This study looked at viral loads after 24 and 48 weeks. Isentress treatment led to a reduction in viral load and after 48 weeks 53% of the children had viral loads below 50 copies/ml.• Additional supportive studies established doses that provide similar effective levels of Isentress in newborn infants as in young children.

What are the risks associated with Isentress?

The most common side effects with Isentress (seen in between 1 and 10 patients in 100) are headache, abdominal pain (stomach ache) and nausea (feeling sick). Side effects in children were comparable to those in adults. The most common serious side effects are immune reconstitution syndrome (symptoms of infection caused by a recovering immune system) and rash. There have also been uncommon reports of rhabdomyolysis (breakdown of muscle fibres). For the full list of side effects and restrictions with Isentress, see the package leaflet.

Why is Isentress authorised in the EU?

Isentress has been shown to be effective in helping control HIV when used with other HIV medicines. The European Medicines Agency therefore decided that Isentress'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 Isentress?

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

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Isturisa

What is Isturisa and what is it used for?

Isturisa is a medicine used to treat adults with Cushing's syndrome, a disease characterised by an excess production of the hormone cortisol by the adrenal glands, two glands situated above the kidneys.Cushing's syndrome is rare, and Isturisa was designated an 'orphan medicine' (a medicine used in rare diseases) on 15 October 2014. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu3141345.Isturisa contains the active substance osilodrostat.

How is Isturisa used?

The medicine can only be obtained with a prescription, and treatment should be started and supervised by a doctor experienced in endocrinology or internal medicine and with access to the appropriate facilities for assessing the patient's response to Isturisa.Isturisa is available as tablets (1, 5 and 10 mg), and the recommended starting dose is 2 mg twice daily. Patients of Asian ancestry should start Isturisa at a dose of 1 mg twice daily. The dose can be gradually increased according to the levels of cortisol in the body, which is measured by regular checks of the urine or blood, up to a maximum dose of 30 mg twice daily. The dose should be reduced or treatment stopped temporarily if the patient experiences certain side effects. For more information about using Isturisa, see the package leaflet or contact your doctor or pharmacist.

How does Isturisa work?

The active substance in Isturisa, osilodrostat, blocks the activity of an enzyme involved in the production of cortisol called 11-beta-hydroxylase. This reduces cortisol production and cortisol levels in the body, thereby relieving the symptoms of the disease.

What benefits of Isturisa have been shown in studies?

Isturisa was shown to be effective at lowering the levels of cortisol in one main study involving 137 patients with Cushing's syndrome. All patients were initially treated with Isturisa for 26 weeks. Thedose was adjusted for each patient until their levels of cortisol were under control and within the normal range.After this initial phase, patients whose cortisol levels were under control (71 patients) were given either Isturisa or placebo (a dummy treatment), and the study looked at the number of patients whose cortisol levels remained under control. After 8 weeks of treatment, 86% (31 out of 36) of patients treated with Isturisa had their cortisol levels under control, compared with 29% (10 out of 34) of patients given placebo.

What are the risks associated with Isturisa?

The most common side effects with Isturisa (which may affect more than 1 in 10 people) are adrenal insufficiency (low levels of cortisol produced by the adrenal glands), tiredness, nausea (feeling sick), headache, vomiting and oedema (swelling).For the full list of side effects and restrictions of Isturisa, see the package leaflet.

Why is Isturisa authorised in the EU?

Isturisa is effective at reducing elevated cortisol levels in patients with Cushing's syndrome. Side effects are considered manageable by adjusting the dose or temporarily stopping treatment. The European Medicines Agency therefore decided that Isturisa'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 Isturisa?

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

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Ivabradine Accord

What is Ivabradine Accord and what is it used for?

Ivabradine Accord 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 (heart disease caused by blockage of the blood vessels that supply the heart muscle). The medicine is used in patients with a normal heart rhythm whose heart rate is at least 70 beats per minute. It is used either in patients who cannot take 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.Ivabradine Accord is also used in patients with long-term heart failure (when the heart cannot pump enough blood to the rest of the body) and a normal heart rhythm 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.Ivabradine Accord contains the active substance ivabradine. It is a 'generic medicine'. This means that Ivabradine Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Procoralan. For more information on generic medicines, see the question-and-answer document here.

How is Ivabradine Accord used?

Ivabradine Accord is available as tablets (5 and 7.5 mg) and 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. When used for angina, treatment should be stopped if symptoms do not improve after 3 months. Also, the doctor will consider stopping treatment if the medicine has only a limited effect on reducing symptoms or reducing the heart rate.

How does Ivabradine Accord work?

The symptoms of angina are caused by the heart muscle not receiving enough oxygenated blood. In stable angina, these symptoms occur during physical effort. The active substance in Ivabradine Accord, ivabradine, blocks the 'If current' in the sinus node, the natural 'pacemaker' that regulates the heart rate. When this current is blocked, the heart rate is lowered, so that the heart has less work to do and needs less oxygenated blood. Ivabradine Accord 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, Ivabradine Accord reduces the stress on the heart, thereby slowing the progression of heart failure and improving symptoms.

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

Because Ivabradine 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 Ivabradine Accord approved?

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

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

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

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Ivabradine Anpharm

What is Ivabradine Anpharm and what is it used for?

Ivabradine Anpharm 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.Ivabradine Anpharm 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.Ivabradine Anpharm contains the active substance ivabradine.

How is Ivabradine Anpharm used?

Ivabradine Anpharm is available as tablets (5 and 7.5 mg) and 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 Ivabradine Anpharm, see the package leaflet or contact your doctor or pharmacist.

How does Ivabradine Anpharm 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 Ivabradine Anpharm, ivabradine, works by blocking the 'If currents' in the sinus node, the natural 'pacemaker' 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. Ivabradine Anpharm 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, Ivabradine Anpharm reduces the stress on the heart, thereby slowing the progression of heart failure and improving symptoms.

What benefits of Ivabradine Anpharm have been shown in studies?

AnginaIvabradine Anpharm 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, Ivabradine Anpharm was more effective than placebo when both were added to atenolol. However, a fifth study in 728 patients showed that adding Ivabradine Anpharm to amlodipine did not provide an additional benefit.A sixth study compared Ivabradine Anpharm 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 Ivabradine Anpharm 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 failureIvabradine Anpharm was compared with placebo in one main study involving over 6,500 patients with long-term moderate to severe heart failure. Results showed that it 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 Ivabradine Anpharm 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 Ivabradine Anpharm?

The most common side effect with Ivabradine Anpharm (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 Ivabradine Anpharm, see the package leaflet.Ivabradine Anpharm 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, breastfeeding or by women who could become pregnant and who are not using appropriate contraceptives. Ivabradine Anpharm must not be taken with a number of other medicines.For the full list of restrictions with Ivabradine Anpharm, see the package leaflet.

Why is Ivabradine Anpharm authorised in the EU?

The European Medicines Agency concluded that Ivabradine Anpharm was shown to be effective in longterm 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 Ivabradine Anpharm was effective in long-term heart failure with an acceptable safety profile. The Agency decided that Ivabradine Anpharm'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 Ivabradine Anpharm?

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

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Ivabradine Zentiva

What is Ivabradine Zentiva and what is it used for?

Ivabradine Zentiva 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 (heart disease caused by blockage of the blood vessels that supply the heart muscle). The medicine is used in patients with a normal heart rhythm whose heart rate is at least 70 beats per minute. It is used either in patients who cannot take beta-blockers (another type of medicine to treat angina) or in combination with a beta-blocker in patients whose disease is not controlled by a beta-blocker alone.Ivabradine Zentiva is also used in patients with long-term heart failure (when the heart cannot pump enough blood to the rest of the body) and a normal heart rhythm 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.Ivabradine Zentiva contains the active substance ivabradine. It is a 'generic medicine'. This means that Ivabradine Zentiva is similar to a 'reference medicine' already authorised in the European Union (EU) called Procoralan. For more information on generic medicines, see the question-and-answer document here.Send a

How is Ivabradine Zentiva used?

Ivabradine Zentiva is available as tablets (5 and 7.5 mg) and 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 decreases persistently below 50 beats per minute or if symptoms of bradycardia (slow heart rate) continue. 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 symptoms or reducing the heart rate.

How does Ivabradine Zentiva work?

The symptoms of angina are caused by the heart not receiving enough oxygenated blood. In stable angina, these symptoms occur during physical effort. The active substance in Ivabradine Zentiva, ivabradine, blocks the 'If current' in the sinus node, the natural 'pacemaker' that regulates the heart rate. When this current is blocked, the heart rate is lowered, so that the heart has less work to do and needs less oxygenated blood. Ivabradine Zentiva 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, Ivabradine Zentiva reduces the stress on the heart, thereby slowing the progression of heart failure and improving symptoms.

How has Ivabradine Zentiva been studied?

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

What are the benefits and risks of Ivabradine Zentiva?

Because Ivabradine 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 Ivabradine Zentiva approved?

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

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

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

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Ivemend

What is Ivemend and what is it used for?

Ivemend is a medicine for preventing nausea (feeling sick) and vomiting caused by chemotherapy cancer medicines.It is used in adults and children from 6 months of age who are undergoing chemotherapy known to cause moderate or severe nausea and vomiting.It contains the active substance fosaprepitant.

How is Ivemend used?

In adults, Ivemend is given as a slow infusion into a vein on the first day of chemotherapy. In children it may be given on the first day or on multiple days through a tube inserted into a large vein near the heart.Ivemend must always be given together with other medicines that prevent nausea and vomiting, including a corticosteroid (such as dexamethasone) and a '5HT3 antagonist' (such as ondansetron). For more information about using Ivemend, see the package leaflet or contact your doctor or pharmacist.

How does Ivemend work?

The active substance in Ivemend, fosaprepitant, is a 'prodrug' of aprepitant. This means that it is converted to aprepitant in the body. Aprepitant is a neurokinin 1 (NK1) receptor antagonist. It stops a chemical in the body called 'substance P' from attaching to the NK1 receptors. When substance P attaches to these receptors, it causes nausea and vomiting. By blocking these receptors, Ivemend can prevent nausea and vomiting, which often happens during and after chemotherapy. Aprepitant has been authorised in the European Union (EU) as Emend since 2003.

What benefits of Ivemend have been shown in studies?

A main study in 2,000 patients with cancer showed that Ivemend was as effective as a Emend another medicine approved for preventing nausea and vomiting. Around 72% of patients treated with either medicine did not have any nausea or vomiting over the five days after receiving chemotherapy.

What are the risks associated with Ivemend?

The most common side effects with Ivemend (seen in between 1 and 10 patients in 100) are increased liver enzymes, headache, hiccups, constipation, dyspepsia (heartburn), loss of appetite and fatigue (weakness or tiredness). For the full list of side effects reported with Ivemend, see the package leaflet.Ivemend must not be used at the same time as pimozide (used to treat mental illness), terfenadine and astemizole (used to treat allergy symptoms) and cisapride (used to relieve certain stomach problems). For the full list of restrictions, see the package leaflet.

Why is Ivemend authorised in the EU?

A main study showed that Ivemend was as effective as Emend at preventing nausea and vomiting in patients undergoing chemotherapy and its side effects are considered to be manageable. The European Medicines Agency therefore decided that Ivemend'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 Ivemend?

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

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Ivozall

What is Ivozall and what is it used for?

Ivozall is a cancer medicine that is used to treat children and adults up to 21 years of age who have acute lymphoblastic leukaemia (ALL), a cancer of the lymphocytes (a type of white blood cell). It is used when the disease has not responded to, or has come back (relapsed) after at least two other treatments and when no other treatment is expected to work.Ivozall contains the active substance clofarabine and is a 'generic medicine'. This means that Ivozall contains the same active substance and works in the same way as a 'reference medicine' already authorised in the EU called Evoltra. For more information on generic medicines, see the question-andanswer document here.

How is Ivozall used?

Ivozall can only be obtained with a prescription. Treatment should be started and supervised by a doctor who has experience in the management of patients with acute leukaemias. It is available as a solution for infusion (drip) into a vein.The recommended dose of Ivozall is based on the patient's height and weight. It is given by infusion lasting 2 hours every day for five days. This cycle of treatment should be repeated every 2 to 6 weeks. Doctors should review treatment in patients whose condition does not improve after one or two treatment cycles.For more information about using Ivozall, see the package leaflet or contact your doctor or pharmacist.

How does Ivozall work?

The active substance in Ivozall, clofarabine, is a cytotoxic agent (a medicine that kills cells that are dividing, such as cancer cells). It belongs to the group of cancer medicines called 'antimetabolites'. Clofarabine is an 'analogue' of adenine, one of the building blocks of the genetic material of cells (DNA and RNA). This means that clofarabine resembles adenine and by taking adenine's place in the body, it interferes with the action of enzymes involved in making genetic material, called 'DNA polymerase' and 'RNA reductase'. This stops the cells making new DNA and RNA and from dividing, thereby slowing down the growth of cancer cells.Send

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

What are the benefits and risks of Ivozall?

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

Why is Ivozall authorised in the EU?

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

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

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Ixiaro

What is Ixiaro and what is it used for?

Ixiaro is a vaccine that helps protect adults and children aged 2 months and older against Japanese encephalitis, a disease that causes inflammation of the brain. Japanese encephalitis can be fatal or lead to long-term disability. It is transmitted by mosquitoes and is most common in Asia, particularly in rural areas. Vaccination with Ixiaro should be considered for people who are at risk of exposure to the Japanese encephalitis virus through travel or work.

How is Ixiaro used?

Ixiaro is given by injection into a muscle, preferably into the shoulder muscle, or into the thigh muscle in young children. In adults, including those aged above 65 years, and children aged 3 years and older, a full dose of Ixiaro (0.5 ml) should be given, and an additional 0.5 ml dose should be given four weeks later. Adults from 18 to 65 years can also receive a rapid vaccination course, where the second dose is given seven days after the first dose.In children aged between 2 months and 3 years, half the adult dose of Ixiaro (0.25 ml) should be given, and an additional 0.25 ml dose should be given four weeks later.It is recommended that individuals who receive the first dose of Ixiaro should receive both doses. The second dose should be given at least one week before potential exposure to the virus. In adults, the second dose can be given up to 11 months after the first.Adults from 18-65 years who are likely to be exposed to the Japanese encephalitis virus again or who are at continuous risk of the disease should receive a booster dose of Ixiaro one to two years later and a second booster dose 10 years after the first booster. Children and adolescents may also receive a booster dose one to two years after the initial vaccination.A booster dose should also be considered for adults aged above 65 years before any further exposure to the Japanese encephalitis virus.Ixiaro can be injected under the skin in people who have a bleeding disorder such as low blood platelet counts or haemophilia.Ixiaro can only be obtained with a prescription. For more information about using Ixiaro, see the package leaflet or contact your doctor or pharmacist.

How does Ixiaro work?

Vaccines work by 'teaching' the immune system (the body's natural defences) how to defend against a disease. Ixiaro contains small amounts of the virus that causes Japanese encephalitis, which has been inactivated (killed) so that it cannot cause the disease. When a person is given the vaccine, the immune system identifies the inactivated virus as 'foreign' and makes antibodies against it. In future, the immune system will be able to produce antibodies quickly and in large numbers when it is exposed to Japanese encephalitis virus again. The antibodies will help to protect against the disease.The vaccine is 'adsorbed'. This means that the virus is fixed onto aluminium compounds, to stimulate a better response. The virus in Ixiaro is grown in mammal cells ('Vero cells') under laboratory conditions.

What benefit of Ixiaro have been shown in studies?

Ixiaro has been shown to trigger the production of antibodies against the Japanese encephalitis virus in 3 main studies:• The first study involved 867 healthy adults and compared Ixiaro with another vaccine for Japanese encephalitis containing viruses grown in mouse brains. Ixiaro (given as 2 doses 4 weeks apart) was as effective as the comparator vaccine at triggering the production of antibodies against the Japanese encephalitis virus. Before vaccination, most of the people in the study had no protective levels of antibodies against the virus. Four weeks after the final injection, 96% of these people who received both doses of Ixiaro had developed protective levels of antibodies (352 out of 365). This was compared with 94% of the people receiving the comparator vaccine (347 out of 370). On average, the levels of antibodies were over 2 times higher in the people receiving Ixiaro than in those receiving the comparator vaccine.• The second main study in 660 adults compared a rapid vaccination course (2 doses given 7 days apart) with the standard vaccination course (2 doses given 4 weeks apart). The 7-day accelerated vaccination course did not produce lower protection than the standard 4-week vaccination course. Long-term antibody levels were similar with both schedules.• The third main study involved 1,869 children aged between 2 months and 18 years. 99% to 100% of children who received both doses of Ixiaro had developed protective levels of antibodies against the Japanese encephalitis virus 4 weeks after the final injection.In addition, the company presented the results of studies looking at the level of protection in adults and in children for up to 3 years after vaccination with Ixiaro, and at the response to booster doses. These additional studies showed that protection against Japanese encephalitis virus lasted for at least 2 to 3 years in most people vaccinated with Ixiaro. They also showed that a booster dose might be needed to maintain high levels of protection, which may be necessary for people at high risk of exposure to the virus.

What are the risks associated with Ixiaro?

The most common side effects with Ixiaro in adults (which may affect more than 1 in 10 people) are headache, myalgia (muscle pain), pain and tenderness at the injection site and tiredness. In children, fever, diarrhoea, influenza-like illness, irritability, and reactions at the injection site (such as redness,pain and tenderness) were the most common side effects (which may affect more than 1 of 10 children). For the full list of side effects of Ixiaro, see the package leaflet.Ixiaro must not be used in people who are hypersensitive (allergic) to any residual substances in the vaccine such as protamine sulphate. Anyone who has an allergic reaction after the first dose of Ixiaro should not receive the second dose. Vaccination must be postponed in people with recent severe fever.For the full list of restrictions, see the package leaflet.

Why is Ixiaro authorised in the EU?

The European Medicines Agency decided that Ixiaro's benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted that the production of the only other vaccine for protection against Japanese encephalitis that was in use outside Asia had been discontinued.

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

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

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Izba

What is Izba and what is it used for?

Izba is an eye-drop solution that is used to reduce intraocular pressure (pressure inside the eye) in adults who have open-angle glaucoma (a disease where the pressure in the eye rises because fluid cannot drain out of the eye) and in adults with ocular hypertension (when the pressure in the eye is higher than normal). It can also be used in children from 3 years of age who have ocular hypertension or childhood glaucoma.Izba contains the active substance travoprost.

How is Izba used?

Izba is available as an eye-drop solution (30 microgram/ml) and can only be obtained with a prescription. The dose is one drop of Izba in the affected eye(s) once a day, preferably in the evening.For further information, see the package leaflet.

How does Izba work?

When pressure in the eye is raised, it can cause damage to the retina (the light-sensitive membrane at the back of the eye) and to the optic nerve that sends signals from the eye to the brain. This can result in serious vision loss and even blindness. By lowering the pressure, Izba reduces the risk of damage.The active substance in Izba, travoprost, is a prostaglandin analogue (a man-made version of a prostaglandin, substances naturally found in the body). In the eye, prostaglandins increase the drainage of the watery fluid (aqueous humour) out of the eyeball. Izba acts in the same way and increases the flow of fluid out of the eye. This helps to reduce the pressure inside the eye.

What benefits of Izba have been shown in studies?

An eye-drop solution containing travoprost at a concentration of 40 microgram/ml has been already authorised in the EU as Travatan since 2001. Izba (30 microgram/ml) has been investigated in a main study involving 864 patients with open-angle glaucoma or ocular hypertension, whose average eye pressure was 27 mmHg. The study showed that Izba was as effective as Travatan at reducing pressure in the eye following 2 weeks, 6 weeks and 3 months of treatment. Both medicines were given as one drop in the affected eye once a day, in the evening. In patients taking Izba, the average eye pressure (measured at 8 am in the morning) was 19.4, 19.3 and 19.2 mmHg following 2 weeks, 6 weeks and 3 months of treatment, respectively, which matched the pressure seen at similar time points in patients taking Travatan (19.5, 19.3 and 19.3 mmHg).Evidence from studies with Izba in adults and with Travatan in children has also been used to work out the effectiveness of Izba in children. In the study of children with glaucoma or ocular hypertension given Travatan, the average eye pressure was reduced by around 27% after 12 weeks. It was calculated that Izba used in children would result in a similar reduction in pressure.

What are the risks associated with Izba?

The most common side effect with Izba (which may affect more than 1 in 10 people) is ocular hyperaemia (increased blood supply to the eye, leading to eye irritation and redness) For the full list of all side effects and restrictions, see the package leaflet.

Why is Izba approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Izba's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted that Izba 30 microgram/ml is as effective as the 40 microgram/ml solution of travoprost. The safety profile of Izba seemed more favourable than that of the higher-strength solution, as side effects were less frequent with Izba. Izba is expected to be effective and safe in children from 3 years of age, based on adult studies and a study of 40 microgram/ml travoprost solution in children.

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

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

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