E.P.A.R s  Editing

Zabdeno

What is Zabdeno and what is it used for?

Zabdeno is a vaccine to protect adults and children aged one year and older against Ebola virus disease caused by Zaire ebolavirus. It is used with another Ebola vaccine called Mvabea as part of a vaccine regimen.Zabdeno contains a virus known as adenovirus which has been modified to allow the production of a protein from Zaire ebolavirus. The adenovirus itself has no effect on humans. Zabdeno only contains asmall part of Zaire ebolavirus and cannot cause Ebola virus disease.

How is Zabdeno used?

Zabdeno can only be obtained with a prescription and is given by a trained healthcare worker. It is given as a single injection, followed by an injection of Mvabea about 8 weeks later. People who are at imminent risk of infection with Ebola virus and have received the Zabdeno and Mvabea injections more than 4 months earlier can receive a booster dose of Zabdeno.Injections are given into the muscle around the shoulder (the deltoid) or a muscle of the thigh.For more information about using Zabdeno, see the package leaflet or contact your doctor or pharmacist.

How does Zabdeno work?

The active substance in Zabdeno will lead to the production of a viral protein found on Zaire ebolavirus. When a person receives the vaccine, the viral protein triggers an immune response. If later on the person comes into contact with the actual virus, the immune system recognises the viral proteins and is prepared to attack the virus, so protecting the person from the disease caused by Ebola virus.

What benefits of Zabdeno have been shown in studies?

Five main studies showed that Zabdeno, when used with Mvabea, can trigger the production of antibodies capable of providing protection against Zaire ebolavirus. The studies involved a total of 3,585 adults and children. Based on animal studies with a fully lethal dose of the virus, the antibody level generated in humans following vaccination with Zabdeno and Mvabea would be expected to leadto around 53% survival if infected with a fully lethal dose. However, the method used in the animal studies results in more severe infection than natural infection in humans. Although the vaccine regimen can provide protection against Ebola virus disease, the level and duration of protection are not yet known and the company will provide further data.

What are the risks associated with Zabdeno?

The most common side effects in adults with Zabdeno (which may affect more than 1 in 10 people) are pain, warmth and swelling at the injection site, tiredness, headache, muscle pain, joint pain and chills.In children and adolescents aged 1 to 17 years, the most common side effects (which may affect more than 1 in 10 people) are pain at the injection site, tiredness, decreased activity, decreased appetite and irritability.For the full list of side effects and restrictions of Zabdeno, see the package leaflet.

Why is Zabdeno authorised in the EU?

Zabdeno, used with Mvabea as part of a 2-dose vaccine regimen, triggers an immune response that can provide protection against Ebola virus disease. Although the level and duration of protection against the virus have not yet been determined, the European Medicines Agency considered that the vaccine's benefits could be of great importance to help control an outbreak and prevent death. Regarding safety, most side effects are mild to moderate in severity and of short duration. The Agency therefore decided that Zabdeno's benefits are greater than its risks and it can be authorised for use in the EU.Zabdeno has been authorised under 'exceptional circumstances'. This is because it has not been possible to obtain complete information about Zabdeno for scientific and ethical reasons. 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 Zabdeno?

Since Zabdeno has been authorised under exceptional circumstances, the company that markets Zabdeno will provide an update on the collection of data on the effectiveness of the vaccine regimen in the intended population on a yearly basis.

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

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

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Zalasta

What is Zalasta?

Zalasta is a medicine containing the active substance olanzapine. It is available as round, yellow tablets (2.5, 5, 7.5, 10, 15 and 20 mg) and as round, yellow 'orodispersible' tablets (5, 7.5, 10, 15 and 20 mg). Orodispersible tablets are tablets that dissolve in the mouth.Zalasta is a 'generic medicine'. This means that Zalasta is similar to 'reference medicines' already authorised in the European Union (EU) called Zyprexa and Zyprexa Velotab. For more information on generic medicines, see the question-and-answer document here.

What is Zalasta used for?

Zalasta is used to treat adults with schizophrenia. Schizophrenia is a mental illness that has a number of symptoms including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (mistaken beliefs). Zalasta is also effective in maintaining improvement in patients who have responded to an initial course of treatment.Zalasta is also used to treat moderate to severe manic episodes (extremely high mood) in adults. It can also be used to prevent the recurrence of these episodes (when symptoms come back) in adults with bipolar disorder (a mental illness causing alternating periods of high mood and depression) who have responded to an initial course of treatment.The medicine can only be obtained with a prescription.

How is Zalasta used?

The recommended starting dose of Zalasta depends on the disease being treated: 10 mg per day is used in schizophrenia and in the prevention of manic episodes, and 15 mg per day in the treatment of manic episodes, unless it is used with other medicines, in which case the starting dose can be 10 mg per day.The dose is adjusted depending on how well the patient responds to and tolerates the treatment. The usual dose range is between 5 and 20 mg per day. The orodispersible tablets, which can be used as an alternative to the tablets, are taken by being placed on the tongue, where they disintegrate quickly in the saliva, or by mixing them in water before swallowing. Patients over 65 years of age and patients who have problems with their liver or kidneys may need a lower starting dose of 5 mg per day.

How does Zalasta work?

The active substance in Zalasta, olanzapine, is an antipsychotic medicine. It is known as an 'atypical' antipsychotic because it is different from the older antipsychotic medicines that have been availablesince the 1950s. Its exact mechanism of action is unknown, but it attaches to several receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by'neurotransmitters', chemicals that allow nerve cells to communicate with each other. It is thought that olanzapine's beneficial effect is due to it blocking receptors for the neurotransmitters5-hydroxytryptamine (also called serotonin) and dopamine. Since these neurotransmitters are involved in schizophrenia and bipolar disorder, olanzapine helps to normalise the activity of the brain, reducing the symptoms of these diseases.

How has Zalasta been studied?

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

What are the benefit and risk of Zalasta?

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

Why has Zalasta been approved?

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

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Zaltrap

What is Zaltrap and what is it used for?

Zaltrap is a cancer medicine used to treat adults with metastatic colorectal cancer (cancer of the large bowel that has spread to other parts of the body) for whom treatment based on another medicine, oxaliplatin, has not worked or the cancer got worse. Zaltrap is used with FOLFIRI, which is a treatment combining the medicines irinotecan, 5-fluorouracil, and folinic acid.The medicine contains the active substance aflibercept.

How is Zaltrap used?

Zaltrap can only be obtained with a prescription and treatment should be supervised by a doctor who is experienced in using cancer medicines.Zaltrap is given as an infusion (drip) into the vein over one hour, at a dose of 4 mg per kilogram body weight. This is then followed by the FOLFIRI treatment. This cycle of treatment is repeated every two weeks, until the disease gets worse or the patient cannot tolerate the treatment. Treatment should be discontinued, delayed, or the dose may have to be adjusted, in patients who develop certain side effects. For further details, see the package leaflet.

How does Zaltrap work?

The active substance in Zaltrap, aflibercept, is a protein that attaches to vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF), substances that circulate in the blood and make blood vessels grow. By binding to VEGF and PlGF, aflibercept stops them having an effect. As a result, the cancer cells cannot develop their own blood supply and are starved of oxygen and nutrients, so helping to slow down the growth of tumours.

What benefits of Zaltrap have been shown in studies?

Zaltrap was investigated in one main study involving 1,226 adults with metastatic colorectal cancer that had not responded to oxaliplatin-based treatment. Zaltrap was compared with placebo (a dummy treatment) when added to FOLFIRI. The main measure of effectiveness was the average length of time that patients survived after treatment.In this study, Zaltrap was more effective than placebo at increasing survival of patients: patients treated with Zaltrap plus FOLFIRI lived an average of 13.5 months, whereas patients treated with placebo and FOLFIRI lived an average of 12.1 months.

What are the risks associated with Zaltrap?

The most common side effects with Zaltrap in combination with FOLFIRI (which may affect more than 20 patients in 100) are leucopenia and neutropenia (low levels of white cells in the blood, including the type that fight infections), diarrhoea, proteinuria (protein in the urine), increased blood levels of liver enzymes (aspartate and alanine transaminases), stomatitis (inflammation of the mouth), tiredness, thrombocytopenia (low blood platelet counts), hypertension (high blood pressure), weight loss, decreased appetite, epistaxis (nose bleeds), abdominal pain, dysphonia (speech disturbance), increases in creatinine in the blood (a marker of kidney problems), and headache. The most common effects that led to treatment being permanently stopped were problems with the circulation including hypertension, infections, tiredness, diarrhoea, dehydration, stomatitis, neutropenia, proteinuria, and pulmonary embolism (a clot in a blood vessel supplying the lungs).For the full list of all side effects reported with Zaltrap, see the package leaflet.Although medicines containing the same active substance are available for injection into the eye, Zaltrap must not be injected into the eye as it was not developed for such use and may cause local damage. For the full list of restrictions, see the package leaflet.

Why is Zaltrap approved?

Although Zaltrap is associated with significant side effects, which can be severe enough to force treatment to be stopped, the results of the large main study show that there is a small but clinically significant benefit in prolonging the life of treated patients in whom previous treatment failed. Overall, the European Medicines Agency decided that Zaltrap'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 Zaltrap?

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

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Zarzio

What is Zarzio?

Zarzio is a solution for injection or infusion (drip into a vein) in a pre-filled syringe. It contains the active substance filgrastim (30 or 48 million units).Zarzio is a 'biosimilar' medicine. This means that Zarzio is similar to a biological medicine that is already authorised in the European Union (EU) and contains the same active substance (also known as the 'reference medicine'). The reference medicine for Zarzio is Neupogen. For more information on biosimilar medicines, see the question-and-answer document here.

What is Zarzio used for?

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

How is Zarzio used?

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

How does Zarzio work?

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

How has Zarzio been studied?

Zarzio was studied to show that it is comparable to the reference medicine, Neupogen.Four studies looked at the levels of neutrophils in the blood in a total of 146 healthy volunteers who received Zarzio or Neupogen. The studies looked at the effects of single and repeated administration of various doses of the medicines, either injected under the skin or infused into a vein. The main measure in these studies was the neutrophil count over the first 10 days of treatment.

What benefit has Zarzio shown during the studies?

Zarzio and Neupogen brought about similar increases in blood neutrophil counts in healthy volunteers over the course of the studies. This was considered sufficient to demonstrate that the benefits of Zarzio are comparable to those of the reference medicine.

What is the risk associated with Zarzio?

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

Why has Zarzio been approved?

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

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

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

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Zavesca

What is Zavesca?

Zavesca is a medicine that contains the active substance miglustat. It is available as capsules (100 mg).

What is Zavesca used for?

Zavesca is used to treat two inherited diseases that affect the way the body handles fats. Both diseases cause a build-up of fatty substances called glycosphingolipids in the body. Zavesca is used to treat the following patients:• adults (aged 18 years and above) with mild to moderate type 1 Gaucher disease. Patients with this disease lack an enzyme called glucocerebrosidase, which results in a glycosphingolipid called glucosylceramide building up in different parts of the body, such as the spleen, liver and bones. Zavesca is used in patients who cannot receive the standard treatment of enzyme replacement therapy (ERT);• patients of all ages with Niemann-Pick type C disease, a potentially fatal disease in which glycosphingolipids build up within cells in the brain and elsewhere in the body. Zavesca is used to treat the neurological symptoms of the disease (symptoms affecting the brain and nerves). These include loss of co-ordination, problems with 'saccadic' (rapid) eye movements that can lead to impaired vision, delayed development, difficulty swallowing, decreased muscle tone, fits and learning difficulties.Because the number of patients with these diseases is low, they are considered 'rare', and Zavesca was designated an 'orphan medicine' (a medicine used in rare diseases) on 18 October 2000 for type 1 Gaucher disease and on 16 February 2006 for Niemann-Pick type C disease.The medicine can only be obtained with a prescription.

How is Zavesca used?

Treatment with Zavesca should be started and monitored by doctors who are experienced in the management of Gaucher or Niemann-Pick type C disease.The recommended starting dose for type 1 Gaucher disease is one capsule three times a day. For Niemann-Pick type C disease, it is two capsules three times a day for patients aged 12 years and over; in younger patients, the dose depends on their weight and height. Zavesca is intended for long-term use.A lower dose should be used in patients with reduced kidney function. The dose should also be reduced temporarily in patients who develop diarrhoea. For further information, see the summary of product characteristics (also part of the EPAR).

How does Zavesca work?

The active substance in Zavesca, miglustat, prevents an enzyme called glucosylceramide synthase from working. This enzyme is involved in the first step of the production of glycosphingolipids. By preventing the enzyme from working, miglustat can reduce the production of glycosphingolipids in cells. This is expected to slow down or prevent the development of the symptoms of type 1 Gaucher disease and to reduce the symptoms of Niemann-Pick type C disease.

How has Zavesca been studied?

For type 1 Gaucher disease, Zavesca was investigated in one main study involving 28 adults with mild to moderate disease who were unable or unwilling to receive ERT. The main part of the study lasted for a year, but 13 patients carried on receiving the medicine for a further two years. The study looked at the effect of Zavesca on the size of the liver and spleen, and at blood counts, such as the levels of haemoglobin (a protein found in red blood cells that carries oxygen around the body) and platelets (components that help the blood to clot).For Niemann-Pick type C disease, Zavesca was studied in one main study involving 31 patients, 12 of whom were less than 12 years old. The study compared the effects of adding Zavesca to standard care with the effects of standard care alone. The main measure of effectiveness was the change in the speed at which the patients made saccadic horizontal eye movements after a year, but the study also looked at other neurological symptoms such as the patients' ability to swallow and their intellectual function. Some patients were treated for up to five and a half years. The company also presented the results of a survey of 66 patients treated with Zavesca.

What benefit has Zavesca shown during the studies?

In the study of type 1 Gaucher disease, there were moderate reductions in the size of the liver (12% reduction) and the spleen (19% reduction) after a year. There were also small improvements in blood counts: on average, the levels of haemoglobin increased by 0.26 g per decilitre and platelet counts increased by 8.29 million per millilitre. The benefits of Zavesca were maintained over three years of continuous treatment.In the study of Niemann-Pick type C disease, the improvement in eye movements was similar in patients treated with and without Zavesca. However, there were signs of improvement in swallowing ability and intellectual function in the patients treated with Zavesca. The survey showed that Zavesca led to a stabilisation or a decrease in the rate at which symptoms got worse in about three-quarters of the patients.

What is the risk associated with Zavesca?

The most common side effects with Zavesca (seen in more than 1 patient in 10) are weight loss, decreased appetite, tremor (shaking), diarrhoea, flatulence (gas) and abdominal pain (stomach ache). For the full list of all side effects reported with Zavesca, see the package leaflet.Zavesca must not be used in people who are hypersensitive (allergic) to miglustat or any of the other ingredients.

Why has Zavesca been approved?

The CHMP decided that Zavesca's benefits are greater than its risks and recommended that it be given marketing authorisation.Zavesca was originally authorised under 'exceptional circumstances' because, as the diseases are rare, limited information was available at the time of approval. As the company had supplied the additional information requested, the exceptional circumstances ended on 23 August 2012.

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Zavicefta

What is Zavicefta and what is it used for?

Zavicefta is an antibiotic used in adults and children aged 3 months and older to treat the following infections:• complicated (difficult to treat) infections of the tissues and organs in the belly (intra-abdominal infections);• complicated (difficult to treat) infections of the urinary tract, including pyelonephritis (kidney infection);• infections of the lungs caught in hospital (hospital-acquired pneumonia), including ventilatorassociated pneumonia (pneumonia caught from a ventilator, a machine that helps a patient to breathe).Zavicefta can also be used for infections of the blood (bacteraemia) associated with any of the above infections.Zavicefta can be used in adults and children aged 3 months and older for infections caused by aerobic Gram-negative bacteria (types of bacteria) when other treatments might not work.Zavicefta contains the active substances ceftazidime and avibactam.

How is Zavicefta used?

Zavicefta is given by infusion (drip) into a vein. The infusion is given over 2 hours, usually 3 times daily. Treatment usually lasts between 5 and 14 days, depending on the type of infection.Zavicefta can only be obtained with a prescription, and prescribers should take into account official guidance on the use of antibiotics.For more information about using Zavicefta, see the package leaflet or contact your doctor or pharmacist.

How does Zavicefta work?

The active substances in Zavicefta are ceftazidime and avibactam. Ceftazidime is an antibiotic called a cephalosporin, which belongs to the wider group 'beta-lactams'. Cephalosporins interfere with the building of cell walls in bacteria. This weakens bacterial cell walls and they break down, causing the bacteria to die.Avibactam blocks the action of bacterial enzymes called beta-lactamases. These enzymes enable bacteria to break down beta-lactam antibiotics such as ceftazidime, making them resistant to the antibiotic's action. By blocking these enzymes, avibactam allows ceftazidime to act against bacteria that would otherwise be resistant.

What benefits of Zavicefta have been shown in studies?

The benefits of Zavicefta have been shown in five main studies in adults.In two studies, the combination of Zavicefta and metronidazole (another antibiotic) was at least as effective as the antibiotic meropenem in 1,490 patients with complicated intra-abdominal infection. In one of the patient groups in the first study, 92% of patients treated with Zavicefta and metronidazole were cured, compared with 93% of patients treated with meropenem. In the second study, 94% of patients treated with Zavicefta and metronidazole were cured, compared with 94% of patients treated with meropenem.A third study looked at 332 patients with complicated intra-abdominal or urinary tract infections caused by Gram-negative bacteria that were resistant to ceftazidime. Zavicefta alone (for urinary tract infection) or in combination with metronidazole (for intra-abdominal infection) was as effective as alternative antibiotics: 91% of patients were cured after treatment with Zavicefta compared with 91% after treatment with the best alternative antibiotic. In addition, disease-causing bacteria were eliminated in 82% of patients after treatment with Zavicefta compared with 63% after treatment with the best alternative antibiotic. These results support Zavicefta's activity when combined with the other studies.In a fourth study, 1,020 patients with complicated urinary tract infections (including pyelonephritis) caused by Gram-negative bacteria were treated with Zavicefta or the antibiotic doripenem. Zavicefta was at least as effective as doripenem: disease-causing bacteria were eliminated in 77% of patients treated with Zavicefta compared with 71% of patients treated with doripenem.In a fifth study in 817 patients with hospital-acquired pneumonia, of whom 280 had ventilatorassociated pneumonia, around 69% of patients treated with Zavicefta were cured compared with 73% of those receiving meropenem.Data on the effectiveness of Zavicefta in treating blood infections come from patients in these 5 studies who also had blood infection. Across all studies, 87% of patients (47 out of 54) who received Zavicefta with or without metronidazole were cured compared with 83% of those who received another antibiotic treatment (39 out of 47).Additional studies have shown that when the medicine is given to children at the recommended doses, levels of the medicine in the blood are sufficient to treat the infection, and comparable to those in adults. The medicine is also absorbed, modified and removed from the body in a similar way across the different age groups of children, regardless of the infections they have. Based on these results, Zavicefta was considered to be effective at treating complicated intra-abdominal and urinary tract infections, hospital-acquired pneumonia, and infections due to aerobic Gram-negative organisms when other treatments might not work in children.In addition, in a study in children from 3 months to under 18 years of age with complicated intraabdominal infection, 92% of patients (56 out of 61) were cured after treatment with Zavicefta plus metronidazole compared with 95% (21 out of 22) of patients who received meropenem. In another study with children from 3 months to under 18 years of age with complicated urinary tract infections, 89% of patients (48 out of 54) were cured after treatment with Zavicefta compared with 83% (19 out of 23) of patients who received cefepime.

What are the risks associated with Zavicefta?

The most common side effects with Zavicefta (which may affect more than 5 in 100 people) are nausea (feeling sick), diarrhoea and a positive result in a Coombs test (a sign of the development of antibodies involved in breaking down red blood cells). For the full list of side effects with Zavicefta, see the package leaflet.Zavicefta must not be used in patients who are hypersensitive (allergic) to the active substances in Zavicefta or any of the other ingredients, or in those who are hypersensitive to other cephalosporin antibiotics or have ever had a severe allergic reaction to another beta-lactam antibiotic (for example penicillin).

Why is Zavicefta approved?

The European Medicines Agency decided that Zavicefta's benefits are greater than its risks and it can be authorised for use in the EU. Zavicefta is effective at treating complicated intra-abdominal and urinary tract infections, and hospital-acquired pneumonia in adults and children. It is also effective at treating these infections in adults when they have spread into the blood. In addition, Zavicefta is effective at treating infections due to aerobic Gram-negative organisms in adults and children when other treatments might not work. Regarding Zavicefta's safety profile, side effects were those expected for the two active substances.

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

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

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Zebinix

What is Zebinix and what is it used for?

Zebinix is an epilepsy medicine used to treat adults with partial-onset seizures (epileptic fits) with or without secondary generalisation. This is a type of epilepsy where too much electrical activity in one side of the brain causes symptoms such as sudden, jerky movements of one part of the body, distorted hearing, sense of smell or vision, numbness or a sudden sense of fear. Secondary generalisation occurs when the overactivity later reaches the whole brain. Zebinix can be taken on its own, in newly diagnosed epilepsy, or can be added to existing antiepileptic medicines.Zebinix can also be used in adolescents and children above 6 years of age, in combination with existing therapies, to treat partial-onset seizures with or without secondary generalisation.Zebinix contains the active substance eslicarbazepine acetate.

How is Zebinix used?

Zebinix can only be obtained with a prescription. It is available as tablets (200 mg, 400 mg, 600 mg and 800 mg) and as a suspension to be taken by mouth.For adults and children weighing 60 kg or more, treatment is started at a dose of 400 mg once a day, before increasing it to the standard dose of 800 mg once a day after one or two weeks. In children weighing less than 60 kg, the starting dose is 10 mg per kg body weight once a day. The dose is then increased after one or two weeks to 20 mg/kg per day and then to 30 mg/kg per day, based on the patient's response. For adults who take Zebinix on its own, a dose up to 1,600 mg may be used. For children and adults who use Zebinix in combination with other medicines the maximum dose is 1,200 mg once a day.Zebinix should not be used in patients with severe kidney problems and the dose should be adjusted in moderately impaired kidney function.For more information about using Zebinix, see the package leaflet or contact your doctor or pharmacist.

How does Zebinix work?

The active substance in Zebinix, eslicarbazepine acetate, is converted into eslicarbazepine in the body. Epilepsy is caused by excessive electrical activity in the brain. For electrical impulses to travel along nerves there needs to be a rapid movement of sodium into the nerve cells. Eslicarbazepine is thought to work by blocking 'voltage-gated sodium channels', which stops sodium entering the nerve cells. This reduces the activity of the nerve cells in the brain, reducing the intensity and the number of seizures.

What benefit of Zebinix have been shown in studies?

Three main studies compared Zebinix with placebo (a dummy treatment) in 1,050 adults with partialonset seizures that were not controlled by other medicines. All of the patients also received other epilepsy medicines. Looking at the results of the three studies taken together, Zebinix 800 mg and 1,200 mg were more effective than placebo at reducing the number of seizures, when used as add-on to other epilepsy medicines. At the start of the study, patients had around 13 seizures per month. Over the 12 weeks of treatment, this fell to 9.8 and 9.0 seizures per month in patients taking Zebinix 800 mg and Zebinix 1,200 mg respectively, compared with 11.7 per month in those taking placebo.Another study compared Zebinix taken on its own with another epilepsy medicine, carbamazepine, in 815 newly diagnosed adults. Zebinix was effective, although slightly less than carbamazepine, at reducing seizures after 6 months of treatment: 71% of patients who took Zebinix and did not prematurely withdraw from the study (276 out of 388 patients) were seizure-free after 6 months compared with 76% of patients taking carbamazepine (300 out of 397 patients).The effects of Zebinix were also studied in children with partial-onset seizures. In these studies, all the children also received other epilepsy medicines. In one study involving 123 children aged 6 to 16 years, Zebinix over 12 weeks halved the number of seizures in 51% of patients (42 out of 83). This compared with 25% of patients (10 out of 40) on placebo. A second study in children aged 2 to 18 years did not find a difference between Zebinix and placebo, this was explained by the fact that lower doses were used.

What are the risks associated with Zebinix?

In clinical trials, around half of the patients treated with Zebinix experienced side effects. Side effects were usually mild to moderate in intensity and occurred mostly in the first week of treatment. For adults, the most common side effects with Zebinix (seen in more than 1 patient in 10) are dizziness, somnolence (sleepiness), headache and nausea. Severe skin reactions, including Stevens-Johnson syndrome, have also been reported with Zebinix.Zebinix must not be used in people who are hypersensitive (allergic) to eslicarbazepine acetate, any of the other ingredients or other carboxamide derivatives (medicines with a similar structure to eslicarbazepine acetate, such as carbamazepine or oxcarbazepine). It must not be used in people with second or third degree atrioventricular block (a problem with electrical transmission in the heart).For the full list of side effects and restrictions with Zebinix, see the package leaflet.

Why is Zebinix authorised?

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

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

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

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Zeffix

What is Zeffix?

Zeffix is a medicine that contains the active substance lamivudine. It is available as tablets (100 mg) and an oral solution (5 mg/ml).

What is Zeffix used for?

Zeffix is used to treat adults (aged 18 years or over) who have chronic (long-term) hepatitis B (a disease of the liver due to infection with the hepatitis B virus). It is used in patients with:• compensated liver disease (when the liver is damaged but works normally), who also show signs that the virus is still multiplying and have signs of liver damage (raised levels of the liver enzyme alanine aminotransferase [ALT] and signs of damage when liver tissue is examined under a microscope). Because the hepatitis B virus can become resistant to Zeffix, the doctor should only consider prescribing Zeffix if other treatments that are less likely to lead to resistance cannot be used;• decompensated liver disease (when the liver does not work normally). To reduce the risk of resistance, Zeffix must be used in combination with another anti-hepatitis B medicine that does not cause resistance in the same way as Zeffix.The medicine can only be obtained with a prescription.

How is Zeffix used?

Treatment with Zeffix should be started by a doctor who has experience in the management of chronic hepatitis B.The recommended dose of Zeffix is 100 mg once a day. The dose needs to be lower in patients who have reduced kidney function. Doses lower than 100 mg need to be given using the oral solution. The duration of treatment depends on the patient's condition and response to treatment.If the hepatitis B virus can still be found in the blood after six months of treatment, the doctor should consider switching treatment or adding another medicine for hepatitis B to reduce the risk of resistance. For more information, see the summary of product characteristics (also part of the EPAR).

How does Zeffix work?

The active substance in Zeffix, lamivudine, is an antiviral agent that belongs to the class 'nucleoside analogues'. Lamivudine interferes with the action of a viral enzyme called DNA polymerase, which is involved in the formation of viral DNA. Lamivudine stops the virus making DNA and prevents it from multiplying and spreading.

How has Zeffix been studied?

Zeffix has been studied in five main studies involving a total of 1,083 adults with compensated liver disease due to chronic hepatitis B. Three studies compared Zeffix with placebo (a dummy treatment), one of which looked particularly at 'HBeAg-negative' patients. These are patients infected with hepatitis B virus that has mutated (changed), leading to a form of chronic hepatitis B that is more difficult to treat. The other two studies compared Zeffix taken on its own with alfa-interferon (another treatment used in chronic hepatitis B) on its own and with the combination of Zeffix and alfa-interferon.In addition, information was presented on the use of Zeffix in patients with decompensated liver disease.There were several measures of effectiveness in the studies. These included looking at how the liver damage had evolved after a year of treatment using a liver biopsy (when a small sample of liver tissue is taken and examined under a microscope), as well as measuring other signs of the disease such as the levels of ALT or of hepatitis B virus DNA circulating in the blood.

What benefit has Zeffix shown during the studies?

In patients with compensated liver disease, Zeffix was more effective than placebo in slowing down the progression of liver disease. About half of the patients taking Zeffix had an improvement in liver damage assessed in a biopsy, compared with about a quarter of the patients who took placebo. Zeffix was as effective as alfa-interferon.In patients with decompensated liver disease, Zeffix also reduced levels of hepatitis B virus DNA and ALT.

What is the risk associated with Zeffix?

The most common side effect with Zeffix (seen in more than 1 patient in 10) is raised ALT levels. For the full list of all side effects or restrictions with Zeffix, see the package leaflet.Zeffix

Why has Zeffix been approved?

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

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Zejula

What is Zejula and what is it used for?

Zejula is a cancer medicine used in women with advanced ovarian cancer, which includes cancer of the ovaries, fallopian tubes (that connect the ovaries to the uterus) or the peritoneum (the lining around the abdomen). It can be used on its own for maintenance (continuing) treatment:• In women newly diagnosed with advanced cancer in whom the cancer has shrunk or disappeared with a platinum-based medicines;• in women whose cancer had relapsed (come back) after responding to previous treatment and in whom the cancer has shrunk or disappeared with a platinum-based medicineOvarian cancer is rare and Zejula was designated an 'orphan medicine' (a medicine used in rare diseases) on 4 August 2010. Further information on the orphan designation can be found here: ema.europa.eu/Find medicine/Human medicines/Rare disease designation Zejula contains the active substance niraparib.

How is Zejula used?

Zejula is available as capsules (100 mg) to be taken by mouth. The dose is 2 or 3 capsules once a day, depending on the patient's weight, platelet count and whether or not the cancer has come back after previous treatment. Treatment should continue for as long as the patient benefits from it. The doctor may interrupt treatment or reduce the dose if the patient has certain side effects.The medicine can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in the use of cancer medicines.For more information about using Zejula, see the package leaflet or contact your doctor or pharmacist.

How does Zejula work?

The active substance in Zejula, niraparib, blocks the action of enzymes called PARP-1 and PARP-2, which help to repair damaged DNA in cells when the cells divide to make new cells. By blocking PARP enzymes, the damaged DNA in cancer cells cannot be repaired, and, as a result, the cancer cells die.

What benefits of Zejula have been shown in studies?

Zejula increased the time women lived without their disease getting worse in two main studies involving over 1,000 women with ovarian cancer, including fallopian tube or peritoneal cancers.One study involved women with high-grade epithelial ovarian cancer that had come back after previous treatment with two or more platinum-based therapies. The women had a lasting response (the cancer had not progressed for at least 6 months) before the last platinum-based therapy. After treatment with Zejula, women lived on average 11.3 months without their disease getting worse compared with 4.7 months in women receiving placebo (a dummy treatment).Another study involved women with advanced high-grade epithelial ovarian cancer that had only been treated with a platinum-based medicine and in whom the cancer had shrunk or disappeared. Women who then continued treatment with Zejula lived 13.8 months without their disease getting worse compared with 8.2 months in women receiving placebo (a dummy treatment).

What are the risks associated with Zejula?

The most common side effects with Zejula (which may affect more than 1 in 10 people) are nausea (feeling sick), thrombocytopenia (low blood platelet counts), tiredness and weakness, anaemia (low red blood cell counts), constipation, vomiting, abdominal (belly) pain, neutropenia (low levels of neutrophils, a type of white blood cell), insomnia (difficulty sleeping), headache, lack of appetite, diarrhoea, dyspnoea (difficulty breathing), hypertension (high blood pressure), back pain, dizziness, cough, joint pain, hot flushes and decrease in white blood cells. Serious side effects include thrombocytopenia and anaemia. For the full list of side effects of Zejula, see the package leaflet.Zejula must not be used in women who are breastfeeding. For the full list of restrictions, see the package leaflet.

Why is Zejula authorised in the EU?

Although treatments for advanced ovarian cancer are available, the disease inevitably comes back. Zejula has been shown to prolong the time before the disease gets worse again in patients who have responded to platinum-based therapies. This may allow treatment for ovarian cancer to be delayed.Regarding safety, side effects are generally manageable with dose reductions.The European Medicines Agency therefore decided that Zejula's benefits are greater than its risks and recommended that it can be authorised for use in the EU.

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

The company that markets Zejula will submit the final analyses of the study on the effectiveness of Zejula in advanced epithelial (FIGO Stages III and IV) high-grade ovarian cancer.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zejula have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zejula are continuously monitored. Side effects reported with Zejula are carefully evaluated and any necessary action taken to protect patients.

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Zelboraf

What is Zelboraf and what is it used for?

Zelboraf is a cancer medicine used to treat adults with melanoma (a type of skin cancer) that has spread to other parts of the body or cannot be surgically removed. Zelboraf is only for patients whose melanoma tumour cells have a specific mutation (genetic change) called 'BRAF V600'.Zelboraf contains the active substance vemurafenib.

How is Zelboraf used?

Zelboraf can only be obtained with a prescription and treatment should be started and supervised by a specialist doctor experienced in treating cancer. Before starting treatment a test must be carried out to make sure that the patient's tumours have the BRAF V600 mutation.Zelboraf is available as tablets (240 mg). The recommended dose is 960 mg (four tablets) twice daily. The first dose is taken in the morning and the second dose in the evening around 12 hours later. Each dose can be taken with or without food, but Zelboraf should be taken in the same way day-to-day.Treatment should be continued until the disease worsens or the side effects become too severe.For more information about using Zelboraf, see the package leaflet or contact your doctor or pharmacist.

How does Zelboraf work?

The active substance in Zelboraf, vemurafenib, is an inhibitor of BRAF, a protein involved in stimulating cell division. In melanoma tumours with the BRAF V600 mutation, an abnormal form of BRAF is present which plays a role in the development of the cancer by allowing uncontrolled division of the tumour cells. By blocking the action of the abnormal BRAF, Zelboraf helps to slow down the growth and spread of the cancer.

What benefits of Zelboraf have been shown in studies?

Zelboraf was compared with the cancer medicine dacarbazine in a main study involving 675 patients with melanoma containing the BRAF V600 mutation whose tumours had spread or could not be surgically removed. Patients were to receive either medicine until their disease got worse or theirtreatment became too toxic for them. The main measures of effectiveness were how long the patients lived (overall survival) and how long they lived without their disease getting worse (progression-free survival).Zelboraf was shown to be effective at prolonging patients' lives and delaying the worsening of the disease. The study showed that patients taking Zelboraf lived on average for 13.2 months compared with 9.9 months for patients on dacarbazine, and it took on average 5.3 months for the disease to worsen in the Zelboraf group compared with 1.6 months in the dacarbazine group.

What are the risks associated with Zelboraf?

The most common side effects with Zelboraf (which may affect more than 3 in 10 patients) include arthralgia (joint pain), tiredness, rash, photosensitivity reaction (sunburn-like reactions following exposure to light), nausea and vomiting (feeling sick and being sick), alopecia (hair loss), diarrhoea, headache, pruritus (itching), skin papilloma (warts) and hyperkeratosis (thickening and toughening of the skin). The most common serious side effects include another type of skin cancer called 'cutaneous squamous cell carcinoma', which is commonly treated by local surgery, keratoacanthoma (benign skin tumour), rash, arthralgia and change in liver test results (increased gamma-glutamyltransferase [GGT]).For the full list of side effects and restrictions with Zelboraf, see the package leaflet.

Why is Zelboraf authorised in the EU?

The European Medicines Agency decided that Zelboraf's benefits are greater than its risks and it can be authorised for use in the EU. The Agency noted that Zelboraf had been convincingly shown to improve overall survival and to delay the worsening of 'BRAF V600 positive' melanoma which has spread or cannot be surgically removed. With regard to its risks, in the main study around half of the patients taking Zelboraf experienced a severe side effect and about one fifth developed cutaneous squamous cell carcinoma. The Agency considered the side effects to be manageable and included recommendations for doctors to help reduce the risks in the product information.

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

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

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Zepatier

What is Zepatier and what is it used for?

Zepatier is an antiviral medicine used to treat adults and children from 12 years of age weighing at least 30 kg with chronic (long-term) hepatitis C, an infectious disease that affects the liver, caused by the hepatitis C virus.Zepatier contains the active substances elbasvir and grazoprevir.

How is Zepatier used?

Zepatier can only be obtained with a prescription and treatment should be started and monitored by a doctor experienced in the management of patients with chronic hepatitis C.There are several varieties (called genotypes) of hepatitis C virus. Zepatier is recommended for use in patients infected with hepatitis C virus genotypes 1a, 1b and 4 who may or may not have compensated liver cirrhosis (scarring of the liver but the liver is still able to work adequately).Zepatier is available as tablets. The usual dose is 50 mg elbasvir and 100 mg grazoprevir taken once a day for 12 weeks. In some cases, treatment may be longer and Zepatier may be used together with another medicine called ribavirin.For more information about using Zepatier, see the package leaflet or contact your doctor or pharmacist.

How does Zepatier work?

The active substances in Zepatier, elbasvir and grazoprevir, block two proteins essential for the hepatitis C virus to multiply. Elbasvir blocks the action of a protein called 'NS5A', while grazoprevir blocks an enzyme called 'NS3/4A protease'. By blocking these proteins, Zepatier stops the hepatitis C virus from multiplying and infecting new cells.

What benefits of Zepatier have been shown in studies?

Zepatier with or without ribavirin has been investigated in eight main studies involving around 2,000 adults infected with hepatitis C virus of various genotypes whose liver was working normally or adequately. In all studies, the main measure of effectiveness was the number of patients whose bloodtests did not show any sign of hepatitis C virus 12 weeks after the end of treatment. Looking at the results of the studies together, 96% of patients with genotype 1b virus (301 out of 312 patients) tested negative for the virus after 12 weeks of treatment with Zepatier. For patients with genotype 1a virus, 93% of patients (483 out of 519 patients) treated with Zepatier tested negative compared with 95% (55 out of 58 patients) on Zepatier with ribavirin. For patients with genotype 4 virus, 94% of patients (61 out of 65 patients) treated with Zepatier tested negative compared with 100% (8 out of 8 patients) treated with Zepatier and ribavirin. Benefit was also seen in patients also infected with HIV or who had chronic (long-term) kidney disease. The available data in patients with genotype 3 virus were not sufficient to support the use of Zepatier for this genotype.A study conducted in 22 patients older than 12 and younger than 18 years of age showed that the way Zepatier is absorbed, processed and removed from the body in this age group and in adults is similar. Zepatier is therefore expected to show similar safety and effectiveness. In addition, in this study all 22 patients tested negative for the virus after 12 weeks of treatment.

What are the risks associated with Zepatier?

The most common side effects with Zepatier (which may affect more than 1 in 10 people) are tiredness and headache.Zepatier must not be used in patients with moderately or severely reduced liver function (Child-Pugh class B or C cirrhosis). It must not be used together with medicines such as the antibiotic rifampicin, certain HIV medicines and ciclosporin (used to prevent organ rejection) since Zepatier may affect the way these medicine work. It must also not be used with the herbal remedy St. John's wort (used for depression and anxiety), or the epilepsy medicines carbamazepine and phenytoin because these medicines may affect the way Zepatier works.For the full list of side effects and restrictions of Zepatier, see the package leaflet.

Why is Zepatier authorised in the EU?

Zepatier has been shown to be highly effective in clearing the hepatitis C virus genotypes 1a, 1b and 4 from the blood of patients with or without compensated cirrhosis, including patients also infected with HIV or who have chronic kidney disease. In most of the studies, treatment with Zepatier was not compared with another treatment or no treatment. This was considered acceptable because chronic hepatitis C virus is very rarely cured without treatment and, at the time the studies started, other antiviral medications such as Zepatier were not available. Zepatier was well tolerated with a favourable safety profile.The European Medicines Agency decided that Zepatier'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 Zepatier?

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

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Zeposia

What is Zeposia and what is it used for?

Zeposia is a medicine used to treat adults with the following diseases:• relapsing-remitting multiple sclerosis (RRMS). Multiple sclerosis is a disease in which the immune system (the body's defences) attacks and damages the protective insulation around the nerves and the nerves themselves in the brain and spinal cord. In RRMS, the patient has flare-ups (relapses) followed by periods with milder or no symptoms (remission). Zeposia is used in patients with active disease, which means that patients have relapses or signs of active inflammation on scans;• ulcerative colitis, a disease causing inflammation and ulcers in the lining of the gut, when the disease is moderately to severely active. Zeposia is used when standard treatment or biological agents (medicines made by cells grown in a laboratory) have not worked well enough or cannot be used by the patient.Zeposia contains the active substance ozanimod.

How is Zeposia used?

Zeposia can only be obtained with a prescription and treatment should be started and supervised by a doctor experienced in the management of multiple sclerosis or ulcerative colitis.It is available as capsules of different strengths and should be taken once a day. To reduce the risk of side effects on the heart, the dose should be built up slowly when starting treatment or after treatment has been interrupted. The starting dose is one 0.23 mg capsule a day for the first 4 days; patients should then take one 0.46 mg capsule a day for 3 days (on days 5, 6 and 7), and then one 0.92 mg capsule daily from day 8 onward.For more information about using Zeposia, see the package leaflet or contact your doctor or pharmacist.

How does Zeposia work?

The active substance in Zeposia, ozanimod, blocks the action of sphingosine-1-phosphate receptors on lymphocytes (cells of the immune system that can attack the body's own tissues in diseases such as multiple sclerosis or ulcerative colitis). By attaching to these receptors, ozanimod stops lymphocytesfrom travelling from the lymph nodes towards the brain, spinal cord or intestine, thus limiting the damage they cause in multiple sclerosis and ulcerative colitis.

What benefits of Zeposia have been shown in studies?

RRMSZeposia was shown to be effective at reducing the number of relapses in two main studies involving a total of 2,666 patients with RRMS.In the first study lasting over one year, the average number of relapses per year in patients treated with the standard dose of Zeposia was about half that in patients treated with another medicine, interferon beta-1a (0.18 versus 0.35 relapses).In the second study, which lasted two years, patients treated with the standard dose of Zeposia had on average 0.17 relapses per year, compared with 0.28 for patients given interferon beta-1a.Ulcerative colitisOne main study showed that Zeposia, taken together with aminosalicylates (anti-inflammatory medicines) and/or corticosteroids, was more effective than placebo (a dummy treatment) in producing or maintaining remission (a period when the disease is not active or causing noticeable symptoms) in adults with moderate to severe ulcerative colitis for whom standard treatment or treatment with biological agents did not work well enough or could not be used.The study was divided into two parts lasting one year in total. One part involved 645 patients and studied the effect of initial (induction) treatment with Zeposia for 10 weeks. The other part involved 457 patients who had responded to the 10-week induction treatment and studied the effect of Zeposia as maintenance treatment for 42 weeks.After induction treatment, around 18% (79 of 429) of the patients taking Zeposia had achieved remission compared with around 6% (13 of 216) of the patients taking placebo. After maintenance treatment, around 37% (85 of 230) of the patients taking Zeposia were in remission compared with 19% (42 of 227) of the patients taking placebo.

What are the risks associated with Zeposia?

The most common side effects with Zeposia are nasopharyngitis (inflammation of the nose and throat), which may affect more than 1 in 10 people, and increased levels of liver enzymes (a sign of liver problems), which may affect up to 1 in 10 people; around 1 person in 100 had to stop treatment during the studies because of increases in liver enzyme levels. For the full list of side effects of Zeposia, see the package leaflet.Zeposia must not be used in patients with severe liver disorders, severe active infections, cancer or weakened immune system. It must not be used in patients with certain heart conditions or who have recently had a stroke, a heart attack or other heart problems. It must also not be used in pregnant women or women who can become pregnant and are not using effective contraception. For the full list of restrictions, see the package leaflet.

Why is Zeposia authorised in the EU?

Zeposia was shown to be effective at reducing the number of relapses in patients with relapsingremitting multiple sclerosis and at improving symptoms in patients with ulcerative colitis in the shortand long term. Its side effects are comparable to those of other medicines that work in a similar way and are considered manageable with appropriate treatment.The European Medicines Agency, therefore, decided that Zeposia'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 Zeposia?

The company that markets Zeposia will provide educational materials for doctors and a guide for patients and their carers with important safety information about the medicine, its risks and its conditions for use. A reminder card will also be given to women who can become pregnant with important information on the need to use effective contraception during treatment with Zeposia.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zeposia have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zeposia are continuously monitored. Side effects reported with Zeposia are carefully evaluated and any necessary action taken to protect patients.

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Zerbaxa

What is Zerbaxa and what is it used for?

Zerbaxa is an antibiotic used to treat adults and children with:• complicated (difficult to treat) infections of tissues and organs within the belly (intra-abdominal infections);• serious kidney infection (acute pyelonephritis);• complicated infections of the urinary tract (structures that carry urine, such as the bladder).It is also used to treat adults with hospital-acquired pneumonia (an infection of the lungs that is caught in the hospital), including ventilator-associated pneumonia (pneumonia in patients using a ventilator, a machine that helps a patient to breathe).Zerbaxa contains the active substances ceftolozane and tazobactam.

How is Zerbaxa used?

Zerbaxa is available for infusion (drip) into a vein and can only be obtained with a prescription. It is given over 1 hour, every 8 hours. The dose and duration of treatment depend on the infection being treated and how the infection responds to the medicine. For children the dose and duration also depend on body weight. For more information about using Zerbaxa, see the package leaflet or contact your doctor or pharmacist.

How does Zerbaxa work?

The active substances in Zerbaxa, ceftolozane and tazobactam, work in different ways. Ceftolozane is atype of antibiotic called a cephalosporin, which belongs to the wider group of antibiotics called betalactams. It works by interfering with the production of molecules that bacteria need to build their protective cell walls. This causes weakness in the bacterial cell walls which then become prone to collapse, ultimately leading to the death of the bacteria.Tazobactam blocks the action of bacterial enzymes called beta-lactamases. These enzymes enable bacteria to break down beta-lactam antibiotics like ceftolozane, making the bacteria resistant to the antibiotic's action. By blocking the action of these enzymes, tazobactam allows ceftolozane to act against bacteria that would otherwise be resistant to this antibiotic .

What benefits of Zerbaxa have been shown in studies?

Zerbaxa has been shown to be at least as effective as other antibiotics in curing infections in three main studies.One study involved 1,083 adults who mostly had kidney infection or in some cases a complicated urinary-tract infection. Zerbaxa successfully treated the infection in about 85% of the cases where it was given (288 of 340), compared with 75% (266 of 353) of those given another antibiotic called levofloxacin.The second study involved 993 adults with complicated intra-abdominal infections. Zerbaxa was compared with another antibiotic, meropenem. Both medicines cured 94% of patients (353 out of 375 given Zerbaxa and 375 out of 399 given meropenem).The third study involved 726 adults who were using a ventilator and who had either hospital-acquired pneumonia or ventilator-associated pneumonia. It found Zerbaxa to be at least as effective as meropenem: the infection had resolved in 54% of patients (197 out of 362) after 7 to 14 days of treatment with Zerbaxa compared with 53% of patients (194 out of 362) on meropenem. Three studies conducted in children younger than 18 years old showed that the way Zerbaxa is absorbed, modified and removed from the body in this age group and in adults is similar. Zerbaxa is therefore expected to show similar effectiveness.

What are the risks associated with Zerbaxa?

The most common side effects with Zerbaxa (which may affect up to 1 in 10 people) are nausea (feeling sick), headache, constipation, diarrhoea,fever and increased liver enzyme levels. Side effects in children are similar to those in adults, with the following additional common side effects (which may affect up to 1 in 10 children): low levels of neutrophils (a type of white blood cell), increased appetite, and dysgeusia (taste disturbance). There is little data on the side effects of Zerbaxa in children younger than 3 months of age with complicated intra-abdominal infections. For the full list of side effects of Zerbaxa, see the package leaflet.Zerbaxa must not be used in people who are hypersensitive (allergic) to Zerbaxa or any of its ingredients, or in those who are hypersensitive to other cephalosporin antibiotics or have ever had a severe allergic reaction to another beta-lactam antibiotic.

Why is Zerbaxa authorised in the EU?

The European Medicines Agency decided that Zerbaxa's benefits are greater than its risks and it can be authorised for use in the EU. The Agency considered that Zerbaxa was effective at curing infections in the patients studied, but acknowledged that only a limited number of patients with complicated urinary tract infections had been included. The Agency also noted that tazobactam is not active against some classes of beta-lactamase that can cause problems of resistance. Regarding safety, side effects were considered to be typical and expected for an antibiotic of this kind.

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

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

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Zercepac

What is Zercepac and what is it used for?

Zercepac is a cancer medicine used to treat the following conditions:• early breast cancer (when the cancer has spread within the breast or to the lymph nodes ['glands'] under the arm but not to other parts of the body) after surgery, chemotherapy (medicines to treat cancer), and radiotherapy (treatment with radiation) if applicable. It can also be used earlier in treatment, in combination with chemotherapy. For cancers that are locally advanced (including those that are inflammatory) or more than 2 cm wide, Zercepac is used before surgery in combination with chemotherapy and then again after surgery on its own;• metastatic breast cancer (cancer that has spread to other parts of the body). It is used on its own when other treatments have not worked or are not suitable. It is also used in combination with other cancer medicines: paclitaxel or docetaxel, or with another type of medicine called an aromatase inhibitor;• metastatic gastric (stomach) cancer, in combination with cisplatin and either capecitabine or fluorouracil (other cancer medicines).Zercepac can only be used when the cancer overexpresses HER2: this means that the cancer produces a protein called HER2 in large quantities on the cancer cells. HER2 is overexpressed in about a quarter of breast cancers and a fifth of gastric cancers.Zercepac is a 'biosimilar medicine'. This means that Zercepac is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Zercepac is Herceptin. For more information on biosimilar medicines, see here.Zercepac contains the active substance trastuzumab.

How is Zercepac used?

Zercepac can only be obtained with a prescription and treatment should be started by a doctor who has experience in the use of cancer medicines.It is given by infusion (drip) into a vein over 90 minutes either once a week or once every 3 weeks for breast cancer, and once every 3 weeks for gastric cancer. For early breast cancer, treatment is given for a year or until the disease comes back, and for metastatic breast or gastric cancer, treatment is continued for as long as it remains effective. The dose depends on the patient's body weight, on the condition being treated and on whether Zercepac is given every week or every 3 weeks.The infusion may cause allergic reactions, so the patient should be monitored during and after the infusion for signs such as fever and chills. Patients who do not have significant reactions to the first 90-minute infusion can receive subsequent infusions over 30 minutes.For more information about using Zercepac, see the package leaflet or contact your doctor or pharmacist.

How does Zercepac work?

The active substance in Zercepac, trastuzumab, is a monoclonal antibody (a type of protein) designed to recognise and attach to the HER2 protein. By attaching to HER2, trastuzumab activates cells of the immune system, which then kill the tumour cells. Trastuzumab also stops HER2 from producing signals that cause the tumour cells to grow.

What benefits of Zercepac have been shown in studies?

Laboratory studies comparing Zercepac with Herceptin have shown that the active substance inZercepac is highly similar to that in Herceptin in terms of structure, purity and biological activity. Studies have also shown that giving Zercepac produces similar levels of the active substance in the body to giving Herceptin.In addition, one study involving 649 patients with previously untreated metastatic breast cancer that overexpressed HER2 showed that Zercepac was as effective as Herceptin in treating the condition. Patients received Zercepac or the reference medicine Herceptin, together with another cancer medicine, docetaxel. A response to treatment after 24 weeks was seen in around 71% of the patients treated with either medicine (231 of 324 given Zercepac, and 232 of 325 given Herceptin).Because Zercepac is a biosimilar medicine, the studies on effectiveness and safety of trastuzumab carried out with Herceptin do not all need to be repeated for Zercepac.

What are the risks associated with Zercepac?

The safety of Zercepac 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 Herceptin. The most common or serious side effects with Zercepac are heart problems, reactions related to the infusion, reduced levels of blood cells (especially white blood cells), infections and lung problems.Zercepac can cause cardiotoxicity (harm to the heart), including heart failure (when the heart does not work as well as it should). Care should be taken if it is given to patients who already have heart problems or high blood pressure, and all patients need to be monitored during and after treatment to check their heart.Zercepac must not be used in people who are hypersensitive (allergic) to trastuzumab, mouse proteins or to any of the other ingredients. It must not be used in patients whose advanced cancer causes serious breathing problems even when resting, or who need oxygen therapy.For the full list of side effects and restrictions, see the package leaflet.

Why is Zercepac authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Zercepac has a highly similar structure, purity and biological activity to Herceptin and is distributed in the body in the same way. In addition, studies in metastatic breast cancer that overexpressed HER2 have shown that the effectiveness of Zercepac infusion is equivalent to that of Herceptin infusion.All these data were considered sufficient to conclude that Zercepac will behave in the same way as Herceptin in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Herceptin, the benefits of Zercepac 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 Zercepac?

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

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Zessly

What is Zessly and what is it used for?

Zessly is an anti-inflammatory medicine for treating the following diseases:• rheumatoid arthritis (disease causing inflammation of the joints);• Crohn's disease (disease causing inflammation of the gut);• ulcerative colitis (inflammation and ulcers in the lining of the gut);• ankylosing spondylitis (inflammation of spine causing back pain);• psoriasis (red, scaly patches on the skin);• psoriatic arthritis (psoriasis with inflammation of the joints).Zessly is used mainly in adults, usually when other medicines or treatments have failed or cannot be used. For Crohn's disease and ulcerative colitis, it is also used in children from 6 years of age. For some conditions, Zessly is also used in combination with another medicine, methotrexate.Zessly is a 'biosimilar medicine'. This means that it is highly similar to another biological medicine (the'reference medicine') that is already authorised in the EU. The reference medicine for Zessly is Remicade. For more information on biosimilar medicines, see here.Zessly contains the active substance infliximab.

How is Zessly used?

Zessly is given as an infusion (drip) into a vein over 2 hours. After each infusion, the patient should be monitored for 1 to 2 hours in case they have an allergic reaction, such as swelling of the mouth, face and throat, skin rash, and difficulty breathing.To reduce the risk of infusion reactions, patients may be given other medicines before or during treatment with Zessly or the infusion may be slowed down.The dose of Zessly and how often it is given depends on the patient's weight and the condition being treated. After the initial doses, it is usually given once every 8 weeks. For more information about using Zessly, see the package leaflet or contact your doctor or pharmacist.Zessly can only be obtained with a prescription and treatment should be started and supervised by a specialist doctor who has experience in the diagnosis and treatment of the diseases that Zessly is used to treat.

How does Zessly work?

The active substance in Zessly, infliximab, is a monoclonal antibody (a type of protein) that attaches to a substance in the body called tumour necrosis factor alpha (TNF-α). This substance is involved in causing inflammation and is found at high levels in patients with the diseases that Zessly is used to treat. By attaching to TNF-α, infliximab blocks its activity and thereby reduces inflammation and other symptoms of the diseases.

What benefits of Zessly have been shown in studies?

Laboratory studies comparing Zessly with Remicade have shown that the active substance in Zessly is highly similar to that in Remicade in terms of structure, purity and biological activity. Studies have also shown that giving Zessly produces similar levels of the active substance in the body to giving Remicade.In addition, Zessly was as effective as Remicade in a study of 650 rheumatoid arthritis patients whose previous treatment with methotrexate alone had not worked well enough. The study looked at the proportion of patients who achieved at least a 20% reduction in ACR scores (a measure of painful, swollen joints and other symptoms) after 14 weeks of treatment. A similar proportion of patients achieved a 20% reduction with both medicines (around 61.1% with Zessly and 63.5% with Remicade).Because Zessly is a biosimilar medicine, the studies on effectiveness and safety carried out with Remicade do not all need to be repeated for Zessly.

What are the risks associated with Zessly?

The safety of Zessly has been evaluated, and on the basis of all the studies carried out the side effects of the medicine are considered to be comparable to those of the reference medicine Remicade.The most common side effects with Zessly (in which may affect more than 1 in 10 people) are viral infections (such as flu and cold sores), headache, upper respiratory tract infection (nose and throat infection), sinusitis (inflammation of the sinuses), nausea (feeling sick), abdominal pain (belly ache), infusion-related reactions and pain. For the full list of side effects of Zessly, see the package leaflet.Zessly must not be used in patients who are hypersensitive (allergic) to infliximab, mouse proteins or any of the other ingredients of Zessly. Zessly must also not be used in patients with tuberculosis, other severe infections, or moderate or severe heart failure (when the heart does not pump blood as well as it should).

Why is Zessly authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Zessly has a highly similar structure, purity and biological activity to Remicade and is distributed in the body in the same way. In addition, studies in patients with rheumatoid arthritis have shown that the safety and effectiveness of Zessly are equivalent to those of Remicade.All these data were considered sufficient to conclude that Zessly will behave in the same way asRemicade in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view wasthat, as for Remicade, the benefit of Zessly outweighs the identified risk and it can be authorised for use in the EU.

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

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

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Zevalin

What is Zevalin?

Zevalin is a kit for the preparation of a 'radiolabelled' infusion (drip into a vein) of the active substance ibritumomab tiuxetan.

What is Zevalin used for?

Zevalin is not used directly, but it must be radiolabelled before use. Radiolabelling is a technique where a substance is tagged (labelled) with a radioactive compound. Zevalin is radiolabelled by mixing it with a solution of radioactive yttrium (90Y) chloride.• The radiolabelled medicine is used to treat adult patients with follicular B cell non Hodgkin's lymphoma. This is a cancer of the lymph tissue (part of the immune system) that affects a type of white blood cell called B lymphocytes, or B cells. Zevalin is used in the following groups of patients:• patients who have gone into remission (reduction in the number of cancerous cells) after their first'induction treatment' (initial chemotherapy treatment) for lymphoma. Zevalin is given as 'consolidation therapy' to improve the remission; patients in whom rituximab (another treatment for non Hodgkin's lymphoma) is no longer effective or whose disease has come back after rituximab treatment.The medicine can only be obtained with a prescription.

How is Zevalin used?

Radiolabelled Zevalin treatment should only be handled and given by someone who is authorised to use radioactive medicines.Before treatment with radiolabelled Zevalin, the patients must first receive an infusion of rituximab (at a dose lower than would be used for treatment) to clear B cells from their circulation, leaving the cancerous B cells in the lymph tissue. This enables Zevalin to deliver radiation more specifically to the cancerous B-cells. This is followed, seven to nine days later, by a second infusion of rituximab and an injection of radiolabelled Zevalin. Zevalin must be given as a slow infusion lasting 10 minutes. The dose of Zevalin is calculated to give the appropriate amount of radioactivity for the patient's condition, based on the blood cell count.

How does Zevalin work?

The active substance in Zevalin, ibritumomab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and bind to a specific structure (called an antigen) that is found in certain cells in the body. Ibritumomab has been designed to target an antigen, CD20, which is present on the surface of all B lymphocytes.When Zevalin is radiolabelled, the radioactive element yttrium 90 (90Y) is attached to ibritumomab. When the radiolabelled medicine is injected into the patient, the monoclonal antibody carries the radioactivity to the target CD20 antigen on the B cells. Once the antibody has bound to the antigen, the radiation can act locally and destroy the lymphoma B cells.

How has Zevalin been studied?

For consolidation therapy, Zevalin has been studied in one main study involving 414 patients who had achieved a partial or complete remission during induction treatment for non Hodgkin's lymphoma. The study compared patients who received Zevalin and patients who received no additional treatment. The main measure of effectiveness was the length of time the patients survived without their disease getting worse.Zevalin has also been studied in a total of 306 patients with non Hodgkin's lymphoma who were not responding to other treatments or whose disease had come back after previous treatment. The main study compared the effectiveness of Zevalin with that of rituximab in 143 patients. In an additional study, 57 patients with follicular lymphoma who had been previously treated and were not responding to rituximab received Zevalin. In both studies, the main measure of effectiveness was the number of patients whose disease responded partially or completely to treatment.

What benefit has Zevalin shown during the studies?

When Zevalin was used as consolidation therapy, patients survived for longer without their disease getting worse than when they received no further treatment. Patients receiving radiolabelled Zevalin survived for an average of 37 months until their disease got worse, compared with 14 months in those who did not receive any further treatment. However, there were too few patients who had received rituximab as part of their induction treatment to determine whether there would be a benefit of using Zevalin as consolidation treatment in these patients.In patients who were not responding to other treatments or whose disease had come back after previous treatment, Zevalin was more effective than rituximab: 80% of the patients receiving radiolabelled Zevalin responded, compared with 56% of the patients receiving rituximab. However, the time taken for the disease to get worse after treatment was the same in both groups (about 10months). In the additional study, radiolabelled Zevalin brought about a response in about half of the patients.

What is the risk associated with Zevalin?

Radiolabelled Zevalin is radioactive and its use may carry a risk of cancer and hereditary defects. The doctor who prescribes it must ensure that the risks linked to the exposure to the radioactivity are lower than the risks from the disease itself. The most common side effects with Zevalin (seen in more than 1 patient in 10) are anaemia (low red blood cell counts), leucocytopenia and neutropenia (low white blood cell counts), thrombocytopenia (low blood platelet counts), asthenia (weakness), pyrexia (fever), rigors (stiffness) and nausea (feeling sick). For the full list of all side effects reported with Zevalin, see the package leaflet.Zevalin should not be used in people who may be hypersensitive (allergic) to ibritumomab, yttrium chloride, mouse proteins or any of the other ingredients. Zevalin must not be used in patients who are pregnant or breast feeding.

Why has Zevalin been approved?

The CHMP decided that Zevalin's benefits are greater than its risks as consolidation therapy after remission induction in previously untreated patients with follicular lymphoma and for the treatment of adult patients with rituximab relapsed or refractory CD20-positive follicular B cell non Hodgkin's lymphoma. The Committee recommended that Zevalin be given marketing authorisation.Zevalin was originally authorised under 'exceptional circumstances' because it had not been possible to obtain complete information about Zevalin. As the company had supplied the additional information requested, the 'exceptional circumstances' ended on 22 May 2008.

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Ziagen

What is Ziagen and what is it used for?

Ziagen is used with other antiviral medicines to treat patients who are infected with human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).Ziagen contains the active substance abacavir.

How is Ziagen used?

Ziagen can only be obtained with a prescription and should be prescribed by a doctor who has experience in managing HIV infection.Before starting treatment with abacavir, all patients should have a test to find out if they have a gene called 'HLA-B (type 5701)'. Patients with this gene are at an increased risk of having an allergic reaction to abacavir, so they should not take Ziagen.Ziagen is available as tablets (300 mg) and as an oral solution (20 mg/ml). The recommended dose for adults and children weighing at least 25 kg is 600 mg daily. This can be taken either as a single daily dose or divided into 300 mg twice a day.In children weighing less than 25 kg the recommended dose depends on body weight.For more information about using Ziagen, see the package leaflet or contact your doctor or pharmacist.

How does Ziagen work?

The active substance in Ziagen, abacavir, is a nucleoside reverse transcriptase inhibitor (NRTI). It works by blocking the activity of reverse transcriptase, an enzyme produced by HIV to make more copies of itself in the cells it has infected and so spread in the body. Ziagen, taken with other antiviral medicines, reduces the amount of HIV in the blood and keeps it at a low level. It 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 Ziagen have been shown in studies?

Six main studies found that Ziagen was more effective than placebo (a dummy treatment) and was as effective as other antiviral medicines at keeping HIV infection under control. The studies included 1,843 HIV-infected adults (aged 18 years and over). Ziagen was taken alone or added to the combination of lamivudine and zidovudine (other antiviral medicines) or the patients' existing HIV treatment. The main measures of effectiveness were changes in the level of HIV in the blood (viral load) and the number of CD4 T-cells in the blood (CD4 cell count). CD4 T-cells are white blood cells that help fight infections and are killed by HIV.In all studies, Ziagen caused a decrease in viral loads in all age groups, particularly when taken with other antiviral medicines. In one of the studies, 77% of the patients taking Ziagen with lamivudine and zidovudine had viral loads below 400 copies/ml after 16 weeks (67 out of 87), compared with 38% of the adults taking lamivudine and zidovudine without Ziagen (33 out of 86). Another study compared the effects of Ziagen taken once and twice a day in combination with lamivudine and efavirenz (other antiviral medicines) in 784 patients. Once daily and twice daily Ziagen had similar effects on viral load.Patients receiving Ziagen also had increases in their CD4 cell counts.Studies were also carried out in HIV-infected patients aged between 3 months and 18 years. One study found that in patients aged over 1 year, Ziagen combined with either lamivudine or zidovudine was more effective than treatment with a combination of lamivudine and zidovudine.In addition, studies were carried out to examine once daily versus twice daily dosing in children and found that once daily and twice daily Ziagen had similar effects on viral load.

What are the risks associated with Ziagen?

The most common side effects with Ziagen (which may affect up to 1 in 10 people) are loss of appetite, headache, nausea (feeling sick), vomiting, diarrhoea, rash, fever, lethargy (lack of energy) and tiredness.Hypersensitivity reactions (allergic reactions) occur in patients taking Ziagen, usually within the first 6 weeks of treatment, and can be life-threatening. The risk of hypersensitivity is higher in patients who have the HLA-B (type 5701) gene. Symptoms almost always include fever or rash, but also very commonly include nausea, vomiting, diarrhoea, abdominal (belly) pain, dyspnoea (difficulty breathing), cough, fever, lethargy, feeling unwell, headache, blood tests showing signs of liver damage and muscle pain. Treatment with Ziagen should be stopped promptly if the patient has a hypersensitivity reaction.For the full list of side effects and restrictions with Ziagen, see the package leaflet.

Why is Ziagen authorised in the EU?

The European Medicines Agency noted that the demonstration of the benefit of Ziagen was based on the results of studies mainly with the medicine taken twice a day in combination with other medicines. The Agency decided that Ziagen'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 Ziagen?

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

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Ziextenzo

What is Ziextenzo and what is it used for?

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

How is Ziextenzo used?

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

How does Ziextenzo work?

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

What benefits of Ziextenzo have been shown in studies?

Laboratory studies comparing Ziextenzo with Neulasta have shown that the active substance in Ziextenzo is highly similar to that in Neulasta in terms of structure, purity and biological activity. Studies have also shown that giving Ziextenzo produces similar levels of the active substance in the body to giving Neulasta.In addition, two studies involving 624 patients who had chemotherapy before or after surgery for breast cancer showed that Ziextenzo was as effective as Neulasta in reducing the duration of neutropenia. Neutropenia lasted 1 day on average with both medicines.Because Ziextenzo is a biosimilar medicine, the studies on effectiveness and safety of pegfilgrastim carried out with Neulasta do not all need to be repeated for Ziextenzo.

What are the risks associated with Ziextenzo?

The safety of Ziextenzo has been evaluated, and on the basis of all the studies carried out the side effects of the medicine are considered to be comparable to those of the reference medicine Neulasta. The most common side effect with Ziextenzo (which may affect more than 1 in 10 people) is pain in the bones. Pain in muscles is also common. For the full list of side effects and restrictions with Ziextenzo, see the package leaflet.

Why is Ziextenzo authorised in the EU?

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

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

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

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Zimbus Breezhaler

What is Zimbus Breezhaler and what is it used for?

Zimbus Breezhaler is an asthma medicine for inhalation. It is used for maintenance (regular) treatment in adults whose asthma is not controlled well enough with inhaled long-acting beta-2 agonist together with a high dose of an inhaled corticosteroid. It should be used for patients who have had at least one asthma attack (exacerbations) in the last year.Zimbus Breezhaler contains the active substances indacaterol, glycopyrronium bromide and mometasone.

How is Zimbus Breezhaler used?

Zimbus Breezhaler is available as capsules for use in the inhaler supplied with the medicine. The medicine can only be obtained with a prescription.The Zimbus Breezhaler capsule is placed in the inhaler and the patient breathes in the powder through the mouth. The patient should inhale the powder from one capsule once daily, at around the same time each day.An electronic sensor is available for use with the medicine. When attached to the inhaler, it records the patient's use of the inhaler and it can send the information to the patient's smartphone or other mobile device. The sensor is optional and it is not needed for using the inhaler.For more information about using Zimbus Breezhaler, see the package leaflet or contact your doctor or pharmacist.

How does Zimbus Breezhaler work?

The three active substances in Zimbus Breezhaler, indacaterol, glycopyrronium bromide and mometasone, have been in use in several inhaled medicines for treating patients with breathing disorders. They work in different ways to allow the patient to breathe more easily.Indacaterol is a long-acting beta-2 adrenergic receptor agonist. It relaxes the muscle around the airways into the lungs by activating targets called beta-2 receptors in the muscle cells. This helps to keep the airways open.Glycopyrronium bromide is a muscarinic receptor antagonist. It blocks muscarinic receptors in muscle cells in the airways. Because these receptors help control the contraction of the airway muscles, blocking them causes the muscles to relax, helping to keep the airways open.Mometasone is a corticosteroid that has anti-inflammatory effects. It works in a similar way to corticosteroid hormones in the body, reducing the activity of the immune system (the body's defences). Mometasone helps to keep the airways clear by blocking the release of substances, such as histamine, that are involved in inflammation and release of mucus in the airways.

What benefits of Zimbus Breezhaler have been shown in studies?

A main study involved 3,092 patients whose asthma was not well controlled on a combination of a long-acting beta-2 agonist and a corticosteroid used by inhalation. Patients had had at least one asthma exacerbation in the previous year. The study measured the change in patients' forced expiratory volume over 1 second (FEV1, the maximum volume of air they could breathe out in 1 second) just before their next dose was due.After 26 weeks of treatment, FEV1 improved by 65 ml more in patients treated with Zimbus Breezhaler than in patients using an inhaler containing equivalent doses of indacaterol and mometasone, two of the three active substances in Zimbus Breezhaler.

What are the risks associated with Zimbus Breezhaler?

The most common side effects with Zimbus Breezhaler (which may affect more than 1 in 10 people) are worsening of asthma and nasopharyngitis (inflammation in the nose and throat). Other common side effects (which may affect up to 1 in 100 people) include upper respiratory tract infection (nose and throat infections) and headache.For the full list of side effects and restrictions of Zimbus Breezhaler, see the package leaflet.

Why is Zimbus Breezhaler authorised in the EU?

In patients whose asthma is not controlled well enough on a combination of an inhaled long-acting beta-2 agonist and high-dose corticosteroid and who have had an exacerbation in the previous year, the improvement in FEV1 with Zimbus Breezhaler was modest but considered to be clinically important. The side effects of Zimbus Breezhaler are similar to those of other inhaled medicines used for treating asthma.The European Medicines Agency therefore decided that Zimbus Breezhaler'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 Zimbus Breezhaler?

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

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Zinforo

What is Zinforo and what is it used for?

Zinforo is an antibiotic. It is used to treat adults and children (including newborn babies) who have:• complicated infections of the skin and soft tissue (tissue below the skin). 'Complicated' means that the infection is difficult to treat;• community-acquired pneumonia (an infection of the lungs that is caught outside of hospital).Prescribers should consider official guidance on the appropriate use of antibiotics.Zinforo contains the active substance ceftaroline fosamil.

How is Zinforo used?

Zinforo is given by infusion (drip) into a vein usually over 5 to 60 minutes. In adults and adolescents from 12 years of age weighing at least 33 kg, the usual dose is 600 mg every 12 hours. For some serious skin infections, the recommended dose is 600 mg every 8 hours, with each infusion lasting 120 minutes. In children and adolescents weighing less than 33 kilograms, the dose depends on the patient's weight.Patients with complicated skin and soft tissue infections should be treated for 5 to 14 days and patients who have community-acquired pneumonia should be treated for 5 to 7 days.The medicine can only be obtained with a prescription. For more information about using Zinforo, see the package leaflet or contact your doctor or pharmacist.

How does Zinforo work?

The active substance in Zinforo, ceftaroline fosamil, is a type of antibiotic called cephalosporin belonging to the group 'beta-lactams'. It interferes with the production of complex molecules called peptidoglycans, which are essential components of bacterial cell walls. It does so by blocking enzymes, called penicillin-binding protein transpeptidases, that are involved in the last steps of bacterial cell wall production. This weakens the bacterial cell walls which then become prone to collapse, ultimately leading to the death of the bacteria.In laboratory studies Zinforo was active against certain bacteria against which other antibiotics belonging to the beta-lactam class do not work (meticillin-resistant Staphylococcus aureus (MRSA) and penicillin non-susceptible Streptococcus pneumoniae (PNSP)).

What benefits of Zinforo have been shown in studies?

Studies in adultsZinforo was as effective as other antibiotics in curing skin and soft tissue infections and pneumonia in adults.In a study of patients with complicated skin and soft tissue infection, 87% of the patients receiving Zinforo were cured (304 out of 351), compared with 86% of the patients receiving the combination of vancomycin and aztreonam (297 out of 347). In a second study, 85% of patients receiving Zinforo were cured (291 out of 342) compared with 86% of the patients receiving the combination of vancomycin and aztreonam (289 out of 338).For community-acquired pneumonia, one study showed that 84% of the patients receiving Zinforo were cured (244 out of 291), compared with 78% of the patients receiving ceftriaxone (233 out of 300). In another study, 81% of patients receiving Zinforo were cured (235 out of 289) compared with 76% of the patients receiving ceftriaxone (206 out of 273).Studies in childrenIn a children's study of complicated skin and soft tissue infection, 94% of the children receiving Zinforo were cured (101 out of 107), compared with 87% of those receiving vancomycin or cefazolin, with or without aztreonam (45 out of 52).Among children with community-acquired pneumonia that required hospital stay, 88% of those on Zinforo were cured (94 out of 107), compared with 89% of those receiving ceftriaxone.Among those with complicated community-acquired pneumonia, 90% of the patients treated with Zinforo were cured, compared with 100% of those receiving ceftriaxone plus vancomycin.

What are the risks associated with Zinforo?

The most common side effects with Zinforo (seen in more than 3% of patients) are diarrhoea, headache, nausea (feeling sick) and pruritus (itching). For the full list of side effects of Zinforo, see the package leaflet.Zinforo must not be used in people who are hypersensitive (allergic) to ceftaroline fosamil or any of the other ingredients. Zinforo must also not be used in patients who are hypersensitive to other antibiotics belonging to the cephalosporin class and in patients who are severely allergic to other betalactam antibiotics. For the full list of restrictions, see the package leaflet.

Why is Zinforo authorised in the EU?

The European Medicines Agency concluded that Zinforo was effective in treating complicated skin and soft tissue infections and community-acquired pneumonia and its side effects in both adults and children were manageable. The Agency also noted that in laboratory studies Zinforo had shown activity against certain bacteria, such as MRSA, against which other beta-lactam antibiotics do not work. However, as there were uncertainties about the effects of Zinforo in patients with certain very severe infections these effects will be investigated in further studies.The Agency decided that Zinforo'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 Zinforo?

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

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Zinplava

What is Zinplava and what is it used for?

Zinplava is a medicine used in adults who have infections due to bacteria called Clostridium difficile that cause severe diarrhoea. It is used to prevent future episodes of diarrhoea in patients who are taking antibiotics to treat their C. difficile infection and who are at high risk of the infection coming back.

How is Zinplava used?

Zinplava is available as a concentrate to be made into a solution for infusion (drip) into a vein. It is given as a single infusion lasting around 1 hour. The recommended dose is 10 mg per kilogram bodyweight.The medicine can only be obtained with a prescription. For further information, see the package leaflet.

How does Zinplava work?

C. difficile bacteria produce toxins that damage the lining of the gut causing diarrhoea which may be severe. After an initial infection, some dormant forms of the bacteria (spores) may persist in the body and eventually produce further toxins, causing the symptoms to return. Bezlotoxumab is a monoclonalantibody (a type of protein) that has been designed to attach to these toxins, blocking their action, thereby preventing further damage and diarrhoea from occurring.

What benefits of Zinplava have been shown in studies?

Zinplava given during antibiotic treatment was shown to be more effective than placebo (a dummy treatment) at preventing a new episode of diarrhoea caused by C. difficile infection in 2 main studies involving a total of 2,655 patients. A new episode of diarrhoea was defined as 3 or more loose stools in 24 or fewer hours.In the first study, 17% of patients given Zinplava (67 out of 386) had a new episode of diarrhoea in the 12 weeks after treatment compared with 28% of patients given placebo (109 out of 395). In the second study, figures were 16% (62 out of 395) for Zinplava and 26% (97 out of 378) for placebo. The effect was mainly seen in patients at higher risk of C. difficile infection coming back (such as older patients or those with a weakened immune system).

What are the risks associated with Zinplava?

The most common side effects with Zinplava (seen in more than 4 in 100 patients) are nausea (feeling sick), diarrhoea, fever and headache. Similar effects have been seen in patients on placebo.For the full list of all side effects and restrictions with Zinplava, see the package leaflet.

Why is Zinplava approved?

Zinplava has been shown to be effective at preventing recurrence of C. difficile infection, particularly in patients at high risk of the infection coming back (which occurs in about 15 to 35% of cases and is particularly difficult to treat). Zinplava is generally well tolerated with side effects similar to those observed in patients on placebo.The Agency's Committee for Medicinal Products for Human Use (CHMP) therefore decided thatZinplava'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 Zinplava?

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

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Zirabev

What is Zirabev and what is it used for?

Zirabev is a cancer medicine that is used to treat adults with the following cancers:• cancer of the colon (large bowel) or the rectum (the last section of the bowel), when it has spread to other parts of the body;• breast cancer that has spread to other parts of the body;• a lung cancer called non-small cell lung cancer when it is advanced or has spread or come back, and cannot be treated with surgery. Zirabev can be used unless the cancer originates in particular cells called squamous cells;• cancer of the kidney (renal cell carcinoma) that is advanced or has spread elsewhere;• epithelial cancer of the ovary, cancer of the fallopian tube (that connect the ovaries to the womb) or the peritoneum (the membrane lining the abdomen) when the cancer is advanced, or in previously treated patients whose cancer has come back (recurrent);• cancer of the cervix (the neck of the womb) that has persisted or come back after treatment, or spread to other parts of the body.Zirabev is used in combination with other cancer medicines, depending on previous treatments or the presence of mutations (genetic changes) in the cancer that affect how well particular medicines work.Zirabev contains the active substance bevacizumab and it is a 'biosimilar medicine'. This means that Zirabev is highly similar to another biological medicine (the 'reference medicine') that is already authorised in the EU. The reference medicine for Zirabev is Avastin. For more information on biosimilar medicines, see here.

How is Zirabev used?

Zirabev can only be obtained with a prescription and treatment should be supervised by a doctor who has experience in the use of cancer medicines.Zirabev is given by infusion (drip) into a vein. The first infusion of Zirabev should last 90 minutes, but subsequent infusions may be given more quickly if the first infusion does not cause troublesome side effects. The dose, which is given every 2 or 3 weeks, depends on the patient's weight, the type of cancer being treated and what other cancer medicines are being used. Treatment is continued until the cancer is no longer controlled. The doctor may decide to interrupt or stop treatment if the patient develops certain side effects.For more information about using Zirabev, see the package leaflet or contact your doctor or pharmacist.

How does Zirabev work?

The active substance in Zirabev, bevacizumab, is a monoclonal antibody (a type of protein) that has been designed to attach to vascular endothelial growth factor (VEGF), a protein that circulates in the blood and encourages the growth of new blood vessels. By attaching to VEGF, Zirabev stops its effect. As a result, the cancer cannot develop its own blood supply and cancer cells are starved of oxygen and nutrients, helping to slow down the growth of tumours.

What benefits of Zirabev have been shown in studies?

Laboratory studies comparing Zirabev with Avastin have shown that the active substance in Zirabev is highly similar to that in Avastin in terms of structure, purity and biological activity. Studies have also shown that giving Zirabev produces similar levels of the active substance in the body to giving Avastin.In addition, a study involving 719 patients with advanced non-small cell lung cancer showed thatZirabev was as effective as Avastin when given with the cancer medicines carboplatin and paclitaxel. The cancer improved in 45% of those given Zirabev (162 of 358 patients) and in 45% of those given Avastin (161 of 361).Because Zirabev is a biosimilar medicine, the studies on effectiveness and safety of bevacizumab carried out with Avastin do not all need to be repeated for Zirabev.

What are the risks associated with Zirabev?

The safety of Zirabev 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 Avastin.The most common side effects with bevacizumab (which may affect more than 1 in 10 people) are hypertension (high blood pressure), tiredness or weakness, diarrhoea and abdominal (belly) pain. The most serious side effects are gastrointestinal perforation (hole in the gut wall), bleeding and arterial thromboembolism (blood clots in the arteries). For the full list of side effects with Zirabev, see the package leaflet.Zirabev must not be used in people who are hypersensitive (allergic) to bevacizumab or any of the other ingredients, to Chinese hamster ovary cell products or other recombinant antibodies. It must not be given to pregnant women.

Why is Zirabev authorised in the EU?

The European Medicines Agency decided that, in accordance with EU requirements for biosimilar medicines, Zirabev has a highly similar structure, purity and biological activity to Avastin and isdistributed in the body in the same way. In addition, a study in non-small cell lung cancer has shown that Zirabev's safety and effectiveness are equivalent to those of Avastin in this condition.All these data were considered sufficient to conclude that Zirabev will behave in the same way as Avastin in terms of effectiveness and safety in its authorised uses. Therefore, the Agency's view was that, as for Avastin, the benefits of Zirabev outweigh the identified risks and it can be authorised in the EU.

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

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

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Zoely

What is Zoely?

Zoely is a medicine available as 24 white 'active' tablets that contain the active substances nomegestrol acetate (2.5 mg) and estradiol (1.5 mg), and four yellow 'inactive' (placebo) tablets that do not contain any active substance.

What is Zoely used for?

Zoely is a contraceptive pill. The medicine can only be obtained with a prescription.

How is Zoely used?

One tablet a day is taken for as long as contraception is required, starting with an active tablet on the first day of the cycle. Zoely comes in blisters containing 28 tablets (24 white tablets followed by 4 yellow tablets), which are taken in sequence using stickers to identify the days of the week for each tablet.

How does Zoely work?

Zoely is a combined contraceptive pill that contains two active substances, nomegestrol acetate (a progestogen) and estradiol (an oestrogen). Estradiol is the same as a hormone naturally produced by the ovaries during a menstrual cycle. Nomegestrol acetate is derived from the hormone called progesterone which is also produced by the ovaries during a menstrual cycle. Zoely works by changingthe body's hormonal balance to prevent ovulation, by altering the cervical mucus and by thinning the endometrium (the lining of the womb).

How has Zoely been studied?

Zoely was investigated in two main studies involving a total of 4,433 women aged 18 to 50 years old. The participants were given either Zoely or another contraceptive pill containing drospirenone and ethinyl estradiol for one year (13 menstrual cycles). The main measure of effectiveness was the number of women aged 18 to 35 who became pregnant during or shortly after treatment, expressed in terms of a pregnancy rate using the 'Pearl Index'. The Pearl Index is a standard way of measuring the effectiveness of contraceptives, which measures how many unwanted pregnancies occur in 100 women-years (corresponding to 1,300 menstrual cycles). A lower Pearl Index represents a lower chance of getting pregnant.No clinical study data on Zoely are available in adolescents under 18 years old.

What benefit has Zoely shown during the studies?

In women aged 18 to 35, the Pearl Index was around 0.4 with Zoely and 0.8 with the comparator medicine in the first study, and around 1.2 with Zoely and 1.9 with the comparator medicine in the second study.

What is the risk associated with Zoely?

The most frequent side effects with Zoely (seen in more than 1 user in 10) are acne and changes to menstrual periods (e.g. absence or irregularity). For the full list of all side effects reported with Zoely, see the package leaflet.Zoely must not be used when a woman has, or has had, blood clots in the veins or arteries or when a woman has some of the risk factors for blood clots. It should not be used in women who have pancreatitis (inflammation of the pancreas), severe liver problems, liver tumours or a history of liver tumours, certain types of cancer, or abnormal bleeding from the genital area whose cause has not been diagnosed. For the full list of restrictions, see the package leaflet.

Why has Zoely been approved?

The CHMP decided that the benefits of Zoely 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 Zoely?

A risk management plan has been developed to ensure that Zoely 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 Zoely, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company will perform a study to further investigate the risk of blood clots.

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Zokinvy

What is Zokinvy and what is it used for?

Zokinvy is a medicine used to treat patients of 12 months and older who are affected by the following rare diseases in which features resembling aging appear in childhood:• Hutchinson-Gilford progeria syndrome;• processing-deficient progeroid laminopathies.The diseases that Zokinvy is used to treat are rare and Zokinvy was designated as 'orphan medicine' on 14 December 2018 for Hutchinson-Gilford progeria syndrome.Zokinvy contains the active substance lonafarnib.

How is Zokinvy used?

Zokinvy can only be obtained with a prescription and treatment should be initiated by doctors with experience in the treatment of patients with premature aging or rare metabolic conditions.Zokinvy is available as capsules to be taken with food twice a day. The starting daily dose (which ranges from 75 to 225 mg) depends on the height and weight of the patient. After 4 months of treatment, the patient may start taking a higher (maintenance) dose.For more information about using Zokinvy, see the package leaflet or contact your doctor or pharmacist.

How does Zokinvy work?

Patients with Hutchinson-Gilford progeria syndrome and with processing-deficient progeroid laminopathies have an accumulation of abnormal forms of progerin or progerin-like proteins, which causes damage to cells and leads to symptoms of aging early in life. Zokinvy prevents a chemical reaction involved in the formation of these abnormal proteins, thereby helping to improve symptoms of the diseases.

What benefits of Zokinvy have been shown in studies?

Two main studies have shown that Zokinvy prolongs the life of patients with Hutchinson-Gilford progeria syndrome and with processing-deficient progeroid laminopathies. The studies involved 62 patients who were given Zokinvy. Three years after start of treatment with Zokinvy only, the patients lived between 2.5 months and about half a year longer than the 62 patients who did not participate in the studies and were not given Zokinvy. At the time of the last follow-up (about 11 years after starting treatment), patients given Zokinvy (and possibly additional treatments) lived an average of 4.3 years longer than untreated patients. However, given the limited data available, the extra years lived could be as low as 2.6 years.

What are the risks associated with Zokinvy?

The most common side effects with Zokinvy (which may affect more than 1 in 10 people) are vomiting, diarrhoea, increased levels of liver enzymes, decreased appetite, nausea, abdominal pain, tiredness, weight loss, constipation and upper respiratory tract infection (nose and throat infection).The most common serious side effects with Zokinvy (which may affect up to 1 in 10 people) are increased levels of liver enzymes, cerebral ischaemia (reduced blood supply to the brain), fever and dehydration.

Why is Zokinvy authorised in the EU?

At the time of the authorisation of Zokinvy there were no other medicines for treating HutchinsonGilford progeria syndrome and processing-deficient progeroid laminopathies. The results from the studies of Zokinvy showed that this medicine can prolong the life of patients with these conditions. The most common side effects, such as diarrhoea, nausea, and vomiting, occurred mainly in the first 4 months of treatment and were manageable.The European Medicines Agency therefore decided that Zokinvy's benefits are greater than its risks and it can be authorised for use in the EU under 'exceptional circumstances'. This is because it has not been possible to obtain complete information about Zokinvy due to the rarity of the disease.Every year, the European Medicines Agency will review any new information that becomes available, and this overview will be updated as necessary.

What information is still awaited for Zokinvy?

Since Zokinvy has been authorised under exceptional circumstances, the company that markets Zokinvy will provide data from a registry of patients treated with the medicine to further evaluate the safety and effectiveness of Zokinvy as well as the quality of life of patients.

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

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

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Zoledronic Acid Accord

What is Zoledronic Acid Accord and what is it used for?

Zoledronic Acid Accord is a medicine used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zoledronic Acid Accord can also be used to treat hypercalcaemia caused by tumours.Zoledronic Acid Accord contains the active substance zoledronic acid and is a 'generic medicine'. This means that Zoledronic Acid Accord contains the same active substance and works in the same way as a 'reference medicine' already authorised in the European Union (EU) called Zometa. For more information on generic medicines, see the question-and-answer document here.

How is Zoledronic Acid Accord used?

Zoledronic Acid Accord can only be obtained with a prescription and must only be prescribed and given by a healthcare professional who has experience in the use of this type of medicine given into a vein.The medicine is given as an infusion (drip) into a vein. The usual dose is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bone metastases (when cancer has spread to the bone) if they have mild to moderately reduced kidney function. It is not recommended for patients with severely reduced kidney function.For more information about using Zoledronic Acid Accord, see the package leaflet or contact your doctor or pharmacist.

How does Zoledronic Acid Accord work?

The active substance in Zoledronic Acid Accord, zoledronic 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 reduces 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, Zoledronic Acid Accord also helps to reduce the amount of calcium released into the blood.

How has Zoledronic Acid Accord been studied?

Studies on the benefits and risks of the active substance in the authorised uses have already been carried out with the reference medicine, Zometa, and do not need to be repeated for Zoledronic Acid Accord.As for every medicine, the company provided studies on the quality of Zoledronic Acid Accord. There was no need for 'bioequivalence' studies to investigate whether Zoledronic Acid Accord is absorbed similarly to the reference medicine to produce the same level of the active substance in the blood. This is because Zoledronic Acid Accord is given by infusion into a vein, so the active substance is delivered straight into the bloodstream.

What are the benefits and risks of Zoledronic Acid Accord?

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

Why is Zoledronic Acid Accord authorised in the EU?

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

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

The company that markets Zoledronic Acid Accord will provide a card to inform patients receiving Zoledronic Acid Accord 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 Zoledronic Acid Accord have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zoledronic Acid Accord are continuously monitored. Side effects reported with Zoledronic Acid Accord are carefully evaluated and any necessary action taken to protect patients.

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Zoledronic Acid Actavis

What is Zoledronic acid Actavis?

Zoledronic acid Actavis is a medicine that contains the active substance zoledronic acid (4 mg). It is available as a concentrate to be made into a solution for infusion (drip) into a vein.Zoledronic acid Actavis is a 'generic medicine'. This means that Zoledronic acid Actavis is similar to a 'reference medicine' already authorised in the European Union (EU) called Zometa. For more information on generic medicines, see the question-and-answer document here.

What is Zoledronic acid Actavis used for?

Zoledronic acid Actavis can be used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zoledronic acid Actavis can also be used to treat the hypercalcaemia caused by tumours.The medicine can only be obtained with a prescription.

How is Zoledronic acid Actavis used?

Zoledronic acid Actavis must only be used by a doctor who has experience in the use of this type of medicine given into a vein.The usual dose of Zoledronic acid Actavis is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bone metastases (when cancer has spread to the bone) if they have mild to moderate problems with their kidneys. It is not recommended for patients with severe kidney problems.

How does Zoledronic acid Actavis work?

The active substance in Zoledronic acid Actavis, zoledronic 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, Zoledronic acid Actavis also helps to reduce the amount of calcium released into the blood.

How has Zoledronic acid Actavis been studied?

The company provided data from the published literature on zoledronic acid. No additional studies were needed as Zoledronic acid Actavis is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Zometa.

What are the benefits and risks of Zoledronic acid Actavis?

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

Why has Zoledronic acid Actavis been approved?

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

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

A risk management plan has been developed to ensure that Zoledronic acid Actavis 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 Zoledronic acid Actavis, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Zoledronic acid Actavis will provide a card to inform patients about the risk of osteonecrosis of the jaw (damage to the bones of the jaw, which could lead to pain, sores in the mouth or loosening of teeth) and to instruct them to contact their doctor if they experience symptoms.

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Zoledronic Acid Hospira

What is Zoledronic Acid Hospira?

Zoledronic Acid Hospira is a medicine that contains the active substance zoledronic acid. It is available as a concentrate (4 mg/5 ml) to be made up into a solution for infusion (drip) into a vein, and as solutions for infusion (4 mg/100 ml and 5 mg/100 ml).Zoledronic Acid Hospira is a 'generic' and a 'hybrid' medicine. This means that it is similar to one or more 'reference medicines' already authorised in the European Union (EU). The reference medicine for the 4 mg/5 ml concentrate and 4 mg/100 ml solution is Zometa. Aclasta is the reference medicine for the 5 mg/100 ml solution.For more information on generic and hybrid medicines, see the question-and-answer document here.

What is Zoledronic Acid Hospira used for?

Zoledronic Acid Hospira 4 mg/5 ml concentrate and 4 mg/100 ml solution are used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). They can also be used to treat the hypercalcaemia caused by tumours.Zoledronic Acid Hospira 5 mg/100 ml solution is used to treat Paget's disease of the bone in adults. This is a long-term disease where the normal process of bone growth is altered, which causes bones to become weakened or deformed.The medicine can only be obtained with a prescription.

How is Zoledronic Acid Hospira used?

For the prevention of bone complications and treatment of hypercalcaemia caused by tumours, the usual dose of Zoledronic Acid Hospira is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D.For the treatment of Paget's disease of the bone, Zoledronic Acid Hospira is given as one infusion lasting at least 15 minutes. An additional infusion, given at least one year after the first one, can be considered if the patient's disease comes back. Patients must have adequate fluids before and after treatment, and should receive adequate supplements of vitamin D and calcium. See the package leaflet for full details.

How does Zoledronic Acid Hospira work?

The active substance in Zoledronic Acid Hospira, zoledronic 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 disease activity in Paget's disease. 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, Zoledronic Acid Hospira also helps to reduce the amount of calcium released into the blood.

How has Zoledronic Acid Hospira been studied?

The company provided data from the published literature on zoledronic acid. No additional studies were needed as Zoledronic Acid Hospira is given by infusion and contains the same active substance as the reference medicines, Zometa and Aclasta.

What are the benefits and risks of Zoledronic Acid Hospira?

Because Zoledronic Acid Hospira is given by infusion and contains the same active substance as the reference medicines, its benefits and risks are taken as being the same as the reference medicines'.

Why has Zoledronic Acid Hospira been approved?

The CHMP concluded that, in accordance with EU requirements, Zoledronic Acid Hospira has been shown to be comparable to Zometa and Aclasta. Therefore, the CHMP's view was that, as for Zometa and Aclasta, the benefit outweighs the identified risks. The Committee recommended that Zoledronic Acid Hospira be given marketing authorisation.

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

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

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Zoledronic Acid Medac

What is Zoledronic acid medac?

Zoledronic acid medac is a medicine that contains the active substance zoledronic acid. It is available as a 4mg/100ml solution for infusion (drip into a vein) and as a 4mg/5ml concentrate for solution for infusion.Zoledronic acid medac is a 'generic medicine'. This means that Zoledronic acid medac is similar to a 'reference medicine' already authorised in the European Union (EU) called Zometa. For more information on generic medicines, see the question-and-answer document here.

What is Zoledronic acid medac used for?

Zoledronic acid medac can be used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zoledronic acid medac can also be used to treat the hypercalcaemia caused by tumours.The medicine can only be obtained with a prescription.

How is Zoledronic acid medac used?

Zoledronic acid medac must only be used by a doctor who has experience in the use of this type of medicine given into a vein.The usual dose of Zoledronic acid medac is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bone metastases (when cancer has spread to the bone) if they have mild to moderate problems with their kidneys. It is not recommended for patients with severe kidney problems.

How does Zoledronic acid medac work?

The active substance in Zoledronic acid medac, zoledronic 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, Zoledronic acid medac also helps to reduce the amount of calcium released into the blood.

How has Zoledronic acid medac been studied?

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

What are the benefits and risks of Zoledronic acid medac?

Because Zoledronic acid medac 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 Zoledronic acid medac been approved?

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

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

A risk management plan has been developed to ensure that Zoledronic acid medac is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Zoledronic acid medac, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Zoledronic acid medac will provide a card to inform patients about the risk of osteonecrosis of the jaw (damage to the bones of the jaw, which could lead to pain, sores in the mouth or loosening of teeth) and to instruct them to contact their doctor if they experience symptoms.

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Zoledronic Acid Mylan

What is Zoledronic acid Mylan?

Zoledronic acid Mylan is a medicine that contains the active substance zoledronic acid. It is available as a 4mg/5ml concentrate for a solution for infusion.Zoledronic acid Mylan is a 'generic medicine'. This means that Zoledronic acid Mylan is similar to a 'reference medicine' already authorised in the European Union (EU) called Zometa. For more information on generic medicines, see the question-and-answer document here.

What is Zoledronic acid Mylan used for?

Zoledronic acid Mylan can be used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zoledronic acid Mylan can also be used to treat the hypercalcaemia caused by tumours.The medicine can only be obtained with a prescription.

How is Zoledronic acid Mylan used?

Zoledronic acid Mylan must only be used by a doctor who has experience in the use of this type of medicine given into a vein.The usual dose of Zoledronic acid Mylan is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bone metastases (when cancer has spread to the bone) if they have mild to moderate problems with their kidneys. It is not recommended for patients with severe kidney problems.

How does Zoledronic acid Mylan work?

The active substance in Zoledronic acid Mylan, zoledronic 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, Zoledronic acid Mylan also helps to reduce the amount of calcium released into the blood.

How has Zoledronic acid Mylan been studied?

The company provided data from the published literature on zoledronic acid. No additional studies in patients were needed as Zoledronic acid Mylan is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Zometa.

What are the benefits and risks of Zoledronic acid Mylan?

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

Why has Zoledronic acid Mylan been approved?

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

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Zoledronic Acid Teva

What is Zoledronic acid Teva?

Zoledronic acid Teva is a medicine that contains the active substance zoledronic acid. It is available as a concentrate (4 mg/5 ml) to be used to make a solution for infusion (drip) into a vein, and as a solution for infusion (4 mg/100 ml).Zoledronic acid Teva is a 'generic medicine'. This means that Zoledronic acid Teva is similar to a 'reference medicine' already authorised in the European Union (EU) called Zometa. For more information on generic medicines, see the question-and-answer document here.

What is Zoledronic acid Teva used for?

Zoledronic acid Teva can be used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zoledronic acid Teva can also be used to treat the hypercalcaemia caused by tumours.The medicine can only be obtained with a prescription.

How is Zoledronic acid Teva used?

Zoledronic acid Teva must only be used by a doctor who has experience in the use of this type of medicine given into a vein.The usual dose of Zoledronic acid Teva is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bone metastases (when cancer has spread to the bone) if they have mild to moderate problems with their kidneys. It is not recommended for patients with severe kidney problems.

How does Zoledronic acid Teva work?

The active substance in Zoledronic acid Teva, zoledronic 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, Zoledronic acid Teva also helps to reduce the amount of calcium released into the blood.

How has Zoledronic acid Teva been studied?

No additional studies were needed as Zoledronic acid Teva is a generic medicine that is given by infusion and contains the same active substance as the reference medicine, Zometa.

What are the benefits and risks of Zoledronic acid Teva?

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

Why has Zoledronic acid Teva been approved?

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

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

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

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Zolgensma

What is Zolgensma and what is it used for?

Zolgensma is a gene therapy medicine for treating spinal muscular atrophy, a serious condition of the nerves that causes muscle wasting and weakness.It is intended for patients with inherited mutations affecting a gene known as SMN1, who have either been diagnosed with SMA type 1 (the most severe type) or have up to 3 copies of another gene known as SMN2.Spinal muscular atrophy is rare, and Zolgensma was designated an 'orphan medicine' (a medicine used in rare diseases) on 19 June 2015. Further information on the orphan designation can be found here: ema.europa.eu/medicines/human/orphan-designations/eu3151509.Zolgensma contains the active substance onasemnogene abeparvovec.

How is Zolgensma used?

Zolgensma is given once as an infusion (drip) into a vein lasting about 1 hour. The infusion should take place in a clinic or hospital under the supervision of a doctor experienced in managing spinal muscular atrophy.Before and after receiving the infusion, the patient will have a number of tests, including liver and blood tests, and will be given corticosteroid medicines to reduce the risk of side effects. The medicine can only be obtained with a prescription. For more information about using Zolgensma, see the package leaflet or contact your doctor or pharmacist.

How does Zolgensma work?

Patients with spinal muscular atrophy have a defect in a gene known as SMN1, which the body needs to make a protein essential for the normal functioning of nerves that control muscle movements. The active substance in Zolgensma, onasemnogene abeparvovec, contains a functional copy of this gene. When injected, it passes into the nerves from where it provides the correct gene to make enough of the protein and thereby restore nerve function.

What benefits of Zolgensma have been shown in studies?

A main study showed that Zolgensma reduces the need for artificial ventilation in babies with spinal muscular atrophy. In this study, 20 out of the 22 babies given Zolgensma were alive and breathing without a permanent ventilator after 14 months, when normally only a quarter of untreated patients would survive without needing a ventilator.The study also showed that Zolgensma can help babies sit unaided for at least 30 seconds. 14 out of the 22 babies given Zolgensma were able to do so after 18 months, a milestone that is never achieved in untreated babies with severe forms of the disease.

What are the risks associated with Zolgensma?

The most common side effects with Zolgensma are raised liver enzymes, injury to the liver(hepatotoxicity), low levels of blood platelets (thrombocytopenia), raised levels of troponin (a measure which indicates damage to the heart muscle), fever and vomiting.For the full list of restrictions and side effects of Zolgensma, see the package leaflet.

Why is Zolgensma authorised in the EU?

The main study of Zolgensma showed that a one-time infusion can improve survival in these patients and reduce the need for a permanent ventilator to breathe. It can also help them reach development milestones. As for its safety, the side effects of Zolgensma are considered manageable; the most common side effect in the study, raised liver enzymes, required treatment with a steroid. The European Medicines Agency therefore decided that Zolgensma's benefits are greater than its risks and it can be authorised for use in the EU.Zolgensma was originally given 'conditional authorisation' because there was more evidence to come about the medicine. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full authorisation.

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

The company that markets Zolgensma will provide educational materials to caregivers with information on how to use the medicine safely, the risks associated with the medicine and how to identify and report side effects. It will also conduct a study of the medicine's safety and effectiveness in the longterm.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zolgensma have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zolgensma are continuously monitored. Side effects reported with Zolgensma are carefully evaluated and any necessary actions taken to protect patients.

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Zolsketil Pegylated Liposomal

What is Zolsketil pegylated liposomal and what is it used for?

Zolsketil pegylated liposomal is a medicine used to treat the following types of cancer in adults:• breast cancer that has spread to other parts of the body in patients at risk of heart problems. Zolsketil pegylated liposomal is used on its own for this disease;• advanced ovarian cancer in women whose previous treatment including a platinum-based cancer medicine has stopped working;• multiple myeloma (a cancer of the white blood cells in the bone marrow), in patients with progressive disease who have received at least one other treatment in the past and have already had, or are unsuitable for, a bone marrow transplantation. Zolsketil pegylated liposomal is used in combination with bortezomib (another cancer medicine);• Kaposi's sarcoma in patients with AIDS who have a very damaged immune system. Kaposi's sarcoma is a cancer that causes abnormal tissue to grow under the skin, on moist body surfaces or on internal organs.Zolsketil pegylated liposomal contains the active substance doxorubicin and is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance called Adriamycin. However, in Zolsketil pegylated liposomal the active substance is enclosed in tiny fatty spheres called liposomes, whereas this is not the case for Adriamycin.

How is Zolsketil pegylated liposomal used?

Zolsketil pegylated liposomal can only be obtained with a prescription. It should only be given under the supervision of a cancer doctor who is specialised in the use of cytotoxic (cell-killing) medicines. It cannot be interchanged with other medicines that contain doxorubicin.Zolsketil pegylated liposomal is given by infusion (drip) into a vein. The dose depends on the condition it is used for and is calculated on the basis of the patient's weight and height. The doctor may stop treatment or reduce the dose if certain side effects occur or if the patient has liver problems.For more information about using Zolsketil pegylated liposomal, see the package leaflet or contact your doctor or pharmacist.

How does Zolsketil pegylated liposomal work?

Doxorubicin, the active substance in Zolsketil pegylated liposomal, is a cytotoxic medicine that belongs to the group 'anthracyclines'. It interferes with the DNA in cancer cells, preventing them from making more copies of DNA. This means that cancer cells cannot divide and eventually die. Zolsketil pegylated liposomal builds up in areas in the body where the blood vessels have an abnormal shape, such as within tumours, where its action is concentrated.Doxorubicin has been available since the 1960s. In Zolsketil pegylated liposomal, it is enclosed in 'pegylated liposomes' (tiny fat particles coated with a substance called polyethylene glycol). This slows down removal of the medicine, allowing it to circulate in the blood for longer. It also reduces its effects on healthy tissues and cells, so it is less likely to cause specific side effects.

What benefits of Zolsketil pegylated liposomal have been shown in studies?

Studies on the benefits and risks of the active substance in the authorised uses have already been carried out with the reference medicine, Adriamycin, and do not all need to be repeated for Zolsketil pegylated liposomal. However, since Adriamycin contains doxorubicin in a different form (not enclosed in pegylated liposomes), the company also presented results from a study in patients with ovarian cancer to show that Zolsketil pegylated liposomal is bioequivalent to Caelyx, another authorised medicine that contains doxorubicin in pegylated liposomal form.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 risks associated with Zolsketil pegylated liposomal?

The most common side effects with Zolsketil pegylated liposomal (which may affect more than 1 in 5 people) are neutropenia (low levels of neutrophils, a type of white blood cell), nausea (feeling sick), leukopenia (low levels of leukocytes, a type of white blood cell), anaemia (low levels of red blood cells), and tiredness.The most common serious side effects with Zolsketil pegylated liposomal (which may affect more than 1 in 50 people) are neutropenia, palmar-plantar erythrodysaesthesia syndrome (hand-foot syndrome; rash and numbness on the palms and soles), leukopenia, lymphopenia (low levels of lymphocytes, a type of white blood cell), anaemia, thrombocytopaenia (low levels of blood platelets), stomatitis (inflammation of the mouth), tiredness, diarrhoea, vomiting, nausea, pyrexia (fever), dyspnoea (difficulty breathing), and pneumonia (infection of the lungs).Zolsketil pegylated liposomal must not be used to treat Kaposi's sarcoma that can be treated effectively with 'local' treatments that only affect the site of the tumour or with alfa interferons.For the full list of side effects and restrictions of Zolsketil pegylated liposomal, see the package leaflet.

Why is Zolsketil pegylated liposomal authorised in the EU?

The European Medicines Agency concluded that, in accordance with EU requirements, Zolsketil pegylated liposomal has been shown to be comparable to the reference medicine and bioequivalent to Caelyx. Therefore, the Agency's view was that the benefits of Zolsketil pegylated liposomal 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 Zolsketil pegylated liposomal?

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

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Zomarist

What is Zomarist and what is it used for?

Zomarist 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 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 blood glucose.Zomarist 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 Zomarist (informed consent).

How is Zomarist used?

Zomarist 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 Zomarist. Taking Zomarist 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 Zomarist and at regular intervals during treatment.The medicine can only be obtained with a prescription. For more information about using Zomarist, see the package leaflet or contact your doctor or pharmacist.

How does Zomarist 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. Zomarist 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 prolongstheir 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 2 diabetes.

What benefits of Zomarist 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 Zomarist 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 Zomarist were absorbed in the body in the same way as when they were taken as separate tablets.

What are the risks associated with Zomarist?

The most common side effects with Zomarist (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 Zomarist, see the package leaflet.Zomarist must not be used in people who are hypersensitive (allergic) to vildagliptin, metformin or any of the other ingredients. Zomarist 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 Zomarist 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 may help patients to stick to their treatment. The European Medicines Agency therefore decided that Zomarist's benefits are greater than its risks and it can be authorised for use in the EU.Zomarist (vildagliptin Zomarist (vildagliptin / metformin hydrochloride)

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

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zomarist have been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zomarist 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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Zometa

What is Zometa?

Zometa is a medicine that contains the active substance zoledronic acid. It is available as a powder (4mg) and solvent, and as a concentrate (4mg/5ml), both of which are made up into a solution for infusion (drip into a vein), and as a pre-prepared solution for infusion (4mg/100ml).

What is Zometa used for?

Zometa can be used to prevent bone complications in adults with advanced cancer that is affecting the bone. This includes fractures (breaks in the bone), spinal compression (when the spinal cord is compressed by the bone), bone disorders needing radiotherapy (treatment with radiation) or surgery, and hypercalcaemia (high levels of calcium in the blood). Zometa can also be used to treat the hypercalcaemia caused by tumours.The medicine can only be obtained with a prescription.

How is Zometa used?

Zometa must only be used by a doctor who has experience in the use of this type of medicine given into a vein.The usual dose of Zometa is one infusion of 4 mg over at least 15 minutes. When used to prevent bone complications, the infusion can be repeated every three to four weeks, and patients should also take supplements of calcium and vitamin D. A lower dose is recommended for patients with bonemetastases (when cancer has spread to the bone) if they have mild to moderate problems with their kidneys. It is not recommended for patients with severe kidney problems.

How does Zometa work?

The active substance in Zometa, zoledronic 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, Zometa also helps to reduce the amount of calcium released into the blood.

How has Zometa been studied?

Zometa has been studied in over 3,000 adults with bone metastases in three main studies looking at its ability to prevent bone damage. Zometa was compared with placebo (a dummy treatment) in two of the studies, and with pamidronate (another bisphosphonate) in the third. The main measure of effectiveness was the number of patients who developed at least one new 'skeletal event' over 13 months. This included any bone complications needing treatment with radiotherapy or surgery, any fractures or any spinal compression.Zometa has also been compared with pamidronate in two main studies involving a total of 287 adults with hypercalcaemia caused by tumours. The main measure of effectiveness was the number of patients whose calcium levels had returned to normal within 10 days after treatment.

What benefit has Zometa shown during the studies?

In the first two studies of patients with bone metastases, the number of patients who developed a new skeletal event was lower with Zometa (33 to 38%) than with placebo (44%). In the third study, Zometa was as effective as pamidronate: 44% of the patients receiving Zometa had at least one skeletal event, compared with 46% of those receiving pamidronate.In patients with hypercalcaemia, Zometa was more effective than pamidronate. Looking at the results of the two studies together, 88% of the patients receiving Zometa had normal calcium levels within 10 days after treatment, compared with 70% of those receiving pamidronate.

What is the risk associated with Zometa?

The most common side effect with Zometa (seen in more than 1 patient in 10) is hypophosphataemia (low blood phosphate levels). Osteonecrosis of the jaw (damage to the bones of the jaw, which could lead to pain, sores in the mouth or loosening of teeth) has been reported uncommonly (seen in between 1 and 10 patients in 1,000). For the full list of all side effects reported with Zometa, see the package leaflet.Zometa must not be used in people who are hypersensitive (allergic) to zoledronic acid, other bisphosphonates or any of the other ingredients. Zometa should not be used in pregnant or breastfeeding women.

Why has Zometa been approved?

The CHMP decided that Zometa'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 Zometa?

A risk management plan has been developed to ensure that Zometa 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 Zometa, including the appropriate precautions to be followed by healthcare professionals and patients.In addition, the company that markets Zometa will provide a card to inform patients about the risk of osteonecrosis of the jaw and to instruct them to contact their doctor if they experience symptoms.

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Zonegran

What is Zonegran?

Zonegran is a medicine that contains the active substance zonisamide. It is available as capsules (25, 50 and 100 mg) and orodispersible tablets (25, 50, 100 and 300 mg). Orodispersible tablets are tablets that dissolve in the mouth.

What is Zonegran used for?

Zonegran is used to treat patients with partial seizures (epileptic fits starting in one part of the brain), including those who have secondary generalisation (where the seizure subsequently spreads to the whole brain). It is used on its own in newly diagnosed adults and as an 'add-on' therapy in adults and children aged 6 years and above already receiving other antiepilepsy medicines.The medicine can only be obtained with a prescription.

How is Zonegran used?

When Zonegran is used on its own in newly diagnosed adults, the recommended starting dose is 100 mg once a day for two weeks, which may be increased by 100 mg at intervals of two weeks. The usual maintenance dose is 300 mg a day.When Zonegran is used as an 'add-on' to existing treatment in adults, the recommended starting dose is 25 mg twice a day. After one week the dose may be increased to 50 mg twice a day and then further increased in steps of 100 mg every week, depending on the patient's response. Zonegran can be given once or twice a day after an appropriate dose is reached. The usual maintenance dose is between 300 and 500 mg a day.When Zonegran is used as an 'add-on' to existing treatment in children aged 6 years and above, the dose depends on body weight; the recommended starting dose is 1 mg per kg of body weight daily. After one or two weeks, the daily dose may be increased in steps of 1 mg per kg every one or two weeks until an appropriate dose is reached. The total dose must not exceed 500 mg a day.Dose increases may need to be made less frequently in patients with liver or kidney problems or those taking certain other medicines. Before stopping Zonegran, the dose should be decreased gradually. For further information, see the package leaflet.

How does Zonegran work?

The active substance in Zonegran, zonisamide, is an anti-epileptic. Epileptic fits are caused by abnormal electrical activity in the brain. Zonisamide works by blocking specific pores on the surface of nerve cells called sodium channels and calcium channels. These channels transmit electrical impulses between nerve cells. By blocking these channels, zonisamide prevents the nerve cells from synchronising their activity and prevents abnormal electrical activity spreading through the brain. This reduces the chances of an epileptic fit. Zonegran also acts on the neurotransmitter gamma-aminobutyric acid (GABA, a chemical that allows nerve cells to communicate with each other).This may help to stabilise electrical activity in the brain.

How has Zonegran been studied?

Zonegran used on its own was compared with carbamazepine, another anti-epileptic medicine, in a main study involving 583 adults newly diagnosed with partial epilepsy. The main measure of effectiveness was the proportion of patients who were seizure-free for a period of six months.Two other main studies, one involving 351 adults and one involving 207 children (between 6 and 17 years old), looked at Zonegran as an add-on to existing treatment. These studies compared Zonegran with placebo (a dummy treatment). In the study involving adults, the main measure of effectiveness was the change in the frequency of partial seizures between the 12 weeks before treatment started and the 18-week period when a stable dose was used. In the study in children, the main measure of effectiveness was the proportion of patients in whom the number of seizures was at least halved between the 8 weeks before treatment started and the 12-week period when a stable dose was used.

What benefit has Zonegran shown during the studies?

Zonegran used on its own was shown to be beneficial in adults with partial seizures: 69.4% of patients on Zonegran were seizure-free for six months. The percentage of patients on carbamazepine who were seizure-free for six months was 74.7%.Zonegran was more effective than placebo at reducing the frequency of seizures when used as an 'addon' to existing treatment. Adults taking 500 mg Zonegran per day had an average reduction in seizure frequency of 51%, compared with 16% in those taking placebo. In children, the number of seizures was at least halved in 50% of the patients taking Zonegran, compared with 31% of those taking placebo.

What is the risk associated with Zonegran?

The most common side effects with Zonegran (seen in more than 1 patient in 10) are loss of appetite, agitation, irritability, confusion, depression, ataxia (an inability to co-ordinate muscle movements), dizziness, memory impairment, somnolence (sleepiness), diplopia (double vision) and decreased blood bicarbonate levels; although the safety profile is similar in children and adults, some side effects arereported more frequently in children than in adults. Zonegran can cause heatstroke and de-hydration, particularly in children, and these need to be treated promptly. Severe rashes have occurred in patients taking Zonegran, including cases of Stevens-Johnson syndrome (a severe, life-threatening type of allergic reaction affecting the skin and mucous membranes). For the full list of all side effects reported with Zonegran, see the package leaflet.Zonegran must not be used in people who are hypersensitive (allergic) to zonisamide, to any of the other ingredients, or to sulphonamides (such as some antibiotics).

Why has Zonegran been approved?

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

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Zonisamide Mylan

What is Zonisamide Mylan and what is it used for?

Zonisamide Mylan is a medicine used to treat patients with partial seizures (epileptic fits starting in one part of the brain), including those who have secondary generalisation (where the seizure subsequently spreads to the whole brain). It is used on its own in newly diagnosed adults and as an 'add-on' therapy in adults and children aged six years and above already receiving other anti-epilepsy medicines.Zonisamide Mylan is a 'generic medicine'. This means that Zonisamide Mylan is similar to a 'reference medicine' already authorised in the European Union (EU) called Zonegran.Zonisamide Mylan contains the active substance zonisamide.

How is Zonisamide Mylan used?

The medicine can only be obtained with a prescription and is available as capsules (25, 50 and 100 mg).When Zonisamide Mylan is used on its own in newly diagnosed adults, the recommended starting dose is 100 mg once a day for two weeks, which may be increased by 100 mg at intervals of two weeks. The usual maintenance dose is 300 mg a day.When Zonisamide Mylan is used as an 'add-on' to existing treatment in adults, the recommended starting dose is 25 mg twice a day. After one or two weeks, the dose may be increased to 50 mg twice a day and then further increased in steps of 100 mg every week or every other week, depending on the patient's response. Zonisamide Mylan can be given once or twice a day after an appropriate dose is reached. The usual maintenance dose is between 300 and 500 mg a day.When Zonisamide Mylan is used as an 'add-on' to existing treatment in children aged six years and above, the dose depends on body weight; the recommended starting dose is 1 mg per kg of body weight daily. After one or two weeks, the daily dose may be increased in steps of 1 mg per kilogram every one or two weeks until an appropriate dose is reached. The usual maintenance dose is between 300 and 500 mg a day for children weighing more than 55 kg and 6 to 8 mg per kg of body weight in children weighing less than 55 kg.Dose increases may need to be made less frequently in patients with liver or kidney problems or those taking certain other medicines. Before stopping Zonisamide Mylan, the dose should be decreased gradually. For further information, see the package leaflet.

How does Zonisamide Mylan work?

The active substance in Zonisamide Mylan, zonisamide, is an anti-epileptic. Epileptic fits are caused by abnormal electrical activity in the brain.Zonisamide is thought to work by blocking specific pores on the surface of nerve cells called sodium channels and calcium channels, through which sodium or calcium normally enter nerve cells. When calcium and sodium enter nerve cells, electrical impulses can be transmitted between the nerve cells. By blocking these channels, zonisamide is expected to prevent abnormal electrical activity spreading through the brain, thereby reducing the chances of an epileptic fit.Zonisamide Mylan also acts on the neurotransmitter gamma-aminobutyric acid (GABA, a chemical that allows nerve cells to communicate with each other). This may help to stabilise electrical activity in the brain.

How has Zonisamide Mylan been studied?

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

What are the benefits and risks of Zonisamide Mylan?

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

Why is Zonisamide Mylan approved?

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

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

A risk management plan has been developed to ensure that Zonisamide Mylan is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Zonisamide Mylan, 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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Zostavax

What is Zostavax?

Zostavax is a vaccine that is available as a powder and solvent to be made up into a solution for injection. The active substance is the attenuated (weakened) varicella-zoster virus.

What is Zostavax used for?

Zostavax is used to vaccinate people aged 50 years or older, to prevent herpes zoster (also known as zoster or shingles) and the long-lasting nerve pain that may follow the disease (post-herpetic neuralgia).The vaccine can only be obtained with a prescription.

How is Zostavax used?

Zostavax is given as a single dose injected under the skin or into the muscle, preferably around the shoulder. In patients who have bleeding problems, the vaccine should be given under the skin.

How does Zostavax work?

Herpes zoster, or shingles, is a disease caused by the reactivation of the varicella-zoster virus, the same virus that causes chickenpox. Shingles develops in people who have had chickenpox earlier in life, generally as a child. After chickenpox, the varicella-zoster virus stays in the body, in the nervous system, in a 'dormant' (inactive) state. Sometimes, after many years, and for reasons which are not fully understood, the virus becomes active again, and the patient develops shingles, a painful,blistering rash typically in one part of the body. The rash takes usually several weeks to clear, and may be followed by severe long-lasting pain (post-herpetic neuralgia) in the area where the rash was.The risk of developing shingles increases with age and seems to be linked to a decline in immunity (protection) against varicella-zoster virus. Zostavax is a vaccine that was shown to 'boost' this immunity, protecting against shingles and the pain associated with it.

How has Zostavax been studied?

The main study of Zostavax compared the vaccine with placebo (a dummy) vaccine in around 39,000 patients aged between 59 and 99 years. The study was a double-blind trial, which means that neither the doctor nor the patient knew what treatment the patient was receiving. The patients were followed for 2 to 4.5 years after vaccination. The main measure of effectiveness was based on the number of people who developed shingles and post-herpetic pain.Two further studies looked at Zostavax in over 1,000 patients aged 50 years or older, of whom 389 were between 50 and 59 years of age. The studies looked at the ability of the vaccine to stimulate the production of antibodies against varicella-zoster virus in the blood, four weeks after injection.

What benefit has Zostavax shown during the studies?

Zostavax was more effective than placebo in preventing shingles. Fewer people developed shingles after vaccination with Zostavax than placebo: 315 of the 19,254 patients who received Zostavax had shingles during the study, compared with 642 of the 19,247 who received placebo. Zostavax was also more effective than placebo in preventing post-herpetic neuralgia: 27 of the Zostavax patients had post-herpetic neuralgia, compared with 80 in the placebo group.The additional two studies showed that patients vaccinated with Zostavax had blood levels of antibodies against varicella-zoster virus that were about two to three times higher four weeks after vaccination. The effect was seen both in patients aged between 50 and 59 years and in those aged 60 years and older.

What is the risk associated with Zostavax?

In studies, the most common side effects with Zostavax are reactions at the site of the injection (redness, pain, swelling, itching, warmth and bruising), headache and pain in the arm or leg. Most of these side effects were mild. For the full list of all side effects reported with Zostavax, see the package leaflet.Zostavax must not be used in people who are hypersensitive (allergic) to any of the components of the vaccine, or to any substances found at trace (very low) levels in the vaccine such as neomycin (an antibiotic). The vaccine must not be used in people who have problems with their immune system, either because they have a disease such as leukaemia, lymphoma, acquired immune deficiency syndrome (AIDS), or because they are taking medicines that affect the immune system. It must also not be used in patients with active untreated tuberculosis or in pregnant women. For the full list of restrictions, see the package leaflet.

Why has Zostavax been approved?

The CHMP decided that Zostavax'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 Zostavax?

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

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Ztalmy

What is Ztalmy and what is it used for?

Ztalmy is a medicine used to treat epileptic seizures in children from 2 to 17 years of age who have a condition known as cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. These patients can continue taking Ztalmy when they become adults if a clear benefit has been observed.The medicine is used in combination with other anti-epileptic medicines.CDKL5 deficiency disorder is rare, and Ztalmy was designated an 'orphan medicine' (a medicine used in rare diseases) on 13 November 2019. Further information on the orphan designation can be found on the EMA website.Ztalmy contains the active substance ganaxolone.

How is Ztalmy used?

The medicine can only be obtained with a prescription, and treatment should be started and supervised by a doctor who has experience in treating patients with epilepsy.Ztalmy is available as a liquid to be taken by mouth and is usually given three times a day. The dose is determined by the patient's weight.For more information about using Ztalmy, see the package leaflet or contact your doctor or pharmacist.

How does Ztalmy work?

The active substance in Ztalmy, ganaxolone, mimics the action of a substance in the body called allopregnanolone. It switches on so-called GABA receptors, which reduces excessive electrical activity in the brain and thus lowers the number of seizures.

What benefits of Ztalmy have been shown in studies?

A main study showed that Ztalmy reduces the frequency of seizures in children and adolescents with CDKL5 deficiency disorder who are taking at least one other epilepsy medicine.The study involved a total of 101 patients with CDKL5 deficiency disorder and compared Ztalmy with placebo (a dummy treatment), both given in addition to existing epilepsy medicines.On average, the monthly number of major seizures was reduced by 29% in the group of patients treated with Ztalmy, and by 6% in the group treated with placebo.

What are the risks associated with Ztalmy?

For the full list of side effects and restrictions with Ztalmy, see the package leaflet.The most common side effects with Ztalmy (which may affect more than 1 in 10 people) include sleepiness and fever.

Why is Ztalmy authorised in the EU?

The main study showed that Ztalmy is effective at reducing the number of seizures in children withCDKL5 deficiency disorder. The side effects are considered manageable. The European Medicines Agency therefore decided that Ztalmy'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 Ztalmy?

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

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Zubsolv

What is Zubsolv and what is it used for?

Zubsolv is a medicine used in adults and adolescents aged over 15 years to treat dependence on opioid (narcotic) drugs such as heroin or morphine.Zubsolv is used in individuals who are also receiving medical, social and psychological support and who have agreed to be treated for their addiction. It contains the active substances buprenorphine and naloxone.Zubsolv is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substances, but Zubsolv contains these at different strengths. The reference medicine for Zubsolv is Suboxone.

How is Zubsolv used?

Because Zubsolv can be misused or cause addiction, it can only be obtained by 'special' prescription and must be used under the supervision of a doctor who has experience in the management of opioid addiction.Zubsolv is available as tablets of various strengths (0.7 mg/0.18 mg, 1.4 mg/0.36 mg,2.9 mg/0.71 mg, 5.7 mg/1.4 mg, 8.6 mg/2.1 mg, 11.4 mg/2.9 mg). The tablets are taken once a day by placing them under the tongue and allowing them to dissolve for up to 10 minutes.On the first day of treatment, the recommended daily dose is one or two tablets of Zubsolv 1.4 mg/0.36 mg or 2.9 mg/0.71 mg. During the next days, the doctor may increase the dose depending on the patient's response, but the daily dose should not be higher than 17.2 mg buprenorphine. Once the patient has been stabilised, the maintenance dose may be reduced gradually if the patients agrees, and eventually treatment may be stopped.For more information, see the package leaflet.

How does Zubsolv work?

Zubsolv contains two active substances: buprenorphine, a partial opioid agonist (it acts like an opioid drug but less powerfully), and naloxone, an opioid antagonist (it counteracts the effects of opioid drugs).Sublingual tablets containing buprenorphine alone have been available in the EU since the mid-1990s for the treatment of opioid addiction. However, buprenorphine tablets have been misused by drug addicts who dissolve the tablets and inject themselves with the resulting solution. The addition of naloxone helps prevent the misuse of the medicine. This is because, when injected, naloxone counteracts the effects of opioids, causing the patient to experience acute withdrawal symptoms.

What benefits of Zubsolv have been shown in studies?

The company provided data from studies with the reference medicine Suboxone and from the published literature showing the benefits of buprenorphine and naloxone in the treatment of opioid dependence.A study involving 125 healthy volunteers showed that some strengths of the Zubsolv tablets produced a lower level of the active substances in the body than the reference product and therefore the two medicines cannot be used interchangeably. The study also showed that Zubsolv tablets dissolved faster and had a better taste than the reference medicine.

What are the risks associated with Zubsolv?

The most common side effects with Zubsolv (which may affect more than 1 in 10 people) are constipation and symptoms of drug withdrawal such as insomnia (difficulty sleeping), headache, nausea (feeling sick), hyperhidrosis (excessive sweating) and pain. Serious side effects include seizures (fits), vomiting, diarrhoea and abnormal results of blood tests for liver function. For the full list of side effects reported with Zubsolv, see the package leaflet.Zubsolv must not be used in patients with severe respiratory insufficiency (inability to breathe properly), severe liver problems, acute alcoholism (excessive alcohol consumption) or delirium tremens (a condition caused by alcohol withdrawal). It must also not be used with the medicines naltrexone and nalmefene, other opioid antagonists used for the treatment of alcohol or opioid dependence. For the full list of restrictions, see the package leaflet.

Why is Zubsolv approved?

Combining buprenorphine and naloxone is an established strategy for managing opioid dependence which prevents misuse of the medicine. As for Suboxone, the European Medicines Agency decided that Zubsolv's benefits are greater than its risks and recommended that it be approved for use in the EU. Since Zubsolv does not produce the same amounts of buprenorphine and naloxone in the blood as the reference medicine, the medicines cannot be used interchangeably.

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

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

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Zutectra

What is Zutectra?

Zutectra is a solution for injection. It is available as a prefilled syringe containing 500 international units (IU) of the active substance, human hepatitis B immunoglobulin.

What is Zutectra used for?

Zutectra is used in adults who have had a liver transplant because of liver failure that was caused by hepatitis B infection. Zutectra is used to prevent re-infection with the hepatitis B virus in patients without active infection (i.e. those who test negative for the presence of the hepatitis B protein (HBsAg) and for hepatitis B DNA (HBV-DNA)). The use of standard antiviral medicines to prevent hepatitis B re-infection should be considered together with Zutectra.The medicine can only be obtained with a prescription.

How is Zutectra used?

Zutectra is given as an injection under the skin once a week or every 2 weeks. The recommended dose normally ranges from 500 IU to 1,000 IU, and exceptionally up to 1,500 IU. The dose is established based on the patient's blood levels of antibodies against the hepatitis B virus.Zutectra treatment starts at least one week after the liver transplant. Before starting Zutectra, the patient will need to receive medicines that contain the same active substance as in Zutectra, but given into a vein.Zutectra injections can be given by the patients themselves or their caregiver once they have been trained appropriately. The patient or caregiver will also be trained on how to keep a treatment diary and what to do if severe side effects occur. For full details, see the summary of product characteristics (also part of the EPAR).

How does Zutectra work?

The active substance in Zutectra, human hepatitis B immunoglobulin, is a purified antibody extracted from human blood. Antibodies are proteins naturally found in the blood that help the body to fight infections and other diseases. Zutectra prevents the patient from being re-infected with hepatitis B by keeping the blood levels of human hepatitis B immunoglobulins high enough, so that they can attach to the virus and stimulate the immune system to destroy it.

How has Zutectra been studied?

Zutectra has been studied in one main study involving 30 adults who had undergone liver transplants. Zutectra treatment was started at least three months after the liver transplant. The main measure of effectiveness was the number of patients who had a blood level of hepatitis B immunoglobulin above 100 IU per litre after 18 to 24 weeks. This level is considered adequate to protect against re-infection with the hepatitis B virus.In another study in 49 patients, Zutectra was given at least one week (approximately 8-11 days) after the liver transplant. The main measure of effectiveness was the number of patients in whom treatment failed, defined as blood levels of hepatitis B immunoglobulins falling below 100 IU per litre or reinfection by hepatitis B virus during the 24 weeks of treatment.

What benefit has Zutectra shown during the studies?

Zutectra has been shown to be effective at maintaining antibody levels required to protect against hepatitis B re-infection.In the first study, all 23 of the patients who completed treatment had antibody levels above 100 IU per litre. In the second study, all of the 49 patients had antibody levels above 100 IU per litre and none of them was re-infected during the 24 weeks of treatment.

What is the risk associated with Zutectra?

The most common side effects with Zutectra (seen in between 1 and 10 patients in 100) are reactions at the injection site, such as pain, urticaria (itchy rash), haematoma (blood under the skin) and erythema (reddening of the skin). For the full list of all side effects reported with Zutectra, see the package leaflet.Zutectra must not be used in people who are hypersensitive (allergic) to the active substance, to any of the other ingredients or to human immunoglobulins. Zutectra must not be given into a blood vessel.

Why has Zutectra been approved?

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

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

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

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Zyclara

What is Zyclara and what is it used for?

Zyclara is a cream used to treat actinic keratosis on the face and balding parts of the scalp. Actinic keratosis is a precancerous, abnormal skin growth that develops after too much exposure to sunlight. Zyclara is used to treat adults whose immune system (the body's natural defences) is working normally when other skin treatments for actinic keratosis cannot be used or are less appropriate. It contains the active substance imiquimod at 3.75% strength (100 mg cream contains 3.75 mg imiquimod).Zyclara is a 'hybrid medicine'. This means that it is similar to a 'reference medicine' containing the same active substance, but Zyclara is available in a different strength. The reference medicine for Zyclara is Aldara, which contains imiquimod at 5% strength.

How is Zyclara used?

Zyclara is available as a 3.75% cream in individual sachets. It can only be obtained with a prescription.One or two sachets of Zyclara are applied in a thin layer to the affected areas of the face or balding scalp once a day before bedtime. The cream should remain on the skin overnight (for about 8 hours) before being washed off. Daily treatment should continue for 2 weeks. This is followed by a 2-week break without treatment and then a further 2 weeks of treatment. For further information, see the package leaflet.The patient's response to treatment should be evaluated 8 weeks after the end of treatment, and a third 2-week course may be considered if needed. If actinic keratosis does not improve enough with Zyclara, a different treatment should be tried.If actinic keratosis is cleared after two 2-week courses but then it comes back, it can be treated again with one or two 2-week treatment courses provided these are given after a break of at least 12 weeks from the original treatment.

How does Zyclara work?

The active substance in Zyclara cream, imiquimod, is an immune response modifier. This means that it uses the immune system to bring about its effect. When imiquimod is applied to the skin, it acts locally on the immune system to trigger the release of cytokines, including interferon. These substances help to kill the abnormal cells in the skin that lead to keratosis.

What benefits of Zyclara have been shown in studies?

Zyclara has been shown to be effective in clearing actinic keratosis from the skin in two main studies involving 479 patients with actinic keratosis on the face and scalp. Two doses of Zyclara (2.5% and 3.75%) were compared with placebo (a dummy treatment) in these studies, and the main measure of effectiveness was the number of patients whose skin was completely cleared of the actinic keratosis after treatment. Around 36% of patients treated with Zyclara 3.75% cream in the two studies had complete clearance compared with around 6% of patients treated with placebo. Zyclara at a lower strength (2.5%) had a lower clearance rate than the 3.75% strength.

What are the risks associated with Zyclara?

Most patients using Zyclara experience side effects on the skin where the medicine was applied (most commonly redness, scab formation, dryness and shedding of the skin). About 11% of patients in studies with Zyclara required treatment to be interrupted due to this kind of side effect on the skin. Some other side effects, including headache and tiredness, were also reported. For the full list of side effects and restrictions with Zyclara, see the package leaflet.

Why is Zyclara approved?

The European Medicines Agency concluded that Zyclara 3.75% cream has been shown to be effective at clearing actinic keratosis from the skin and that its use did not raise significant safety concerns. Treatment with Zyclara has the advantage of being easier to adhere to than Aldara treatment because it has a simpler dosing regimen. In addition, its lower strength allows it to be used across larger areas of the skin and thereby treat more of the affected skin.The Agency therefore decided that Zyclara'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 Zyclara?

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

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Zydelig

What is Zydelig and what is it used for?

Zydelig is a cancer medicine that is used to treat chronic lymphocytic leukaemia (CLL, a cancer of a type of white blood cells called B lymphocytes) and follicular lymphoma (another cancer that affects Blymphocytes).In CLL, Zydelig is used in combination with another medicine (rituximab or ofatumumab) in patients who have received at least one previous treatment and in patients whose cancer cells have genetic mutations (changes) called 17p deletion or TP53 mutation and who cannot be treated with any other therapy.In follicular lymphoma, Zydelig is used on its own in patients whose disease has not improved with two previous treatments.Zydelig contains the active substance idelalisib.

How is Zydelig used?

Zydelig can only be obtained with a prescription and it should be prescribed by a doctor experienced in using cancer medicines.Zydelig is available as 100 mg and 150 mg tablets. The recommended dose is 150 mg twice a day, and treatment should be continued for as long as the patient improves or remains stable and the side effects are tolerable. If the patient has severe side effects, treatment must be stopped and can be restarted at a lower dose of 100 mg twice a day.All patients treated with Zydelig should also be given preventive medication against the lung infection Pneumocystis jirovecii pneumonia, and this should be continued for up to 6 months after stopping treatment with Zydelig. Patients should also be monitored for infection and have regular blood tests to measure the level of white blood cells. Zydelig should not be started in patients with any generalised infection (infection that has spread with symptoms affecting the whole body, such as fever and chills).For more information about using Zydelig, see the package leaflet or contact your doctor or pharmacist.

How does Zydelig work?

The active substance in Zydelig, idelalisib, blocks the effects of an enzyme called PI3K-delta. This enzyme plays a role in the growth, migration and survival of white blood cells but is overactive in blood cancers, where it enables the survival of the cancer cells. By targeting this enzyme and blocking its effects, idelalisib causes death of the cancer cells, thereby delaying or stopping the progression of the cancer.

What benefits of Zydelig have been shown in studies?

In a main study of 220 patients with previously treated CLL, Zydelig was more effective at treating the cancer than placebo (a dummy treatment) when both were given in combination with rituximab: 75% of patients taking Zydelig had an improvement in their disease compared with 15% of patients receiving placebo. Zydelig was also more effective than placebo in patients who had a specific genetic mutation in their cancer cells that makes them unsuitable for certain other therapies.Zydelig with ofatumumab was more effective than ofatumumab alone in the treatment of CLL. In a study of 261 previously treated CLL patients, it took over 16 months on average before the disease got worse in patients treated with Zydelig plus ofatumumab, compared with 8 months in those treated with ofatumumab alone.Another main study evaluated Zydelig in patients with different lymphomas, including 72 patients with follicular lymphoma that had failed two previous treatments. Zydelig was effective, with 54% of patients with follicular lymphoma having either a complete or partial response to treatment.

What are the risks associated with Zydelig?

The most common side effects with Zydelig (which may affect more than 1 in 10 people) are infections(including lung infection caused by Pneumocystis jirovecii, and cytomegalovirus infections), neutropenia (low levels of neutrophils, a type of white blood cell), lymphocytosis (increased levels of lymphocytes, another type of white blood cell), diarrhoea, blood tests showing changes in the liver, rash, fever and increased blood fat levels.For the full list of side effects and restrictions of Zydelig, see the package leaflet.

Why is Zydelig authorised in the EU?

The European Medicines Agency noted that data from the main studies showed high response rates with Zydelig in patients with chronic lymphocytic leukaemia and follicular lymphoma. Zydelig was also effective in chronic lymphocytic leukaemia patients whose cancer cells have the 17p deletion or TP53 mutation, who usually have a poor outcome.In addition, the safety of the medicine was considered acceptable. The Agency therefore concluded that Zydelig'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 Zydelig?

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

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Zykadia

What is Zykadia and what is it used for?

Zykadia is a cancer medicine used on its own to treat adults with a type of lung cancer called nonsmall-cell lung cancer (NSCLC), when the disease is advanced. It is only used if the NSCLC is 'ALKpositive', which means that the cancer cells have certain defects affecting the gene responsible for a protein called ALK (anaplastic lymphoma kinase).Zykadia contains the active substance ceritinib.

How is Zykadia used?

Zykadia can only be obtained with a prescription and treatment must be started and supervised by a doctor who is experienced in using cancer medicines. The presence of genetic defects affecting ALK ('ALK-positive' status) has to be confirmed in advance by appropriate methods.The medicine is available as capsules (150 mg). The recommended dose is 450 mg (3 capsules) once a day taken with food at the same time each day. The doctor may decide to reduce the dose or stop treatment temporarily if side effects occur. In certain cases treatment should be permanently stopped.For more information about using Zykadia, see the package leaflet or contact a doctor or pharmacist.

How does Zykadia work?

ALK belongs to a family of proteins called receptor tyrosine kinases, which are involved in the growth of cells and the development of new blood vessels that supply them. In patients with ALK-positive NSCLC, an abnormal form of ALK is produced that stimulates the cancer cells to divide and grow in an uncontrolled fashion. The active substance in Zykadia, ceritinib, works by blocking the activity of ALK, thereby reducing the growth and spread of the cancer.

What benefits of Zykadia have been shown in studies?

Zykadia has been shown to be effective at treating advanced, ALK-positive NSCLC in three main studies in patients whose disease progressed despite previous treatment with the medicine crizotinib:In two of these studies, involving 303 patients, the medicine was not compared with any other treatment. Response to treatment was assessed using body scans and standardised criteria used for solid tumours, with complete response being when the patient had no remaining signs of the cancer. In one study 56% of patients given Zykadia (92 of 163) were considered by the treating doctors to have shown a complete or partial response to the medicine. The average length of response was 8.3 months. In the second study, the overall response rate was 41% (57 of 140 patients) and the average length of response was 10.6 months.In the third study in 231 patients, Zykadia was compared with standard chemotherapy (medicines to treat cancer). Results showed that patients given Zykadia lived for an average of 5.4 months without their disease getting worse (progression-free survival) compared with 1.6 months in patients given standard chemotherapy.Zykadia has also been shown to be effective at treating patients who had not been treated before in a study in 376 patients. Patients given Zykadia lived for an average of 16.6 months without their disease getting worse compared with 8.1 months in patients given standard chemotherapy.

What are the risks associated with Zykadia?

The most common side effects with Zykadia (which may affect 1 or more people in 10) are diarrhoea, nausea (feeling sick), vomiting, tiredness, abnormal liver tests, abdominal (belly) pain, decreased appetite, weight loss, constipation, rash, increases in the level of a waste product called creatinine in the blood (a possible sign of kidney problems), oesophageal disorder (problems affecting the food pipe) and anaemia (low levels of red blood cells). The most common severe reactions (which may affect 1 or more people in 20) are abnormal liver tests, tiredness, diarrhoea, nausea, vomiting and hyperglycaemia (high blood sugar).For the full list of side effects and restrictions with Zykadia, see the package leaflet.

Why is Zykadia authorised in the EU?

Zykadia has been shown to be effective at treating patients whose disease progressed during or shortly after treatment with crizotinib and who currently have very limited treatment options, as well as patients who have not been treated before. Regarding safety, the adverse effects with Zykadia generally appeared manageable.The European Medicines Agency therefore decided that Zykadia's benefits are greater than its risks and recommended that it be approved for use in the EU.Zykadia was originally given 'conditional approval' because there was more evidence to come about the medicine. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full approval.

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

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

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Zyllt

What is Zyllt?

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

What is Zyllt used for?

Zyllt is used in adults to prevent atherothrombotic events (problems caused by blood clots and hardening of the arteries). Zyllt can be given to the following groups of patients:• patients who have recently had a myocardial infarction (heart attack). Zyllt can be started between a few days and 35 days after the attack;• patients who have had a recent ischaemic stroke (stroke caused by failure of the blood supply to part of the brain). Zyllt can be started between seven days and six months after the stroke;• patients with peripheral arterial disease (problems with blood flow in the arteries);• patients who have a condition known as 'acute coronary syndrome', when it should be given with aspirin (another medicine that prevents blood clots), including patients who have had a stent inserted (a short tube placed in an artery to prevent it closing up). Zyllt can be used in patients who are having myocardial infarction with 'ST segment elevation' (an abnormal reading on the electrocardiogram or ECG) when the doctor thinks that they would benefit from the treatment. It can also be used in patients who do not have this abnormal reading on the ECG, if they have unstable angina (a severe type of chest pain) or have had a 'non-Q-wave' myocardial infarction. The medicine can only be obtained with a prescription.

How is Zyllt used?

The standard dose of Zyllt is one 75 mg tablet once a day, taken with or without food. In acute coronary syndrome, Zyllt is used together with aspirin and treatment generally starts with a loading dose of four 75 mg tablets. This is then followed by the standard 75 mg dose once a day for at least four weeks (in ST segment elevation myocardial infarction) or for up to 12 months (in non-ST segment elevation syndrome).

How does Zyllt work?

The active substance in Zyllt, clopidogrel, 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 aggregating (sticking together). Clopidogrel stops the platelets aggregating by blocking a substance called ADP from attaching to a special 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.

How has Zyllt been studied?

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

What are the benefit and risk of Zyllt?

Because Zyllt 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 Zyllt been approved?

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

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Zynlonta

What is Zynlonta and what is it used for?

Zynlonta is a medicine for treating two types of B-cell lymphoma (a type of blood cancer):• diffuse large B-cell lymphoma (DLBCL);• high-grade B-cell lymphoma (HGBL).Zynlonta is used to treat adults with B-cell lymphoma that has come back (relapsed) after two or more treatments or that did not respond to previous treatment (refractory).Diffuse large B-cell lymphoma is rare, and Zynlonta was designated an 'orphan medicine' (a medicine used in rare diseases) on 20 August 2021. Further information on the orphan designation can be found here: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-21-2481 Zynlonta contains the active substance loncastuximab tesirine.

How is Zynlonta used?

Zynlonta can only be obtained with a prescription and treatment should be started and supervised by a doctor with experience in using cancer medicines.Zynlonta is given as an infusion (drip) into a vein over 30 minutes every 3 weeks. Treatment can continue for as long as the patient benefits from it and does not have intolerable side effects. The dose depends on the patient's body weight. If certain side effects develop, the doctor may decide to reduce the dose or to interrupt or stop treatment with Zynlonta.Before starting treatment, patients should be given dexamethasone (an anti-inflammatory medicine) to help reduce possible side effects of treatment.For more information about using Zynlonta, see the package leaflet or contact your doctor or pharmacist.

How does Zynlonta work?

In patients with B-cell lymphoma, B-cells (a type of white blood cell) have become cancerous. The active substance of Zynlonta, loncastuximab tesirine, is made up of a monoclonal antibody (a type ofprotein) combined with a cytotoxin (a substance that kills cells) called SG3199. The monoclonal antibody attaches to a protein called CD19 on the B-cells, including cancerous B-cells, and the medicine enters these cells. When Zynlonta is inside the B-cells, SG3199 is released and kills them.

What benefits of Zynlonta have been shown in studies?

The effect of Zynlonta was investigated in a main study with 145 patients with relapsed or refractory B-cell lymphoma. In this study, Zynlonta was not compared with any other treatment for B-cell lymphoma. The study showed that 48.3% (70 out of 145) of the patients responded to treatment with Zynlonta, with about 25% (36 out of 145) of them showing no sign of cancer (complete response).

What are the risks associated with Zynlonta?

The most common side effects with Zynlonta (which may affect more than 1 in 5 people) are increased levels of gamma glutamyltransferase (GGT, a liver enzyme), neutropenia (low levels of neutrophils, a type of white blood cell), tiredness, anaemia (low levels of red blood cells), thrombocytopenia (low levels of blood platelets), nausea (feeling sick), peripheral oedema (swelling due to fluid retention, especially of the ankles and feet) and rash.The most common serious adverse reaction (which may affect up to 1 in 20 people) are febrile neutropenia (low levels of white blood cells with fever), abdominal pain, dyspnoea (difficulty breathing), pleural effusion (fluid around the lungs) and lung infection.For the full list of side effects of Zynlonta, see the package leaflet.

Why is Zynlonta authorised in the EU?

The prognosis for patients with relapsed or refractory B-cell lymphoma is extremely poor. At the time of approval of Zynlonta, the available treatment options for these patients were limited and not satisfactory.Although more data are needed to confirm the results of the main study, the European Medicines Agency considered that Zynlonta showed a clinically meaningful favourable effect and met an unmet medical need. Overall, the safety of Zynlonta is similar to other B-cell lymphoma medicines of the same type and seems generally manageable.Zynlonta has therefore been given 'conditional authorisation'. This means that that the European Medicines Agency decided that the benefits of Zynlonta are greater than its risks, but the company will have to provide additional evidence after authorisation.Conditional authorisation is granted on the basis of less comprehensive data than are normally required. It is granted for medicines that fulfil an unmet medical need to treat serious diseases and when the benefits of having them available earlier outweigh any risks associated with using the medicines while waiting for further evidence. Every year, the Agency will review any new information that becomes available until data become comprehensive and this overview will be updated as necessary.

What information is still awaited for Zynlonta?

Since Zynlonta has been given conditional authorisation, the company that markets Zynlonta will provide further data on its long-term safety and on its safety and effectiveness in patients with B-cell lymphoma when used in combination with another cancer medicine.

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

The company that markets Zynlonta will ensure that healthcare professionals receive patient alert cards to give to patients. The patient alert card contains important safety information on the increased risk of photosensitivity reactions, signs and symptoms of such reactions, and instructions on how to avoid exposure to direct and indirect sunlight when using Zynlonta. Patients are advised to contact a healthcare professional if they have photosensitivity reactions.Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zynlonta have also been included in the summary of product characteristics and the package leaflet.As for all medicines, data on the use of Zynlonta are continuously monitored. Suspected side effects reported with Zynlonta are carefully evaluated and any necessary action taken to protect patients.

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Zynrelef

What is Zynrelef and what is it used for?

Zynrelef is a painkiller used in adults to reduce pain from small to medium-sized wounds after an operation. It contains the active substances bupivacaine and meloxicam.

How is Zynrelef used?

Zynrelef is a prolonged-release solution that is applied to the wound during surgery before the wound is closed. Prolonged-release means that the active substances are released slowly over several hours after application.The medicine can only be obtained with a prescription and it should be used in a setting (such as a hospital) where trained staff and equipment are available to treat patients who get side effects involving the heart or central nervous system.For more information about using Zynrelef, see the package leaflet or contact your doctor or pharmacist.

How does Zynrelef work?

Bupivacaine is a local anaesthetic which temporarily numbs the area to which it has been applied by blocking pain signals to the brain. Meloxicam, a non-steroidal anti-inflammatory drug (NSAID), reduces pain and inflammation and strengthens the effect of bupivacaine.

What benefits of Zynrelef have been shown in studies?

Two main studies in 830 patients have shown that Zynrelef is effective at reducing pain from small to medium-sized wounds following surgery. The main measure of effectiveness was a total pain score for a 72-hour period, with lower scores indicating better pain control.In the first study involving patients who had surgery to remove a bunion, the pain score in patients treated with Zynrelef was 323 compared with 445 for patients receiving placebo (a dummy treatment) and 393 for patients receiving bupivacaine (standard treatment). In the second study involving patients who had surgery to repair a hernia, the pain score was 269 with Zynrelef compared with 351for patients receiving placebo and 342 for patients receiving bupivacaine. In both these studies Zynrelef had some effect in reducing the use of opioid pain medication after surgery.

What are the risks associated with Zynrelef?

The most common side effect with Zynrelef (which may affect more than 1 in 10 people) is dizziness.Zynrelef should not be used in patients with hypersensitivity (allergy) to the active substances or to any amide-type local anaesthetic or an NSAID including acetylsalicylic acid (also known as aspirin). The medicine should also not be used in women during the last 3 months of pregnancy, in patients who have undergone certain heart surgeries or who have severe heart failure (when the heart does not pump as well as it should), poor liver function or severe kidney failure (inability of the kidneys to work properly) that is not being treated with dialysis (to remove unwanted fluids and substances from the blood).For the full list of side effects and restrictions with Zynrelef, see the package leaflet.

Why is Zynrelef authorised in the EU?

Zynrelef has been shown to provide effective pain relief from small to medium-sized wounds after surgery. Its effect on reducing the need for opioid pain relief was considered modest but clinically significant. The medicine's side effects are similar to those of bupivacaine alone and are considered manageable. The European Medicines Agency therefore decided that Zynrelef'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 Zynrelef?

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

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Zypadhera

What is Zypadhera?

Zypadhera is a medicine that contains the active substance olanzapine. It is available as a powder and solvent that are made up into a prolonged-release suspension for injection. 'Prolonged release' means that the active substance is released slowly over a few weeks after being injected.

What is Zypadhera used for?

Zypadhera is used to maintain the improvement in symptoms in patients with schizophrenia who have already been stabilised on an initial course of olanzapine taken by mouth. Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (mistaken beliefs).The medicine can only be obtained with a prescription.

How is Zypadhera used?

Zypadhera is given by deep injection into the buttock muscle by a doctor or nurse who has been trained in giving this type of injection.Zypadhera is given at doses of 150, 210 or 300 mg every two weeks, or 300 or 405 mg every four weeks. The dose depends on the dose of olanzapine that the patient was previously taking by mouth. Patients should be monitored closely for signs of relapse (a return of symptoms) during the first one to two months of treatment, and the dose adjusted if necessary.Zypadhera is not recommended for patients over 65 years of age. However, patients aged between 65 and 75 years or patients with kidney or liver problems may use Zypadhera if an effective and welltolerated dose of oral olanzapine has been found. A lower starting dose may be necessary in patients whose bodies may break olanzapine down slowly, such as those with moderate liver problems.Zypadhera must not be injected into a vein or under the skin. In rare cases, patients receiving Zypadhera may experience symptoms of olanzapine overdose after injection if the medicine is accidentally injected into a vein. Symptoms of overdose include sedation (sleepiness) and delirium (confusion). Because patients should be monitored by qualified staff for these symptoms for at least three hours after injection, they should receive Zypadhera at a centre with the appropriate facilities to deal with a potential overdose. Patients who have symptoms of overdose should continue to be monitored until the symptoms have passed.

How does Zypadhera work?

The active substance in Zypadhera, olanzapine, is an antipsychotic medicine. It is known as an 'atypical' antipsychotic because it is different from the older antipsychotic medicines that have been available since the 1950s. Olanzapine attaches to several different receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by 'neurotransmitters', chemicals that allow nerve cells to communicate with each other. It is thought that olanzapine's beneficial effect is due to it blocking receptors for the neurotransmitters 5-hydroxytrypamine (also called serotonin) and dopamine. Since these neurotransmitters are involved in schizophrenia, olanzapine helps to normalise the activity of the brain, reducing the symptoms of the disease.Olanzapine has been authorised in the European Union (EU) since 1996. It is available as tablets, orodispersible tablets (tablets that dissolve in the mouth) and rapidly acting injections in Zyprexa, Zyprexa Velotab and other medicines. The olanzapine in Zypadhera is presented as a 'pamoate' salt, which makes the olanzapine less soluble. As a result, the active substance is released slowly for more than four weeks after injection of Zypadhera.

How has Zypadhera been studied?

Because olanzapine has already been authorised in the EU as Zyprexa, the company used some of the data from Zyprexa to support the use of Zypadhera.Zypadhera has been studied in two main studies involving adults with schizophrenia. The first looked at the initial treatment of schizophrenia and the second looked at the maintenance of response to olanzapine treatment:• the study of initial treatment compared the effects of three doses of Zypadhera with those of placebo (dummy injections) in 404 patients. The main measure of effectiveness was the change in symptoms measured on a standard scale for schizophrenia after eight weeks;• the study of maintenance treatment compared the effects of four doses of Zypadhera with those of olanzapine taken by mouth in 1,065 patients. Three of the doses of Zypadhera were 'high' (300 mg and 150 mg every two weeks, and 405 mg every four weeks) and one was 'low' (45 mg every four weeks). All of the patients in this study had been stabilised with other treatments for schizophrenia and had been taking olanzapine by mouth for at least six weeks before the study began. The main measures of effectiveness were the time taken for symptoms to get worse and the number of patients whose symptoms got worse over 24 weeks.

What benefit has Zypadhera shown during the studies?

In the study of the initial treatment of schizophrenia, Zypadhera was more effective than placebo. Symptom scores were around 100 points at the start of the study, but had fallen by around 25 points in the patients receiving Zypadhera after eight weeks, compared with around 9 points in the patients receiving placebo. The effectiveness of Zypadhera was greater than placebo from the second week of treatment onwards.In the study looking at the maintenance of response to olanzapine treatment, Zypadhera was as effective as olanzapine taken by mouth: 10% of the patients receiving Zypadhera every two weeks had a worsening of symptoms, compared with 7% of those taking olanzapine by mouth. The 'high' doses of Zypadhera were more effective at preventing a worsening of symptoms than the 'low' dose.

What is the risk associated with Zypadhera?

The most common side effects with Zypadhera (seen in more than 1 patient in 10) are weight gain, somnolence (sleepiness), orthostatic hypotension (sudden drop in blood pressure on standing up) and raised levels of prolactin (a hormone). For the full list of all side effects reported with Zypadhera, see the package leaflet.Zypadhera must not be used in patients who are hypersensitive (allergic) to olanzapine or any of the other ingredients. It must also not be used in patients at risk of narrow-angle glaucoma (raised pressure inside the eye).

Why has Zypadhera been approved?

The CHMP noted that Zypadhera is effective both in the initial treatment of schizophrenia and in maintaining a response to treatment in schizophrenia. However, it noted that prolonged-release injections are not suitable for use as initial treatment, because the medicine takes at least a week to reduce symptoms and patients may need rapid control of symptoms. In addition, it is not possible to stop treatment after giving a prolonged-release injection, which would not be suitable for patients experiencing side effects. The Committee decided that Zypadhera's benefits are greater than its risks and recommended that Zypadhera be given marketing authorisation.

Which measures are being taken to ensure the safe use of Zypadhera?

The company that makes Zypadhera will provide an educational programme for doctors, nurses and pharmacists and a card for patients in all Member States, reminding them of how to use the medicine safely. These will include information on what to do before and after each injection, the differences between Zypadhera and other injectable medicines containing olanzapine, and the recommendations on how patients should be monitored.

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Zyprexa

What is Zyprexa?

Zyprexa is a medicine containing the active substance olanzapine. It is available as tablets (2.5, 5, 7.5, 10, 15 and 20 mg) and as a powder to be made up into a solution for injection.

What is Zyprexa used for?

Zyprexa is used to treat adults with schizophrenia. Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (mistaken beliefs). Zyprexa is also effective in maintaining improvement in patients who have responded to an initial course of treatment.Zyprexa is also used to treat moderate to severe manic episodes (extremely high mood) in adults. It can also be used to prevent the recurrence of these episodes (when symptoms come back) in adults with bipolar disorder (a mental illness with alternating periods of high mood and depression) who have responded to an initial course of treatment.Zyprexa is usually taken by mouth as tablets, but the injection can be used for the rapid control of agitation or disturbed behaviour in adults with schizophrenia or a manic episode, when taking the medicine by mouth is not appropriate.The medicine can only be obtained with a prescription.

How is Zyprexa used?

The recommended starting dose of Zyprexa tablets depends on the disease being treated: 10 mg per day is used in schizophrenia and in the prevention of manic episodes, and 15 mg per day in the treatment of manic episodes, unless it is used with other medicines, in which case the starting dose can be 10 mg per day. The dose is adjusted according to how well the patient responds to and tolerates the treatment. The usual dose range is between 5 and 20 mg per day.The usual dose when using the injection is 10 mg as a single injection into a muscle. This can be followed if needed by a further injection of 5 or 10 mg two hours later.Lower doses may be needed for patients over 65 years of age (5 mg per day for the tablets and 2.5 to 5 mg for the injection) and for patients who have reduced liver or kidney function (5 mg per day for both the tablets and injection).In all cases, the maximum dose of Zyprexa that can be given in a day, using tablets or injection, is 20 mg.

How does Zyprexa work?

The active substance in Zyprexa, olanzapine, is an antipsychotic medicine. It is known as an 'atypical' antipsychotic because it is different from the older antipsychotic medicines that have been available since the 1950s. Its exact mechanism of action is unknown, but it attaches to several different receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by 'neurotransmitters', chemicals that allow nerve cells to communicate with each other. It is thought that olanzapine's beneficial effect is due to it blocking receptors for the neurotransmitters 5hydroxytrypamine (also called serotonin) and dopamine. Since these neurotransmitters are involved in schizophrenia and in bipolar disorder, olanzapine helps to normalise the activity of the brain, reducing the symptoms of these diseases.

How has Zyprexa been studied?

In schizophrenia, Zyprexa tablets have been studied in about 3,000 adults, in which their effectiveness was compared with that of placebo (a dummy treatment) or haloperidol (another antipsychotic medicine). All four studies lasted six weeks, but the patients stayed on the medicine for up to a year or more.In the treatment of acute manic episodes in adults with bipolar disorder, Zyprexa tablets were compared with placebo, haloperidol or valproate (another medicine used in manic episodes) in five studies, including one where patients were also receiving other medicines. In the prevention of manic episodes, Zyprexa tablets were studied in 1,162 adults. Their effectiveness was compared with that of placebo or lithium (another medicine used in bipolar disorder).The injection was studied in 581 adults with schizophrenia (compared with placebo or injected haloperidol) and 228 manic adults (compared with placebo or injected lorazepam, another medicine used in manic episodes).In all studies, the effectiveness of Zyprexa was assessed using various symptom-rating scales.

What benefit has Zyprexa shown during the studies?

In all studies, Zyprexa as tablets and as injections was more effective at improving symptoms than placebo. Zyprexa tablets were at least as effective as the medicines they were compared with for the treatment of schizophrenia (haloperidol), the treatment of moderate to severe manic episodes(haloperidol and valproate), and the prevention of recurrence in patients with bipolar disorder (lithium). The injection was also shown to be more effective than lorazepam (at a relatively low dose) in manic patients, and as effective as haloperidol in schizophrenia.

What is the risk associated with Zyprexa?

The most common side effects with Zyprexa (seen in more than 1 patient in 10) are somnolence(sleepiness), weight gain, orthostatic hypotension (sudden drop in blood pressure on standing up) and raised levels of prolactin (a hormone). For the full list of all side effects reported with Zyprexa, see the package leaflet.Zyprexa must not be used in people who are hypersensitive (allergic) to olanzapine or any of the other ingredients. It must also not be used in patients at risk of narrow-angle glaucoma (raised pressure inside the eye).

Why has Zyprexa been approved?

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

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Zyprexa Velotab

What is Zyprexa Velotab?

Zyprexa Velotab is a medicine that contains the active substance olanzapine. It is available as 'orodispersible' tablets (5, 10, 15 and 20 mg). Orodispersible tablets are tablets that dissolve in the mouth.

What is Zyprexa Velotab used for?

Zyprexa Velotab is used to treat adults with schizophrenia. Schizophrenia is a mental illness that has a number of symptoms, including disorganised thinking and speech, hallucinations (hearing or seeing things that are not there), suspiciousness and delusions (mistaken beliefs). Zyprexa Velotab is also effective in maintaining improvement in patients who have responded to an initial course of treatment.Zyprexa Velotab is also used to treat moderate to severe manic episodes (extremely high mood) in adults. It can also be used to prevent the recurrence of these episodes (when symptoms come back) in adults with bipolar disorder (a mental illness causing alternating periods of high mood and depression) who have responded to an initial course of treatment.The medicine can only be obtained with a prescription.

How is Zyprexa Velotab used?

The recommended starting dose of Zyprexa Velotab depends on the disease being treated: 10 mg per day is used in schizophrenia and in the prevention of manic episodes, and 15 mg per day in the treatment of manic episodes, unless it is used with other medicines, in which case the starting dose can be 10 mg per day. The dose is adjusted according to how well the patient responds to andtolerates the treatment. The usual dose range is between 5 and 20 mg per day. The orodispersible tablets are taken by being placed on the tongue, where they disintegrate quickly in the saliva, or by mixing them in water before swallowing. Patients over 65 years of age and patients who have reduced liver or kidney function may need a lower starting dose of 5 mg per day.

How does Zyprexa Velotab work?

The active substance in Zyprexa Velotab, olanzapine, is an antipsychotic medicine. It is known as an 'atypical' antipsychotic because it is different from the older antipsychotic medicines that have been available since the 1950s. Its exact mechanism of action is unknown, but it attaches to several different receptors on the surface of nerve cells in the brain. This disrupts signals transmitted between brain cells by 'neurotransmitters', chemicals that allow nerve cells to communicate with each other. It is thought that olanzapine's beneficial effect is due to it blocking receptors for the neurotransmitters 5-hydroxytrypamine (also called serotonin) and dopamine. Since these neurotransmitters are involved in schizophrenia and in bipolar disorder, olanzapine helps to normalise the activity of the brain, reducing the symptoms of these diseases.

How has Zyprexa Velotab been studied?

Zyprexa Velotab contains the same active substance as another medicine called Zyprexa that has been authorised in the European Union (EU) since 1996. Because of this, the studies done with Zyprexa were used to support the use of Zyprexa Velotab. Three studies were also carried to show that, when taken by mouth, the two medicines produce equivalent levels of olanzapine in the blood.

What benefit has Zyprexa Velotab shown during the studies?

Like Zyprexa, Zyprexa Velotab was more effective at improving symptoms than placebo (a dummy treatment). Zyprexa Velotab was as effective as the medicines that it was compared with for the treatment of adults with schizophrenia, the treatment of moderate to severe manic episodes in adults, and the prevention of recurrence in adults with bipolar disorder.

What is the risk associated with Zyprexa Velotab?

The most common side effects with Zyprexa Velotab (seen in more than 1 patient in 10) are somnolence (sleepiness), weight gain, orthostatic hypotension (sudden drop in blood pressure on standing up) and raised levels of prolactin (a hormone). For the full list of all side effects reported with Zyprexa Velotab, see the package leaflet.Zyprexa Velotab must not be used in people who are hypersensitive (allergic) to olanzapine or any of the other ingredients. It must also not be used in patients at risk of narrow-angle glaucoma (raised pressure inside the eye).

Why has Zyprexa Velotab been approved?

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

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Zytiga

What is Zytiga and what is it used for?

Zytiga is a medicine used to treat cancer of the prostate (a gland of the male reproductive system) in adult men when the cancer is metastatic (has spread to other parts of the body).Zytiga is used together with the medicines prednisone or prednisolone in the following situations:• when the cancer is newly diagnosed, high risk and still sensitive to hormones; Zytiga is then used in combination with a treatment called androgen deprivation therapy;• when medical castration (using medicines to stop the production of male hormones) with an androgen deprivation therapy has not worked or no longer works in men who have either no symptoms or only mild symptoms of the disease, and who do not yet need chemotherapy (cancer medicines);• when medical or surgical castration and chemotherapy containing docetaxel have not worked or no longer work.Zytiga contains the active substance abiraterone acetate.

How is Zytiga used?

Zytiga is available as tablets (250 and 500 mg) and can only be obtained with a prescription.The recommended dose of Zytiga is 1,000 mg taken once a day at least two hours after eating and at least one hour before further food. If patients develop liver problems treatment should be stopped. Treatment may be resumed at a reduced dose if liver function returns to normal.For further information, see the package leaflet.

How does Zytiga work?

The active substance in Zytiga, abiraterone acetate, is changed in the body to abiraterone which stops the body producing testosterone, a male hormone. Abiraterone does this by blocking an enzyme called CYP17 found in the testes and elsewhere in the body. Because the cancer needs a supply of testosterone to survive and grow, by reducing the production of testosterone, Zytiga may slow the growth of the prostate cancer.

What benefits of Zytiga have been shown in studies?

Zytiga was compared with placebo (a dummy treatment) in three main studies. In the studies, patients were also treated with prednisone or prednisolone.One study involved 1,209 patients with newly diagnosed, high-risk, hormone-sensitive, metastatic prostate cancer. The main measure of effectiveness was how long patients lived without their disease getting worse. Patients treated with Zytiga lived for an average of 33 months without their disease getting worse, compared with around 15 months for patients given placebo.The second study involved 1,088 men with metastatic prostate cancer who had either no symptoms or only mild symptoms of the disease and for whom castration treatment had not worked or had stopped working. Patients treated with Zytiga lived for an average of around 16 months without their disease getting worse, compared with around 8 months in patients given placebo.In a third study involving 1,195 men with metastatic prostate cancer whose disease had got worse despite surgical or medical castration treatment and chemotherapy with docetaxel, the main measure of effectiveness was overall survival (how long the patients lived). Patients treated with Zytiga lived for just under 15 months from the start of treatment compared with just under 11 months for patients given placebo.

What are the risks associated with Zytiga?

The most common side effects with Zytiga (seen in more than 1 patient in 10) are urinary tract infection, hypokalaemia (low blood potassium levels), high blood pressure, peripheral oedema (swelling of the limbs due to fluid retention) and increases in liver enzymes. Other important side effects include heart problems, liver problems, fractures and allergic alveolitis (a lung reaction causing cough and shortness of breath). For the full list of all side effects reported with Zytiga, see the package leaflet.Zytiga must not be used in patients with severely reduced liver function. It is not for use in women and must not be given to women who are or who may be pregnant. For the full list of restrictions, see the package leaflet.

Why is Zytiga approved?

The European Medicines Agency decided that Zytiga's benefits are greater than its risks and recommended that it be approved for use in the EU. The Agency noted that Zytiga in combination with prednisone or prednisolone has been shown to either delay progression of the disease or improve survival compared with placebo. Zytiga is well tolerated and its risks are considered manageable.

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

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

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