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Author: Actelion Registration Ltd.


Long information

What is it?

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

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Table of Contents
What is it used for?
How is it used?
How does it work?
How has it been studied?
What benefits has it shown during the studies?
What is the risk associated?
Why has it been approved?

What is it used for?

Zavesca is used to treat two rare, 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 in the following patients:
- adults with mild to moderate type 1 Gaucher disease. Patients with this disease lack an enzyme called glucocerebrosidase, resulting 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) given by infusion (drip into a vein);
- adults, adolescents and children 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, increased 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 it 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 by mouth three times a day. For Niemann-Pick type C disease, the recommended dose is two capsules three times a day for adults and adolescents. The dose depends on weight and height in children below 12 years. Zavesca can be taken with or without food. It is intended for long-term use.

The dose should be reduced in patients with kidney problems and, on a temporary basis, in patients who develop diarrhoea. Zavesca has not been studied in patients with liver problems. For further information, see the Summary of Product Characteristics (also part of the EPAR).

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How does it 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 it been studied?

For mild to moderate type 1 Gaucher disease, the effectiveness of Zavesca was investigated in one main study involving 28 patients 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 measured if Zavesca had an effect on the size of the liver and spleen, and if it improved blood counts, such as the levels of haemoglobin (a protein found in red blood cells that carries oxygen around the body) and platelet counts (components that help the blood to clot).
For Niemann-Pick type C disease, the effectiveness of 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 (measures used to relieve symptoms) with 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. A survey of 66 patients treated with Zavesca was also carried out.

What benefits has it shown during the studies?

In the study of type 1 Gaucher disease, there was a reduction in liver organ size of 12% and a reduction in spleen size of 19% after a year. 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?

The most common side effects with Zavesca (seen in more than 1 patient in 10) are weight loss, 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 should not be used in people who may be hypersensitive (allergic) to miglustat or any of the other ingredients.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Zavesca?s benefits are greater than its risks for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease for whom ERT is unsuitable, and of progressive neurological manifestations in adult and paediatric patients with Niemann-Pick type C disease. The Committee recommended that Zavesca be given marketing authorisation.
Zavesca has been authorised under ?Exceptional Circumstances? because, as the disease is rare, it has not been possible to obtain complete information on the medicine. Every year, the European Medicines Agency (EMEA) will review any new information that may become available and this summary will be updated as necessary.

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