Index of drugs

Treatment of mild to moderate type 1 Gaucher disease in adult patients; the preparation can only be used in patients who can not undergo enzyme replacement therapy. Treatment of progressive neurological symptoms in adult patients and children with Niemann-Pick type C disease.

1 capsule contains 100 mg of miglustat.

Miglustat is an inhibitor of glucosylceramide synthase, the enzyme responsible for the first stage of the synthesis of most glycolipids.In vitro glucosylceramide synthase is inhibited by miglustat from IC₅₀ 20-37 μM. In addition, it was demonstrated experimentallyin vitro inhibitory effect of non-lysosomal glycosylceramidase. The inhibitory effect of glucosylceramide synthase is the basis for the therapy consisting in the reduction of substrates in Gaucher disease. In patients with Niemann-Pick type C disease, treatment with miglustat may reduce the progress of clinically relevant neurological symptoms. Miglustat is rapidly absorbed in healthy patients. The maximum plasma concentration occurs about 2 hours after taking the dose. Co-administration of food reduces the rate of absorption (C._maxdecreased by 36% and t_max delayed by 2 h), but has no statistically significant effect on the degree of absorption of miglustat (AUC decreased by 14%). Miglustat does not bind to plasma proteins. It is mainly excreted by the kidneys in the urine containing 70-80% of the dose of the drug in an unchanged form. T_0,5 is 6-7 hours.

Hypersensitivity to miglustat or to any of the excipients.

In patients with type 1 Gaucher disease and patients with Niemann-Pick type C disease, participating in clinical trials have experienced tremors during treatment - a dose reduction usually within a few days may relieve tremor, but sometimes it may be necessary to stop treatment. During the use of the drug, gastrointestinal events were observed, mainly diarrhea, which is most likely associated with intestinal suppression of disaccharidase activities, such as sucrose-isomaltase in the gastrointestinal tract, leading to a reduction in the absorption of disacharidases from food. Clinical observations show that the gastrointestinal actions subsided after an individual change in diet (eg reduced consumption of sucrose, lactose and other carbohydrates), taking the drug between meals and / or after the administration of antidiarrheal drugs, e.g. loperamide. Some patients may need a transient dose reduction. In patients with chronic diarrhea or other persistent symptoms of the gastrointestinal tract, in which the described procedure did not bring improvement, it is necessary to carry out diagnostics in accordance with the principles of clinical practice. The medicine has not been studied in patients who have been diagnosed with serious gastrointestinal disease, including inflammatory bowel disease in the past. The drug should be used with caution in patients with impaired renal and hepatic function (limited experience). It is not recommended for patients with severe renal impairment (creatinine clearance below 30 ml / min / 1.73 m² pc.). Although no direct comparisons have been made with enzyme replacement therapy (ETZ) in the treatment of previously untreated patients with type 1 Gaucher disease, there is no evidence of an advantage of both efficacy and safety of the drug over ETZ. Specific efficacy and safety studies have not been performed in patients with severe Gaucher disease. Regular monitoring of vitamin B is recommended₁₂ (risk of vitamin B deficiency₁₂ in patients with type 1 Gaucher disease) and monitoring of platelet counts (patients with type 1 Gaucher disease who have changed ETZ treatment to the drug have observed a small reduction in non-bleeding blood platelet counts). The effectiveness of the treatment of neurological symptoms of the drug in patients with Niemann-Pick type C disease should be examined regularly, eg every 6 months; continuation of treatment should be re-approved after at least 1 year of treatment.In some patients with Niemann-Pick type C treated with the drug, a small reduction in platelet count not related to bleeding was observed; in such patients, it is recommended to monitor the number of platelets. In some children with Niemann-Pick type C disease, a lower rate of growth was observed in the early phase of miglustat treatment, which may be accompanied or decreased after a reduced weight gain; the growth of children and adolescents treated with the drug should be monitored. If treatment continues, the benefit / risk balance should be reassessed. The drug has not been established for children and adolescents with type 1 Gaucher disease between the ages of 0 and 17 years. There is limited experience in the use of this medicine in patients with Niemann-Pick type C disease under the age of 4 years.

Miglustat passes through the placental barrier and should not be used during pregnancy. There are no adequate data from the use of miglustat in pregnant women. Animal studies have shown reproductive toxicity, including dystocia. The potential danger to humans is unknown. The drug should not be taken while breastfeeding. It is not known whether miglustat is excreted in breast milk. Studies in rats show adverse effects of miglustat on sperm parameters (motility and morphology) leading to reduced fertility. As long as no additional information is available, it is recommended that men planning to have children stop taking the drug and use reliable methods of contraception for the Next three months. Women of childbearing potential should use contraception. Men should use effective contraception while taking the medicine.

Very common: weight loss, decreased appetite, tremors, diarrhea, flatulence and abdominal pain. Common: thrombocytopenia, depression, insomnia, weakness of libido, peripheral neuralgia, ataxia, amnesia, paraesthesia, hypoesthesia, headache, dizziness, nausea, vomiting, abdominal distension / discomfort, constipation, indigestion, muscle cramps, muscle weakness, fatigue, asthenia , chills and malaise, incorrect results of nerve conduction tests.

Orally.Gaucher disease typi I. Adults: the recommended starting dose is 100 mg 3 times a day, in patients with diarrhea it may be necessary to temporarily reduce to 100 mg once or twice daily.Niemann-Pick disease type C. Adults and adolescents (> 12 years): the recommended dose is 200 mg 3 times a day. Children <12 years: the dose is determined depending on the body surface -> 1.25 m²: 200 mg 3 times a day, pc. 0.88-1.25 m²: 200 mg twice daily, pc. 0.73-0.88 m²: 100 mg 3 times a day, pc. 0.47-0.73 m²: 100 mg twice daily, pc. ≤0.47 m²: 100 mg once a day.Impaired renal function: Creatinine clearance 50-70 ml / min / 1.73 m²pc. treatment starts with a dose of 100 mg twice daily in patients with type 1 Gaucher disease and 200 mg twice daily (in patients aged <12 years per pc) in patients with Niemann-Pick type C disease; Creatinine clearance 30-50 ml / min / 1.73 m² The treatment starts with 100 mg once daily dosing in patients with type 1 Gaucher disease and 100 mg twice daily (in patients aged <12 years per pc) in patients with Niemann-Pick disease type C; creatinine clearance <30 ml / min / 1.73 m² pc. application is not recommended.
The drug can be taken with or without food.