Long-term enzyme replacement therapy in patients with type 1 Gaucher disease
Composition:
1 vial contains 400 U of velaglucerase alfa (after reconstitution, 1 ml of solution contains 100 U of velaglucerase alfa).
Action:
Welaglucerase alfa produced in the human fibroblast cell line HT-1080 using recombinant DNA technology. It is a glycoprotein whose monomer has a mass of about 63 kDa, has 497 amino acids and the same amino acid sequence as the naturally occurring human enzyme - glucocerebrosidase. There are 5 potential N-glycosylation sites, of which four are occupied. Velaglucerase alfa is produced to contain predominantly mannose-rich glycans and to support the internalization of the enzyme by mannose receptor-mediated endogenous phagocytic cells. Velaglucerase alfa supplements deficiency or replaces beta-glucocerebrosidase, an enzyme that catalyses the hydrolysis of glucocerebroside into Glucose and ceramide in the lysosome, thereby reducing the amount of glucocerebroside accumulated and correcting the pathophysiology underlying the Gaucher disease. Velaglucerase alfa increases hemoglobin concentration and platelet count, and reduces liver and spleen volume in patients diagnosed with type 1 Gaucher disease. Serum velaglucerase alfa increases sharply during the first 20 min of a 60-minute infusion and then reaches a steady state while the maximum concentration ( Cmax) is usually achieved in the last 20 minutes of infusion. After completion of the infusion, the velaglucerase alfa serum concentration drops sharply according to single-phase or biphasic regimen, and the mean half-life ranges from 5 to 12 min for doses of 15, 30, 45 and 60 IU / kg. The high clearance of velaglucerase alfa from serum (on average from 6.7 to 7.6 ml / min / kg) is consistent with the rapid uptake of velaglucerase alfa into macrophages via mannose receptors. The range of clearance of velaglucerase alfa in pediatric patients (4 to 17 years of age) is in the range of clearance values in adult patients (age from 19 to 62 years).
Contraindications:
Severe allergic reaction to the active substance or to any of the substances in a helper.
Precautions:
Like any intravenous protein, the drug can cause hypersensitivity reactions. Therefore, appropriate immediate medical care should be available when administering velaglucerase alfa. If a severe reaction occurs, comply with the principles of modern standards of emergency medicine. Caution should be exercised when treating patients who have previously experienced symptoms of hypersensitivity while receiving other enzyme replacement therapy. During the treatment, reactions caused by infusion may occur (including: headache and dizziness, low or high blood pressure, nausea, fatigue, fever). The treatment of these reactions should depend on the severity of the response and should include: slowdown of the infusion rate, treatment with drugs such as antihistamines, antipyretics and / or corticosteroids, and / or discontinuation and restart of treatment with an extended infusion time. Preventive treatment with antihistamines and / or corticosteroids may prevent further reactions in cases where symptomatic treatment was necessary. Preventive treatment has not been routinely administered prior to administration of velaglucerase alfa infusions during clinical trials. In the event of a severe reaction caused by infusion and in the absence or disappearance of the drug should be tested for antibodies against velaglucerase alfa. The sodium content (12.15 mg of sodium in 1 vial) should be taken into consideration when using the drug in patients on a low sodium diet.
Pregnancy and lactation:
Animal studies do not indicate harmful effects on pregnancy, embryonal / embryonic development, parturition or postnatal development; no data are available on the use of velaglucerase alfa in pregnant women. Caution should be exercised when prescribing to pregnant women. It is not known whether velaglucerase alfa is excreted in human milk. Caution should be exercised when prescribing to a breast-feeding woman.
Intravenous: 60 units / kg every 2 weeks. The dose can be adjusted individually for each patient based on achieved and maintained therapeutic goals. In clinical trials, doses ranging from 15 to 60 units / kg were used. served every 2 weeks. Doses> 60 units / kg not studied. Patients currently being treated for type 1 Gaucher disease by means of enzyme replacement therapy using imiglucerase may switch to velaglucerase alfa therapy at the same dose and dose frequency.Way of giving. The drug should be administered as a 60-minute intravenous infusion through a 0.22 μm filter. Therapy should be supervised by a physician experienced in the treatment of patients with Gaucher disease. Administration at home under the supervision of a healthcare professional may only be considered for patients who have received at least 3 infusions and have tolerated the infusion well.
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