Generic Name for ZAVESCA
Miglustat 100mg; caps.
Pharmacological Class for ZAVESCA
Glucosylceramide synthase inhibitor.
Manufacturer of ZAVESCA
Indications for ZAVESCA
Mild to moderate type 1 Gaucher disease when enzyme replacement therapy is not feasible.
Adult dose for ZAVESCA
≥18yrs: 100mg 3 times daily; may reduce to 100mg once or twice daily if diarrhea or tremor occurs. Mild renal impairment (CrCl 50–70mL/min): 100mg twice daily. Moderate renal impairment (CrCl 30–50mL/min): 100mg once daily. Severe renal impairment: not recommended.
Children's dosing for ZAVESCA
<18yrs: not recommended.
Contraindications for ZAVESCA
Warnings/Precautions for ZAVESCA
Perform neurological evaluations at baseline, then periodically at 6-month intervals. Reevaluate and consider discontinuation if signs/symptoms of peripheral neuropathy develop (eg, numbness, tingling). GI disease (eg, inflammatory bowel). Use effective methods of contraception during therapy; men should maintain contraception for 3 months after treatment. Elderly. Labor & delivery. Nursing mothers: not recommended.
Interactions for ZAVESCA
May antagonize imiglucerase.
Adverse Reactions for ZAVESCA
Diarrhea, weight loss, tremor, flatulence, abdominal pain, GI disturbances, weakness, headache, dizziness, paresthesia, cramps, thrombocytopenia, reduced spermatogenesis, peripheral neuropathy.
How is ZAVESCA supplied?
美格鲁特(Miglustat)胶囊剂以商品名zavesca 于2003年7月获得美国FDA批准，由美国ACTELION PHARMS公司研制，治疗因葡萄糖酶脑苷脂酶活性降低所引起的Ⅰ型戈谢氏病的药物。
使用方法：推荐剂量为1次100mg，1日3次，若患者出现腹泻和震颤等不良反应，剂量可减少为1日1～2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min /1.73m2)推荐剂量为1次100mg，1日2次；对轻度肾脏功能受损者(肌酐清除率为50～70ml/min /1.73m2)推荐剂量为1次100mg，1日2次；对中度肾脏功能受损者(肌酐清除率为30～50ml/min /1.73m2)推荐剂量为1次100mg，1日1次；对重度肾脏功能受损者不宜应用。
Miglustat (Zavesca®) is a low-molecular-weight inhibitor of glucosylceramide synthase and α-glucosidase. Zavesca® (100 mg miglustat) is indicated for the oral treatment of adult patients with mild to moderate type 1 Gaucher disease, and may only be used in those patients for whom enzyme replacement therapy is unsuitable. It is approved for this indication in 37 countries including the US and EU since 2003. Zavesca® is also approved in the EU for the treatment of progressive neurological manifestations in adult and pediatric patients with Niemann-Pick type C disease.
Miglustat in type 1 Gaucher disease
The MAINTENANCE trial is evaluating the long-term safety and efficacy of miglustat as maintenance therapy after a switch from enzyme replacement therapy (ERT) in mild-to-moderate adult type 1 Gaucher disease patients with stable disease. Enrollment in the MAINTENANCE trial was completed during the second quarter of 2008. Results of this study are expected to become available in 2010.
Available clinical data
Zavesca® (miglustat) 100 mg is the only oral drug available for the treatment of type 1 Gaucher disease, and was approved on the basis of three international open-label clinical trials. The rationale for the use of miglustat in type 1 Gaucher disease is to help balance the overall level of glucosylceramide by reducing its production to a level compatible with breakdown by residual glucocerebrosidase activity, a unique mode of action known as "substrate reduction therapy". Bone manifestations of type 1 Gaucher disease were evaluated in three open-label clinical studies in patients treated with miglustat 100 mg t.i.d. for up to two years (n = 72). In a pooled analysis of uncontrolled data, bone mineral density Z-scores at the lumbar spine and femoral neck increased by more than 0.1 units from baseline in 27 (57%) and 28 (65%) of the patients with longitudinal bone density measurements. There were no events of bone crisis, avascular necrosis or fracture during the treatment period.
2008 – EU approval for a type II variation for miglustat and bone disease in type 1 Gaucher disease
2008 – Zavesca® launched in Turkey and Brazil
2007 – Zavesca® approved in Australia
2005 – Zavesca® launched in Canada
2004 – Zavesca® launched in the US and Switzerland
2003 – Zavesca® launched in the EU
2002 – Zavesca® in-licensed; marketing authorization granted by European Commission
Key scientific literature
Pastores G.M. et al. Effect of miglustat on bone disease in adult patients with type 1 Gaucher disease: a pooled analysis of three multinational Open-label studies. Clinical Therapeutics. 29: 1645-53; 2007.
Elstein D. et al. Oral maintenance clinical trial with miglustat for type 1 Gaucher disease: switch from or combination with intravenous enzyme replacement. Blood. 110: 2296-2301; 2007.
Giraldo P. et al. Short-term effect of miglustat in every day clinical use in treatment-naïve or previously treated patients with type 1 Gaucher’s disease. Haematologica. 91:125-8; 2006.
Elstein D. et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type 1 Gaucher disease.. J Inherit Metab Dis 27: 757-66; 2004.