YARGESA

Absorption: After a 100 mg oral dose, the time to maximum observed plasma concentration of miglustat (t max ) ranged from 2 to 2.5 hours in Gaucher patients. Plasma concentrations show a biexponential decline, characterized by a short distribution phase and a longer elimination phase. The effective half-life of miglustat is approximately 6 to 7 hours, which predicts that steady-state will be achieved by 1.5 to 2 days following the start of three times daily dosing. Miglustat, dosed at 50 and 100...

The efficacy of miglustat capsules in type 1 Gaucher disease has been investigated in two open-label, uncontrolled trials and one randomized, open-label, active-controlled trial with enzyme replacement given as imiglucerase. Patients who received miglustat capsules were treated with doses ranging from 100 to 600 mg a day, although the majority of patients were maintained on doses between 200 to 300 mg a day. Efficacy parameters included the evaluation of liver and spleen organ volume, hemoglobin concentration, and platelet count. A total of 80 patients were exposed to miglustat capsules during...

The following serious adverse reactions are described below and elsewhere in the labeling:

• Peripheral Neuropathy [see Warnings and Precautions (5.1) ]
• Tremor [see Warnings and Precautions (5.2) ]
• Diarrhea and weight loss [see Warnings and Precautions (5.3) ]
• Reductions in platelet count [see Warnings and Precautions (5.4) ] The most common adverse reactions (incidence ≥ to 5%) are: diarrhea, weight loss, stomach pain, gas, nausea and vomiting, headache including migraine, tremor, leg...

None None ( 4 )

• Peripheral neuropathy: Perform baseline and follow-up neurological evaluations at 6-month intervals in all patients ( 5.1 ).
• Tremor: Reduce dose to ameliorate tremor or discontinue treatment if tremor does not resolve within days of dose reduction ( 5.2 ).
• Diarrhea and weight loss: Evaluate for underlying gastrointestinal disease in patients who do not respond to usual interventions (e.g. diet modification) ( 5.3 ).
• Reductions in Platelet count: Mild reductions in platelet counts without...

7 DRUG INTERACTIONS While co-administration of miglustat capsules appeared to increase the clearance of imiglucerase by 70%, these results are not conclusive because of the small number of patients studied and because patients took variable doses of imiglucerase [see Clinical Pharmacology (12.3) ]. Co-administration of YARGESA and imiglucerase may lead to increased clearance of imiglucerase ( 7 )...