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Pulmonary Conditions: Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease. PRECAUTIONS Text Continues Below
Drug-Drug Interactions (see Clinical Pharmacology: Clinical Pharmacokinetics: Drug-drug Interactions) Effect of ARICEPTŪ on the Metabolism of Other Drugs: No in vivo clinical trials have investigated the effect of ARICEPTŪ on the clearance of drugs metabolized by CYP 3A4 (e.g. cisapride, terfenadine) or by CYP 2D6 (e.g. imipramine). However, in vitro studies show a low rate of binding to these enzymes (mean Ki about 50-130 mM), that, given the therapeutic plasma concentrations of donepezil (164 nM), indicates little likelihood of interference. Whether ARICEPTŪ has any potential for enzyme induction is not known. Formal pharmacokinetic studies evaluated the potential of ARICEPTŪ for interaction with theophylline, cimetidine, warfarin, digoxin and ketoconazole. No effects of ARICEPTŪ on the pharmacokinetics of these drugs were observed. Effect of Other Drugs on the Metabolism of ARICEPTŪ: Ketoconazole and quinidine, inhibitors of CYP450, 3A4 and 2D6, respectively, inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known. In a 7-day crossover study in 18 healthy volunteers, ketoconazole (200mg q.d.) increased mean donepezil (5mg q.d.) concentrations (AUC0-24 and Cmax) by 36%. The clinical relevance of this increase in concentration is unknown. Inducers of CYP 2D6 and CYP 3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of ARICEPTŪ. Formal pharmacokinetic studies demonstrated that the metabolism of ARICEPTŪ is not significantly affected by concurrent administration of digoxin or cimetidine. Page: << Prev | 1 | 2 | 3 | 4 | Next >>
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