Torpezil 5/Torpezil 10 Drug Interactions

Effect of Donepezil Hydrochloride Tablets on the Metabolism of Other Drugs: No in vivo clinical trials have investigated the effect of donepezil hydrochloride tablets 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 K about 50 to 130 μM), that, given the therapeutic plasma concentrations of donepezil (164 nM), indicates little likelihood of interference. Based on in vitro studies, donepezil shows little or no evidence of direct inhibition of CYP2B6, CYP2C8 and CYP2C19 at clinically relevant concentrations.
Whether donepezil hydrochloride tablets have any potential for enzyme induction is not known. Formal pharmacokinetic studies evaluated the potential of donepezil hydrochloride tablets for interaction with theophylline, cimetidine, warfarin, digoxin and ketoconazole. No effects of donepezil hydrochloride tablets on the pharmacokinetics of these drugs were observed.
Effect of Other Drugs on the Metabolism of Donepezil Hydrochloride Tablets: Ketoconazole and quinidine, strong inhibitors of CYP450 3A and 2D6, respectively, inhibit donepezil metabolism in vitro. Whether there is a clinical effect of quinidine is not known.
Population pharmacokinetic analysis showed that in the presence of concomitant CYP2D6 inhibitors donepezil AUC was increased by approximately 17% to 20% in Alzheimer's disease patients taking donepezil hydrochloride tablets 10 mg. This represented an average effect of weak, moderate, and strong CYP2D6 inhibitors. In a 7-day crossover study in 18 healthy volunteers, ketoconazole (200 mg q.d.) increased mean donepezil (5 mg q.d.) concentrations (AUC_{0 to 24} and C_max) by 36%. The clinical relevance of this increase in concentration is unknown.
Inducers of CYP 3A (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil hydrochloride tablets. Formal pharmacokinetic studies demonstrated that the metabolism of donepezil hydrochloride tablets is not significantly affected by concurrent administration of digoxin or cimetidine.
An in vitro study showed that donepezil was not a substrate of P-glycoprotein. 
Drugs Highly Bound to Plasma Proteins: Drug displacement studies have been performed in vitro between this highly bound drug (96%) and other drugs such as furosemide, digoxin, and warfarin. Donepezil hydrochloride at concentrations of 0.3 to 10 micrograms/mL did not affect the binding of furosemide (5 micrograms/mL), digoxin (2 ng/mL), and warfarin (3 micrograms/mL) to human albumin. Similarly, the binding of donepezil hydrochloride to human albumin was not affected by furosemide, digoxin and warfarin.