Effects of other drugs on the metabolism of donepezil: Ketoconazole and quinidine, inhibitors of CYP450, 3A4 and 2D6, respectively, inhibit donepezil metabolism in vitro. Therefore, these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine could inhibit the metabolism of donepezil.
Inducers of CYP2D6 and CYP 3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil. Since the magnitude of an inhibiting or inducing effect is unknown, such drug combinations should be used with care.
Pharmacokinetic studies showed that the metabolism of donepezil is not significantly affected by concurrent administration of digoxin or cimetidine.
Effect of donepezil on the metabolism of other drugs: In vitro studies show a low rate of donepezil binding to CYP3A4 and CYP2D6 isoenzymes, which, given the therapeutic plasma concentrations of donepezil, indicates the little likelihood of interferences.
The administration of donepezil had no clinically significant effect on the pharmacokinetics of ketoconazole.
It is not known whether donepezil has any potential for enzyme induction.
Formal pharmacokinetic studies evaluated the potential of donepezil for interaction with theophylline, cimetidine, warfarin, and digoxin. No significant effects on the pharmacokinetics of these drugs were observed.
Anticholinergics: Cholinesterase inhibitors have the potential to interfere with the activity of anticholinergic medications because of their mechanism of action.
Cholinomimetics and other cholinesterase inhibitors (e.g., succinylcholine, bethanecol): A synergistic effect may be expected when cholinesterase inhibitors are given concurrently with succinylcholine, similar neuromuscular blocking agents or cholinergic agonist such as bethanechol.
Drugs highly bound to plasma proteins (e.g., furosemide, digoxin, warfarin): Donepezil did not affect the binding of furosemide, digoxin and warfarin to human albumin. Similarly, the binding of donepezil to human albumin was not affected by furosemide, digoxin and warfarin.