Donepezil Cimetidine

Clinically important, potentially hazardous interactions with bethanechol, cimetidine, donepezil, edrophonium, physostigmine, pilocarpine, rivastigmine, succinylcholine, tacrine... 

Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified. Three of the human metabolites of donepezil have not undergone extensive safety tests in animals. These comprise two O-demethylated derivatives and an N-oxidation product. Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 and undergoes glucuronidation. The rate of metabolism of donepezil is slow and does not appear to be saturable. These findings are consistent with the results from formal pharmacokinetic studies which showed that donepezil and/or its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine, or digoxin... 

P.J. Tiseo, C.A. Perdomo, L.T. Friedhoff, Concurrent administration of donepezil HC1 and cimetidine assessment of pharmacokinetic changes following single and multiple doses, Br. J. Cline. Pharmacol. 46 (1998) 25-29. 

Cimetidine possibly increases the effects of tacrine. Cimetidine does not appear to significantly affect the pharmacokinetics of donepezil or galantamine, and ranitidine does not affect the bioavailability of galantamine. 

In one study, donepezil 5 mg daily was given to 18 healthy subjects with cimetidine 800 mg daily. It was found that after one week of concurrent use the maximum serum levels and AUC of donepezil were increased by 13% and 10%, respectively. Donepezil had no effect on the pharmacokinetics of cimetidine. None of the increases in donepezil levels were considered to be clinically relevant. ... 

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