Ketoconazole Donepezil

Donepezil Ketoconazole Inhibited metabolism of donepezil Monitor for donepezil toxicity dose reduction not empirically necessary... 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Drugs that may affect donepezil are CYP450 3A4 and 2D6 inhibitors (eg, ketoconazole, quinidine) and CYP450 3A4 and 2D6 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin). Drugs that may be affected by donepezil include anticholinergics, cholinometics/cholinesterase inhibitors, NSAIDs. 

Donepezil, rivastigmine, and galantamine are newer cholinesterase inhibitors with adequate penetration into the CNS and a spectrum of action more limited to indirect cholinomimetic effects than tacrine s. The cholinesterase inhibitors should be used with caution in patients receiving other drugs that inhibit cytochrome P450 enzymes (eg, ketoconazole, quinidine see Chapter 4 Drug Biotransformation). 

Donepezil 5 mg produced no change in plasma concentrations of ketoconazole 200 mg (40). 

Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HCl and ketoconazole assessment of pharmacokinetic changes following single and multiple doses. Br J Clin Pharmacol 1998 46(Suppl l) 30-4. 

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