Interactions : אינטראקציות

4.5   Interaction with other medicinal products and other forms of interaction

Donepezil hydrochloride and/or any of its metabolites do not inhibit the metabolism of theophylline, warfarin, cimetidine or digoxin in humans. The metabolism of donepezil hydrochloride is not affected by concurrent administration of digoxin or cimetidine. In vitro studies have shown that the cytochrome P450 isoenzymes 3A4 and to a minor extent 2D6 are involved in the metabolism of donepezil. Drug interaction studies performed in vitro show that ketoconazole and quinidine, inhibitors of CYP3A4 and 2D6 respectively, inhibit donepezil metabolism. Therefore these and other CYP3A4 inhibitors, such as itraconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine could inhibit the metabolism of donepezil. In a study in healthy volunteers, ketoconazole increased mean donepezil concentrations by about 30%.
Enzyme inducers, such as rifampicin, phenytoin, carbamazepine and alcohol may reduce the levels of donepezil. Since the magnitude of an inhibiting or inducing effect is unknown, such drug combinations should be used with care. Donepezil hydrochloride has the potential to interfere with medications having anticholinergic activity. There is also the potential for synergistic activity with concomitant treatment involving medications such as succinylcholine, other neuro-muscular blocking agents or cholinergic agonists or beta blocking agents that have effects on cardiac conduction.

Cases of QTc interval prolongation and Torsade de Pointes have been reported for donepezil.
Caution is advised when donepezil is used in combination with other medicinal products known to prolong the QTc interval and clinical monitoring (ECG) may be required. Examples include:
•     Class IA antiarrhythmics (e.g. quinidine)
•     Class III antiarrhythmics (e.g. amiodarone, sotalol)
•     Certain antidepressants (e.g. citalopram, escitalopram, amitriptyline)
•     Other antipsychotics (e.g. phenothiazine derivatives, sertindole, pimozide, ziprasidone)
•     Certain antibiotics (e.g. clarithromycin, erythromycin, levofloxacin, moxifloxacin)