Drug interactions between Demerol and Tagamet

MONITOR: Coadministration with cimetidine may increase the plasma concentrations of meperidine. The proposed mechanism is cimetidine inhibition of meperidine metabolism via hepatic microsomal enzymes. In eight young, healthy volunteers, cimetidine (1200 mg orally per day for 7 days) decreased total body clearance and volume of distribution of meperidine (70 mg single intravenous dose) by 22% and 13%, respectively, compared to administration of meperidine alone. The peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of the pharmacologically active metabolite, normeperidine, was reduced by 29% and 23%, respectively. In another study, ranitidine (150 mg twice a day) was found to have no significant effect on the pharmacokinetics of meperidine in eight healthy volunteers.

MANAGEMENT: Caution is advised if meperidine must be used with cimetidine. Patients should be closely monitored for potentially excessive or prolonged central nervous system and respiratory depression. Ambulatory patients should be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them. Patients should also be advised to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Alternatively, use of another H2-antagonist such as famotidine, nizatidine, or ranitidine may be considered, as these agents have not been shown to significantly affect CYP450 metabolism.