Drug Interaction Report

Coadministration with proton pump inhibitors or H2-receptor antagonists may modestly affect the pharmacokinetics of prasugrel, but does not appear to alter its antiplatelet effects. The proposed mechanism is delayed prasugrel dissolution due to increased gastric pH. In 24 healthy subjects, administration of a single 60 mg dose of prasugrel following pretreatment with lansoprazole 30 mg/day for 7 days resulted in a 29% decrease in the peak plasma concentration (Cmax) of the active metabolite of prasugrel and a nonsignificant (12%) decrease in the metabolite's systemic exposure (AUC) compared to administration of prasugrel alone. Lansoprazole had no significant effect on the response to prasugrel as measured by ADP-induced platelet aggregometry. Similarly, daily coadministration of ranitidine reduced the Cmax of the prasugrel active metabolite by 14%, but did not significantly change the AUC or Tmax. No dosage adjustment for prasugrel is necessary when coadministered with drugs that elevate gastric pH, including proton pump inhibitors and H2-receptor antagonists. However, administration of the 60 mg prasugrel loading dose without concomitant use of proton pump inhibitors may provide most rapid onset of action.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.