Drug Interactions between dabigatran and Quinidex Extentabs

MONITOR: Coadministration with potent inhibitors of P-glycoprotein such as quinidine may significantly increase the bioavailability of dabigatran following oral administration of dabigatran etexilate, which is a substrate of the efflux transporter. In three female study subjects administered dabigatran with 600 mg quinidine sulfate, systemic exposure to dabigatran was approximately twice that expected with dabigatran alone. In another study, administration of dabigatran over 3 days in combination with quinidine (200 mg every 2 hours up to a total dose of 1000 mg) on the third day resulted in a 56% increase in dabigatran peak plasma concentration (Cmax) and a 53% increase in systemic exposure (AUC) compared to administration of dabigatran alone. In a phase 3 clinical trial of dabigatran etexilate for the prevention of stroke and systemic embolism in patients with atrial fibrillation, concomitant administration of quinidine and dabigatran etexilate did not appear to increase the relative risk of bleeding compared to the combination of warfarin and quinidine.

MANAGEMENT: Caution is advised if dabigatran is used in combination with quinidine. Pharmacologic response to dabigatran should be monitored more closely whenever quinidine is added to or withdrawn from therapy, and the dabigatran dosage adjusted as necessary. Patients should be monitored for the development of anemia and bleeding complications during coadministration.