Drug Interactions between atazanavir / cobicistat and dabigatran

MONITOR: Coadministration with cobicistat may increase the plasma concentrations of dabigatran, particularly in patients with renal impairment. The mechanism is inhibition of P-glycoprotein (P-gp) by cobicistat. In a single-center, two-arm, single-sequence, open-label study, dabigatran AUC and Cmax each increased by 127% when administered simultaneously with cobicistat (p-value less than 0.001 for AUC and Cmax). When administration of dabigatran and cobicistat was separated by 2 hours, dabigatran AUC and Cmax increased by 110% and 99%, respectively (p-value less than 0.001 for AUC and Cmax). In addition, thrombin time (TT) at 24 hours post-dose increased by 51% and 46% when cobicistat was given simultaneously and separated, respectively, compared to dabigatran alone (p-value less than 0.001 for both).

MANAGEMENT: Coadministration of dabigatran with cobicistat is not recommended in certain patients with renal impairment. If concomitant use is necessary, clinical and laboratory monitoring is recommended and the dabigatran dosage should be adjusted as necessary. Patients should be monitored closely for the development of bleeding complications.