No pharmaceutical opinion available for this interaction.
Cobicistat can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.
3A4 (major) and 2D6 (minor).
3A4 (strong) et 2D6 (moderate), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3.
Choose an antiretroviral that does not have this interaction.
Transporters: P-gp (enterocyte), MATE-1, liver catalyzed by esterases, UGT (less than 10%)
Possible increase of adverse effects.
Choose an alternative.
If this combination cannot be avoided, give only after considering increased risk of bleeding: co-administration with antiplatelet (including aspirin or NSAIDs), age > 75 years, weight < 60kg, impaired renal function, systemic corticosteroids,
history or active gastrointestinal bleeding, recent surgery (eyes, brain), thrombocytopenia (eg chemotherapy), HAS-BLED ≥ 3.
Use this combination with caution.
Prefer warfarin or low molecular weight heparin (LMWH).
|150 mg||150 mg|
|150 mg *||150 mg †|
|x 1 *||x 1 †|
|+ 99% (2x)||+ 127% (2.3x)|
|+ 110% (2.1x)||+ 127% (2.3x)|
Ref #3341 : * Dabigatran given 2 hours before cobicistat.
† Dabigatran given simultaneously with cobicistat.
Unlike ritonavir, cobicistat significantly increased dabigatran concentrations weither being administered simultaneously or 2 hours after dabigatran. The anticoagulant effect was also increased, with a 46-51% increase in thrombin time (TT) at 24 hours and a 30-33% increase in TT-AUC. Researchers conclude that dabigatran should be co-administered with cobicistat with caution by decreasing dabigratran dosing or by spacing administration with cobicistat by ≥4 hours, in addition with close monitoring of its anticoagulant effect.
The product monograph recommended dose adjustments when used for prevention of venous thrombophlebitis after surgery:
A. With potent P-gp inhibitors (as ketoconazole): Avoid administration.
B. With P-gp inhibitors (amiodarone, quinidine, verapamil°): Consider dose reduction. See product monograph for indications.
C. With P-gp inhibitors (amiodarone, quinidine, vérapamil°) and moderate renal impairment (ClCre 30-50 ml/min) : Consider a greater dose reduction. See product monograph for indications.
D. With other P-gp inhibitors (cyclosporine, itraconazole, posaconazole, nelfinavir, ritonavir, saquinavir) : Exercer un suivi plus étroit.
° For verapamil, it is also recommended to avoid concurrent administration. Give dabigatran 2 hours before verapamil.