Document made available to the pharmacist to communicate a drug interaction to the doctor.DOWNLOAD
Darunavir / cobicistat can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.
3A4 (major) and 2D6 (minor)
3A4 (potent) and 2D6 (weak), 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%)
Increased risk 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).
Adverse effects of dabigatran: Bleeding (suspect bleeding if there is a drop in hemoglobin and/or hematocrit or hypotension), anemia, hematoma, hematuria, epistaxis, gastrointestinal disorders (abdominal pain, diarrhea, dyspepsia and nausea), gastrointestinal and urinary hemorrhage.
Ref #3341 : Unlike ritonavir, cobicistat significantly increased dabigatran concentrations (2-2.3-fold) 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.
See dabigatran + cobicistat.
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.