Document made available to the pharmacist to communicate a drug interaction to the doctor.DOWNLOAD
Elvitegravir / Cobicistat can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.
Elvitegravir 3A4 and then UGT1A1/3; Cobicistat 3A4 (major) and 2D6 (minor)
Elvitegravir : 2C9 (moderate)
Cobicistat : 3A4 and 2D6 (potent), P-gp, MATE 1, BCRP, OATP1B1 and OATP1B3
Choose an antiretroviral that does not have this interaction.
P-gp and MATE-1, mainly eliminated in the urine (85%).
Possible increased anticoagulant effect and associated risk of bleeding.
Use this combination with caution.
A dose reduction to 110 mg BID should be considered.
Monitor for adverse effects.
A dose reduction to 75 mg BID should be considered in patients with moderate renal impairment.
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 #2368 : Some studies have shown a significant increase in dabigatran bioavailability when administered with P-gp inhibitors (ketoconazole and glecaprévir/pibrentasvir). The product monograph recommends caution when co-administering certain P-gp inhibitors, including but not limited to cyclosporine, itraconazole, nelfinavir, posaconazole, ritonavir, saquinavir, tacrolimus and tipranavir as they may increase systemic exposure to dabigatran.
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.