No pharmaceutical opinion available for this interaction.
Darunavir / ritonavir can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.
2C9, 2C19, 2C8 (moderate), UGT (moderate)
3A4 (strong), 2D6 (moderate), 2B6 (probable)
Transporters: P-gp (enterocyte), MATE-1, liver catalyzed by esterases, UGT (less than 10%)
Probably without any clinical consequence.
No a priori dosage adjustment is recommended.
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.
Some studies have shown a significant increase in dabigatran bioavailability when administered with P-gp inhibitors. While others showed no interaction.
Ref #3341 : Contrary to expectations, in a study with 16 healthy subjects, no significant changes in dabigatran exposure were observed with simultaneous ritonavir administration, possibly due to mixed induction and inhibition of P-gp by ritonavir. Researchers conclude that dabigatran could likely be co-administred with ritonavir.
Ref # 3133: In addition, a sub-analysis of the Re-Ly study (18,113 patients with atrial fibrillation receiving dabigatran 150 or 110 mg BID) mentions that P-gp inhibitors modestly increase dabigatran plasma concentration and that the risk of major bleeding and stroke was not different between patients on warfarin and dabigatran patients with concomitant use of P-gp inhibitors.
Ref #3158 : Case report showed no interaction when dabigatran administered to a patient on lopinavir/ritonavir. In this case report the patient had initially received 75 mg BID with low Cmin measured. With 110 mg BID dose, measured concentration was comparable to the concentrations obtained in the Re-Ly study.
Ref #3398 : Case report of a 60-year old HIV+ man taking combined antiretroviral therapy (containing atazanavir/ritonavir) with concomitant use of dabigatran. Combination was tolerated, dabigatran blood levels within the expected range and there was no evidence of bleeding or other adverse effects. This case suggests that dabigatran may be a viable option.
Ref #3399 : Another case report showed no interaction when using dabigatran with darunavir/ritonavir.
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.