Atazanavir / ritonavir


Potential interaction.

Available pharmaceutical opinion

Document made available to the pharmacist to communicate a drug interaction to the doctor.


Atazanavir / ritonavir can inhibit the intestinal P-gp and increase the plasma concentration of Dabigatran.

Atazanavir / ritonavir

Pharmacodynamic effects


Alternative solution(s)


Pharmacodynamic effects

Possible increased anticoagulant effect and associated risk of bleeding.


No a priori dosage adjustment is recommended.

Use with caution when co-administered with a P-gp inhibitor especially in patients with mild or moderate renal impairment.

Monitor for adverse effects.

A decrease in dosage may be necessary.

A 2-hour dose separation between medications or a dose reduction to 110 mg BID should be considered in patients with moderate renal impairment.

See comments.

Alternative solution(s)

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.


Pharmacokinetic parameters


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 : Contrary to expectations, in this 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 ritonavir100 mg QD in patients with no renal impairment.
Note: Co-administration of dabigatran with higher daily doses of ritonavir has not been studied.

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.

  • 2638
    Dabigatran (Pradaxa), Boehringer Ingelheim, Ontario, Canada, 23 mars 2020.
  • 3341
    Kumar P, Gordon LA, Brooks KM, George JM, Kellogg A et al. Differential influence of the antiretroviral pharmacokinetic enhancers ritonavir and cobicistat on intestinal P-glycoprotein transport and the pharmacokinetic/pharmacodynamic disposition of dabigatran. Antimicrob Agents Chemother. 2017 Oct 24; 61(11).
  • 3528
    Wiggins BS, Dixon DL Neyens RR, Page RL et al. Select Drug-Drug Interactions With Direct Oral Anticoagulants: JACC Review Topic of the Week. J Am Coll Cardiol. 2020 Mar 24; 75 (11): 1341-50.
  • 3133
    Reilly PA, Connolly SJ, Ezekowitz MD, Haertter S, Noack H, Wallentin L, Yusuf S Concomitant use of Pglycoprotein inhibitors with dabigatran or warfarin in the RE-LY trial. ESC 2011, 33rd Cong of the European Society of Cardiology (ESC), Paris, 27-31 Aug 2011. Eur Heart J 32 (Suppl 1), 6 (2011).
  • 3658
    Lingineni K, Farhan N, Kim S, Cristofoletti R, Gordon LA, et al. Quantitative benefit-risk assessment of P-gp mediated drug-drug interactions (DDIs) of dabigatran co-administered with pharmacokinetic enhancers in patients with renal impairment. Clin Pharmacol Ther, 2021; 109 (1): 193-200.
  • 3158
    Barco S, Coppens M, van den Dool EJ, et al. Successful co-administration of dabigatran etexilate and protease inhibitors ritonavir/lopinavir in a patient with atrial fibrillation. Thromb Haemost 2014; 112: 836-8.
  • 3398
    Perram J, Joseph J, Holloway C. Novel oral anticoagulants and HIV: dabigatran use with antiretrovirals. BMJ Case Rep. 2015 Nov 20.
  • 3399
    Kakadiva PP, Higginson RT and Fulco PP. Ritonavir-Boosted Protease Inhibitors but Not Cobicistat Appear Safe in HIV-Positive Patients Ingesting Dabigatran. Antimicrob agents Chemother 2018 Jan 25; 62(2).
  • 2693
    Horn JR, Hansten PD. Dabigatran : a new oral anticoagulant. Pharmacy times 2010; 12(10): 59.
  • 2694
    Pradax (dabigatran). Pharmacist’s Letter/Prescriber’s Letter 2011; 27(1): 270119.
  • 2971
    Egan G, Hughes CA, Ackman ML. Drug interactions between antiplatelet or novel anticoagulant medications and antiretroviral medications. Ann Pharmacother. 2014 Jun; 48 (6): 734-40.
  • 2973
    INESSS : Anticoagulothérapie par le dabigatran. Décembre 2011.
  • 2998
    Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC et al. Updated European Heart Rythm association practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace, 2015 Oct; 17(10): 1467-507.
  • 2999
    Wigle P, Hein B, Bloomfield HE et al. Update guidelines on outpatient anticoagulantion. American Family Physician 2013; 87(8); 557-566.
  • 3004
    Ageno W, Gallus AS, Wittkowsky A et al. Oral anticoagulant therapy guidelines. CHEST 2012; 141(2): E44S-E88S.
  • 3132
    Gordon LA, Hadigan C, McManus M, et al. Influence of separated and concomitant administration of ritonavir on the anticoagulant effect of dabigatran etexilate in healthy volunteers. 15th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy, Washington DC USA, 19-21 may 2014. Abstract P_14.