Darunavir / ritonavir



Available pharmaceutical opinion

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


Darunavir / ritonavir can inhibit the CYP 3A4 and P-gp and increase the plasma concentration of Apixaban.

Darunavir / ritonavir

Pharmacodynamic effects


If possible, consider an alternative.

Alternative solution(s)

Bictegravir, dolutegravir, raltegravir or rilpivirine.


Pharmacodynamic effects

Increased risk of severe bleeding including hemorrhage.


The canadian monograph contraindicates this combination.

For patients receiving a 5 or 10 mg BID dose of apixaban, the US Product Monograph suggests a 50% dose reduction when given with potent CYP3A4 or P-gp inhibitors.

This combination, however, should be avoided in patients already taking apixaban 2.5 mg BID or with two or more risk factors for bleeding (elderly ≥ 80 years, low weight ≤ 60 kg, serum creatinine ≥ 133 μmol/L).

Monitor the clinical efficacy and appearance of adverse effects.

See comments.

Alternative solution(s)

Prefer warfarin or potentially dabigatran or low molecular weight heparin (LMWH).


Adverse effects of apixaban : nausea, symptoms of bleeding and anemia. We should also follow CBC closely to detect thrombocytopenia and anemia that may result from apixaban administration.


Pharmacokinetic parameters


Ref #2690 : A pharmacokinetic study with a strong CYP3A4 inhibitor, ketoconazole, has shown an increase in apixaban AUC and Cmax of 2-fold and 1.6-fold, respectively. With diltiazem, a moderate CYP3A4 inhibitor, an increase was observed in apixaban AUC and Cmax of 1.3-fold and 1.4-fold, respectively.

Currently available data are not sufficient to define a clear recommendation. In addition, we do not have a specific marker to monitor the efficacy of apixaban or antidote.

Thus, the apixaban monograph considers as contraindicated concomitant administration of this drug with agents that inhibit both CYP3A4 and P-gp. Warfarin can be used as an alternative (see warfarin and PI/r).

However, if the association can be avoided, the American monograph recommends lowering the dose to 2.5 mg BID if the patient has no risk factors for bleeding. The association, however, should be avoided in patients already taking apixaban 2.5 mg bid or with two or more risk factors for bleeding (elderly ≥ 80 years, low weight ≤ 60 kg, serum creatinine ≥ 133 μmol/L).

Ref #3695 : This article reports the successful use of reduced dose apixaban to treat and prevent thromboembolic complications in six people living with HIV on ART boosted with ritonavir or cobicistat and may support US recommendations.

  • 2386
    Darunavir (Prezista), Janssen, Ontario, Canada, 23 mai 2018.
  • 2969
    Apixaban, Angita Pharma Inc., Québec, Canada, 20 septembre 2023.
  • 2970
    Apixaban (Eliquis) Prescribing Information, Bristol-Myers Squibb - Pfizer, New Jersey - New York, USA, April 2021.
  • 2690
    Frost C, Wang J, Nepal S, Schuster A, Zhang D, Yu Z et al. Effect of ketoconazole and diltiazem on the pharmacokinetics of apixaban, an oral direct factor Xa inhibitor. J Clin Pharmacol 2009; 49: 1123. Abstract 139.
  • 3151
    U.S. Department of Health and Human services (DHHS) : Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Disponible : https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/whats-new. Publié le 6 décembre 2023. Consulté le 20 février 2024.
  • 3695
    Nisly SA, Stevens BN. Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: A case for apixaban. Int J STD AIDS. 2019 Jun; 30 (7) : 718-722.
  • 3694
    Sabourin AA, Patel T, Saad S, Renner E, Mouland E, et al. Management of anticoagulation in patients with human immunodeficiency virus/acquired immunodeficiency virus. Thromb Res. 2021 Apr: 200: 102-108.
  • 2691
    Vakkalagadda B, Frost C, Wang J, Nepal S, Schuster A, Zhang D et al. Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of factor Xa. J Clin Pharmacol 2009; 49:1124. Abstract 143.
  • 2692
    Wong PC, Pinto DJP and Zhang D. Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor. J Thromb 2011; 31:478–492.
  • 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.
  • 3000
    Wang L, Zhang D, Raghavan N, et al. In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010 Mar; 38(3): 448-58.
  • 3001
    Jalota A, Scarabelli TM, Saravolatz L, Bakhsh MU, Agrawal P et al. Novel anticoagulants for stroke prevention in patients with atrial fibrillation. Cardiovasc Drugs Ther. 2014 Jun; 28(3): 247-62.
  • 3002
    Nutescu E. Apixaban : a novel oral inhibitor of factor Xa. Am J health Syst Pharm 2012; 69(13): 1113-26.
  • 3003
    Raghavan N, Frost CE, Yu Z et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009; 37: 74–81.
  • 2999
    Wigle P, Hein B, Bloomfield HE et al. Update guidelines on outpatient anticoagulantion. American Family Physician 2013; 87(8); 557-566.
  • 2997
    Bleeding with dabigatran, rivaroxaban, apixaban. No antidote, and little clinical experience. Prescrire Int. 2013 Jun; 22 (139): 155-9.
  • 3131
    European Commission Approves Eliquis (apixaban) for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), and Prevention of Recurrent DVT and PE. Bristol-Myers-Squibb, New York. Disponible : http://news.bms.com/press-release/european-commission-approves-eliquis-apixaban-treatment-deep-vein-thrombosis-dvt-and-p. Publié 29 juillet 2014. Consulté le 10 juin 2015.
  • 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.