Liverpool HIV Interactions

Potential Interaction

Darunavir + ritonavir (DRV/r)

Apixaban

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by darunavir/ritonavir, thereby increasing the bleeding risk. The product labels for apixaban do not recommend the concomitant use with strong dual CYP3A4 and P-gp inhibitors, although the US label gives the option to use apixaban at a reduced dose if needed. Note, patients already receiving apixaban at a dose of 2.5 mg twice daily should avoid coadministration with strong dual CYP3A4 and P-gp inhibitors. Of interest, there are case reports of no adverse outcomes in HIV infected patients treated with a reduced dose of apixaban (2.5 mg twice daily) while on ritonavir or cobicistat boosted regimens which supports the option of dose reduction given in the US label.

Description:

Coadministration has not been studied. Co-administration of boosted darunavir with apixaban may increase concentrations of the anticoagulant due to CYP3A and/or P-gp inhibition which may lead to an increased bleeding risk. The use of boosted darunavir and this anticoagulant is not recommended.

Prezista Summary of Product Characteristics, Janssen-Cilag Ltd, September 2022.

Concentrations of apixaban may be increased when co-administered with darunavir/ritonavir. Due to potentially increased bleeding risk, dosing recommendations for coadministration of apixaban with darunavir/ritonavir depend on the apixaban dose. Refer to apixaban dosing instructions for co-administration with P-gp and strong CYP3A inhibitors in apixaban prescribing information.

Prezista Prescribing Information, Janssen Pharmaceuticals Inc, March 2023.

A case was reported of a 73-year-old man with a history of AF, resolved left ventricular thrombus, and who was receiving darunavir/ritonavir (800/100 mg twice daily) for the treatment of HIV. Apixaban was initiated at 2.5 mg as recommended by the US Prescribing Information in the presence of ritonavir. The patient did not suffer thrombus or bleeding and was discharged 4 days later. Apixaban was continued indefinitely. The authors conclude this case adds to a growing body of evidence that apixaban may be safely coadministered at a reduced dose with ritonavir.

Use of apixaban in atrial fibrillation with ritonavir-boosted antiretroviral therapy: a case report. Lomakina V , Sozio SJ, and Tekle J. J Pharm Pract, 2023, 36(3):728-732.

No adverse outcomes were reported in six HIV infected patients treated with a reduced dose of apixaban (2.5 mg twice daily) while on ritonavir or cobicistat boosted regimens (DRV/r [n=3], ATV/r, LPV/r, EVG/c). The US product label for apixaban recommends to avoid concomitant use or to reduce apixaban dose by half (i.e. 2.5 mg twice daily) in presence of strong dual inhibitors of CYP3A4 and P-gp; the European label does not recommend coadministration. This case series of real-world experiences supports the option of dose reduction.

Ritonavir- or cobicistat-boosted antiretroviral therapy and direct oral anticoagulants: a case for apixaban. Nisly SA, Stevens BN. Int J STD AIDS, 2019, Int J STD AIDS. 2019, 30(7):718-722.

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