Key result
Coadministration of a single 10 mg dose of rivaroxaban with antiretroviral therapy including ritonavir and darunavir resulted in severe postoperative bleeding and a significantly elevated rivaroxaban trough level of 75 ng/mL.
Case Report (n=1)
No
Concomitant administration of rivaroxaban and antiretroviral protease inhibitors can result in significantly elevated rivaroxaban levels and severe bleeding due to CYP3A4 and P-glycoprotein inhibition.
May warrant caution with rivaroxaban in patients on ritonavir-boosted ARVs; hypothesis-generating case that leaves open interaction magnitude.
A 62-year-old man was admitted to hospital for elective revision of a left total hip arthroplasty. His history was significant for human immunodeficiency virus (HIV) infection for which he was taking the following antiretroviral agents (ARVs): etravirine, ritonavir, darunavir, raltegravir and tenofovir/emtricitabine. Rivaroxaban 10 mg daily was commenced on the second postoperative day for venous thromboembolism (VTE) prophylaxis. Approximately 24 h later, the patient developed hypotension and anaemia, accompanied by thigh swelling due to bleeding at the surgical site. Fluid resuscitation was commenced with red cell transfusion. The prothrombin time (PT) was prolonged at 24.3 (10.6-15.3) s, and a rivaroxaban level taken 24 h after administration was 75 ng/mL. Rivaroxaban was ceased, the PT normalised within 24 h of stopping the drug, and the patient made an uneventful recovery. None of the other coadministered drugs are known to interact with rivaroxaban, or are likely to, based on their metabolic pathways. Rivaroxaban, a substrate for cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), is contraindicated in patients concomitantly treated with strong inhibitors of both these systems, e.g. protease inhibitors (PIs) such as ritonavir (based on in vitro data and a pharmacokinetic study in healthy volunteers). No published data are available on the PI darunavir, a moderate inhibitor; however, concomitant use with rivaroxaban should also be avoided. A prolonged PT and a rivaroxaban trough level greater than eight times that predicted from pharmacokinetic modelling suggests that bleeding was due to increased exposure to rivaroxaban, probably due to an interaction with ritonavir and darunavir. This is supported by a Drug Interaction Probability Scale (DIPS) score of 8. An interaction between a single dose of rivaroxaban and ARVs may be clinically significant; therefore, the patient's medication history should be extensively evaluated to identify any potential interactions.
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Corallo et al. (2015) conducted a case report in HIV infection and postoperative VTE prophylaxis (n=1). Rivaroxaban coadministered with antiretroviral therapy (ritonavir, darunavir) was evaluated on Bleeding event and rivaroxaban trough level. Coadministration of a single 10 mg dose of rivaroxaban with antiretroviral therapy including ritonavir and darunavir resulted in severe postoperative bleeding and a significantly elevated rivaroxaban trough level of 75 ng/mL.
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