MajorHIV protease inhibitor / pharmacokinetic booster×Direct oral anticoagulants (factor Xa inhibitors)
Updated · Methodology
Mechanism
Ritonavir strongly inhibits CYP3A4 and P-glycoprotein, both clearance routes of rivaroxaban. Ritonavir 600 mg twice daily raised rivaroxaban AUC 2.5-fold and peak concentration 1.6-fold. The EU SmPCs of rivaroxaban and ritonavir do not recommend the combination, and the FDA labels say to avoid it. None of these labels lists the pair as a contraindication.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage, gross haematuria with renal colic, spontaneous retroperitoneal haematomas. Symptoms may appear within days of co-prescription.
Management
Avoid the combination. In a patient with HIV, choose a ritonavir-free antiretroviral regimen where possible or switch the anticoagulant. Warfarin is an option with frequent INR checks: ritonavir lowers R-warfarin levels, and the ritonavir SmPC advises INR monitoring. Another option is a short course of low molecular weight heparin. Nirmatrelvir with ritonavir for COVID-19 also contains ritonavir, and its SmPC does not recommend use with rivaroxaban.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.
Summary of a multi-drug list →
Medicine list: everything you take in one place →
Sources
- FDA: Xarelto (rivaroxaban) prescribing information (2026)– FDA label, DailyMed setid 10db92f9-2300-4a80-836b-673e1ae91610, version 65, revised 09/2026, sections 5.2 and 7.4
- FDA: Norvir (ritonavir) prescribing information (2026)– AbbVie. NORVIR (ritonavir) tablets, oral solution, oral powder. Prescribing information, DailyMed setid 2849298e-de6e-47bb-8194-56e075b33fc3, section 7.2
- EMA: Xarelto (rivaroxabán) – ficha técnica en CIMA (2026)– AEMPS CIMA, Xarelto 20 mg comprimidos recubiertos con película, nº registro 08472018 (EU/1/08/472), secciones 4.3, 4.4 y 4.5
- EMA: Norvir (ritonavir) – ficha técnica en CIMA (2026)– AEMPS CIMA, Norvir 100 mg comprimidos recubiertos con película, nº registro 96016005 (EU/1/96/016), secciones 4.3 y 4.5