MajorSystemic antimycotics. Imidazole derivatives×Direct oral anticoagulants (factor Xa inhibitors)
Updated · Methodology
Mechanism
Ketoconazole strongly inhibits CYP3A4 and P-glycoprotein, both clearance routes of rivaroxaban. Ketoconazole 400 mg daily raised rivaroxaban AUC 2.6-fold and peak concentration 1.7-fold. The EU SmPCs of rivaroxaban and oral ketoconazole do not recommend the combination, and the FDA labels say to avoid it. No label 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. For dermatophytosis, terbinafine is the usual choice instead of oral ketoconazole; for systemic mycoses, echinocandins. If a short course of oral ketoconazole is needed, switch rivaroxaban to a parenteral anticoagulant for that period.
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 (2023)– ; DailyMed setid 10db92f9-2300-4a80-836b-673e1ae91610
- 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: Ketoconazole Esteve (formerly Ketoconazole HRA) 200 mg tablets – Summary of Product Characteristics (2026)– EMA EPAR product information, Ketoconazole HRA / Ketoconazole Esteve 200 mg tablets (EU/1/14/965), sections 4.3 and 4.5