Box 1: Clinical scenarios with the potential to increase bleeding risk in patients who are taking rivaroxaban*
ScenarioDetailsSuggested management
Combined P-gp and strong CYP3A4 inhibitorAntifungals: posaconazole, itraconazole, ketoconazole
Macrolide: clarithromycin
Avoid these medications
Combined P-gp and/or moderate CYP3A4 inhibitorAntimicrobials: erythromycin, ciprofloxacin, fluconazole, voriconazole, isoniazid
Antidepressants: fluoxetine, fluvoxamine, sertraline
Antihypertensives: verapamil, diltiazem
Antiarrhythmic: amiodarone
Antivirals for HIV: atazanavir, efavirenz, telaprevir
Use these medications with caution; consider a lower dose of rivaroxaban
Concomitant use of drugs affecting hemostasisAnti-inflammatory agents: NSAIDs
Antiplatelet agents: ASA, clopidogrel, prasugrel, ticagrelor
Use these medications with caution; re-evaluate need for antiplatelet therapy
Dietary productsGrapefruit juice, dietary quinineUse these products with caution
Renal failureCrCl 30–49 mL/minDecrease the dose of rivaroxaban (to 15 mg/d)
CrCl < 30 mL/minAvoid use of rivaroxaban
Liver failureChild–Pugh class B and CAvoid use of rivaroxaban
  • Note: ASA = acetylsalicylic acid, CrCl = creatinine clearance, CYP = cytochrome P450, NSAID = nonsteroidal anti-inflammatory drug, P-gp = P-glycoprotein.

  • * Sources: Mueck and associates,7 rivaroxaban product monograph9 and the Department of Medicine, Indiana University (

  • Based on expert opinion; this guidance must be interpreted in patient-specific context.

  • The list of potential moderate CYP3A4 inhibitors is not exhaustive; for a more comprehensive list, see the list prepared by the Department of Medicine, Indiana University (