Box 1: Clinical scenarios with the potential to increase bleeding risk in patients who are taking rivaroxaban*

Scenario	Details	Suggested management^†
Combined P-gp and strong CYP3A4 inhibitor	Antifungals: posaconazole, itraconazole, ketoconazole Macrolide: clarithromycin	Avoid these medications
Combined P-gp and/or moderate CYP3A4 inhibitor^‡	Antimicrobials: 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 hemostasis	Anti-inflammatory agents: NSAIDs Antiplatelet agents: ASA, clopidogrel, prasugrel, ticagrelor	Use these medications with caution; re-evaluate need for antiplatelet therapy
Dietary products	Grapefruit juice, dietary quinine	Use these products with caution
Renal failure	CrCl 30–49 mL/min	Decrease the dose of rivaroxaban (to 15 mg/d)
Renal failure	CrCl < 30 mL/min	Avoid use of rivaroxaban
Liver failure	Child–Pugh class B and C	Avoid 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 (http://medicine.iupui.edu/clinpharm/ddis/clinical-table).
↵† 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 (http://medicine.iupui.edu/clinpharm/ddis/clinical-table).