OBJECT DRUGS

Anticoagulants, Oral:

• Apixaban (Eliquis)
• Rivaroxaban (Xarelto)

PRECIPITANT DRUGS

Antimicrobials:

• Ciprofloxacin (Cipro, etc.)
• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Isoniazid (INH)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Quinupristin (Synercid)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

These antimicrobials inhibit CYP3A4 and may increase the plasma concentration of apixaban and rivaroxaban. Since apixaban and rivaroxaban are also substrates for P-glycoprotein, precipitant drugs that inhibit both CYP3A4 and P-glycoprotein may produce a larger increase in anticoagulant concentrations.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Fluconazole appears to be a less potent inhibitor of CYP3A4; but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4.
• Macrolide Antibiotics: Azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4 and are unlikely to interact. (*not available in US).
• Monitor: Monitor for altered rivaroxaban effect if one of these antimicrobials is initiated, discontinued or changed in dosage; adjustments of rivaroxaban dosage may be needed. If rivaroxaban is initiated in the presence of therapy with one of these agents, consider conservative doses of rivaroxaban.