OBJECT DRUGS

• Eplerenone (Inspra)

PRECIPITANT DRUGS

Antimicrobials:

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

Comment:

Eplerenone is metabolized primarily by CYP3A4, and inhibitors of CYP3A4 may produce marked increases the serum levels of eplerenone. This may increase the risk of eplerenone toxicity, and the manufacturer states that eplerenone is contraindicated with potent CYP3A4 inhibitors.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4, and has been shown to produce moderate increases in plasma eplerenone concentrations. Terbinafine (Lamisil) does not appear to affect CYP3A4, and would not be expected to interact with eplerenone.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4. (*not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
• Monitor: If CYP3A4 inhibitors are used with eplerenone, monitor for excessive eplerenone effects such as hypotension and hyperkalemia; reduce eplerenone dose as needed.