OBJECT DRUGS
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:
Lomitapide is metabolized by CYP3A4, and inhibitors of CYP3A4 can produce dramatic increases in lomitapide plasma concentrations. For example, the strong CYP3A4 inhibitor, ketoconazole, produced a 27-fold increase in lomitapide AUC. Because increased lomitapide plasma levels can cause substantial toxicity, particularly hepatotoxicity, combining lomitapide with strong (or moderate) CYP3A4 inhibitors is considered contraindicated.
Class 1: Avoid Combination
- Avoid: These enzyme inhibitors should not be given to patients receiving lomitapide due to the risk of serious hepatotoxicity and other toxic effects.
- Use Alternative:
- Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4, and would not be expected to interact with lomitapide.
- 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.