OBJECT DRUGS
PRECIPITANT DRUGS
Enzyme Inhibitors:
- Alprazolam (Xanax, etc.)
- Bicalutamide (Casodex)
- Cilostazol (Pletal)
- Cimetidine (Tagamet, etc.)
- Contraceptives, Oral
- Fluoxetine (Prozac, etc.)
- Ranolazine (Ranexa)
- Ticagrelor (Brilinta)
- Zileuton (Zyflo, etc.)
Comment:
Lomitapide is metabolized by CYP3A4, and even these "weak" inhibitors of CYP3A4 can produce increases in lomitapide plasma concentrations. For example oral contraceptives (considered weak CYP3A4 inhibitors) produced about a doubling of lomitapide exposure. Because increased lomitapide plasma levels can cause substantial toxicity, particularly hepatotoxicity, combining lomitapide with weak CYP3A4 inhibitors may require a reduction in lomitapide dosage.
Class 3: Assess Risk & Take Action if Necessary
- Circumvent/Minimize: It would be prudent to limit lomitapide dosage to 30 mg/day in patients also taking any of these "weak" CYP3A4 inhibitors.
- Consider Alternative:
- Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) are unlikely to affect CYP3A4 activity, even though the lomitapide product information suggests that ranitidine is a weak CYP3A4 inhibitor.
- Antidepressants: Sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4.
- Monitor: If these combinations are used, monitor for evidence of lomitapide toxicity (eg, hepatotoxicity).