OBJECT DRUGS

• Lomitapide (Juxtapid)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Amprenavir (Agenerase)
• Aprepitant (Emend)
• Atazanavir (Reyataz)
• Boceprevir (Victrelis)
• Ceritinib (Zykadia)
• Cobicistat (Stribild)
• Conivaptan (Vaprisol)
• Cyclosporine (Neoral, etc.)
• Darunavir (Prezista)
• Delavirdine (Rescriptor)
• Dronedarone (Multaq)
• Fluvoxamine (Luvox, etc.)
• Grapefruit
• Imatinib (Gleevec)
• Indinavir (Crixivan)
• Lapatinib (Tykerb)
• Mifepristone (Korlym)
• Nefazodone
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Invirase)
• Telaprevir (Incivek)

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: Use an alternative to the enzyme inhibitor if possible.
• Antidepressants: Sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro), venlafaxine (Effexor), and paroxetine (Paxil) appear less likely to inhibit CYP3A4. Fluoxetine (Prozac) appears to be only a weak inhibitor of CYP3A4.
• Grapefruit: Orange juice does not appear to inhibit CYP3A4.