OBJECT DRUGS

• Lomitapide (Juxtapid)

PRECIPITANT DRUGS

Calcium Channel Blockers:

• Diltiazem (Cardizem, etc.)
• Nicardipine (Cardene, etc.)
• Nifedipine (Procardia, etc.)
• Verapamil (Isoptin, etc.)

Comment:

Lomitapide is metabolized by CYP3A4, and calcium channel blockers that inhibit CYP3A4 are likely to produce substantial 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. There is substantial evidence that diltiazem and verapamil inhibit CYP3A4, and some evidence that nicardipine and nifedipine inhibit CYP3A4; there is little evidence that other calcium channel blockers inhibit CYP3A4, although the product information for lomitapide suggests that amlodipine may inhibit lomitapide metabolism.

Class 1: Avoid Combination

• Avoid: These calcium channel blockers 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.
• Calcium channel blockers: Calcium channel blockers other than diltiazem, nicardipine, nifedipine, and verapamil are less likely to inhibit the metabolism of lomitapide. Nonetheless, it would be prudent to monitor for lomitapide toxicity (i.e. hepatotoxicity) if any calcium channel blocker is given concurrently.