Drug Interactions between lomitapide and vadadustat

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of lomitapide, which is primarily metabolized by the isoenzyme. Weak CYP450 3A4 inhibitors increase lomitapide exposure by approximately 2-fold according to the product labeling.

MONITOR CLOSELY: Coadministration of lomitapide with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. In a premarketing clinical trial, 34% (10/29) of patients treated with lomitapide had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times the upper limit of normal (ULN) or greater, and 14% (4/29) had at least one elevation in ALT or AST 5 times ULN or greater. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase. Lomitapide also increases hepatic fat, with or without concomitant increases in transaminases. In the same study, the median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with lomitapide may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. Clinical data suggest that hepatic fat accumulation is reversible after stopping treatment with lomitapide, although the long-term consequences are unknown.

MANAGEMENT: The maximum recommended dosage of lomitapide is 30 mg daily when used in combination with weak CYP450 3A4 inhibitors such as amiodarone, atorvastatin, bicalutamide, cyclosporine, danazol, isoniazid, ivacaftor, lapatinib, nilotinib, pazopanib, zafirlukast, and zileuton. Caution is advised because these agents may also have additive hepatotoxic effects with lomitapide. Patients treated with lomitapide should have serum ALT, AST, alkaline phosphatase, and total bilirubin monitored prior to initiation of treatment and regularly during treatment in accordance with the product labeling, and the dosing adjusted or interrupted as necessary. Since alcohol may increase levels of hepatic fat and induce or exacerbate liver injury, the manufacturer recommends that patients taking lomitapide not consume more than one alcoholic drink per day. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.