Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia

Purpose: The pharmacology, pharmacokinetics, and clinical efficacy and safety of lomitapide in the management of homozygous familial hypercholesterolemia (HoFH) are reviewed.

Summary: Lomitapide (Juxtapid, Aegerion Pharmaceuticals) is an oral microsomal triglyceride transfer protein (MTP) inhibitor indicated for the treatment of patients with HoFH, a rare form of hypercholesterolemia that can lead to premature atherosclerotic disease. In clinical trials, the use of lomitapide alone or in combination with other lipid-lowering modalities reduced plasma concentrations of low-density lipoprotein Cholesterol (LDL-C) by a mean of more than 50%. Lomitapide is associated with significant gastrointestinal adverse effects and increases in hepatic fat levels. Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin; dose adjustment is recommended when lomitapide is used concurrently with these agents. In patients receiving concomitant warfarin, the International Normalized Ratio (INR) should be closely monitored, as lomitapide use may increase INR values. The recommended initial dosage of lomitapide is 5 mg once daily, with subsequent upward dose adjustment at specified intervals according to tolerability. Lomitapide is contraindicated in patients with moderate-to-severe liver disease, patients with sustained abnormal liver function tests, patients taking strong or moderate CYP3A4 inhibitors, and pregnant patients.

Conclusion: Lomitapide is an oral MTP inhibitor approved for the treatment of HoFH. This agent appears to be a realistic option for patients with HoFH who are unable to attain their LDL-C goal or cannot tolerate statin therapy.