Pharmacology Update

Lomitapide Capsules (Juxtapid™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The first inhibitor of the microsomal triglyceride transport protein (MTP) has been approved for the treatment of homozygous familial hypercholesterolemia (HoFH). MTP is a key protein in the assembly and secretion of apolipoprotein B (ApoB)-containing lipoprotein in the liver and intestine.1 Inhibition of MTP by lomitapide affects the synthesis of chylomicrons and very low-density lipoprotein (VLDL). Lomitapide is marketed by Aegerion Pharmaceuticals as Juxtapid. It is only available through a restricted program, the Juxtapid Risk Evaluation and Mitigation Strategy program.


Lomitapide is indicated as an adjunct to a low-fat diet (< 20% of energy from fat) and other lipid-lowering treatments (e.g., LDL-apheresis) to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), ApoB, and non-high-density lipoprotein (non-HDL) cholesterol in patients with HoFH.1


The recommended initial dose is 5 mg once daily.1 The dose may be titrated to 10 mg once daily after 2 weeks based on safety/tolerability. The dose may be further titrated at a minimum of 4-week intervals to 20 mg, 40 mg, and to a maximum of 60 mg daily. Transaminase levels should be obtained before any dose increase. The dose should be adjusted if alanine (ALT) or aspartate aminotransferases (AST) is three times the upper limit of normal or higher. The capsule should be taken with water and without food at least 2 hours after the evening meal. Daily supplements of vitamin E, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid should be taken. In patients with mild liver dysfunction, the dose should not exceed 40 mg per day. Coadministration of lomitapide and moderate or strong inhibitors of CYP3A4 is contraindicated and should not exceed 30 mg/ day with weak CYP3A4 inhibitors (e.g., atorvastatin).

Potential Advantages

Familial hypercholesterolemia is difficult to treat. Current lipid-modifying therapies, even combined with LDL-apheresis, rarely achieve optimal LDL levels. Lomitapide offers an option for these patients who are at extremely high risk for cardiovascular disease and premature death.

Potential Disadvantages

Lomitapide has potential for hepatotoxicity.1 Treatment causes elevation of liver transaminases and increases hepatic fat (hepatic steatosis). ALT and AST should be measured before starting therapy. Gastrointestinal adverse events are common, with diarrhea (79%), nausea (65%), dyspepsia (38%), and vomiting (34%) being most common.1 Adhering to a low-fat diet reduces the risk of gastrointestinal adverse events. Lomitapide is contraindicated in pregnancy.


The safety and efficacy of lomitapide was studied in a single-arm, 78-week trial in 29 patients with HoFH.1,2 This cohort had a mean age of 30.7 years, 55% male, and mainly Caucasian (86%). All patients were either homozygotes or compound heterozygotes for mutations in the LDLR gene or genes affecting LDL-receptor functionality.2 Treatment included statins (93%) and ezetimibe (76%), and 62% received apheresis. After stabilizing treatment regimens, subjects were initiated on 5 mg daily, and titrated up to 60 mg/day at 4-week intervals based on safety and tolerability (including transaminase levels). The primary endpoint was percent change in LDL-C from baseline at week 26. Twenty-three patients completed the 26-week assessment as well as the 78-week study. Four of six patients discontinued the study due to adverse events. Lomitapide produced statistically significant changes in LDL-C (-40%), TC (-36%), ApoB (-39%), and triglycerides (-45%). While the lipid-lowering effect was reduced at week 78, these remain statistically significant.2 HDL cholesterol and ApoA-I levels were reduced significantly at week 26, but returned to levels similar to baseline at week 78. Hepatic fat increased from 1% at baseline to 8.6% by week 26 and seemed to stabilize thereafter.2

Clinical Implications

HoFH is a functional mutation in both LDL-receptor alleles or those that affect LDL receptor functionality, or skin fibroblast LDL-receptor activity (< 20% or normal, or untreated total cholesterol > 500 mg/dL and triglycerides < 300 mg/dL, and both parents with documented untreated total cholesterol > 250 mg/dL).1 Treatment includes low-fat diet and other lipid-lowering treatments, including LDL-aphersis. Lomitapide provides another option for patients with this rare, life-threatening condition. The wholesale cost is $18,030 for a 28-day supply of the 10 mg dose and $22,630 for the 20 mg dose.


1. Juxtapid Prescribing Information. Cambridge, MA: Aegerion Pharmaceuticals, Inc.; December 2012.

2. Cuchel M, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: A single-arm, open-label, phase 3 study. Lancet 2013;381:40-46.