Lomitapide is a cholesterol lowering agent that acts by inhibition of the microsomal triglyceride transfer protein and is used to treat the severe lipid abnormalities of familial hypercholesterolemia. Lomitapide is associated with mild, asymptomatic and self-limited serum aminotransferase elevations during therapy that are usually accompanied by an increase in hepatic fat. Long term therapy with lomitapide has been linked to development of steatohepatitis and hepatic fibrosis.


Lomitapide (loe mi' ta pide) is a potent, orally available inhibitor of the hepatic microsomal triglyceride transfer protein (MTTP) and is used to treat severe forms of familial hypercholesterolemia. MTTP is responsible for transferring triglyceride to apolipoprotein B in the liver which is necessary for the assembly of very low density lipoproteins, the precursors of low density lipoproteins (LDL). Inhibition of apolipoprotein B assembly leads to a marked decrease in circulating LDL cholesterol and triglycerides. Lomitapide is typically used as an adjunct to a low-fat diet and other cholesterol-lowering treatments including statins. Lomitapide was approved for use in the United States in 2012, but its indications were limited to patients with homozygous familial hypercholesterolemia. Use of lomitapide can be associated with serum aminotransferase elevations and increase in hepatic fat. Because of the risk of liver injury, lomitapide is available only as a part of a "Risk Evaluation and Mitigation Strategy" [REMS] that requires regular monitoring of liver tests. Lomitapide is available in capsules of 5, 10, 20, 30, 40 and 60 mg under the trade name Juxtapid. The recommended dose is 5 mg daily initially, with subsequent increases based upon tolerance and effectiveness to a maximum of 60 mg daily. Side effects are not uncommon and include diarrhea, nausea, dyspepsia and abdominal pain that are ameliorated and partially prevented by strict adherence to a low fat diet. Lomitapide can also cause marked drug-drug interactions and increase toxicities of other medications (statins, warfarin, antibiotics). Chronic use of lomitapide can result in fat-soluble vitamin malabsorption and deficiencies.


Lomitapide is associated with a moderately high rate of serum aminotransferase elevations during therapy, levels above 3 times the upper limit of normal (ULN) occurring in 34% of patients. Aminotransferase elevations above 10 times ULN have also been reported which can necessitate drug discontinuation. Despite the frequency of ALT elevations, however, increases in serum bilirubin and alkaline phosphatase levels are rare and there have been no reports of clinically apparent acute liver injury with jaundice. Chronic therapy with lomitapide can be associated with fluctuations in serum aminotransferase levels and accumulation of liver fat. In some instances, the increase in liver fat is from baseline levels of <2% to as high as 10% to 40%. At least one instance of steatohepatitis and progressive hepatic fibrosis has been reported in a patient receiving lomitapide long term. The hepatic steatosis is reversed upon stopping lomitapide and generally does not progressively accumulate. The reason why some patients develop liver test abnormalities and accumulate significant amounts of liver fat on lomitapide therapy while others do not, is not clear. The effect is clearly dose related and serum enzyme elevations generally improve with dose modification. The frequency of liver test abnormalities and their association with steatohepatitis led to the requirement for a Risk Evaluation and Mitigation Strategy for lomitapide and it is only available for patients registered in a REMS program.

Likelihood score: C (probable cause of clinically significant liver injury).

Mechanism of Injury

The cause of hepatic injury from lomitapide appears to be a direct effect of its mechanism of action in inhibiting triglyceride transport out of hepatocytes, which leads to hepatocyte steatosis and, in some instances, liver injury. Lomitapide is also extensively metabolized in the liver, primarily via CYP 3A4 and is very sensitive to inhibitors of this microsomal enzyme. Thus, strong CYP 3A4 inhibitors can cause a marked increase in lomitapide levels. Furthermore, lomitapide can compete with other medications in CYP 3A4 metabolism and cause increases in their levels. Lomitapide is also an inhibitor of P-glycoprotein and can increase the absorption of its substrates.

Outcome and Management

The ALT elevations associated with lomitapide therapy are not uncommon and are often accompanied by increases in hepatic steatosis which may ultimately lead to steatohepatitis and significant chronic liver injury. The REMS management program calls for dose adjustment or drug discontinuation based upon the degree of serum aminotransferase elevations. Patients receiving lomitapide should also be advised to follow a low fat diet and take fat soluble vitamin supplements. Lomitapide can also cause drug-drug interactions and caution should be used in co-administration of lomitapide with other inhibitors or substrates of CYP 3A4, P-glycoprotein substrates and warfarin.

Drug Class: Antilipemic Agents



Lomitapide – Juxtapid®


Antilipemic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 20 May 2019

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    (Expert review of hepatotoxicity published in 1999, before the availability of lomitapide).
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    (7.6 year old girl with familial hypercholesterolemia was treated with lomitapide and after 3.5 years LDL-cholesterol levels fell from 428 to 266 mg/dL and ALT and AST levels remained unchanged).
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    (Among 11 children at 10 centers in 8 countries treated with lomitapide, LDL-cholesterol levels fell from a mean of 419 to a nadir of 177 mg/dL, and 3 had ALT elevations but were managed with dose adjustment without stopping therapy).