Products
Lomitapide is commercially available in capsule form (Juxtapid, Lojuxta). It was approved in the United States in 2012 and in the EU in 2013. The drug has not yet been registered in many countries.
Structure and properties
Lomitapide (C39H37F6N3O2, Mr = 693.7 g/mol) is present in the drug as lomitapide mesilate, a white powder that is sparingly soluble in water. It is a biphenyl and piperidine derivative and a carboxamide.
Effects
Lomitapide (ATC C10AX12) has lipid-lowering properties. The effects are due to selective inhibition of the microsomal triglyceride transfer protein (MTP), which is located in the endoplasmic reticulum of cells and is a key protein in the formation of apolipoprotein B lipoproteins in the liver and intestine. Inhibition reduces the formation of chylomicrons and VLDL and lowers LDL-C and cholesterol and triglycerides. Lomitapide has a long half-life of up to 40 hours and therefore only needs to be administered once daily.
Indications
As adjunctive therapy for the treatment of homozygous familial hypercholesterolemia. Lomitapide may be used in conjunction with other lipid-lowering agents or blood washing (apheresis).
Dosage
According to the SmPC. Capsules are taken once daily in the evening and fasting, at least two hours after dinner. During treatment, fat-soluble vitamins and fatty acids must be substituted.
Contraindications
Lomitapide is contraindicated in hypersensitivity, during pregnancy, in combination with moderate to strong CYP3A4 inhibitors, liver disease, and liver dysfunction. For complete precautions, see the drug label.
Interactions
Lomitapide is a substrate of CYP3A4 and a P-gp inhibitor. CYP inhibitors may lead to a relevant increase in plasma concentrations. Other drug-drug interactions have been described with warfarin, statins, P-gp substrates, and ion-exchange resins.
Adverse effects
The most common potential adverse effects include digestive disturbances such as diarrhea, nausea, vomiting, dyspepsia, and abdominal pain. They occur as a result of reduced fat absorption. Lomitapide has hepatotoxic properties and may promote the development of fatty liver and liver disease. Therefore, attention to precautions is critical (e.g., interactions, regular measurement of liver enzymes, dosage).
