Lomitapide
Microsomal triglyceride transfer protein (MTP) inhibitors
Microsomal triglyceride transfer protein (MTP) inhibitorsPregnancy: contraindicated
Contraindicated: it can harm the fetus; a negative pregnancy test is needed before starting and effective contraception during treatment.
An oral MTP inhibitor that blocks VLDL and chylomicron assembly. Used with other lipid drugs in homozygous familial hypercholesterolaemia.
Also called: lomitapide mesylate
Quick facts
- Group
- Microsomal triglyceride transfer protein (MTP) inhibitors
- Target
- Microsomal triglyceride transfer protein (MTP), large subunit
- Key effects
- Diarrhoea · Abdominal pain · Weight loss
- Monitor
- Liver enzymes · LDL cholesterol
- ATC
- C10AX12
No doses: the clinician sets them by the current guideline.
Mechanism of action
Lomitapide inhibits microsomal triglyceride transfer protein in the endoplasmic reticulum of liver and intestinal cells. Without MTP, triglycerides cannot be loaded onto apolipoprotein B, so VLDL (liver) and chylomicrons (gut) are not assembled or secreted. Less VLDL means less LDL, regardless of LDL receptor function; total cholesterol and apo B fall as well.
- Inhibits MTP in liver and gut cells
- Triglycerides are not loaded onto apolipoprotein B
- VLDL and chylomicron secretion falls
- LDL falls even without working LDL receptors
Indications
- Homozygous familial hypercholesterolaemia, with a low-fat diet and other lipid-lowering treatments, to lower LDL, total cholesterol, apo B and non-HDL cholesterol Familial hypercholesterolemia →
Adverse effects
Common
- Diarrhoea, nausea, vomiting (very common)
- Abdominal pain, bloating, gas, indigestion
- Weight loss
- Headache, dizziness, back pain
Contraindications
- Pregnancy
- Moderate or severe liver disease or unexplained raised liver tests
- Strong or moderate CYP3A4 inhibitors
Key interactions
- CYP3A4 inhibitors (strong ones contraindicated) and grapefruit
- Raise lomitapide levels and liver toxicity.
- Bile acid sequestrants (colestyramine, colesevelam, colestipol)
- Separated by at least four hours.
- Alcohol and other liver-toxic drugs (including paracetamol)
- Add to liver injury risk; alcohol is kept to a minimum.
What is monitored
- Liver enzymes (ALT, AST), alkaline phosphatase and bilirubin before and during treatment
- LDL cholesterol
- Gastrointestinal symptoms and hydration
- Pregnancy test before starting
Administration and safety
- Oral capsule, once a day with water on an empty stomach, at least a couple of hours after the evening meal.
- A strict low-fat diet and a daily vitamin supplement accompany treatment.
- Distributed only through a restricted programme (REMS) because of liver toxicity.
- Bile acid sequestrants are separated by at least four hours.
Pregnancy and breastfeeding
Contraindicated: it can harm the fetus; a negative pregnancy test is needed before starting and effective contraception during treatment.
Nursing care
- Before: liver tests, alcohol use, full medicine list (CYP3A4 inhibitors), pregnancy test.
- During: liver tests; ask about nausea, vomiting, right upper abdominal pain, yellowing, dark urine.
- Teach the low-fat diet, the vitamin supplement and to avoid grapefruit.
- Teach to limit alcohol.
Pharmacokinetics
- Absorption
- Oral; taken without food, at least a couple of hours after the evening meal, to limit GI effects.
- Metabolism
- Liver, by CYP3A4.
Test yourself
Think of the answer, then tap the question to see it.
Which organ toxicity is the main concern with lomitapide?
The liver: raised transaminases and fatty liver.
Why is lomitapide useful when LDL receptors are absent?
It reduces VLDL production upstream, so it does not depend on LDL receptor clearance.
Why is grapefruit avoided with lomitapide?
Grapefruit inhibits CYP3A4, which metabolizes lomitapide, raising its levels and liver toxicity.
Connections
← Back to the class: Microsomal triglyceride transfer protein (MTP) inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Lomitapide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.