Lomitapide
Regulatory sources consulted
Approved indications
- Adjunct to a low-fat diet and other lipid-lowering treatments, with or without LDL apheresis, in patients aged 5 years or older with homozygous familial hypercholesterolemia, genetically confirmed when possible.
- In the United States, adjunct to a low-fat diet, exercise and other LDL-C-lowering therapies in adults and pediatric patients aged 2 years and older with homozygous familial hypercholesterolemia.
Contraindications
Absolute
- Hypersensitivity to lomitapide or excipients.
- Moderate or severe hepatic impairment or persistently unexplained abnormal liver tests.
- Significant or chronic intestinal disease, including inflammatory disease or malabsorption.
- Strong or moderate CYP3A4 inhibitors; under CIMA, also simvastatin >40 mg.
- Pregnancy.
Clinical warnings
- Major warning · ALT/AST elevations and hepatic steatosis may occur, with possible progression to steatohepatitis and cirrhosis. Measure liver tests before starting, monthly or before each increase during the first year, and thereafter at least every 3 months and before increasing. — https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
- Major warning · Gastrointestinal reactions are very common and may cause dehydration; titrate gradually, maintain a low-fat diet, and reduce or interrupt according to severity. — https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
Drug interactions
- ModerateStrong or moderate CYP3A4 inhibitors
Mechanism: They may increase lomitapide exposure several-fold.
Recommendation: Do not combine; interrupt lomitapide if inhibitor treatment is unavoidable.
https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
- ModerateAtorvastatin or other weak CYP3A4 inhibitors
Mechanism: They may increase lomitapide exposure.
Recommendation: Separate by 12 hours; with atorvastatin, lomitapide may also be reduced by half.
https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
- ModerateCYP3A4 inducers
Mechanism: They accelerate metabolism and may reduce lomitapide effectiveness.
Recommendation: Avoid when possible and monitor lipid response.
https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
- ModerateWarfarin
Mechanism: Lomitapide increases concentrations of both warfarin enantiomers by approximately 30% and may increase INR.
Recommendation: Monitor INR regularly, especially after any lomitapide dose change, and adjust warfarin according to clinical response.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61a0be9d-ee58-43e0-b5cb-141011835081
- ModerateSimvastatin or lovastatin
Mechanism: Lomitapide increases their exposure and the risk of myopathy, including rhabdomyolysis.
Recommendation: FDA: reduce simvastatin by 50% when starting lomitapide and limit it to 20 mg/day, or to 40 mg/day only if 80 mg/day was previously tolerated for at least one year without muscle toxicity; consider reducing lovastatin. CIMA: simvastatin >40 mg is contraindicated.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61a0be9d-ee58-43e0-b5cb-141011835081https://cima.aemps.es/cima/dochtml/ft/113851002/FT_113851002.html
- ModerateP-glycoprotein substrates
Mechanism: P-gp inhibition by lomitapide may increase their absorption.
Recommendation: Consider reducing the P-gp substrate dose during concomitant use.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61a0be9d-ee58-43e0-b5cb-141011835081
- ModerateBile acid sequestrants
Mechanism: They may interfere with lomitapide absorption.
Recommendation: Separate lomitapide administration by at least 4 hours before or after.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=61a0be9d-ee58-43e0-b5cb-141011835081
Adverse events
Common (≥1%)
Diarrhea · Nausea · Vomiting · Dyspepsia · Abdominal pain or discomfort · Flatulence or distension · Constipation · Decreased appetite · Increased ALT or AST · Weight loss
Pregnancy and lactation
Contraindicated during pregnancy. Confirm absence of pregnancy and start effective contraception before treatment; continue contraception during treatment and for 2 weeks after the last dose. Add another contraceptive method if vomiting or diarrhea reduces oral contraceptive effectiveness. CIMA advises deciding whether to discontinue breastfeeding or the medicine according to its importance to the mother; the FDA label does not recommend breastfeeding during treatment.
Recent literature (PubMed)
El consenso europeo actualizado sobre hipercolesterolemia familiar homocigota sitúa el tratamiento combinado como base y contempla añadir lomitapida o evinacumab para acercarse al objetivo de C-LDL o reducir la necesidad de aféresis.
Revisión de terapias para hipercolesterolemia familiar homocigota: lomitapida, inhibidor de la proteína microsomal de transferencia de triglicéridos, reduce el C-LDL aproximadamente un 50 % con independencia de la función residual del receptor LDL; la mayoría de pacientes requiere tratamiento combinado.
Revisión narrativa de tratamientos hipolipemiantes establecidos y emergentes que incluye lomitapida entre las nuevas moléculas pequeñas para modificar los lípidos.