LOMAIRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOMAIRA (LOMAIRA).
Lomitapide inhibits microsomal triglyceride transfer protein (MTP), which is responsible for the assembly and secretion of apolipoprotein B-containing lipoproteins in the liver and intestine, thereby reducing plasma levels of LDL-C, triglycerides, and other lipids.
| Metabolism | Primarily metabolized by CYP3A4; minor pathways via CYP1A2, 2C8, 2C19, and 2D6. Also undergoes glucuronidation and oxidation. |
| Excretion | Renal: 70% unchanged; Biliary/Fecal: 20% as metabolites; 10% other. |
| Half-life | Terminal elimination half-life: 12 hours; clinical context: steady-state achieved in 2-3 days. |
| Protein binding | 95% bound primarily to albumin. |
| Volume of Distribution | Vd: 0.3 L/kg; indicates moderate tissue distribution, primarily confined to extracellular fluid. |
| Bioavailability | Oral: 80%. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 10-15 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours; clinical notes: duration may be prolonged in hepatic impairment. |
100 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min). Not recommended in severe renal impairment (eGFR <30 mL/min) or ESRD. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment recommended; use caution due to potential age-related renal function decline. Clinical studies included limited patients ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOMAIRA (LOMAIRA).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not established. Due to potential for serious adverse reactions in nursing infants, advise against breastfeeding during therapy and for at least 3 weeks after last dose. |
| Teratogenic Risk | Pregnancy Category X: LOMAIRA (letrozole) is contraindicated in pregnancy due to teratogenic effects including fetal malformations (e.g., craniofacial defects, cardiac anomalies) and embryotoxicity. Risk in first trimester is highest; second and third trimester exposure may cause fetal harm based on animal studies. |
■ FDA Black Box Warning
Risk of hepatotoxicity: lomitapide may cause elevations in serum aminotransferases and hepatic steatosis. Liver function monitoring is required.
| Serious Effects |
["Known hypersensitivity to lomitapide","Moderate to severe hepatic impairment (Child-Pugh class B or C)","Clinically significant liver disease including active liver disease or unexplained persistent elevations in serum aminotransferases","Pregnancy and breastfeeding"]
| Precautions | ["Monitor liver function tests before and during treatment; discontinue if ALT/AST > 3x ULN with symptoms or >5x ULN without symptoms.","Avoid or minimize alcohol consumption due to increased risk of hepatotoxicity.","Monitor for fat-soluble vitamin deficiencies; supplement if needed.","Dose adjustments required when co-administered with strong CYP3A4 inhibitors or inducers."] |
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| Fetal Monitoring |
| Monitor pregnancy status before and during therapy (negative pregnancy test within 7 days of start). Use effective contraception during treatment. If exposure occurs, monitor fetal development via ultrasound and assess for potential anomalies. |
| Fertility Effects | LOMAIRA may impair fertility in females by disrupting ovulation and menstrual cyclicity; effects are generally reversible upon discontinuation. In males, may cause reversible reductions in sperm count and motility. |