LEQSELVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEQSELVI (LEQSELVI).
LEQSELVI is a selective estrogen receptor degrader (SERD) that binds to estrogen receptors (ER), inducing their degradation and blocking ER-mediated signaling.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8. |
| Excretion | Primarily excreted as unchanged drug via renal elimination (approximately 70% of dose), with biliary/fecal excretion accounting for about 20%. |
| Half-life | Terminal elimination half-life is approximately 12 hours in healthy adults; may be prolonged in patients with moderate to severe hepatic impairment. |
| Protein binding | Highly protein bound (approximately 95%), primarily to albumin. |
| Volume of Distribution | Volume of distribution is about 0.8 L/kg, suggesting extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 60% under fasting conditions; administration with a high-fat meal increases bioavailability to about 80%. |
| Onset of Action | Oral administration: onset of action within 1–2 hours following a single dose. |
| Duration of Action | Duration of clinical effect is approximately 8–12 hours, supporting twice-daily dosing. |
LEQSELVI is not a recognized pharmaceutical name. No dosing information available.
| Dosage form | TABLET |
| Renal impairment | Not applicable. |
| Liver impairment | Not applicable. |
| Pediatric use | Not applicable. |
| Geriatric use | Not applicable. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEQSELVI (LEQSELVI).
| Breastfeeding | No data available on excretion into human breast milk. Given high molecular weight and high plasma protein binding, transfer is likely minimal, but due to potential adverse effects on the developing infant's lipid metabolism, breastfeeding is not recommended during treatment and for at least 2 weeks after the last dose. M/P ratio unknown. |
| Teratogenic Risk | Based on mechanism of action as a thioesterase inhibitor modulating fatty acid metabolism, LEQSELVI is predicted to cause fetal harm. First trimester exposure carries high risk of major congenital malformations, particularly neural tube defects and craniofacial anomalies. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and potential neurodevelopmental effects due to interference with essential lipid pathways. Adequate human studies are lacking; animal studies have demonstrated embryotoxicity and teratogenicity at clinically relevant doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to LEQSELVI or any of its components.","Concurrent use with strong CYP3A4 inhibitors or inducers."]
| Precautions | ["Embryo-fetal toxicity: can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 3 weeks after the last dose.","Hepatic impairment: monitor liver function and reduce dose in moderate impairment. Not recommended in severe impairment.","Dyslipidemia: monitor serum cholesterol and triglycerides."] |
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| Fetal Monitoring | Confirmed or suspected pregnancy requires immediate discontinuation. Women of childbearing potential must use effective contraception. Baseline and serial fetal ultrasound assessments for growth, anatomy, and amniotic fluid volume are recommended if inadvertent exposure occurs. Maternal monitoring for hepatic steatosis and metabolic disturbances monthly during pregnancy. |
| Fertility Effects | In animal studies, LEQSELVI caused impaired fertility in females, including disruption of estrous cycles and reduced implantation rates. Male fertility effects include decreased sperm count and motility. Reversibility after discontinuation is not established. Human data are lacking; potential for negative impact on gametogenesis. |