ORSERDU
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORSERDU (ORSERDU).
Selective estrogen receptor degrader (SERD) that binds to estrogen receptor alpha (ERα), induces conformational changes leading to receptor degradation, and inhibits estrogen-dependent tumor growth.
| Metabolism | Primarily metabolized by CYP3A4 and UGT1A9; minor contribution from CYP2C8. |
| Excretion | Primarily via hepatic metabolism; less than 1% of the dose excreted unchanged in urine; approximately 60% of dose recovered in feces as metabolites. |
| Half-life | 34 hours (range 20–60 hours) at steady state; supports once-daily dosing. |
| Protein binding | >99.5% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 700 L (10 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 100% (relative to oral solution); no IV formulation available. |
| Onset of Action | Clinical response (tumor shrinkage) observed at first disease assessment at 8 weeks; no immediate single-dose effect. |
| Duration of Action | Continuous with daily dosing; clinical benefit maintained until disease progression or unacceptable toxicity. |
345 mg orally once daily with food, continued until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data in severe renal impairment (CrCl <30 mL/min) to recommend a dose. |
| Liver impairment | For Child-Pugh A (mild): 274 mg once daily. For Child-Pugh B (moderate): 185 mg once daily. Child-Pugh C (severe): not recommended. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment required; clinical studies included patients aged ≥65 years with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORSERDU (ORSERDU).
| Breastfeeding | It is unknown whether elacestrant is excreted in human milk. Due to potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. M/P ratio is not available. |
| Teratogenic Risk | ORSERDU (elacestrant) is an estrogen receptor antagonist. Based on its mechanism of action and animal studies, there is potential for fetal harm. No adequate human data are available. Use is not recommended during pregnancy; advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Known hypersensitivity to elacestrant or any excipients; concomitant use with strong CYP3A4 inducers; pregnancy. Relative: severe hepatic impairment (Child-Pugh C); severe renal impairment (CrCl <30 mL/min).
| Precautions | Dyslipidemia; embryo-fetal toxicity; musculoskeletal pain; nausea; increased creatinine levels; asthenia; decreased appetite; vomiting; diarrhea; constipation; headache; hot flush; dyspepsia; arthralgia; back pain; fatigue; insomnia; dizziness; anemia; hypokalemia; hypocalcemia; hypoalbuminemia; increased alkaline phosphatase; increased ALT; increased AST; increased bilirubin; increased GGT; increased lipase; increased amylase; renal impairment; hepatic impairment; QT prolongation; bradycardia; electrolyte abnormalities; concomitant use with strong CYP3A4 inhibitors or inducers; pregnancy; lactation. |
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| Fetal Monitoring | Monitor for maternal adverse effects such as dyslipidemia, nausea, and musculoskeletal pain. No specific maternal-fetal monitoring recommendations beyond standard pregnancy management. If unintentional exposure occurs during pregnancy, consider fetal monitoring per obstetric guidelines. |
| Fertility Effects | Based on animal studies, elacestrant may impair fertility in females of reproductive potential due to effects on ovarian function. The reversibility is unknown. |