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. |
| Molecular Weight | 442.5 |
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 | Contraindicated due to teratogenic risk based on animal studies; use effective contraception. |
| 2nd trimester | Contraindicated due to embryofetal toxicity; avoid use during second trimester. |
| 3rd trimester | Contraindicated due to risk of fetal harm; avoid use during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for ORSERDU (ORSERDU).
| Placental transfer | Animal studies demonstrate placental transfer; expected in humans given molecular weight <500 Da. |
| Breastfeeding | Not recommended during treatment and for at least 1 week after last dose due to potential serious adverse reactions in nursing infants. Unknown if excreted in human milk. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to elacestrant or any excipientsPregnancy
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment due to CYP3A4 inhibition. Administer with food to improve bioavailability and reduce gastrointestinal side effects. No other specific dietary restrictions. |
Loading safety data…
| L5 - Contraindicated |
| 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. |
| 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. |
| Clinical Pearls | ORSERDU (elacestrant) is an oral selective estrogen receptor degrader (SERD) approved for ER+/HER2- advanced breast cancer with ESR1 mutations after progression on endocrine therapy. Monitor for dyslipidemia and musculoskeletal pain. Administer with food to reduce nausea. Dose modifications recommended for moderate hepatic impairment. Avoid concomitant use with strong CYP3A4 inhibitors or inducers. Baseline and periodic lipid panel required. |
| Patient Advice | Take ORSERDU with food at the same time each day. Swallow tablets whole, do not crush or chew. · If you miss a dose, skip it and take the next dose at the scheduled time; do not double the dose. · Contact your healthcare provider if you experience severe muscle or joint pain, nausea, vomiting, or signs of liver problems (yellowing skin, dark urine). · Your doctor will monitor your cholesterol and triglyceride levels before and during treatment. · Inform your doctor about all medications, including over-the-counter drugs and supplements, especially those affecting CYP3A4 (e.g., certain antifungals, antibiotics, grapefruit juice). |