Imlunestrant, an estrogen receptor antagonist, is an antineoplastic agent.1
Imlunestrant is used for the treatment of adults with estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 (ESR1)-mutated, advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.1, 2, 3 Select patients for imlunestrant therapy based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA-approved test.1
Safety and efficacy of imlunestrant have been established in a phase 3, randomized, open-label, active-controlled trial (EMBER-3) in adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer, who were previously treated with an aromatase inhibitor either alone or in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor.1, 2 Patients included were required to have progressed within 12 months of completing neoadjuvant or adjuvant aromatase inhibitor therapy with no systemic treatment for recurrent disease, or >12 months after neoadjuvant or adjuvant endocrine therapy or de novo metastatic disease and progressed on only one line of aromatase inhibitor therapy.1 Patients received imlunestrant 400 mg orally once daily, an investigator's choice of endocrine therapy (fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter or exemestane 25 mg orally once daily), or an additional investigational combination regimen.1 Randomization was stratified by previous treatment with CDK4/6 inhibitor, presence of visceral metastasis, and geographic region.1 The major efficacy outcome was investigator assessed progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.1 Other efficacy measures included overall survival (OS), blinded independent review committee (BIRC)-assessed PFS, and objective response rate (ORR).1
Among the 256 patients with ESR1-mutated breast cancer who received imlunestrant or an investigator's choice of endocrine therapy, the median age was 61 years (range: 28-85).1 All patients were female, of which 11% were premenopausal/perimenopausal; 61% were White, 26% Asian, 4% Black, 4% American Indian or Alaskan Native, and 19% Hispanic/Latino.1 The baseline Eastern Cooperative Oncology Group (ECOG) performance status was 0 (63%) or 1 (37%) and most patients had visceral metastases (59%).1 Of the patients enrolled, 21% had received no endocrine therapy and 79% had received one line of endocrine therapy in the advanced or metastatic setting; 70% of patients were treated with a prior CDK4/6 inhibitor, 2.3% in the adjuvant setting and 67% in the advanced or metastatic setting.1 Imlunestrant demonstrated a significant and clinically meaningful improvement in investigator-assessed PFS and PFS according to RECIST v1.1 compared with an investigator's choice of endocrine therapy (fulvestrant or exemestane).1, 3 Treatment with imlunestrant reduced the hazard of disease progression or death by 38%.1, 3 PFS assessment based on a BIRC was consistent with the investigator assessment.1 The median PFS was 5.5 months in patients receiving imlunestrant and 3.8 months in patients receiving an investigator's choice of endocrine therapy.1 At the time of PFS analysis, OS data was immature with 31% of deaths in the ESR1-mutated population.1 The ORR was 14.3% in the imlunestrant group and 7.7% in the fulvestrant or exemestane group, with a complete response in 0.9% and 0% of patients and a partial response in 13.4% and 7.7% of patients, respectively.1
Guidelines from the American Society of Clinical Oncology (ASCO) provide recommendations for the treatment of HR-positive, HER2-negative, metastatic breast cancer.5, 6 ASCO recommends a CDK4/6 inhibitor with endocrine therapy as first-line treatment.5 Second and third-line treatment options include targeted therapies based on tumor genomics and prior endocrine therapy.5 For patients with tumors harboring ESR1 who had no prior endocrine therapy, only received tamoxifen, or no prior recent aromatase inhibitor, the ASCO guideline recommends elacestrant or fulvestrant and everolimus.5 Additionally for patients with no prior CDK4/6 inhibitor treatment with tumors harboring ESR1 , ASCO recommends fulvestrant, aromatase inhibitor, or tamoxifen monotherapy.6 For patients with tumors harboring ESR1 who have recurrence while on or with recent exposure to endocrine therapy, the ASCO guideline recommends elacestrant.5 Imlunestrant is not currently discussed in the ASCO guidelines.5, 6
Imlunestrant is administered orally on an empty stomach, at least 2 hours before, or 1 hour after, food at approximately the same time each day.1
The tablets should be swallowed intact and should not be chewed, crushed, or split.1
If a dose is vomited or missed by 6 or more hours, patients should not take an extra dose.1 The next dose should be taken at the regularly scheduled time.1
Store imlunestrant tablets at 20-25ºC (excursions permitted to 15-30ºC).1
Dosage of imlunestrant tosylate is expressed in terms of imlunestrant.1
For the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1 -mutated, advanced or metastatic breast cancer, the recommended adult dosage of imlunestrant is 400 mg once daily.1
Continue treatment until disease progression or unacceptable toxicity occurs.1
Premenopausal or perimenopausal women and men should receive a gonadotropin-releasing hormone (GnRH) agonist according to current clinical practice standards.1
Dosage Modification for Toxicity
If a dosage modification is required, reduce the dosage of imlunestrant to 200 mg once daily.1 Permanently discontinue imlunestrant in patients who are unable to tolerate 200 mg once daily.1 The recommended imlunestrant dosage modifications for adverse reactions are provided in Table 1.1
Adverse Reaction | Dosage Modification Based on Severity |
|---|---|
Hepatotoxicity | Persistent or Recurrent: AST/ALT >3-5 × ULN: Suspend until toxicity resolves to baseline or to >ULN-3 × ULN. Resume at same dose level. If AST/ALT at baseline is within the normal range: AST/ALT >5-20 × ULN OR If AST/ALT at baseline is above ULN: AST/ALT ≥3 × baseline (if AST/ALT ≥1.5 x ULN at baseline) OR AST/ALT >8 × ULN (whichever is the lower threshold): Suspend until toxicity resolves to baseline or to >ULN-3 × ULN. Resume at next lower dose level or discontinue if receiving 200 mg daily. AST/ALT >20 × ULN OR ALT or AST ≥3 × ULN concurrent with total bilirubin ≥2 × ULN (if ALT or AST <1.5 × ULN at baseline), in the absence of cholestasis OR ALT or AST ≥2 × baseline concurrent with total bilirubin ≥2 × ULN (if ALT or AST ≥1.5 × ULN at baseline), in the absence of cholestasis: Discontinue. |
Other adverse reactions (except hepatotoxicity) | Persistent or recurrent Grade 2 that does not resolve with maximal supportive measures within 7 days to baseline or Grade 1: Suspend until toxicity resolves to baseline or ≤Grade 1. Resume at same dose level. Grade 3 or 4 (except non-hepatic asymptomatic laboratory changes): Suspend until toxicity resolves to baseline or ≤Grade 1. Resume at next lower dose level. |
Dosage Modification for Concomitant Use with Strong CYP3A Inhibitors
Avoid concomitant use with strong CYP3A inhibitors.1 If concomitant use cannot be avoided, decrease the imlunestrant dosage to 200 mg once daily.1
Dosage Modification for Concomitant Use with Strong CYP3A Inducers
Avoid concomitant use with strong CYP3A inducers.1 If concomitant use cannot be avoided, increase the imlunestrant dosage to 600 mg once daily.1
The recommended dosage of imlunestrant for patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment is 200 mg once daily.1 No dosage adjustment is required in patients with mild (Child-Pugh A) hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Fetal/Neonatal Morbidity and Mortality
Based on the mechanism of action of imlunestrant and animal findings, the drug can cause fetal harm if administered to pregnant females.1 In an animal reproduction study, oral administration of imlunestrant to pregnant rats during organogenesis caused embryo-fetal mortality and structural abnormalities at maternal exposures that were below the human exposure at the recommended dose.1
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with imlunestrant and for 1 week after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with imlunestrant and for 1 week after the last dose.1
There are no available human data on the use of imlunestrant in pregnant women; however, based on findings of animal reproductive studies and its mechanism of action, imlunestrant can cause embryo-fetal harm when administered to pregnant females.1
Verify pregnancy status in females of reproductive potential prior to initiating imlunestrant.1
It is not known whether imlunestrant or its metabolites are distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production.1 Due to the potential for serious adverse reactions in the breastfed infant, advise lactating women to not breastfeed during treatment and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Based on findings in animals, imlunestrant may impair fertility in females and males of reproductive potential.1 Findings in animals were reversible.1
Advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.1
Safety and efficacy of imlunestrant have not been established in pediatric patients.1
In the EMBER-3 study, 118 patients were ≥65 years of age and 37 patients were ≥75 years of age.1 No overall difference in safety or effectiveness of imlunestrant were observed between geriatric patients and younger adults.1
Imlunestrant AUC increased 2.2-fold in subjects with moderate hepatic impairment (Child-Pugh B) and 3.1-fold in patients with severe hepatic impairment (Child-Pugh C).1 No clinically significant differences in the pharmacokinetics of imlunestrant were observed in patients with mild hepatic impairment (Child-Pugh A).1
No clinically significant differences in the pharmacokinetics of imlunestrant were observed in patients with mild to moderate renal impairment.1 The effect of severe renal impairment [estimated glomerular filtration rate (GFR) 15 to 29 mL/min] and renal impairment requiring dialysis on imlunestrant pharmacokinetics is unknown.1
The most common adverse reactions (≥10%), including laboratory abnormalities, reported with imlunestrant in clinical studies were decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST and ALT, fatigue, diarrhea, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.1
Imlunestrant is a cytochrome P-450 (CYP) isoenzyme 3A substrate.1
In vitro studies indicate that imlunestrant is an inhibitor of CYP2B6 and CYP2C9 but is not an inhibitor of CYP1A2.1 Imlunestrant is not an inducer of CYP1A2, CYP2B6, or CYP2C9.1
Imlunestrant inhibits P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1 Imlunestrant is not a substrate of BCRP, organic cation transporter (OCT) 1, organic anion transporting polypeptide (OATP) 1B1, or OATP1B3.1
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
No clinically significant differences in the pharmacokinetics of midazolam (CYP3A substrate), repaglinide (CYP2C8 substrate), omeprazole (CYP2C19 substrate), or dextromethorphan (CYP2D6 substrate) were observed when used concomitantly with imlunestrant.1
Concomitant use of a strong CYP3A inhibitor increases imlunestrant exposure, which may increase the risk of imlunestrant-associated adverse reactions.1 When the strong CYP3A4 inhibitor itraconazole was administered concomitantly with imlunestrant for multiple days, peak plasma concentrations of imlunestrant increased by 1.9-fold and AUC increased by 2.1-fold.1
Avoid concomitant use of imlunestrant with strong CYP3A inhibitors.1 If concomitant use cannot be avoided, reduce the dosage of imlunestrant.1
Concomitant use of a strong CYP3A inducer decreases imlunestrant exposure, which may reduce effectiveness of imlunestrant.1 When the strong CYP3A inducer carbamazepine was administered concomitantly with imlunestrant for multiple days, peak plasma concentrations of imlunestrant decreased by 29% and AUC decreased by 42%.1
Avoid concomitant use of imlunestrant with strong CYP3A inducers.1 If concomitant use cannot be avoided, increase the dosage of imlunestrant.1
Drugs Affecting or Affected by Transport Systems
Concomitant use of the P-gp inhibitor quinidine with imlunestrant did not have a clinically meaningful effect on the pharmacokinetics of imlunestrant.1
Imlunestrant increases exposure of P-gp and BCRP substrates, which may increase the risk of adverse reactions related to these substrates.1 When the P-gp substrate digoxin was administered concomitantly with imlunestrant, peak plasma concentrations of digoxin increased 1.6-fold and AUC increased 1.4-fold.1 When the BCRP substrate rosuvastatin was administered concomitantly with imlunestrant, peak plasma concentrations of rosuvastatin increased 1.6-fold and AUC increased 1.5-fold.1
Avoid concomitant use of imlunestrant with P-gp or BCRP substrates unless otherwise recommended in the Prescribing Information of these drugs where minimal concentration changes may lead to serious adverse reactions.1
Concomitant use of omeprazole and imlunestrant did not have a clinically meaningful effect on the pharmacokinetics of imlunestrant.1
Imlunestrant is an estrogen receptor (ER) antagonist that specifically targets ERα.1 In vitro studies show that imlunestrant promotes ERα degradation, resulting in suppression of ER-dependent gene transcription and reduced proliferation of (ER)-positive breast cancer cells.1 Imlunestrant has demonstrated anti-tumor activity both in vitro and in vivo in (ER)-positive breast cancer xenograft models, including those harboring ESR1 mutations.1
Steady state of imlunestrant is reached in approximately 6 days.1 The absolute oral bioavailability of imlunestrant after a single oral 400 mg dose is 10%.1 Imlunestrant median time to maximum plasma concentration is 4 hours.1 Following administration of imlunestrant with a low-fat meal, imlunestrant AUC increased by 2-fold and peak plasma concentrations increased by 3.6-fold.1 The effects of a high-fat meal on imlunestrant exposure are unknown.1 Imlunestrant is >99% protein bound.1 The elimination half-life of imlunestrant is 30 hours.1 Imlunestrant is metabolized by sulfation, CYP3A4, and direct glucuronidation.1 After a single 400 mg dose of imlunestrant to healthy subjects, 97% of the dose was recovered in feces (62% unchanged) and 0.3% in urine.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Imlunestrant is available through designated specialty pharmacies.4 Contact the manufacturer, Eli Lilly and Company, for more information.4
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 200 mg (of imlunestrant) | Inluriyo® | Eli Lilly and Company |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions March 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Eli Lilly and Company. INLURIYO (generic name) ORAL prescribing information. 2025 Sep.
2. Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392(12):1189-1202. doi:10.1056/NEJMoa2410858
3. US Food and Drug Administration. Center for Drug Evaluations and Research Application Number: 218881Orig1s000 Multi-Discipline Review. From the FDA website. Accessed 2025 Dec 2.
4. Savings & Support. From Inlueiyo website. Accessed 2025 Dec 2. [Web]
5. Burstein HJ, DeMichele A, Fallowfield L, et al. Endocrine and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer-capivasertib-fulvestrant: ASCO rapid recommendation update. J Clin Oncol. 2024;42(12):1450-1453.
6. Burstein HJ, DeMichele A, Somerfield MR, Henry NL; Biomarker Testing and Endocrine and Targeted Therapy in Metastatic Breast Cancer Expert Panels. Testing for ESR1 mutations to guide therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2023;41(18):3423-3425.