AHFS Class:

• Antineoplastic Agents 10:00

Brands:

• Inluriyo^®

Generic Name(s):

• Imlunestrant Tosylate

Imlunestrant is an estrogen receptor antagonist.1

Imlunestrant has the following uses:

Imlunestrant is indicated for treatment of adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.1

General

Imlunestrant tosylate is available in the following dosage form(s) and strength(s):

Tablets: 200 mg of imlunestrant1

Dosage

Adults

Dosage and Administration

• Select patients for treatment based on the presence of ESR1 mutations.1
• Administer orally on an empty stomach at least 2 hours before food, or 1 hour after food.1 Swallow the tablets whole. Do not split, crush, or chew the tablets.
• The recommended dosage is 400 mg orally once daily until disease progression or unacceptable toxicity.1
• Reduce the dose in patients with moderate or severe hepatic impairment.1
• Dosage modifications may be required for adverse reactions and drug interactions.1 See Full Prescribing Information for additional information.1
• Pre/perimenopausal women and men should receive a gonadotropin-releasing hormone agonist (GnRH) according to current clinical practice standards.

Contraindications

None.1

Warnings/Precautions

Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, imlunestrant can cause fetal harm when administered to a pregnant woman.1 In an animal reproduction study, oral administration of imlunestrant to pregnant rats during the period of organogenesis led to embryo-fetal mortality and structural abnormalities at maternal exposures that were below the human exposure at the recommended dose based on AUC.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

Specific Populations

Pregnancy

Based on findings in animals and its mechanism of action, imlunestrant can cause fetal harm when administered to a pregnant woman.1 There are no available human data on imlunestrant use in pregnant women to inform a drug-associated risk.1 In an animal reproduction study, oral administration of imlunestrant to pregnant rats during the period of organogenesis led to embryo-fetal mortality and structural abnormalities at maternal exposures below the human exposure at the recommended dose based on AUC.1 Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 The background risk of major birth defects and miscarriage for the indicated population is unknown.1 However, the background risk in the U.S.1 general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies.1

Lactation

There are no data on the presence of imlunestrant or its metabolites in human milk, its effects on the breastfed child, or on milk production.1 Because of the potential for serious adverse reactions in the breastfed child, advise lactating women to not breastfeed during treatment with imlunestrant and for 1 week after the last dose.1

Females and Males of Reproductive Potential

Imlunestrant can cause fetal harm when administered to a pregnant woman.1

Verify the pregnancy status in females of reproductive potential prior to initiating imlunestrant.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

Based on findings in animals, imlunestrant may impair fertility in females and males of reproductive potential.1 Findings in animals were reversible.1

Verify the pregnancy status in females of reproductive potential prior to initiating imlunestrant.1

Pediatric Use

The safety and effectiveness of imlunestrant have not been established in pediatric patients.1

Geriatric Use

Of 327 patients who received imlunestrant in the EMBER-3 study, 118 patients were ≥ 65 years of age and 37 patients were ≥ 75 years of age.1 No overall differences in safety or effectiveness of imlunestrant have been observed between patients 65 years of age and older and younger adult patients.1

Hepatic Impairment

Reduce the dose of imlunestrant in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.1 No dosage modification is recommended for patients with mild hepatic impairment (Child-Pugh A).1

Renal Impairment

No clinically significant differences in the pharmacokinetics of imlunestrant have been observed based on mild to moderate (eGFR 30 to 89 mL/min, estimated by CKD-EPI equation) renal impairment.1

The effect of severe (eGFR 15 to 29 mL/min) renal impairment and renal impairment requiring dialysis on imlunestrant pharmacokinetics is unknown.1

Common Adverse Effects

The most common (incidence ≥10%) adverse reactions, including laboratory abnormalities were hemoglobin decreased, musculoskeletal pain, calcium decreased, neutrophils decreased, AST increased, fatigue, diarrhea, ALT increased, triglycerides increased, nausea, platelets decreased, constipation, cholesterol increased, and abdominal pain.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A Inhibitors: Avoid concomitant use of imlunestrant with strong CYP3A inhibitors.1 If concomitant use cannot be avoided, reduce the dosage of imlunestrant.1
• Strong CYP3A Inducers: Avoid concomitant use of imlunestrant with strong CYP3A inducers.1 If concomitant use cannot be avoided, increase the dosage of imlunestrant.1 Imlunestrant is a CYP3A substrate.1 Concomitant use of a strong CYP3A inducer decreases imlunestrant exposure, which may reduce effectiveness of imlunestrant.1
• P-gp or BCRP Substrates: Avoid concomitant use unless otherwise recommended in the Prescribing Information for P-gp or BCRP substrates where minimal concentration changes may lead to serious adverse reactions.1 Imlunestrant inhibits both P-gp and BCRP.1 Imlunestrant increases exposure of P-gp and BCRP substrates, which may increase the risk of adverse reactions related to these substrates.1

Actions

Mechanism of Action

Imlunestrant is an estrogen receptor (ER) antagonist that binds to ERα.1 In vitro, imlunestrant induced degradation of ERα, leading to inhibition of ER-dependent gene transcription and cellular proliferation in ER+ breast cancer cells.1 Imlunestrant demonstrated in vitro and in vivo anti-tumor activity in ER+ breast cancer xenograft models, including models with ESR1 mutations.1

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information).1
• Advise patients that hypercholesterolemia and hypertriglyceridemia may occur while taking imlunestrant.1 Inform patients that lipid profile monitoring will be performed prior to starting and periodically while taking imlunestrant.1
• Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females to inform their healthcare provider of a known or suspected pregnancy.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
• Advise women not to breastfeed during treatment with imlunestrant and for 1 week after the last dose.1
• Advise males and females of reproductive potential that imlunestrant may impair fertility.1
• Advise patients to inform their healthcare providers of all concomitant medications, including prescription medicines, over the counter drugs, and herbal products.1
• Instruct patients to take imlunestrant at approximately the same time each day and to swallow the tablet(s) whole.1 Tablets should not be chewed, crushed, or split prior to swallowing.1
• Advise patients to take imlunestrant without food, either 2 hours before food or 1 hour after food.1
• Instruct patient that if a dose of imlunestrant is missed by more than 6 hours or vomiting occurs, skip the dose and take the next dose the following day at its regularly scheduled time.1

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Only references cited for selected revisions after 1984 are available electronically.

1. Eli Lilly and Company. INLURIYO (generic name) ORAL prescribing information. 2025 Sep.