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Inluriyo ™ (imlunestrant) tablets
200 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
Can Inluriyo® (imlunestrant) be used in patients with hepatic impairment?
The recommended dosage of imlunestrant for patients with moderate or severe hepatic impairment is 200 mg once daily. No dosage modification is recommended for patients with mild hepatic impairment. Dosage modifications are provided for hepatotoxicity.
Content Overview
Imlunestrant Dose Modification for Hepatotoxicity
Use in Patients With Hepatic Impairment
Hepatic Safety in EMBER-3
- Study Inclusion Criteria Related to Hepatic Function
- Incidence of AST/ALT Increases Among Patients in EMBER-3
- Characterization of Transaminase Elevations in EMBER-3
- Transaminase Elevations by Age in EMBER-3
Imlunestrant Pharmacokinetics and Safety in Females With Normal Versus Impaired Hepatic Function
Imlunestrant Dose Modification for Hepatotoxicity
Patients should have their aspartate aminotransferase/alanine aminotransferase levels monitored during imlunestrant therapy as clinically indicated.1 Recommended Imlunestrant Dosage Modifications for Hepatotoxicity provides the recommended imlunestrant dosage modification for hepatotoxicity.
Figure 2 description: Imlunestrant dose modification for hepatotoxicity depends on liver enzyme elevations (ALT and AST).
If AST/ALT >3.0-5.0× ULN is persistent or recurrent, withhold imlunestrant until toxicity resolves to baseline or to >ULN-3.0× ULN, and resume dose at the same dose level.
If baseline AST/ALT is normal and levels rise to >5.0-20.0× ULN; or, if baseline AST/ALT is already elevated, and levels rise to ≥3.0× baseline (if baseline was ≥1.5× ULN), or >8.0× ULN, whichever is the lower threshold; withhold until toxicity resolves to baseline or to >ULN-3.0× ULN and resume at next lower dose level or discontinue if receiving 200 mg daily.
If AST/ALT >20.0× ULN, or ALT or AST ≥3.0× ULN with TBL ≥2.0× ULN (if baseline ALT or AST <1.5× ULN), in the absence of cholestasis; or ALT or AST ≥2.0× baseline with TBL ≥2.0× ULN (if baseline ALT or AST ≥1.5× ULN), in the absence of cholestasis; discontinue imlunestrant.
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; TBL = total bilirubin; ULN = upper limit of normal.
Refer to the Prescribing Information for dosage modification guidelines and other relevant safety information for abemaciclib when used in combination with imlunestrant.1
Use in Patients With Hepatic Impairment
The recommended dosage of imlunestrant for patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment is 200 mg once daily. Monitor for increased adverse reactions.1
No dosage modification is recommended for patients with mild hepatic impairment (Child-Pugh A).1
Refer to the Prescribing Information for dosage modification for severe hepatic impairment for abemaciclib when used in combination with imlunestrant.1
Hepatic Safety in EMBER-3
EMBER-3 (NCT04975308) is a phase 3, randomized, open-label study of imlunestrant monotherapy, investigator's choice of endocrine therapy (fulvestrant or exemestane), and imlunestrant in combination with abemaciclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer previously treated with endocrine therapy ± a cyclin-dependent kinase 4/6 inhibitor.2,3
Study Inclusion Criteria Related to Hepatic Function
In order to be eligible for participation in the EMBER-3 clinical trial, patients were required to have adequate hepatic function, defined as
- total bilirubin of ≤1.5× upper limit of normal (ULN), and
- ALT and AST of ≤3× ULN.3
Patients with Gilbert's syndrome with a total bilirubin ≤2.0× ULN and direct bilirubin within normal limits were permitted.3
Incidence of AST/ALT Increases Among Patients in EMBER-3
Incidence of Increased AST/ALT in EMBER-3 (Safety Population) presents the incidence of AST/ALT increases among patients in the EMBER-3 clinical trial.
TEAE, (%) | Imlunestrant Monotherapyb | SOC ETc | Imlunestrant + Abemaciclibd | |||
Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | Any Grade | Grade ≥3 | |
AST increase | 41 (12.5) | 3 (0.9) | 41 (12.7) | 3 (0.9) | 34 (16.3) | 5 (2.4) |
ALT increase | 34 (10.4) | 1 (0.3) | 33 (10.2) | 2 (0.6) | 28 (13.5) | 10 (4.8) |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; SOC ET = standard of care endocrine therapy; TEAE = treatment-emergent adverse event.
Note: Adverse events were assessed and graded according to the Common Terminology Criteria for Adverse Events, version 5.0, of the National Cancer Institute.
aIncluded 859 patients that initiated treatment.
bImlunestrant 400 mg was given once daily orally.
cInvestigator's choice of exemestane 25 mg given once daily orally or fulvestrant 500 mg given as intramuscular injection on days 1 and 15 of cycle 1 and then day 1 only of each subsequent 28-day cycle.
dImlunestrant 400 mg was given once daily orally and abemaciclib 150 mg was given twice daily orally.
One (0.3%) patient in the imlunestrant monotherapy group experienced a serious adverse event (AE) of hepatotoxicity.3
No new safety signals were identified with 14 months of additional follow-up from the primary outcome analysis of EMBER-3 (data cutoff date: August 18, 2025), and the safety profile of both monotherapy and the combination remained consistent with previous findings.4
Characterization of Transaminase Elevations in EMBER-3
The incidence/severity, time to onset, duration, and management of increased transaminase levels in the 3 treatment arms of the EMBER-3 trial is summarized in Characterization of Transaminase Elevations in the Safety Population of EMBER-3.
Elevated Transaminasesb | Imlunestrant Monotherapyc (N=327) | SOC ETd (N=324) | Imlunestrant + Abemaciclibe (N=208) |
Grade, % | |||
Any grade AE | 16 | 15 | 20 |
Grade 1 AE | 11 | 9 | 12 |
Grade 2 AE | 3 | 5 | 3 |
Grade ≥3 AE | 1 | 1 | 5 |
Patients, % | |||
Patients with >1 occurrences of AE | 8 | 9 | 12 |
Patients with >1 occurrences of grade ≥3 AE | <1 | <1 | 2 |
Dose interruption/reduction/discontinuation | 2/1/1 | <1/0/0 | |
Median days | |||
Time to onset (Q1-Q3) | 58 (16-197) | 43 (15-185) | 66 (29-195) |
Duration of grade 2 AE (range) | 27 (11-97) | 29 (5-86) | 19 (3-82) |
Duration of grade ≥3 AE (range) | 5 (4-27) | 2 (2-2) | 9 (2-58) |
Abbreviations: AE = adverse event; SOC ET = standard of care endocrine therapy.
Note: Adverse events were assessed for severity according to the Common Terminology Criteria for Adverse Events version 5.0 at baseline and at every visit throughout the study. Labs were assessed at baseline, at every cycle, and approximately 30 days after discontinuation of study therapy.
aThe safety population included all patients who received at least one dose of any study drug.
bIncludes increased ALT, AST, and hepatic enzymes, drug induced liver injury, hypertransaminaesemia, and hepatotoxicity.
cImlunestrant 400 mg was given once daily orally.
dInvestigator's choice of exemestane 25 mg given once daily orally or fulvestrant 500 mg given as intramuscular injection on days 1 and 15 of cycle 1 and then day 1 only of each subsequent 28-day cycle.
eImlunestrant 400 mg was given once daily orally and abemaciclib 150 mg was given twice daily orally.
fAll 6 (2.9%) patients had both study drugs interrupted.
gAll 5 (2.4%) patients had both study drugs reduced.
hPatients who discontinued both drugs.
iOne additional patient (0.5%) each discontinued only one of the study drugs and continued the other.
Most transaminase elevations were
- low grade
- reversible
- required few dose adjustments or discontinuations, and
- were comparable between arms (16% with imlunestrant monotherapy vs 15% with SOC ET).5,6
Three patients in the imlunestrant arm had postbaseline ALT/AST increases >3× ULN and total bilirubin increases >2× ULN. All 3 patients had alkaline phosphatase >3× ULN and other risk factors for elevated laboratory values.6
In the imlunestrant + abemaciclib arm, 20% of patients reported transaminase elevations, with grade ≥3 events reported in 5% of patients. Grade ≥3 events were of short duration with median of 9 days and 2% of patients experiencing ≥2 occurrences. These events were managed with dose adjustments.6
Transaminase Elevations by Age in EMBER-3
Incidence of Transaminase Elevations in Imlunestrant and Imlunestrant + Abemaciclib Treatment Arms in EMBER-3 shows the incidence of transaminase elevations by age in imlunestrant and imlunestrant + abemaciclib treatment arms in EMBER-3.
Transaminase increased, n (%) | Severity | Imlunestrant | Imlunestrant + Abemaciclib | ||
<65 years | ≥65 years | <65 years | ≥65 years | ||
AST increased | Any grade | 30 (14) | 11 (9) | 20 (17) | 14 (16) |
Grade ≥3 | 2 (1.0) | 1 (0.8) | 3 (3) | 2 (2) | |
ALT increased | Any grade | 25 (12) | 9 (8) | 14 (12) | 14 (16) |
Grade ≥3 | 1 (0.5) | 0 | 4 (3) | 6 (7) | |
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; N = number of patients in the total safety population; n = number of patients in the specified category.
Imlunestrant Pharmacokinetics and Safety in Females With Normal Versus Impaired Hepatic Function
Imlunestrant is mostly excreted in the feces and has an absolute oral bioavailability of ∼10%.7
JZLG Study
Study JZLG was a phase 1, open-label study evaluating pharmacokinetics and safety following a single oral dose (in a fasted state) of imlunestrant in subjects with normal hepatic function compared to those with hepatic impairment. Subjects were postmenopausal females of nonchildbearing potential.8,9 Phase 1 JZLG Study Design summarizes the JZLG study design and methods.
Figure 2 description: In the phase 1, open-label JZLG study, postmenopausal females of nonchildbearing potential were assigned to four different treatment arms, according to Child-Pugh score. Group 1 included 9 females with normal hepatic function, Group 2 included 6 females with mild hepatic impairment, Group 3 included 6 females with moderate hepatic impairment, and Group 4 included 6 females with severe hepatic impairment. Participants in Groups 1 through 3 received a single dose of imlunestrant 400 mg and those in Group 4 received a single reduced dose of 200 mg. Blood samples were then collected for pharmacokinetic and safety analyses up to 10 days postdose.
Abbreviations: PK = pharmacokinetic; R2PD = recommended phase 2 dose.
Among participants with mild hepatic impairment (Child-Pugh A) compared with participants with normal hepatic function, there were no significant differences in
In participants with moderate hepatic impairment (Child-Pugh B) compared with participants with normal hepatic function, there were significant increases in AUC(0-tlast) of 120%, AUC(0-∞) of 122%, and no significant difference in Cmax.8,9
In participants with severe hepatic impairment (Child-Pugh C) compared with participants with normal hepatic function, there were significant increases in dose-normalized AUC(0-tlast) of 191% and dose-normalized AUC(0-∞) of 206%, and no significant difference in dose-normalized Cmax observed.8,9
Imlunestrant, administered as a single oral dose in the fasted state, was well tolerated by all participants in the study. AEs were reported by 2 participants with moderate hepatic impairment and severe hepatic impairment, respectively. Nausea and headache were the only AEs reported by ≥1 participant.8
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Inluriyo [package insert]. Indianapolis, IN: Eli Lilly and Company; 2026.
2A study of imlunestrant, investigator's choice of endocrine therapy, and imlunestrant plus abemaciclib in participants with ER+, HER2- advanced breast cancer (EMBER-3). ClinicalTrials.gov identifier: NCT04975308. Updated July 11, 2025. Accessed August 29, 2025. https://clinicaltrials.gov/ct2/show/NCT04975308
3Jhaveri KL, Neven P, Casalnuovo ML, et al; EMBER-3 Study Group. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392(12):1189-1202. https://doi.org/10.1056/NEJMoa2410858
4Jhaveri KL, Neven P, Casalnuovo ML, et al. Imlunestrant with or without abemaciclib in advanced breast cancer: updated efficacy results from the phase III EMBER-3 trial. Ann Oncol. 2026;37(4):532-543. https://doi.org/10.1016/j.annonc.2025.11.018
5O'Shaughnessy J, Bidard FC, Neven P, et al. Imlunestrant with or without abemaciclib in advanced breast cancer (ABC): safety analyses from the phase III EMBER-3 trial. Poster presented at: 61st Annual Meeting of the American Society of Clinical Oncology (ASCO); May 30-June 3, 2025; Chicago, IL. Accessed May 29, 2025. https://meetings.asco.org/abstracts-presentations/248581
6O'Shaughnessy J, Bidard FC, Neven P, et al. Imlunestrant with or without abemaciclib in advanced breast cancer: safety analyses from the EMBER-3 trial. NPJ Breast Cancer. Published online April 27, 2026. https://doi.org/10.1038/s41523-026-00950-z
7Datta-Mannan A, Czeskis B, Shanks E, et al. Evaluation of the disposition and absolute bioavailability of imlunestrant in healthy volunteers. Poster presented at: Annual Meeting of the American Association of Pharmaceutical Scientists (AAPS) - PharmSci 360; October 20-23, 2024; Salt Lake City, UT. Accessed November 4, 2024. https://aaps2024.eventscribe.net/ajaxcalls/PosterInfo.asp?PosterID=679049
8Datta-Mannan A, White S, Shanks E, et al. Evaluation of pharmacokinetics and safety of imlunestrant in participants with hepatic impairment. Poster presented at: 47th Annual Meeting of the San Antonio Breast Cancer Symposium (SABCS); December 10-13, 2024; San Antonio, TX.
9Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Date of Last Review: March 30, 2026