Overview
11 DESCRIPTION INLURIYO tablets contain imlunestrant, an estrogen receptor antagonist. The chemical name for imlunestrant tosylate is (5R)-5-(4-(2-(3-(flouromethyl)azetidin-1-yl)ethoxy)phenyl)-8-(trifluoromethyl)-5H-( 1 )benzopyrano(4,3-c)quinolin-2-ol, tosylate salt (1:1). Imlunestrant tosylate is a white to practically white to yellow powder with the empirical formula C 29 H 24 F 4 N 2 O 3 .
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Imlunestrant is an estrogen receptor (ER) antagonist that binds to ERα. In vitro, imlunestrant induced degradation of ERα, leading to inhibition of ER-dependent gene transcription and cellular proliferation in ER+ breast cancer cells. Imlunestrant demonstrated in vitro and in vivo anti-tumor activity in ER+ breast cancer xenograft models, including models with ESR1 mutations. 12.2 Pharmacodynamics Imlunestrant exposure-response relationships and the time course of pharmacodynamics have not been fully characterized. Cardiac Electrophysiology At 2 times the mean maximum concentration observed with the approved recommended dose, a mean increase in the QTc interval >20 msec was not observed. 12.
Indications
- 1 INDICATIONS AND USAGE INLURIYO is indicated for the treatment of adults with estrogen receptor (ER)-positive, 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. INLURIYO TM is an estrogen receptor antagonist 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 )
Common Doses
- 400 mg
- 200 mg
- 600 mg
Dosage
2 DOSAGE AND ADMINISTRATION Select patients for treatment based on the presence of ESR1 mutations. ( 2.1 ) The recommended dosage is 400 mg orally once daily, on an empty stomach. ( 2.2 ) Reduce the dose in patients with moderate or severe hepatic impairment ( 2.4 , 8.6 ) Dosage modifications may be required. ( 2.3 , 2.4 , 2.5 ) 2.1 Patient Selection Select patients for treatment of ER-positive, HER2-negative advanced or metastatic breast cancer with INLURIYO based on the presence of ESR1 mutation(s) in a plasma specimen using an FDA-approved test [see Indications and Usage ( 1 ) and Clinical...
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A Inhibitors: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, decrease the INLURIYO dosage. ( 2.5 , 7.1 ) Strong CYP3A Inducers: Avoid concomitant use with INLURIYO. If concomitant use cannot be avoided, increase the INLURIYO dosage ( 2.5 , 7.1 ). 7.1 Effects of Other Drugs on INLURIYO Strong CYP3A Inhibitors Avoid concomitant use of INLURIYO with strong CYP3A inhibitors. If concomitant use cannot be avoided, reduce the dosage of INLURIYO [see Dosage and Administration ( 2.5 ), Clinical Pharmacology ( 12.3 )] .