INLURIYO Film-coated tablet Ref.[116183] Active ingredients: Imlunestrant

Food effect

Imlunestrant exposures in the presence of a high-fat meal are unknown. The dose should be taken in the fasted state as higher exposures may occur with food.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially "sodium-free".

Imlunestrant is metabolized by sulfation, CYP3A4 oxidation and direct glucuronidation.

Potential for other medicinal products to effect imlunestrant

Strong CYP3A inducers

Coadministration of imlunestrant with carbamazepine (a strong CYP3A inducer) decreased the area under the concentration-time curve (AUC) and maximum concentration (C_max) of imlunestrant by 42% and 29%, respectively. Concomitant use of strong CYP3A inducers should be avoided. If strong CYP3A inducers cannot be avoided, the imlunestrant dose should be increased by 200 mg once daily (see section 4.2).

Strong CYP3A inhibitors

Coadministration of imlunestrant with itraconazole (a strong CYP3A inhibitor) increased the AUC and C_max of imlunestrant by 2.11-fold and 1.87-fold, respectively. Concomitant use of strong CYP3A inhibitors should be avoided. If strong CYP3A inhibitors cannot be avoided, the imlunestrant dose should be decreased by 200 mg once daily (see section 4.2).

Gastric acid reducing agents

Coadministration of imlunestrant with omeprazole (a proton pump inhibitor) had no clinically meaningful effect on the pharmacokinetics of imlunestrant.

Potential for imlunestrant to effect other medicinal products

CYP2D6 substrates

Imlunestrant increased the AUC and C_max of dextromethorphan (a CYP2D6 substrate) by 1.33-fold and 1.43-fold, respectively. Caution should be used when coadministering imlunestrant with CYP2D6 substrates for which a small increase in concentration leads to significant adverse events.

P-glycoprotein (P-gp) substrates

Imlunestrant increased the AUC and C_max of digoxin (a P-gp substrate) by 1.39-fold and 1.60-fold, respectively. Caution should be used when coadministering imlunestrant with P-gp substrates for which a small increase in concentration leads to significant adverse events.

BCRP substrates

Imlunestrant increased the AUC and C_max of rosuvastatin (a BCRP substrate) by 1.49-fold and 1.65-fold, respectively. Caution should be used when coadministering imlunestrant with BCRP substrates for which a small increase in concentration leads to significant adverse events.

Women of childbearing potential/Contraception in males and females

The pregnancy status of females of reproductive potential should be verified prior to starting treatment.

Females and males of reproductive potential should be advised to use highly effective contraception during treatment and for at least 1 week after the last dose (see section 5.3).

Pregnancy

There are no data from the use of imlunestrant in pregnant women. Based on the mechanism of action of imlunestrant and findings from embryofoetal toxicity studies in animals, imlunestrant can cause foetal harm when administered to pregnant women (see section 5.3). Imlunestrant should not be used during pregnancy and in women of childbearing potential not using contraception. If pregnancy occurs during treatment, the patient must be informed of the potential hazard to the foetus and potential risk of miscarriage.

Breast-feeding

It is unknown whether imlunestrant or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in the breast-fed infant, use during lactation is contraindicated (see section 4.3).

Fertility

Based on findings from animal studies (see section 5.3) and its mechanism of action, imlunestrant may impair fertility in females and males of reproductive potential.

Imlunestrant has no or negligible influence on the ability to drive and use machines. However, since fatigue and asthenia have been reported with imlunestrant, caution should be observed by those patients who experience this adverse reaction when driving or operating machinery.

Summary of the safety profile

The most common and clinically relevant adverse reactions were ALT increased (34.3%), AST increased (33.2%), fatigue (25.7%), diarrhoea (22.5%), nausea (20.1%), and vomiting (9.0%).

Adverse reactions leading to discontinuations of treatment in more than 1 patient included ALT increased (0.8%) only.

Tabulated list of adverse reactions

The frequencies of adverse drug reactions (ADRs) displayed below are based on pooled data in 378 patients, treated with 400 mg imlunestrant once daily from a randomised, open-label, multicenter Phase 3 study (EMBER-3) and an open-label, multicenter, dose escalation and dose expansion phase 1a/1b study (EMBER).

In the following tables, adverse reactions are listed in order of MedDRA body system organ class and frequency. Frequency gradings are: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), and not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 3. Adverse drug reactions in patients receiving imlunestrant:

^a Consolidated term consisting of analogous preferred terms.
^b Consolidated term consisting of preferred terms: arthralgia, myalgia, musculoskeletal discomfort, musculoskeletal chest pain, musculoskeletal pain, pain in extremity, neck pain.
^c Based on laboratory assessments.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.