Elinzanetant

Strong CYP3A4 Inhibitors and grapefruit (juice): Avoid concomitant use with LYNKUET. ( 7.1 ) Moderate CYP3A4 Inhibitors: Reduce LYNKUET dosage to 60 mg once daily. ( 2.3 , 7.1 )21 Strong and Moderate CYP3A4 Inducers: Avoid concomitant use with LYNKUET. ( 7.1 )

7.1 Effects of Other Drugs on LYNKUET Elinzanetant is primarily metabolized via CYP3A4 enzyme. Table 3 describes drug interactions where concomitant use of another drug affects LYNKUET. Table 3: Drug Interactions: Concomitant Use of Other Drugs Affect the Use of LYNKUET Strong and Moderate CYP3A4 Inhibitors See www.fda.gov/CYPandTransporterInteractingDrugs for examples of strong and moderate CYP3A4 inhibitors, and CYP3A4 inducers. Prevention or Management Strong CYP3A4 Inhibitors and grapefruit (juice): Avoid concomitant use. Moderate CYP3A4 Inhibitors: Reduce the LYNKUET dosage [see Dosage and Administration (2.2) ].

Clinical Effect(s) Strong and moderate CYP3A4 inhibitors increase elinzanetant exposure, which may increase the risk of LYNKUET-associated adverse reactions [see Clinical Pharmacology (12.3) ]. Strong and Moderate CYP3A4 Inducers Prevention or Management Strong and moderate CYP3A4 inducers: Avoid concomitant use. Clinical Effect(s) Strong and moderate CYP3A4 inducers decrease elinzanetant exposure, which may reduce the effectiveness of LYNKUET.

7.2 Effects of LYNKUET on Other Drugs CYP3A4 Substrates Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A4 substrates where minimal concentration changes may lead to serious adverse reactions. See www.fda.gov/CYPandTransporterInteractingDrugs for examples of CYP3A4 substrates. Elinzanetant is a weak inhibitor of CYP3A4. Concomitant use of LYNKUET increases exposure of CYP3A4 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions related to these substrates.

8.1 Pregnancy Risk Summary LYNKUET is contraindicated in pregnancy [see Contraindications (4) ]. If pregnancy occurs during the use of LYNKUET, discontinue treatment. Based on findings from animal reproduction studies, LYNKUET may cause pregnancy loss or stillbirth but not fetal malformations when administered during pregnancy. There are no data on the use of LYNKUET in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal reproduction studies in rats, an increase in total litter loss or stillbirth and a decrease of neonatal pup viability was observed within the range of human therapeutic exposure when dams were treated orally throughout gestation and lactation [i.e., gestation day 6 to lactation day 21]. There was an increase in percentage of pre- and post-implantation embryo loss and decrease in fetal body weights at 16-fold the human therapeutic exposure when rat dams were treated orally prior to mating and through the early embryonic period [i.e., 22 days before mating to post-coitum day 6].

In rabbits, there was marked body weight loss and decreased food consumption in dams treated orally during gestation day 7 to 19 at doses equivalent to human therapeutic exposure (see Data ). Data Animal Data In a fertility and early embryonic development study in female rats, once daily oral doses of elinzanetant were administered 22 days before mating through post-coitum day 6. Increased percentage of pre-implantation and post-implantation embryo loss, resulting in reduced litter size, and lower fetal body weights were seen at the dose of 100 mg/kg/day (14-fold the AUC (0-24) at the human therapeutic dose).

These effects were not observed following dosing at 25 mg/kg/day (3-fold the AUC (0-24) at the human therapeutic dose). In an embryo-fetal development study in pregnant rats, once daily oral doses of elinzanetant were administered throughout organogenesis from gestation day 6 to 17. No evidence of embryo-fetal lethality or teratogenicity occurred at doses ≤100 mg/kg/day (23-fold the AUC (0-24) at the human therapeutic dose) and no maternal toxicity occurred at doses ≤25 mg/kg/day (7-fold the AUC (0-24) at the human therapeutic dose).

In an embryo-fetal development study in pregnant rabbits, twice daily oral doses of elinzanetant were administered throughout organogenesis from gestation day 7 to 19. Maternal toxicity in the form of marked body weight loss and decreased food consumption leading to early sacrifice in 4 out of 27 females was observed at the highest tested dose…