IMPORTANT SAFETY INFORMATION

Contraindications: LYNKUET^® is contraindicated in pregnancy. Exposure to LYNKUET may cause pregnancy loss or stillbirth when administered during pregnancy.

Warnings and Precautions:

Central Nervous System Depressant Effect and Daytime Impairment:

In the three OASIS trials, nervous system effects (including somnolence, fatigue, vertigo, dizziness and presyncope) occurred in 11.9% of patients on LYNKUET compared to 3.5% on placebo. Advise patients about the potential for somnolence and other nervous system effects. Advise patients who experience these effects to refrain from driving or engaging in hazardous occupations or activities until the effects have resolved.

Hepatic Transaminase Elevations:

Elevations in serum transaminase [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] concentrations equal to or greater than three times the upper limit of normal (ULN) occurred in 0.6% of patients receiving LYNKUET and 0.4% of patients receiving placebo up to 12 weeks in three clinical trials. Perform baseline bloodwork (including ALT, AST, alkaline phosphatase, and total and direct bilirubin) prior to initiation of LYNKUET to evaluate for hepatic function and injury. Do not start therapy if serum transaminase concentration is equal to or exceeds two times the ULN or if the total bilirubin is equal to or exceeds two times the ULN. Perform follow-up evaluations of hepatic transaminase concentration 3 months after initiation of therapy.

Advise patients to discontinue LYNKUET immediately and seek medical attention including hepatic laboratory tests if they experience signs or symptoms that may suggest liver injury (new onset fatigue, decreased appetite, nausea, vomiting, pruritus, jaundice, pale feces, dark urine, or abdominal pain).

Discontinue LYNKUET if transaminase elevations exceed five times the ULN or if transaminase elevations exceed three times the ULN and total bilirubin exceeds two times the ULN.

Risk of Pregnancy Loss:

LYNKUET is contraindicated for use in pregnancy. Findings from animal studies suggest that LYNKUET can cause pregnancy loss or stillbirth. Exclude pregnancy in females of reproductive potential prior to initiating LYNKUET. Advise females of reproductive potential to use effective contraception during treatment with LYNKUET and for 2 weeks after stopping LYNKUET.

Risk of Seizures in Patients with a History of Seizures:

Seizure was reported in one patient with a history of seizures in the clinical trials of LYNKUET. In addition, convulsions were observed in studies conducted in male and female rats. Use LYNKUET with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold.

Most Common Adverse Reactions:

The most frequently reported (≥5%) adverse reactions with LYNKUET vs placebo in a 52-week study were: headache (9.6% vs 7.0%), fatigue (7.3% vs 2.9%), dizziness (6.1% vs 1.9%) and somnolence (5.1% vs 1.3%).

Drug Interactions:

Effects of Other Drugs on LYNKUET

Strong CYP3A4 Inhibitors and Grapefruit (Juice): Concomitant use of LYNKUET with strong CYP3A4 inhibitors and grapefruit (juice) should be avoided as it may increase the risk of LYNKUET-associated adverse reactions.

Moderate CYP3A4 Inhibitors: Reduce LYNKUET dose if administered concomitantly with moderate CYP3A4 inhibitors as it may increase the risk of LYNKUET-associated adverse reactions.

Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of LYNKUET with strong and moderate CYP3A4 inducers.

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, as it may increase the risk of adverse reactions related to these substrates.

Use in Specific Populations:

Pregnancy

LYNKUET is contraindicated in pregnancy. If pregnancy occurs during the use of LYNKUET, discontinue treatment.

Hepatic Impairment

LYNKUET is not recommended in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

Renal Impairment

The effect of end-stage renal disease (eGFR <15 mL/min), with or without hemodialysis, on the pharmacokinetics of LYNKUET has not been studied.

INDICATION

LYNKUET (elinzanetant) is indicated for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause.

For important information about LYNKUET, please see the Full Prescribing Information.