AHFS Class:

• Central Nervous System Agents, Miscellaneous 28:92

Brands:

• Lynkuet^®

Generic Name(s):

• Elinzanetant

Elinzanetant is a neurokinin 1 (NK1) and neurokinin 3 (NK3) receptor antagonist.1

Elinzanetant has the following uses:

Elinzanetant is indicated for the treatment of moderate to severe vasomotor symptoms due to menopause.1

General

Elinzanetant is available in the following dosage form(s) and strength(s):

Capsules: 60 mg1

Dosage

Adults

Dosage and Administration

• Exclude pregnancy in females of reproductive potential.1
• Perform baseline hepatic laboratory tests to evaluate for hepatic function and injury [including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), and serum bilirubin (total and direct)] before initiating treatment with elinzanetant.1 Do not start elinzanetant if ALT or AST is ≥2 times upper limit of normal (ULN) or if the total bilirubin is ≥ 2 times ULN.1
• The recommended dosage of elinzanetant is 120 mg (two 60-mg capsules) orally once daily at bedtime at about the same time each day.1 If a dose is missed at bedtime, take the next dose as scheduled on the following day.1 Do not take two doses on the same day to make up for a missed dose.1
• Take elinzanetant with or without food.1 Take elinzanetant with water and swallow capsules whole.1 Do not cut, crush or chew capsules.1
• See Full Prescribing Information for dosage modification recommendations for drug interactions.1

Contraindications

Elinzanetant is contraindicated in pregnancy.1 Exposure to elinzanetant may cause pregnancy loss or stillbirth when administered during pregnancy.1

Warnings/Precautions

CNS Depressant Effects 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 elinzanetant compared to 3.5% on placebo.1 Advise patients about the potential for somnolence and other nervous system effects.1 Advise patients who experience these effects to refrain from driving or engaging in hazardous occupations or activities until the effects have resolved.1

Hepatic Transaminase Elevations

Elevations in serum transaminase (ALT and/or AST) concentrations equal to or greater than three times the ULN occurred in 0.6% of patients receiving elinzanetant and 0.4% of patients receiving placebo up to 12 weeks in three clinical trials.1 Perform baseline bloodwork (including ALT, AST, alkaline phosphatase, and total and direct bilirubin) prior to initiation of elinzanetant to evaluate for hepatic function and injury.1 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.1 Perform follow- up evaluations of hepatic transaminase concentration 3 months after initiation of therapy.1 Advise patients to discontinue elinzanetant 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).1 Discontinue elinzanetant 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.1 Exclude alternative causes of hepatic laboratory test elevations.1

Risk of Pregnancy Loss

Elinzanetant is contraindicated for use in pregnancy.1 Findings from animal studies suggest that elinzanetant can cause pregnancy loss or stillbirth.1 Exclude pregnancy in females of reproductive potential prior to initiating elinzanetant.1 Advise females of reproductive potential to use effective contraception during treatment with elinzanetant and for 2 weeks after stopping elinzanetant.1

Risk of Seizures in Patients with History of Seizures

Seizure was reported in one patient with a history of seizures in the clinical trials of elinzanetant.1 In addition, convulsions were observed in studies conducted in male and female rats.1 Use elinzanetant with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold.1

Specific Populations

Pregnancy

Elinzanetant is contraindicated in pregnancy.1 If pregnancy occurs during the use of elinzanetant, discontinue treatment.1 Based on findings from animal reproduction studies, elinzanetant may cause pregnancy loss or stillbirth but not fetal malformations when administered during pregnancy.1 There are no data on the use of elinzanetant in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 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].1 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].1 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.1

Lactation

There are no data on the presence of elinzanetant or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production.1 Elinzanetant is present in animal milk.1 When a drug is present in animal milk, it is likely that the drug will be present in human milk.1

Females and Males of Reproductive Potential

Based on findings from animal reproduction studies, elinzanetant may cause pregnancy loss or stillbirth when administered during pregnancy.1 Fetal malformations were not observed in those studies.1

Exclude pregnancy before initiating treatment with elinzanetant.1 Perform pregnancy testing if pregnancy is suspected during treatment with elinzanetant, and discontinue treatment if pregnancy is confirmed.1

Pregnancy should be prevented in women of reproductive potential by using effective contraception during and for 2 weeks after stopping treatment because elinzanetant can cause pregnancy loss or stillbirth.1

Pediatric Use

The efficacy and safety of elinzanetant in pediatric patients have not been established, and elinzanetant is not indicated in this population.1

Geriatric Use

There have not been sufficient numbers of geriatric women involved in clinical trials utilizing elinzanetant to determine whether those over 65 years of age differ from younger women in their response to elinzanetant.1

Hepatic Impairment

No dose adjustment is required in patients with mild (Child-Pugh A) hepatic impairment.1 Moderate (Child-Pugh B) hepatic impairment increased the exposure of elinzanetant.1 Elinzanetant has not been studied in individuals with severe (Child-Pugh C) hepatic impairment.1 Elinzanetant is not recommended in patients with moderate or severe hepatic impairment.1

Renal Impairment

No dose adjustment is required for patients with mild to severe [estimated glomerular filtration rate (eGFR) 15 to < 90 mL/min] renal impairment.1 The effect of end-stage renal disease (eGFR <15 mL/min) (with or without hemodialysis) on the pharmacokinetics of elinzanetant has not been studied.1

Common Adverse Effects

The most frequently reported (≥5%) adverse reactions were headache, fatigue, dizziness and somnolence.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Strong CYP3A4 Inhibitors and grapefruit (juice): Avoid concomitant use with elinzanetant.1
• Moderate CYP3A4 Inhibitors: Reduce elinzanetant dosage to 60 mg once daily.1
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use with elinzanetant.1

Actions

Mechanism of Action

Elinzanetant is a neurokinin 1 (NK1) and neurokinin 3 (NK3) receptor antagonist.1 Inhibition of Substance P and Neurokinin B through antagonism of NK1 and NK3 receptor signaling on kisspeptin/neurokinin B/dynorphin (KNDy) neurons can modulate neuronal activity in thermoregulation associated with hot flashes.1 Elinzanetant has higher affinity for human NK1 receptors (pKi values of 8.7 to 10.2) and NK3 receptors (pKi values of 8.0 to 8.8) than for human NK2 receptors (pKi values of approximately 6.0).1

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).1
• Advise patients who experience somnolence and other nervous system effects to refrain from driving or engaging in hazardous occupations or activities until the effects have resolved.1
• Advise patients that bloodwork to evaluate for hepatic functions and injury will be obtained at baseline and three months after initiating therapy.1 Advise patients to discontinue elinzanetant 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).1
• Exclude pregnancy in females of reproductive potential prior to initiating elinzanetant.1 Advise females of reproductive potential to use effective contraception during treatment with elinzanetant and for two weeks after discontinuing treatment and to discontinue elinzanetant if pregnancy is confirmed.1
• Advise patients to report any history of seizures or conditions that potentially lower the seizure threshold.1
• Advise patients to take elinzanetant once daily at bedtime with water and swallow capsules whole.1 Advise patients not to cut, crush or chew capsules.1 Instruct patients requiring a dosage modification (i.e., one 60 mg capsule once daily) to partially peel back the foil covering the blister cell to expose only one of the two capsules.1 Instruct patients to store the remaining capsule in the original blister card in the carton until the next dose.1
• Advise patients to report their use of any other prescription or nonprescription medications or dietary supplements.1

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Only references cited for selected revisions after 1984 are available electronically.

1. Bayer HealthCare Pharmaceuticals, Inc. LYNKUET (elinzanetant) ORAL prescribing information. 2025 Oct.