ELINZANETANT CAP,ORAL

Clinical Criteria Summary

Treatment of moderate to severe vasomotor symptoms (VMS) due to menopause
Naturally or surgically postmenopausal women aged 40–65 years
Women aged 18–70 receiving endocrine therapy for hormone receptor-positive breast cancer or prevention, with at least 35 moderate-to-severe VMS per week associated with endocrine therapy

CNS depressant effect and daytime impairment: Advise patients to refrain from driving or hazardous activities until effects resolve; onset typically occurs within 10 days of initiation
Hepatic transaminase elevations: Obtain baseline hepatic bloodwork (AST, ALT, alkaline phosphatase, total and direct bilirubin) prior to initiation; do not initiate if transaminases or total bilirubin are 2 or more times ULN. Recheck hepatic bloodwork at 3 months after initiation and counsel on signs/symptoms of liver injury. Discontinue if transaminases are elevated greater than 5x ULN or if transaminases are elevated greater than 3x ULN and total bilirubin exceeds 2x ULN
Risk of pregnancy loss: Exclude pregnancy in patients of reproductive potential; require effective contraception during treatment and for two weeks after stopping
Risk of seizures: Use with caution in patients with a history of seizures or conditions that lower the seizure threshold

Strong CYP3A4 inhibitors: Avoid concomitant use
Moderate CYP3A4 inhibitors: Reduce elinzanetant dose
Strong CYP3A4 inducers: Avoid concomitant use
CYP3A4 substrates: Elinzanetant is a weak CYP3A4 inhibitor and increases exposure of CYP3A4 substrates; avoid concomitant use unless otherwise recommended for the specific substrate

Renal impairment: No dosage adjustment needed for eGFR ≥15 mL/min; no data on eGFR <15 mL/min or dialysis
Hepatic impairment: No adjustment for mild (Child-Pugh A); not recommended for moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment
Lactation: No data

Demonstrated efficacy in reducing frequency and severity of moderate to severe VMS and improving sleep disturbances compared to placebo
Indirect comparisons suggest similar efficacy to fezolinetant for VMS, with a possible advantage on sleep outcomes
Indirect comparisons indicate superiority over paroxetine and desvenlafaxine for reducing VMS frequency
Cost is significantly higher than other nonhormonal options (SSRIs, SNRIs, gabapentin)

Females with moderate to severe vasomotor symptoms (VMS) associated with menopause or due to endocrine treatment for hormone receptor positive breast cancer or its prevention
Contraindication or intolerance to menopausal hormone therapy (MHT) or patient preference to avoid
Contraindication, intolerance, or insufficient response to one non-neurokinin pathway nonhormonal treatment for VMS

Baseline AST, ALT, or total bilirubin ≥ 2 times the upper limit of normal
Concomitant use of strong and moderate CYP3A4 inducers and strong CYP3A4 inhibitors
Pregnancy
History of seizures or a condition that lowers seizure threshold
Moderate or severe hepatic impairment (Child-Pugh B or C)

For females who can become pregnant: Exclude pregnancy prior to receiving elinzanetant
For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 2 weeks after stopping treatment

Perform baseline liver function testing before initiating elinzanetant (ALT, AST, ALP, total and direct bilirubin)
Perform follow-up liver function testing at 3 months (and if any signs or symptoms of liver injury occur)
Discontinue elinzanetant if transaminase elevations are greater than 5 times upper limit of normal or if transaminase elevations are greater than 3 times upper limit of normal and the total bilirubin greater than 2 times upper limit of normal
Patients should be advised on signs and symptoms of hepatotoxicity and when to seek medical attention

Potential for central nervous system depressant effects and impact on driving or hazardous work discussed
Providers are advised to periodically reassess and discuss the need for continued treatment with patients, given the finite duration of VMS
Consider periodic assessment of liver function during extended treatment