Elinzanetant Capsules (Lynkuet)

By William Elliott, MD, FACP, and James Chan, PharmD, PhD

The U.S. Food and Drug Administration has approved elinzanetant, a second non-hormonal neurokinin receptor antagonist, following fezolinetant (Veozah), for the treatment of vasomotor symptoms (VMS) associated with menopause. Both drugs modulate neuronal activity in the thermoregulatory center associated with hot flashes, although there are differences in neurokinin receptor selectivity. Fezolinetant is a neurokinin 3 (NK3) antagonist, while elinzanetant is an antagonist of both neurokinin 1 (NK1) and NK3. Elinzanetant is distributed by Bayer HealthCare Pharmaceuticals, Inc., as Lynkuet.

Indications

Elinzanetant is indicated for the treatment of moderate to severe VMS caused by menopause.¹

Dosage

The recommended dose is 120 mg (two 60-mg capsules) orally daily at bedtime with or without food.¹ Elinzanetant is available as 60-mg capsules.

Potential Advantages

Elinzanetant is a dual NK3 and NK1 antagonist, compared to fezolinetant, which is solely an NK3 antagonist. This may improve sleep quality compared with fezolinetant.^2,3

Potential Disadvantages

Elinzanetant is contraindicated for use in pregnancy. Females of reproductive potential should use effective contraception during treatment.¹ Elinzanetant is a substrate for cytochrome P450 3A4 (CYP3A4). Concomitant use with strong and moderate CYP3A4 inducers, strong CYP3A4 inhibitors, and grapefruit juice should be avoided.¹ Headache has been reported with elinzanetant, but not with fezolinetant.² Other adverse reactions include fatigue (7.3% vs. 2.9% in the placebo arm, respectively), dizziness (6.1% vs. 1.9% in the placebo arm, respectively), somnolence (5.1% vs. 1.3% in the placebo arm, respectively), abdominal pain (4.5% vs. 2.5% in the placebo arm, respectively), and rash (4.2% vs. 1.6% in the placebo arm, respectively), based on study participants (n = 627) exposed to elinzanetant or placebo up to 52 weeks.¹ Elinzanetant may cause elevation of serum transaminases (alanine transaminase and/or aspartate aminotransferase). Testing of transaminases is recommended before starting elinzanetant and after three months of therapy.¹ Driving ability could be impaired in some individuals taking elinzanetant.¹

Comments

NK3 receptors are believed to be involved in the disruption of thermoregulation, triggering VMS.³ The main ligand for NK3 is neurokinin B, while substance P is the main ligand for NK1.⁴ The efficacy of elinzanetant was evaluated in two randomized, double-blind, placebo-controlled, Phase III trials (OASIS 1 and OASIS 2).^1,5 Study participants, 40- to 65-year-old menopausal women experiencing ≥ 50 moderate to severe hot flashes (including nighttime hot flashes) over seven days, were randomized to elinzanetant (n = 199 [OASIS 1], n = 200 [OASIS 2]) or placebo (n = 197 [OASIS 1], n = 200 [OASIS 2]) arms for 12 weeks, followed by elinzanetant for 14 weeks. The study participants had a mean age of 55 years, 80% were white, the average baseline VMS frequency was 14.6, the mean severity was 2.5, and the Patient-Reported Outcomes Measurement Information System Sleep Disturbance 8b total T score (PROMIS SD SF 8b total T score) was 60.9. Coprimary endpoints were mean change in frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12, measured by the electronic hot flash daily diary. Secondary endpoints included PROMIS SD SF total T score and Menopause-specific Quality of Life questionnaire total score to week 12. Elinzanetant treatment showed a statistically significant reduction vs. placebo in the frequency of hot flashes (-3.29, -3.04 [OASIS -1]; -3.22, -3.24 [OASIS -2]) over 24 hours at weeks 4 and 12, respectively. The severity of VMS was significantly reduced (-0.33, -0.40 [OASIS -1]; -0.22, -0.29 [OASIS -2]) over 24 hours at weeks 4 and 12, respectively. At week 4, approximately 63% of participants taking elinzanetant achieved at least a 50% reduction in the frequency of VMS, compared to approximately 31% on placebo.⁵ By week 26, > 80% of study participants achieved at least 50% reduction in VMS frequency, including those who switched to elinzanetant after week 12. Benefit was consistent across different participant subgroups (e.g., age, ethnicity, body mass index, and smoking status) with benefit observed as early as week 1.^1,5 Elinzanetant also improved sleep disturbance and menopause-related quality of life.³ Elinzanetant does not appear to cause endometrial abnormalities beyond the expected background rate.¹

Clinical Implications

A systematic review and meta-analysis suggest that both fezolinetant and elinzanetant are associated with beneficial outcomes in menopausal women with VMS.² Elinzanetant may provide a larger effect size in terms of frequency and severity reduction and greater improved sleep quality compared to fezolinetant.² While elinzanetant may cause elevation of hepatic transaminases, in contrast to fezolinetant, it does not carry a box warning for risks of hepatotoxicity. Elinzanetant may offer an improved non-hormonal treatment over fezolinetant for VMS associated with menopause in terms of effectiveness and safety. Neither drug significantly affects other consequences of menopause, such as loss of bone mineral density, vaginal dryness, and hypoactive sexual desire disorder. The cost of elinzanetant is $625 for a 30-day supply.

William T. Elliott, MD, FACP, is Assistant Clinical Professor of Medicine, University of California, San Francisco.

James Chan, PharmD, PhD, is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

References

1. Bayer HealthCare Pharmaceuticals, Inc. Lynkuet prescribing information. Revised October 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219469s000lbl.pdf
2. Menegaz de Almeida A, Oliveira P, Lopes L, et al. Fezolinetant and elinzanetant therapy for menopausal women experiencing vasomotor symptoms: A systematic review and meta-analysis. Obstet Gynecol. 2025;145(3):253-261.
3. Cagnacci A, Xholli A, Fiamberti M, Londero AP. Neurokinin antagonists to treat vasomotor symptoms — Possible implications for long-term health and disease. J Clin Med. 2025;14(19):6852.
4. Hager M, Goldstein T, Fitz V, Ott J. Elinzanetant, a new combined neurokinin-1/-3 receptor antagonist for the treatment of postmenopausal vasomotor symptoms. Expert Opin
   Pharmacother. 2024;25(7):783-789.
5. Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the treatment of vasomotor symptoms associated with menopause: OASIS 1 and 2 randomized clinical trials. JAMA. 2024;332(6):1343-1354.