What is the recommended dosing of Lynkuet (elinzanetant) for a woman with moderate‑to‑severe menopausal vasomotor symptoms, including adjustments for strong CYP3A4 inhibitors or inducers, hepatic impairment, and renal impairment?

Lynkuet (Elinzanetant) Dosing for Menopausal Vasomotor Symptoms

Standard Dosing Recommendation

The recommended dose of Lynkuet (elinzanetant) is 120 mg orally once daily for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. 1

• This dosing regimen achieves sustained and near-complete inhibition of both NK-1 (>99%) and NK-3 (>94.8%) receptors throughout the 24-hour dosing interval 2
• Peak drug concentrations are reached within one hour, with a terminal elimination half-life of approximately 15 hours 3
• The oral bioavailability is 36.7% and is dose-independent within the therapeutic range 2

Effect of Food on Absorption

• A high-fat breakfast affects the oral absorption of elinzanetant 2
• Administer consistently with regard to meals to maintain stable drug exposure

Dose Adjustments for Drug Interactions

Strong CYP3A4 Inhibitors

• No specific dose adjustment guidance is currently available in the published literature for concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) 2
• Given that elinzanetant clearance is 7.26 L/h and likely involves hepatic metabolism, caution is warranted when co-administering with strong CYP3A4 inhibitors 2

Strong CYP3A4 Inducers

• No specific dose adjustment guidance is currently available for concomitant use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's wort) 2
• Strong inducers may reduce elinzanetant exposure and potentially decrease efficacy 2

Dose Adjustments for Hepatic Impairment

• No specific dosing recommendations for hepatic impairment are currently published 3, 2
• Notably, phase IIb clinical trials showed no evidence of drug-related hepatotoxicity and no serious adverse events related to liver function 3
• The clearance of elinzanetant is 7.26 L/h, suggesting hepatic involvement in drug elimination 2

Dose Adjustments for Renal Impairment

• No specific dosing recommendations for renal impairment are currently published 2
• The population pharmacokinetic analysis did not identify renal function as a significant covariate affecting elinzanetant clearance 2

Clinical Efficacy Timeline

• Significant reduction in VMS frequency begins at week 4, with mean reductions of 3.0-3.3 hot flashes per day compared to placebo 1
• Maximum efficacy is achieved by week 12, with sustained reductions of 3.2 hot flashes per day and severity improvements of 0.3-0.4 points 1
• Sleep disturbances and menopause-related quality of life show significant improvement by week 12 1

Safety Profile

• Elinzanetant is well-tolerated with a favorable safety profile 1, 3
• Drug-related adverse events occur in approximately 20.75% of patients (vs. 11.70% with placebo) 4
• Headache is the most common adverse event, occurring in 8.0% of patients (vs. 2.54% with placebo) 4
• No serious adverse events or hepatotoxicity were reported in phase IIb trials 3

Important Clinical Considerations

• The 120 mg once-daily dose was selected for phase III trials based on optimal efficacy and tolerability demonstrated in phase IIb studies 3
• Elinzanetant provides larger effect sizes for VMS frequency and severity reduction compared to fezolinetant, with mean differences of 2.99 hot flashes per day (vs. 2.54 for fezolinetant 45 mg) 4
• Sleep quality improvement is particularly robust with elinzanetant, showing a mean difference of 4.65 points on sleep disturbance scales 4

Common Pitfalls to Avoid

• Do not assume dose adjustments are needed for age, BMI, or history of oophorectomy—the population pharmacokinetic model identified no intrinsic factors requiring dose modification other than food effects 2
• Do not discontinue therapy prematurely—efficacy continues to improve through week 12 1
• Monitor for headache, particularly during treatment initiation, as this is the most common adverse event requiring clinical attention 4