Lemborexant Maximum Dose
The maximum recommended dose of lemborexant is 10 mg once daily at bedtime. 1, 2, 3
Standard Dosing
Lemborexant should be initiated at 5 mg once nightly, with the option to increase to a maximum of 10 mg based on clinical response. 3, 4
The medication must be taken when the patient can dedicate at least 7 hours to sleep before planned awakening. 3
Peak plasma concentration occurs 1-3 hours after administration, with an effective half-life of 17-19 hours. 1, 3
Dose Modifications with CYP3A Inhibitors
When lemborexant is co-administered with weak CYP3A inhibitors (such as fluoxetine or ranitidine), the maximum dose should be reduced to 5 mg. 2
Co-administration with moderate CYP3A inhibitors (such as erythromycin or verapamil) or strong CYP3A inhibitors (such as itraconazole or fluconazole) should be avoided entirely, unless a 2.5 mg dose formulation is available in your country. 2
Lemborexant is primarily metabolized by CYP3A4/5, making it highly susceptible to drug-drug interactions with CYP3A inhibitors. 2, 3
Physiologically-based pharmacokinetic modeling demonstrates that strong CYP3A inhibitors significantly increase lemborexant exposure, necessitating dose reduction or avoidance. 2
Efficacy at Maximum Dose
The 10 mg dose demonstrated significant improvements in sleep efficiency, latency to persistent sleep, and wake after sleep onset compared to placebo in clinical trials. 4
In adults ≥65 years, both 5 mg and 10 mg doses showed sustained efficacy through 12 months of treatment. 5
The utility function combining efficacy and safety identified doses ranging from 2.5-10 mg as optimal for treating insomnia while minimizing next-morning residual sleepiness. 4
Safety Considerations at Maximum Dose
Adverse effects are dose-dependent, with somnolence occurring in approximately 10% of patients at the 10 mg dose. 3
Headache and nightmares affect 2-5% of patients at 10 mg. 3
Rare but serious adverse effects include sleep paralysis, hypnagogic/hypnopompic hallucinations, cataplexy-like symptoms, complex sleep behaviors, and emergence of depression or suicidal ideation. 3
No clinically relevant next-morning residual sleepiness was observed at doses through 10 mg based on Karolinska Sleepiness Scale, Digital Symbol Substitution Test, and Psychomotor Vigilance Test assessments. 1
Plasma concentration at 9 hours post-dose was only 27% of maximum concentration following 10 mg dosing, supporting minimal residual effects during wake time. 1
Important Clinical Caveats
Neither tolerance to sedation nor withdrawal effects on discontinuation have been observed with lemborexant. 3
Age, sex, and race do not significantly affect lemborexant pharmacokinetics, pharmacodynamics, or safety, eliminating the need for dose adjustments based on these factors. 1
Never exceed 10 mg daily, as higher doses (15 mg and 25 mg) were studied but not approved due to unfavorable risk-benefit profiles. 1, 4