Lemborexant levels in breast milk after single doses in healthy, lactating women

Aims The aim of this study is to determine the cumulative amount of lemborexant (a competitive dual orexin receptor antagonist approved to treat adults with insomnia) excreted in human breast milk and the relative infant dose (RID) as a proportion of daily maternal dose. Methods E2006‐A001‐010 was a single‐centre, open‐label study that enrolled lactating women (≥18 years) who breastfed for ≥5 weeks postpartum. After overnight fasting, subjects received a single 10‐mg oral dose of lemborexant. Using a standardized electric pump, milk was sampled before and ≤240 h (10 days) after dosing; combined and total volume were recorded. The cumulative total amount of lemborexant excreted, fraction of dose excreted, daily infant dose and RID were calculated. Lemborexant concentration in human milk was assessed by liquid chromatography with tandem mass spectrometry. Results Eight subjects completed the study. The mean cumulative total amount of lemborexant reached 0.0174 mg (coefficient of variation [CV] 54.5%; 0.174% of lemborexant 10 mg administered) in breast milk at 240 h (10 days); ~70% of excreted lemborexant accumulated in the first 24 h. For an infant weighing 6 kg, the daily infant dose was 0.00290 mg kg−1 (CV 54.5%) and the RID was 1.96% (CV 63.1%) of daily maternal dose. Mild treatment‐emergent adverse events were reported in 4 subjects; these all resolved by end of study. Conclusion Trace quantities of lemborexant were found in human breast milk. Lemborexant was well tolerated by healthy lactating women.