Lorazepam during breastfeeding: a pharmacokinetic case report and exploratory pharmacovigilance assessment – a contribution from the ConcePTION project

Introduction Knowledge regarding lorazepam use during breastfeeding is limited and so are quantitative data on lorazepam transfer into human milk. Lorazepam transfer to human milk was characterized in a single case and pharmacovigilance databases were explored. Methods A clinical lactation study was conducted in a breastfeeding mother who used lorazepam as needed for anxiety symptoms (single 1 mg oral dose, 6.5 months postpartum). Serial human milk (n = 6) and maternal plasma (n = 2) samples were collected over 24 h. Concentration-time data were used to calculate plasma and milk AUC 0–24h (linear trapezoidal interpolation), milk-to-plasma (M/P) ratios, daily and relative infant dose (DID, RID). Because of the a priori pragmatic design (limited sampling), published plasma concentration–time profiles following oral dose were searched, digitized and dose-normalized to derive a plasma AUC 0–24h . Pharmacovigilance data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and Eudravigilance were analyzed for “ lorazepam related exposure via human milk ”. Results Milk concentrations ranged from 0.65 to 2.10 ng/mL, with highest levels at 1.5 h. The milk AUC 0–24h was 25.36 ng*h/mL. Literature-derived plasma AUC 0–24h was 158.94 ng*h/mL resulting in an AUC-based M/P ratio of 0.16, calculated DID was 218 ng/kg/day. Assuming milk intakes of 150 and 200 mL/kg/day, estimated DID values were 176.26 and 235.02 ng/kg/day respectively, corresponding to RID values of 1.35% and 1.80%, increasing up to 3.85% upper-bound estimates. The RID therapeutic was 0.44%, increasing to 0.81% in upper-bound estimates. FAERS identified 25 reports of lorazepam exposure via human milk, Eudravigilance one, with mainly central nervous system (CNS) related symptoms. In all these cases, lorazepam was part of CNS polypharmacy, while no lorazepam monotherapy related events were retrieved. Conclusion These findings suggest low infant exposure following occasional single, low-dose lorazepam use during breastfeeding. While interpretation should remain cautious given the single-case design, the single low dose, limited plasma sampling, and milk concentrations below the validated lower limit of quantification, the available pharmacokinetic data suggest low estimated infant exposure following occasional low-dose lorazepam use. Pharmacovigilance findings provided contextual information but should not be interpreted as confirmatory evidence of safety.