Transfer of Probenecid and Cephalexin into Breast Milk

Objective: To report a case of the transfer of probenecid and cephalexin into human milk. Case Summary: A breast-fed infant of a 30-year-old woman being treated with oral probenecid and cephalexin for a breast infection developed severe diarrhea and associated symptoms. To investigate whether the maternal drug treatment was causative, milk was collected over a dose interval at steady-state, and concentrations of probenecid and cephalexin were measured by HPLC. The average concentrations of probenecid and cephalexin in milk were 964 and 745 μg/L, respectively, corresponding to absolute and relative infant doses of 145 μg/kg/day and 0.7% for probenecid and 112 μg/kg/day and 0.5% for cephalexin. The infant's adverse effects were rated as possible for probenecid and probable for cephalexin based on the Naranjo probability scale. Discussion: On the basis of the calculated relative infant doses for both probenecid and cephalexin in milk and the notional 10% level of concern for infant exposure, neither drug would be expected to cause significant systemic effects. However, local adverse effects, notably diarrhea, were observed. The Naranjo probability scale rating suggested that cephalexin was more likely than probenecid to be the cause of the infant's diarrhea. Conclusions: When using cephalexin/probenecid to treat breast infections in lactating women, clinicians should anticipate the possibility of adverse gastrointestinal effects in the breast-fed infant.