Distribution and excretion of fluoxetine and norfluoxetine in human milk

Aims To characterize milk/plasma (M/P) ratio and infant dose, for fluoxetine and norfluoxetine, in breast‐feeding women taking fluoxetine for the treatment of depression, and to determine the plasma concentration of these drugs in their infants. Methods Fourteen women (mean age 32.2 years) taking fluoxetine (mean dose 0.51 mg kg−1 day−1 ) and their infants (mean age 3.4 months) were studied. Fluoxetine and norfluoxetine in plasma and milk were measured by high‐performance liquid chromatography over a 24 h dose interval in four patients, and by single point data collection in 10 patients. Infant exposure was estimated as the product of estimated milk production, and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight‐adjusted maternal dose. Results Mean M/P values of 0.68 (95% CI 0.52–0.84) and 0.56 (95% CI 0.35–0.77) were calculated for fluoxetine and norfluoxetine, respectively. Mean total infant exposure (fluoxetine equivalents) was estimated to be 6.81% (range 2.15–12%) of the weight‐adjusted maternal dose of fluoxetine. Contributions from fluoxetine and norfluoxetine were approximately equal. Fluoxetine (range 20–252 μg l−1 ) was detected in five of the nine infants from whom samples were collected, and norfluoxetine (range 17–187 μg l−1 ) was detected in seven of the nine infants. The highest of these concentrations was about 70% of the maternal plasma concentrations. Conclusions The mean combined dose of fluoxetine and norfluoxetine transmitted to infants via breast milk is below the 10% notional level of concern. However, there was considerable interpatient variability in estimated infant dose and in some of the patients, the dose was >10%. Further, since adverse effects have been observed in breast‐fed infants, careful monitoring of the infants is mandatory. Neonates exposed to these drugs in utero had higher concentrations of fluoxetine and norfluoxetine and are at greater risk of adverse effects.