Distribution and Excretion of Fluoxetine and Norfluoxetine in Human Milk.

Abstract

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 mg l −1 ) was detected in five of the nine infants from whom samples were collected, and norfluoxetine (range 17-187 mg l −1 ) was detected in seven of the nine infants. The highest of these concentrations was about 70% of the maternal plasma concentrations. ConclusionsThe 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.Keywords: fluoxetine, human milk, in utero exposure, infant dose, norfluoxetine similar potency as a serotonin reuptake inhibitor [2].Patients range 23-44 years; mean body weight 67.3 kg, range

Fluoxetine inhibits the extracellular signal regulated kinase pathway and suppresses growth of cancer cells

“…40 However, such doses are normally not achieved in vivo. The FLX concentrations in plasma after standard therapeutic doses (40 mg per day, 30 days) reach plasma levels around 1 μM, 3,49 which is much lower than concentrations necessary to inhibit ERK1/2 kinases pathway in cancer cells, as observed in our study. However, due to its lipophylic properties, fluoxetine has ability to accumulate in tissues, where its concentrations could reach much higher levels, up to 20-fold more than in plasma, as reported for brain tissue.…”

The Effectiveness of Various Postpartum Depression Treatments and the Impact of Antidepressant Drugs on Nursing Infants

“…Exceptions to this were relatively high infant levels of nefazodone in 1 infant 68 and fluoxetine in 3 other infants. 32,33 In each of these cases, disconcerting symptoms were seeneg, increased crying, vomiting, diarrhea, colic, and decreased sleep with fluoxetine, 32,33 and drowsiness, lethargy, hypothermia, and poor feeding with nefazodone. 68 The infant whose mother had taken nefazodone was preterm, which may have contributed to the problem.…”

Antidepressant use during breastfeeding

“…Adverse events in breastfed infants exposed to newer antidepressants through breast milk have been suspected in a few cases, and more often after exposure to fluoxetine and citalopram than after exposure to other drugs [7,27,[35][36][37][38][39][40]. The effects observed have mostly been subtle and unspecific, and may even have arisen by coincidence.…”

“…The effects observed have mostly been subtle and unspecific, and may even have arisen by coincidence. For example, crying, irritability, decreased feeding and watery stools have been described in a few cases for fluoxetine [35][36][37]. For citalopram, hypotonia, colic, decreased feeding and sleep difficulties have been reported in single cases [38,39].…”