Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants

Br J Clin Pharmacol. 2002 Jan;53(1):17-22. doi: 10.1046/j.0306-5251.2001.01518.x.


Aims: To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants.

Methods: Six women (mean age 34.5 years, mean weight 84.3 kg) taking venlafaxine (median dose 244 mg day(-1), range 225-300 mg day(-1)) and their seven infants (mean age 7.0 months, mean weight 7.3 kg) were studied. V and ODV in plasma and milk were measured by high-performance liquid chromatography over a 12 h dose interval at steady-state. Infant exposure was estimated as the product of estimated milk production rate (0.15 l kg(-1)day(-1)) and average drug concentration in milk, normalized to body weight and expressed as a percentage of the weight-adjusted maternal dose.

Results: Mean M/PAUC values of 2.5 (range 2.0-3.2) and 2.7 (range 2.3-3.2) were calculated for V and ODV, respectively. The mean maximum concentrations (95% CI) of V and ODV in milk were 1161 (95% CI, 588, 1734) microg l(-1) and 796 (362, 1230) microg l(-1). Mean infant exposure was 3.2% (1.7, 4.7%) for V and 3.2% (1.9, 4.9%) for ODV (as V equivalents). V was detected in the plasma of one out of seven infants studied (5 microg l(-1)), while ODV was detected in four of the infants, at concentrations ranging from 3 to 38 microg l(-1). All of the infants in the study were healthy, as reported by their mothers and/or by clinical examination on the study day.

Conclusions: The concentrations of V and ODV in breast milk were 2.5 and 2.7 times those in maternal plasma. The mean total drug exposure (as venlafaxine equivalents) of the breastfed infants was 6.4% (5.5-7.3%), which is below the 10% notional level of concern. There were no adverse effects in any of the infants. The data support the use of V in breastfeeding. Nevertheless, since low concentrations of ODV were detected in the plasma of four out of the seven infants studied, we recommend breastfed infants should be monitored closely. Each decision to breast feed should be made as an individual risk:benefit analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / blood
  • Antidepressive Agents / pharmacokinetics*
  • Area Under Curve
  • Breast Feeding*
  • Confidence Intervals
  • Cyclohexanols / blood
  • Cyclohexanols / pharmacokinetics*
  • Desvenlafaxine Succinate
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Lactation / metabolism
  • Male
  • Milk, Human / metabolism*
  • Serotonin Uptake Inhibitors / blood
  • Serotonin Uptake Inhibitors / pharmacokinetics
  • Venlafaxine Hydrochloride


  • Antidepressive Agents
  • Cyclohexanols
  • Serotonin Uptake Inhibitors
  • Venlafaxine Hydrochloride
  • Desvenlafaxine Succinate