Venlafaxine in Pregnancy and Breastfeeding
      
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Venlafaxine (EffexorŽ)
Antidepressant .Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

Molecular weight: 313.87. The degree of plasma protein binding of venlafaxine is approximately 27% at concentrations ranging from 2.5 to 2215 ng/mL. The degree of plasma protein binding of ODV is approximately 30%  at concentrations ranging from 100 to 500 ng/mL [1].

CATEGORY:C

"Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 11 times (rat) or 12 times (rabbit) the maximum recommended human daily dose on a mg/kg basis, or 2.5 times (rat) and 4 times (rabbit) the human daily dose on a mg/m 2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. These effects occurred at 10 times (mg/kg) or 2.5 times (mg/m 2 ) the maximum human daily dose. The no effect dose for rat pup mortality was 1.4 times the human dose on a mg/kg basis or 0.25 times the human dose on a mg/m 2 basis."[1]

Venlafaxine appears to cross the human placenta near term [2].

In a prospective study pregnancy outcomes of 150 women exposed to venlafaxine during first trimester were compared with the pregnancy outcomes of a group of pregnant women who received selective serotonin reuptake inhibitor antidepressants and a group of women who received nonteratogenic drugs. The majority of the women in the venlafaxine group took 75 mg/day (range 37.5 to 300 mg/day) of venlafaxine immediate release form. Among the 150 women who were exposed to venlafaxine during pregnancy, 125 had live births, 18 had spontaneous abortions and seven had therapeutic abortions; two of the babies had major malformations. Birthweight, gestational age at delivery, and the rate of major malformations did not differ amongst the three groups [3].

The small number of human pregnancies exposed to venlafaxine to date are insufficient to allow a general conclusion regarding the teratogenic risk of venlafaxine.
 

BREAST FEEDING: Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV) are excreted into human milk. In a small case series of three lactating women taking venlafaxine for depression the mean milk/plasma ratio for venlafaxine was 4.1 (range 2.8-4.8) and 3.1 for ODV (range 2.8-3.8). The mean total infant dose (as V equivalents) was 7.6% (range 4.7-9.2%) of the maternal weight-adjusted dose, with approximately equal amounts of V (3.5%) and ODV (4.1%) in the dose. Although ODV was detected in the plasma of all three infants no adverse effects were noted in the infants [4].

Hendrick V, et al. also found ODV in the plasma of two breast fed infants whose mothers were treated with venlafaxine 75 and 150 mg/day. Neither infant experienced adverse effects from venlafaxine exposure through breast milk, and their development appeared to be normal  over the first year [5].


NEONATAL SIDE EFFECTS: Restlessness, hypertonia, jitteriness, irritability and poor feeding occurred in a neonate after maternal use of venlafaxine for depression during pregnancy. The diagnosis was confirmed by a temporary improvement after administration of a low dose (1 mg) of venlafaxine to the boy. The symptoms ceased after 8 days [6].

SEARCH LITERATURE

1. Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004: 3413-3415
2. Hostetter A, et al. Amniotic fluid and umbilical cord blood concentrations of antidepressants in three women.Biol Psychiatry. 2000;48:1032-4.MEDLINE
3.Einarson A, et al.. Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry. 2001;158:1728-30. MEDLINE
4. Ilett KF, Hackett LP, Dusci LJ, Roberts MJ, Kristensen JH, Paech M, Groves A, Yapp P. Distribution and excretion of venlafaxine and O-desmethylvenlafaxine in human milk. Br J Clin Pharmacol. 1998;45:459-62. MEDLINE
5. Hendrick V, et al. Venlafaxine and breast-feeding.[Letter]Am J Psychiatry. 2001;158:2089-90.  MEDLINE
6. de Moor RA et al. [Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy] Ned Tijdschr Geneeskd. 2003;147:1370-2. MEDLINE

Created: 11/3/2002
Last Update: 4/12/2004

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