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 .
"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
Venlafaxine appears to cross the human placenta near term .
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 .
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 .
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 .
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 .
Physicians Desk Reference 57th ed. Montvale, NJ: Thomson PDR; 2004:
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.
Hendrick V, et al. Venlafaxine and breast-feeding.[Letter]Am J Psychiatry.
6. de Moor RA et al. [Withdrawal symptoms in a neonate following exposure to
venlafaxine during pregnancy] Ned Tijdschr Geneeskd. 2003;147:1370-2.
Last Update: 4/12/2004