Ondansetron (ZofranŽ tablets and injection)
Antiemetic. Selective 5-HT 3 receptor antagonist .
Molecular weight: 365.9. Plasma protein binding of ondansetron as
measured in vitro was 70% to 76%, with binding constant over the pharmacologic
concentration range (10 to 500 ng/mL).
Reproduction studies have been performed in pregnant rats and rabbits at daily
doses up to 15 and 30 mg/kg per day respectively, and have revealed no evidence of impaired fertility
or harm to the fetus due to ondansetron .
In one case report ondansetron 8 mg IV TID was used to successfully treat hyperemesis gravidarum
in a woman
from approximately 11 to 13 weeks gestation. She gave birth to a term healthy infant . Tincello
and Johnstone also used ondansetron intermittently every trimester to treat
hyperemesis gravidarum in one patient with no apparent adverse effects
on the mother or infant .
In a randomized controlled trial comparing ondansetron with promethazine
for the treatment of hyperemesis gravidarum 15 patients were treated with
ondansetron at a mean gestational age of 11 weeks'. Patients were given an
initial dose of ondansetron 10 mg IV with additional doses as need TID.
Ondansetron demonstrated no benefit over promethazine in patients
hospitalized for hyperemesis gravidarum. The authors of
the study suggested that increasing ondansetron dosages or using a
continuous infusion might have improved the treatment response. Pregnancy
outcomes were not reported for either group .
In two additional case reports of pregnant women treated with ondansetron
during the third trimester both mothers delivered normal infants [5, 6].
A prospective observational study by The Motherisk and The Mothersafe
Programs compared the pregnancy outcomes of 176 women who had used
ondansetron during the first trimester of pregnancy with women who had used
other antiemetics (including Diclectin, metoclopramide, phenothiazines, and
ginger) during the first trimester, and women who had nonteratogenic
exposures during the first trimester. There was no statistically significant
difference between the three groups in terms of major malformations, live
births, miscarriages, stillbirths, therapeutic abortions, birthweight , or
gestational age at the time of delivery. However, in the ondansetron group,
there were three cases of hypospadias which was not statistically
significant. The authors of the study point out that the lack of statistical
significance may have been due to the small sample size .
While the above reports are reassuring the number of reported cases is
small to draw firm conclusions
regarding the teratogenic risk of
ondansetron in human pregnancy.
BREAST FEEDING: It is not known whether ondansetron is excreted into human milk.