Zofran Use In Pregnancy & Lactation

Pregnancy: Risk Summary: In human epidemiological studies, an increase in orofacial clefts was observed in infants of women administered ondansetron during the first trimester of pregnancy. Regarding cardiac malformations, the epidemiological studies showed conflicting results (see Human data as follows). Reproductive studies in rats and rabbits did not show evidence of harm to the fetus (see Animal data as follows).
The use of ondansetron in pregnancy is not recommended.
Human Data: Three epidemiological studies in the US assessed the risk of specific congenital anomalies, including orofacial clefts and cardiac malformations in offspring born to mothers exposed to ondansetron during the first trimester of pregnancy.
One cohort study with 88,467 pregnancies exposed to ondansetron showed an increased risk of oral clefts (3 additional cases per 10,000 women treated, adjusted relative risk (RR), 1.24 (95% CI 1.03-1.48)) without an apparent increase in risk of cardiac malformations. A separately published subgroup analysis of 23,877 pregnancies exposed to intravenous ondansetron did not find an increased risk of either oral clefts or cardiac malformations.
One case-control study using population-based birth defect registries with 23,200 cases across two datasets showed an increased risk of cleft palate in one dataset and no increased risk in the other dataset. There was no increased risk of cardiac malformations in this study.
The second cohort study with 3,733 pregnancies exposed to ondansetron found an increased risk of ventricular septal defect, adjusted RR 1.7 (95% CI 1.0-2.9), but no statistically significant increase in risk of cardiac malformations.
Animal Data: In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ondansetron up to 15 mg/kg/day and 30 mg/kg/day, respectively, during the period of organogenesis. With the exception of a slight decrease in maternal body weight gain in the rabbits, there were no significant effects of ondansetron on the maternal animals or the development of the offspring. At doses of 15 mg/kg/day in rats and 30 mg/kg/day in rabbits, the maternal dose was approximately 6 and 24 times the maximum recommended human oral dose of 24 mg/day, respectively, based on body surface area. In a pre- and postnatal developmental toxicity study, pregnant rats received oral doses of ondansetron up to 15 mg/kg/day from Day 17 of pregnancy to litter Day 21. With the exception of a slight reduction in maternal body weight gain, there were no effects upon the pregnant rats and the pre- and postnatal development of their offspring, including reproductive performance of the mated F1 generation. At a dose of 15 mg/kg/day in rats, the maternal dose was approximately 6 times the maximum recommended human oral dose of 24 mg/day based on BSA.
Lactation: Risk Summary: It is not known whether ondansetron (Zofran) is transferred into human milk. There are no data on the effects of ondansetron (Zofran) on the breastfed child or the effects of ondansetron (Zofran) on milk production. However, it has been demonstrated that ondansetron passes into the milk of lactating animals (rats). It is therefore recommended that mothers receiving ondansetron should not breast-feed their babies.
Females and males of reproductive potential: Pregnancy testing: Pregnancy status should be verified for females of reproductive potential prior to starting the treatment with ondansetron (Zofran).
Contraception: Females of reproductive potential should be advised that it is possible that ondansetron (Zofran) can cause harm to the developing fetus. Sexually active females of reproductive potential are recommended to use effective contraception (methods that result in less than 1% pregnancy rates) when using ondansetron (Zofran) during the treatment and for two days after stopping treatment with ondansetron (Zofran).
Infertility: There is no effect of ondansetron (Zofran) on fertility.