ONDANSETRON

Fetal Risk Summary

Ondansetron is a potent antiemetic indicated for the prevention and treatment of chemotherapy-induced nausea and vomiting. No adverse effects on fertility or on the fetus were observed in reproduction studies in rats and rabbits at IV doses up to 4 mg/kg/day (1).

Ondansetron has been used in the treatment of hyperemesis gravidarum (2,3,4,5 and 6). A 21-year-old primigravida with severe nausea and vomiting was treated unsuccessfully for approximately 4 weeks, beginning at 6 weeks' gestation, with IV metoclopramide, 10 mg 3 times daily, rectal dimenhydrinate, 100 mg twice daily, and IV fluids (2). Because her condition was considered life-threatening for both herself and her fetus, ondansetron 8 mg IV 3 times daily was instituted at 11 weeks' gestation and continued for 14 days. Significant improvement was noted in the patient's condition from the 2nd day of therapy. The woman eventually gave birth at term to a healthy 3.2-kg girl.

A second report on the use of ondansetron for severe nausea and vomiting in pregnancy involved a 22-year-old woman with renal impairment and nephrotic syndrome (3). Treatment with the antiemetic was begun at 30 weeks' gestation with 8 mg IV 3 times daily for 1 day, then orally (dose not specified) until 33 weeks' gestation. A healthy 2052-g female infant was delivered at 36 weeks by elective cesarean section. The infant remained in good health at an unspecified follow-up period.

A randomized, double-blind study, first published as an abstract (4) and then as a full report (5), compared IV ondansetron (10 mg) (N=15) with IV promethazine (50 mg) (N=15) for the treatment of hyperemesis gravidarum. Both drugs were given as an initial dose followed by as-needed doses every 8 hours. The mean gestational ages of the two groups at the start of therapy were 11.0 and 10.2 weeks, respectively. No differences were observed between the two groups in terms of duration of hospitalization, nausea score, number of doses received, treatment failures, and daily weight gain. The only adverse effect observed was sedation in eight women who received promethazine compared with none in the ondansetron group. No mention was made of the pregnancy outcomes in either group.

Ondansetron, 8 mg IV twice daily, was administered to a woman at 14 weeks' gestation after 6 weeks of unsuccessful therapy with intermittent use of promethazine, prochlorperazine, metoclopramide, and IV hydration (6). IV ondansetron was able to control her vomiting, but not her nausea, and 2 days later she was converted to oral therapy (4 mg) that was taken intermittently (once or twice daily) until 33 weeks' gestation. Nausea occurred throughout her pregnancy, with occasional episodes of vomiting. She eventually delivered a healthy, 2.7-kg male infant at 39 weeks' who was doing well at early follow-up.

Breast Feeding Summary

No reports describing the use of ondansetron during human lactation or measuring the amount, if any, excreted in human milk have been located. The drug has been found in the milk of lactating rats (1). Because of this and its relatively low molecular weight (about 366), excretion into human breast milk should be expected. The effects of exposure to the drug on a nursing infant are unknown.

References

1. Product information. Zofran. Glaxo Wellcome, 1997.
2. Guikontes E, Spantideas A, Diakakis J. Ondansetron and hyperemesis gravidarum. Lancet 1992;340:1223.
3. World MJ. Ondansetron and hyperemesis gravidarum. Lancet 1993;341:185.
4. Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A prospective, randomized, double-blind comparison of the serotonin antagonist ondansetron to a standardized regimen of promethazine for hyperemesis gravidarum. A preliminary investigation (abstract). Am J Obstet Gynecol 1995;172:299.
5. Sullivan CA, Johnson CA, Roach H, Martin RW, Stewart DK, Morrison JC. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol 1996;174:1565–8.
6. Tincello DG, Johnstone MJ. Treatment of hyperemesis gravidarum with the 5-HT3 antagonist ondansetron (Zofran). Postgrad Med J 1996;72:688–9.