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#192 Bringing Up the Best Evidence: Ondansetron in nausea/vomiting of pregnancy

What are the benefits and risks of ondansetron for nausea and vomiting of pregnancy?

Ondansetron may reduce nausea or vomiting of pregnancy by 25% for one in two users, compared to doxylamine/pyridoxine. There is real uncertainty if ondansetron in pregnancy is associated with any risk to the fetus. Some observational studies suggesting congenital or cardiac defects may be increased by as much as 1% but these are inconsistent and not supported by better evidence.  

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  • One randomized controlled trial (RCT), 36 patients, comparing ondansetron to doxylamine/pyridoxine for five days, results statistically significant:1 
    • Reduction on 100-point scale:  
      • Nausea: 51 ondansetron versus 20. 
      • Vomiting: 41 versus 17. 
    • Achieved 25% symptom reduction: 
      • Nausea: 92% ondansetron versus 41%. 
      • Vomiting: 77% versus 35%. 
      • Number Needed to Treat: 2-3. 
    • Limitations: Used low-dose, immediate release form of doxylamine/pyridoxine. 
  • Two RCTs from Malaysia and Iran, 160 and 83 patients respectively, found ondansetron (intravenous2 or oral3) at least as good as metoclopramide in hyperemesis gravidarum.2,3 
HarmsObservational studies with inconsistent results of malformation.  
  • Major malformation overall:  
    • Five cohort studies found no increased risk,4-8 including the highest quality study1 and two under-powered studies.7,8 
    • One cohort found increased risk with ondansetron 4.7% versus 3.5% no ondansetron [Odds Ratio (OR) 1.3, 1.0-1.7].9   
      • From published abstract only, apparently from same database as the highest quality study (above).   
  • Cardiac:  
    • The highest quality study found no increased risk.4  
    • Two found increased risk:5,9  
      • OR 2.0 (1.3-3.1)9 again published as abstract only. 
      • OR 1.62 (1.04-2.14),5 including septal defects Relative Risk 2.05 (1.19-3.28). 
  • Cleft palate:  
    • Two cohorts4,5 and case-control10 found increased no risk.  
    • One case-control study found increased risk OR=2.37 (1.18-4.76).11  
    • One case-control study found decreased risk OR=0.4 (0.2-0.8).10 
  • Limitations of harm studies: Cannot prove causation, possible detection and indication bias, not all birth defects investigated,11 recall bias,11 multiple comparisons (about 70),11 and clinical significance and severity of malformations unknown.5,9-11 Additional risk factors for birth defects unknown. 
  • Baseline risk of major malformations ~4%.12   
  • Women frequently overestimate risks of malformations from medications.13  

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Juliana Rey-Parra MD PhD CCFP

1. Oliveira LG, Capp SM, You WB, et al. Obstet Gynecol. 2014 Oct; 124(4):735-42.

2. Abas MN, Tan PC, Azmi N, et al. Obstet Gyneol. 2014; 123:1272-9.

3. Kashifard M, Basirat Z, Kashifard M, et al. Clin Exp Obstet Gynecol. 2013; 40:127-30.

4. Pasternak B, Svanström H, Hviid A. N Engl J Med. 2013 Feb 28; 368(9):814-23.

5. Danielsson B, Wikner BN, Källén B. Reprod Toxicol. 2014 Dec; 50:134-7.

6. Colvin L, Gill AW, Slack-Smith L, et al. Biomed Res Int. 2013; 2013:909860.

7. Asker C, Norstedt Wikner B, Källén B. Eur J Clin Pharmacol. 2005 Dec; 61(12):899-906.

8. Einarson A, Maltepe C, Navioz Y, et al. [Abstract] BJOG. 2004 Sep; 111(9):940-3.

9. Anderson JT, Jiminez-Solem E, Poulsen H. [Abstract] Available at: Last Accessed: December 18, 2016.

10. Van Bennekom CM, Parker SE, Anderka M, et al. [Abstract]. Pharmacoepidemiol Drug Saf. 2015; 24:1-587.

11. Anderka M, Mitchell AA, Louik C, et al. Birth Defects Res A Clin Mol Teratol. 2012 Jan; 94(1):22-30.

12. US Department of Health and Human Services. Reviewer Guidance: Evaluating the risks of drug exposure in human pregnancies. April 2005. Available at: Last Accessed: December 18, 2016.

13. Petersen I, McCrea RL, Lupatelli A, et al. BMJ Open. 2015 Jun 1; 5(6):e007390.

Authors do not have any conflicts of interest to declare.