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#186 Doxylamine and Pyridoxine for Nausea and Vomiting of Pregnancy: A review of “retch”ed evidence

What is the safety and efficacy of doxylamine/pyridoxine (Diclectin®) in nausea and vomiting of pregnancy?

Doxylamine/B6 appears safe short-term and may be slightly better than placebo in reducing nausea and vomiting in pregnancy (~1 point better on 15-point scale)B6 alone may have similar effect on nausea but other effects unclearResults are at high risk of bias due to initially undeclared industry support and methodological concerns.   

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  • Five systematic reviews of 22-37 observational studies (17,000-50,000 pregnant women) exposed to antihistamines like doxylamine.1-5 Many authors have industry affiliations.1,3-5    
    • No reliable effect on malformations with doxylamine.1-5  
  • Four systematic reviews:6-9 Not discussed as did not include largest Randomized Controlled Trail (RCT), published 2017.10 
  • 2017 publication of 1970s industry-sponsored (eight arm) RCT: 2,359 women of doxylamineB6, and dicylomine alone or in various combinations, or placebo, for seven days.10  
    • Percent improvement from baseline for doxylamine/B6 versus placebo, statistically significant:   
      • Moderate undefined “effectiveness” (78% versus 57%).  
      • Nausea (75% versus 52%); not vomiting. 
      • Patients rated doxylamine/B6 better on nausea and vomiting.  
    • B6 alone better than placebo for nausea (68% versus 52%), but not statistically better for vomiting, overall effectiveness or patient ratings 
    • Drowsiness: 5.6% versus 3% (placebo)Number Needed to Harm=38. 
    • Limitations: Only 66% completed study, questionable data integrity, possible selective reporting. 
  • Industry-sponsored RCT (259 women) of doxylamine/B6 or placebo.11  
    • ~1-point decrease in 15-point nausea/vomiting scale at day 15.  
    • No change in individual nausea, vomiting, retching scores.12  
  • US RCT (36 women) found ondansetron superior to doxylamine/B6 in reducing nausea (3 out of 10-point scale better) but not vomiting.13 
    • Limitations: Used ½ dose doxylamine. 
  • Older studies less reliable.6 
  • Disclosed and undisclosed conflicts of interest raise concerns around some of the analysis and reporting of doxylamine/B6 research.14 
  • Cochrane review states “lack of high quality evidence to support any particular intervention”, including doxylamine/B6, B6 alone, metoclopramide, or ginger.6 
  • Guidelines recommend first-line: Antihistamines, phenothiazines (like prochlorperazine), or ginger (UK),15 B6 alone (US),16 or doxylamine/B6 (US, Canada).16,17

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  • Adrienne J Lindblad BSP ACPR PharmD
  • Sudha Koppula MD MCISc CCFP FCFP

1. Seto A, Einarson T, Koren G. Am J Perinatol. 1997 Mar; 14(3):119-24.

2. Chin JW, Gregor S, Persaud N. Am J Perinatol. 2014 Sep; 31(8):701-10.

3. Etwel F, Faught LH, Rieder MJ, et al. Drug Saf. 2017 Feb; 40(2):121-32.

4. Mazzotta P, Magee LA. Drugs. 2000 Apr; 59(4):781-800.

5. McKeigue PM, Lamm SH, Linn S, et al. Teratology. 1994 Jul; 50(1):27-37.

6. Matthews A, Haas DM, O'Mathúna DP, et al. Cochrane Database Syst Rev. 2015 Sep 8; (9):CD007575.

7. Festin M. BMJ Clin Evid. 2014 Mar 19; 2014. pii: 1405.

8. McParlin C, O'Donnell A, Robson SC, et al. JAMA. 2016 Oct 4; 316(13):1392-401.

9. O'Donnell A, McParlin C, Robson SC, et al. Health Technol Assess. 2016 Oct; 20(74):1-268.

10. Zhang R, Persaud N. PLoS One. 2017; 12(1):e0167609.

11. Koren G, Clark S, Hankins GDV, et al. Am J Obstet Gynecol. 2010; 203:571.e1-7.

12. Koren G, Hankins GDV, Caritis SN, et al. Am J Obstet Gynecol (research letter). 2016; 214:664-6.

13. Oliveira LG, Capp SM, You WB, et al. Obstet Gynecol. 2014; 124:735-42.

14. Pimlott N, Kvern B, Woollard R. Can Fam Physician. 2017; 63:13-4.

15. RCOG Green-top Guideline No. 69. June 2016. Available at: Last Accessed: March 8, 2017.

16. [No authors listed]. Obstet Gynecol. 2015; 126(3):e12-24.

17. Campbell K, Rowe H, Azzam H, et al. JOGC. 2016; 38(12):1127-37.

Authors do not have any conflicts of interest to declare.