Ondansetron for Nausea During Pregnancy – Is There a Risk for Birth Defects?

BACKGROUND AND PURPOSE:

• Ondansetron, a serotonin receptor antagonist, may be used as a last resort in women with nausea and vomiting in pregnancy
  • Data currently is limited regarding birth defect risk
• Lavecchia et al. (Journal of Obstetrics and Gynaecology Canada, 2018) examined the association between prenatal exposure to ondansetron, to treat nausea during pregnancy, and congenital malformations

METHODS:

• Systematic database search and extraction
  • RCTs, cohort, and case-control studies that reported fetal outcomes of prenatal ondansetron exposure

RESULTS:

• 10 epidemiological studies out of 690 were included:
  • 5 large retrospective cohort studies | 2 prospective observational studies | 2 population-based case-controls | 1 retrospective case series
  • Only 3 large population-based cohort studies that were designed to specifically evaluate the risk of ondansetron exposure and congenital malformations
  • Most studies evaluated exposure during the first trimester
• One case-control study identified an association between prenatal exposure to ondansetron and cleft palate and another cohort study found an increased risk of cardiovascular defects
  • Neither of these findings were reproduced in the other studies, in particular the large population-based cohort study (including 1849 ondansetron pregnancies)
  • Study showing cardiovascular defects indicates that the majority of ondansetron exposure was after 56 days (following cardiac organogenesis)
  • Study showing clefting could be due to confounding due to exposure to multiple medications

CONCLUSION:

• The authors state that their “literature and rigorous independent review of all data on ondansetron use in pregnancy and the risk of congenital malformations did not yield significant safety concerns.”
• Further investigation, using large prospective cohort studies, is needed to confirm these findings

Learn More – Primary Sources:

Ondansetron in Pregnancy and the Risk of Congenital Malformations: A Systematic Review

Are Drug Interactions between Antibiotics and Hormonal Birth Control a Reality or Myth?

BACKGROUND AND PURPOSE: 

• Limited data regarding hormonal contraception and antibiotics 
• Rifamycin antibiotics (rifampin, rifabutin) induce key hepatic enzymes that are part of hormonal birth control pathway metabolism but this mechanism may not be generalizable to other more common antibiotics 
• There is data that most pharmacists recommend backup contraception for women who use antibiotics with hormonal contraception due to concern for unintended pregnancy 
• Simmons et al. (AJOG, 2018) sought to examine potential interactions between non-rifamycin antibiotics and hormonal contraceptives 

METHODS: 

• Systematic review 
  • Search included trials, cohort, case-control, and pharmacokinetic studies when non-rifamycin antibiotics and hormonal contraceptive that addressed: 
  • pregnancy rates 
  • pharmacodynamics 
  • pharmacokinetic outcomes  
• Reviews were independently assessed by two authors to avoid bias 
• Risk of bias was assessed using the USPSTF evidence grading system 
• Findings were tabulated by drug class 

RESULTS: 

• Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring 
• Ethinyl estradiol was affected when administered with dirithromycin (a macrolide) and showed increased clearance but this effect was not seen with any other drug 
• Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics 
• There was no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with any antibiotic 
• No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic 

CONCLUSION: 

• Clinical and pharmacokinetic outcome studies do not support the existence of a drug interaction between hormonal birth control and non-rifamycin antibiotics 
• Authors do note that  
  • There may be individual differences in drug metabolism and they suggest a small subset of women (likely <1%) may be at risk for hormonal contraceptive failure when taking antibiotics  
  • Switching to another contraceptive or backup method if compliance is good and there is an unintended pregnancy 
  • Obesity may play a role in drug metabolism that could impact these study results 

Learn More – Primary Sources: 

Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review