Which is safer in pregnancy, Reglan (metoclopramide) or Zofran (ondansetron)?

Metoclopramide (Reglan) is Safer than Ondansetron (Zofran) in Pregnancy

Metoclopramide is the safer antiemetic choice during pregnancy, particularly in the first trimester, due to its more established safety profile and lower risk of congenital malformations compared to ondansetron. 1, 2

Safety Comparison

Metoclopramide (Reglan)

• First Trimester Safety: No significant increase in risk of major congenital defects based on meta-analysis of six cohort studies including 33,000 first-trimester exposures 1
• Specific Risk Data: Odds ratio for congenital defects is 1.14 (99% CI 0.93-1.38) - not statistically significant 1
• Dosing: Commonly used at 5-10 mg orally every 6-8 hours for pregnancy-related nausea 1
• Side Effects: May cause drowsiness and extrapyramidal effects, which are reversible upon discontinuation 1

Ondansetron (Zofran)

• First Trimester Concerns: Associated with a marginal increase in cleft palate and cardiovascular malformations, particularly ventricular septal defects 1, 2
• Specific Risk Data: 0.03% absolute increase in orofacial defects and 0.3% increase in ventricular septal defects 1
• Guideline Position: ACOG recommends using ondansetron only on a case-by-case basis for persistent symptoms, preferably after 10 weeks of pregnancy 2
• Recommended Use: Should be reserved as a second-line therapy when first-line treatments have failed 1, 2

Clinical Decision Algorithm

1. First-line antiemetic in pregnancy:

   • Vitamin B6 (pyridoxine) with or without doxylamine
   • Phenothiazines
   • Metoclopramide (if above options insufficient)

2. Second-line therapy (only if first-line fails):

   • Ondansetron, preferably after 10 weeks gestation
   • Methylprednisolone for severe hyperemesis gravidarum (avoid before 10 weeks due to oral cleft risk)

3. Timing considerations:

   • First trimester: Strongly prefer metoclopramide over ondansetron
   • After first trimester: Either medication can be used, but metoclopramide remains preferred due to better overall safety profile

Efficacy Comparison

While both medications have similar efficacy for treating nausea and vomiting in pregnancy:

• Multiple randomized controlled trials show comparable antiemetic effects between ondansetron and metoclopramide for hyperemesis gravidarum 3, 4, 5
• A meta-analysis of 5 RCTs (695 patients) found no significant difference in efficacy between the two medications 5
• Ondansetron may have fewer side effects like drowsiness (12.5% vs 30%) and dry mouth (10% vs 23.8%) 3

Important Caveats

• For cancer patients receiving chemotherapy during pregnancy, both medications can be used safely beyond the first trimester 1
• When treating severe hyperemesis gravidarum requiring hospitalization, the risk-benefit assessment may shift if metoclopramide is ineffective
• Neither medication is associated with increased risk of miscarriage 6

Bottom Line

For pregnant women requiring antiemetic therapy, metoclopramide should be the preferred choice, especially in the first trimester, due to its established safety profile. Ondansetron should be reserved for cases where metoclopramide and other first-line treatments have failed, and preferably used after 10 weeks gestation.