Is metronidazole (Flagyl) contraindicated in pregnancy?

Metronidazole Use During Pregnancy

Metronidazole is contraindicated during the first trimester of pregnancy, but may be safely used after the first trimester. 1, 2, 3

Contraindications and Safety Profile

• First Trimester: Metronidazole is explicitly contraindicated during the first trimester of pregnancy according to both CDC guidelines and FDA labeling 1, 3
• Second and Third Trimesters: The medication can be used after the first trimester, with the CDC supporting its use during the second trimester as it does not represent a major teratogenic risk 2
• Recommended Dosing: When needed after the first trimester, the recommended dose is 2g orally in a single dose 1

Treatment Considerations for Specific Conditions

For Trichomoniasis

• First trimester: Avoid metronidazole completely
• After first trimester: Metronidazole 2g orally in a single dose 1

For Bacterial Vaginosis

• First trimester: Clindamycin vaginal cream is the preferred treatment 2
• After first trimester: Metronidazole 500mg orally twice daily for 7 days 2

Evidence on Teratogenicity

Despite the contraindication in the first trimester, the overall evidence on teratogenicity is somewhat reassuring:

• Meta-analyses have found no significant increase in birth defects with metronidazole exposure (odds ratio 0.93,95% CI 0.73-1.18) 4
• A prospective controlled cohort study found no difference in major malformation rates between metronidazole-exposed and control pregnancies (1.6% vs 1.4%) 5

However, more recent animal studies have raised concerns:

• A 2023 study in rats showed potential for maternal and fetal hepatotoxicity, decreased fetal viability, and increased fetal defects 6

Important Clinical Considerations

• Breastfeeding: Metronidazole is secreted in human milk in concentrations similar to plasma levels. The FDA recommends considering discontinuation of either nursing or the drug due to potential tumorigenicity shown in animal studies 3

• Potential Benefits: Treatment of bacterial vaginosis and trichomoniasis during pregnancy may help prevent adverse outcomes such as preterm birth and low birth weight 7

• Risk of Spontaneous Abortion: Some research has associated metronidazole with increased risk of spontaneous abortion (70% increased risk in one study), though this may be confounded by the severity of the underlying infection 8

Clinical Algorithm for Metronidazole Use in Pregnancy

1. Determine trimester of pregnancy

   • If first trimester: Avoid metronidazole
   • If second or third trimester: Proceed to next step

2. Assess indication

   • For trichomoniasis: Use metronidazole 2g orally in a single dose
   • For bacterial vaginosis: Use metronidazole 500mg orally twice daily for 7 days

3. Monitor for adverse effects

   • Advise patient to report any unusual symptoms
   • Consider follow-up evaluation 1 month after treatment for high-risk pregnant women

4. Counsel regarding alcohol

   • Advise complete avoidance of alcohol during treatment and for 24 hours afterward to prevent disulfiram-like reactions 2