Is Metronidazole (Flagyl) safe to use during pregnancy?

Metronidazole Use During Pregnancy

Metronidazole should be avoided during the first trimester of pregnancy but can be safely used after the first trimester when clinically indicated for conditions such as bacterial vaginosis, trichomoniasis, or other anaerobic infections. 1, 2

Safety Profile and Recommendations

• First trimester use:

  • Contraindicated during the first trimester according to CDC guidelines 1
  • Clindamycin cream 2% applied intravaginally at bedtime for 7 days is the preferred treatment for bacterial vaginosis during this period 1

• Second and third trimester use:

  • Safe to use after the first trimester 1
  • For bacterial vaginosis: 500mg orally twice daily for 7 days 1
  • For trichomoniasis: 2g orally in a single dose 1
  • Can be given for pouchitis, perianal Crohn's disease, or intra-abdominal abscesses 3

Evidence on Fetal Safety

• FDA classifies metronidazole as Pregnancy Category B 2
• Animal reproduction studies have shown no evidence of impaired fertility or harm to the fetus at doses up to five times the human dose 2
• No fetotoxicity was observed in pregnant mice at 20 mg/kg/day (approximately 1.5 times the most frequently recommended human dose) 2
• A prospective controlled cohort study found no difference in the rate of major malformations between metronidazole-exposed pregnancies and controls (1.6% vs. 1.4%) 4

Important Precautions

• Metronidazole crosses the placental barrier rapidly 2
• Patients should avoid alcohol during treatment and for 24 hours afterward to prevent disulfiram-like reactions 1
• Common side effects include gastrointestinal disturbances, metallic taste, and potential for peripheral neuropathy with prolonged use 1

Clinical Considerations for Specific Conditions

Bacterial Vaginosis

• Untreated BV in pregnancy increases risk of preterm birth, low birth weight, and chorioamnionitis 1
• After first trimester, metronidazole 500mg orally twice daily for 7 days (95% cure rate) is recommended 1

Trichomoniasis

• For treatment after first trimester: metronidazole 2g orally in a single dose 1
• Note that one study found that metronidazole treatment for asymptomatic trichomoniasis between 16-23 weeks did not reduce preterm birth and showed potential harm 5

Other Anaerobic Infections

• Metronidazole can be used for pouchitis, perianal Crohn's disease, or intra-abdominal abscesses 3
• Amoxicillin-clavulanic acid is an alternative safe option during pregnancy 3

Important Cautions

• A meta-analysis found that metronidazole as the only antibiotic administered in the second trimester was associated with a higher rate of preterm delivery in high-risk populations (OR 1.31; 95% CI 1.08-1.58) 6
• Due to concerns about mutagenicity, use during pregnancy should be restricted to cases where alternative treatments have been inadequate 2, 7
• Follow-up evaluation 1 month after treatment completion is recommended for high-risk pregnant women 1

When treatment for bacterial vaginosis or trichomoniasis is necessary during pregnancy, the timing of therapy and selection of antimicrobial agent should be carefully considered based on trimester, severity of infection, and potential risks versus benefits.