Is metronidazole (Flagyl) safe to use during pregnancy?

Metronidazole Safety in Pregnancy

Metronidazole is safe to use during pregnancy when clinically indicated, with the strongest evidence supporting its use after the first trimester, though current guidelines from the CDC and ACOG confirm no teratogenic risk even in early pregnancy. 1, 2

Trimester-Specific Safety Profile

First Trimester

• Topical metronidazole (0.75-1%) is safe throughout all trimesters due to minimal systemic absorption and can be used without restriction 1
• Oral metronidazole has historically been avoided in the first trimester due to theoretical concerns, but meta-analyses have not demonstrated teratogenic or mutagenic effects in humans 1, 2, 3
• The FDA classifies metronidazole as pregnancy category B, indicating no evidence of fetal harm in animal studies 2, 3
• For bacterial vaginosis in the first trimester, clindamycin vaginal cream 2% is preferred as first-line treatment (one full applicator intravaginally at bedtime for 7 days) to minimize theoretical first-trimester concerns 1, 4

Second and Third Trimesters

• Oral metronidazole is safe and recommended for appropriate indications after the first trimester 1
• The recommended regimen is metronidazole 250 mg orally three times daily for 7 days 1, 2
• Alternative regimen: metronidazole 500 mg twice daily for 7 days 1
• Meta-analyses show no association with preterm birth, low birth weight, or congenital anomalies when used in later trimesters 4

Clinical Indications Requiring Treatment

Bacterial Vaginosis

• All symptomatic pregnant women should be tested and treated for bacterial vaginosis 1
• Bacterial vaginosis is associated with serious complications including premature rupture of membranes, chorioamnionitis, preterm labor, preterm birth, postpartum endometritis, and post-cesarean wound infection 1, 2
• High-risk pregnant women should be screened and treated at the first prenatal visit to potentially reduce preterm delivery 1

Other Indications

• Trichomoniasis: metronidazole 2g orally as a single dose is recommended 2
• Inflammatory bowel disease: metronidazole can be given for pouchitis, perianal Crohn's disease, or intra-abdominal abscesses from fistulizing Crohn's disease 1

Critical Safety Precautions

Vitamin K Considerations

• Long-term maternal therapy could theoretically risk neonatal bleeding by inhibiting vitamin K synthesis 5, 2
• If prolonged therapy is necessary, treat both mother and neonate with phytomenadione (vitamin K) 5, 2

Breastfeeding

• Metronidazole is present in breast milk at concentrations similar to plasma 3
• If a single 2g oral dose is used during lactation, stop breastfeeding for 12-24 hours after the dose 5, 2

Alcohol Avoidance

• Patients must avoid alcohol during treatment and for 24 hours afterward due to potential disulfiram-like reactions 2

Common Pitfalls to Avoid

• Do not withhold treatment for symptomatic infections based on outdated teratogenicity concerns—the benefits of treating symptomatic infections outweigh theoretical risks 1
• Do not use metronidazole gel intravaginally during first trimester—existing data do not support topical gel use in early pregnancy, though topical cream formulations are acceptable 4
• Do not routinely treat male sex partners for bacterial vaginosis—this does not influence treatment response or reduce recurrence rates 2, 4
• For trichomoniasis, treating sex partners increases cure rates and should be done 1

Evidence Quality

The safety profile is supported by multiple meta-analyses showing no consistent association between metronidazole use during pregnancy and adverse fetal outcomes 1, 2. The FDA drug label confirms that reproduction studies in rats at doses up to five times the human dose revealed no evidence of impaired fertility or harm to the fetus 3. While metronidazole has shown carcinogenic activity in chronic rodent studies, this has not translated to human teratogenicity 3, 6.

Human studies spanning nearly four decades confirm metronidazole is not teratogenic regardless of trimester 6. One 2021 review noted a potential association with spontaneous abortion, but this should be interpreted cautiously given the confounding factor of genitourinary infection severity 7.