Is Metrogyl (Metronidazole) safe to use during pregnancy?

Metronidazole (Metrogyl) Safety in Pregnancy

Metronidazole is safe and recommended for appropriate indications after the first trimester of pregnancy, with the CDC and multiple guidelines supporting its use for bacterial vaginosis and trichomoniasis starting in the second trimester. 1

Trimester-Specific Recommendations

First Trimester

• Avoid oral metronidazole during the first trimester - the FDA labels metronidazole as contraindicated for trichomoniasis treatment in the first trimester 2, and traditional concerns about potential teratogenicity persist despite meta-analyses showing no evidence of human teratogenicity 1, 3
• Topical metronidazole (0.75-1%) is safe throughout all trimesters due to significantly lower systemic absorption compared to oral formulations 1
• Clindamycin vaginal cream 2% is the preferred first-line treatment for bacterial vaginosis in the first trimester, administered as one full applicator intravaginally at bedtime for 7 days 1, 3
• If systemic therapy is absolutely necessary in the first trimester, oral clindamycin 300 mg twice daily for 7 days can be used as an alternative 3

Second and Third Trimesters

• Oral metronidazole 250 mg three times daily for 7 days is the recommended regimen for bacterial vaginosis after the first trimester 4, 1, 5
• Alternative regimens include metronidazole 500 mg twice daily for 7 days or a single 2g oral dose 4, 1
• For trichomoniasis, metronidazole 2g orally in a single dose is the recommended treatment with cure rates of 90-95% 4, 5
• Meta-analyses have shown no association between metronidazole exposure during later trimesters and preterm birth, low birth weight, or congenital anomalies 3

Clinical Indications Requiring Treatment

Bacterial Vaginosis

• All symptomatic pregnant women should be tested and treated for bacterial vaginosis 1, 5
• Bacterial vaginosis is associated with serious adverse pregnancy outcomes including premature rupture of membranes, chorioamnionitis, preterm labor, preterm birth, postpartum endometritis, and post-cesarean wound infection 1, 5, 3
• High-risk pregnant women (those with prior preterm delivery) should be screened and treated at the first prenatal visit, ideally at the earliest part of the second trimester 4, 1
• Treatment in high-risk women may reduce the risk of preterm delivery 1, 3

Trichomoniasis

• Vaginal trichomoniasis is associated with adverse pregnancy outcomes, particularly premature rupture of membranes and preterm delivery 4
• Treatment of sex partners increases cure rates and reduces transmission 4, 5

Safety Evidence and Reassurance

Human Studies

• Multiple studies and meta-analyses have not demonstrated a consistent association between metronidazole use during pregnancy and teratogenic or mutagenic effects 1, 5
• A prospective controlled cohort study of 228 women (86.2% with first-trimester exposure) found no difference in major malformation rates compared to controls (1.6% vs 1.4%) 6
• Nearly four decades of published literature indicates metronidazole is not teratogenic regardless of trimester 7
• The FDA classifies metronidazole as pregnancy category B, indicating no evidence of harm in animal studies, though adequate human studies are lacking 3, 2

Animal Studies Context

• Animal studies showing carcinogenic activity involved chronic, high-dose administration (approximately 33 times the recommended human dose) in mice and rats 2
• Reproduction studies in rats at doses up to five times the human dose revealed no evidence of impaired fertility or harm to the fetus 2

Important Clinical Caveats

Dosing Considerations

• Lower doses are recommended during pregnancy to minimize fetal exposure 4, 1
• The 250 mg three times daily regimen is preferred over higher single-dose regimens during pregnancy 4, 1

Vitamin K Considerations

• Long-term maternal therapy could theoretically risk neonatal bleeding by inhibiting vitamin K synthesis 1
• If prolonged therapy is used, treat both mother and neonate with phytomenadione (vitamin K) 1

Breastfeeding

• If a single 2g oral dose is used during lactation, stop breastfeeding for 12-24 hours after the dose 1
• Metronidazole is secreted in human milk in concentrations similar to plasma 2

Partner Treatment

• Routine treatment of male sex partners is NOT recommended for bacterial vaginosis, as it does not influence treatment response or reduce recurrence rates 5, 3
• For trichomoniasis, treating sex partners IS recommended to increase cure rates 4, 5

Alcohol Avoidance

• Patients should avoid alcohol during metronidazole treatment and for 24 hours afterward due to potential disulfiram-like reaction 5

Common Pitfalls to Avoid

• Do not use metronidazole gel intravaginally during the first trimester - existing data do not support topical metronidazole agents during pregnancy for systemic infections 3
• Do not use clindamycin vaginal cream in later pregnancy - evidence from three trials shows increased adverse events (prematurity and neonatal infections) after use 3
• Metronidazole gel is not effective for trichomoniasis despite being effective for bacterial vaginosis 5
• Patients allergic to oral metronidazole should NOT receive metronidazole gel vaginally 5