Flagyl (Metronidazole) Use During Pregnancy
Metronidazole is safe to use during the second and third trimesters of pregnancy, but should be avoided in the first trimester where clindamycin vaginal cream is the preferred alternative. 1
First Trimester: Avoid Oral Metronidazole
The CDC recommends clindamycin vaginal cream 2% as first-line treatment during the first trimester, administered as one full applicator intravaginally at bedtime for 7 days. 1
Oral metronidazole is contraindicated in the first trimester due to traditional concerns about potential teratogenicity, although meta-analyses have not demonstrated teratogenicity in humans. 1, 2
Topical metronidazole (0.75-1%) is safe throughout all trimesters due to significantly lower systemic absorption compared to oral administration. 2
If clindamycin vaginal cream is contraindicated, oral clindamycin 300 mg twice daily for 7 days can be used as an alternative to minimize systemic exposure during the first trimester. 1
Second and Third Trimesters: Metronidazole is Safe
The CDC recommends oral metronidazole 250 mg three times daily for 7 days as the preferred treatment for bacterial vaginosis during the second and third trimesters. 1, 3
Alternative regimens include metronidazole 2g orally in a single dose, clindamycin 300 mg orally twice daily for 7 days, and metronidazole gel 0.75% intravaginally. 1
Meta-analyses show no association between metronidazole exposure during later trimesters and preterm birth, low birth weight, or congenital anomalies. 1
Multiple studies have not demonstrated consistent associations between metronidazole use during pregnancy and teratogenic or mutagenic effects in newborns. 3
FDA Classification and Safety Data
The FDA classifies metronidazole as pregnancy category B, indicating no evidence of harm to the fetus in animal studies at doses up to five times the human dose, though adequate human studies are lacking. 1, 4
Metronidazole crosses the placental barrier and enters fetal circulation rapidly. 4
Reproduction studies in rats at doses up to five times the human dose revealed no evidence of impaired fertility or harm to the fetus. 4
Clinical Rationale for Treatment
Bacterial vaginosis is associated with serious adverse pregnancy outcomes including premature rupture of membranes, preterm labor, preterm birth, postpartum endometritis, and post-cesarean wound infection. 1, 2
Treatment of bacterial vaginosis in high-risk pregnant women may reduce the risk of preterm delivery. 1, 2
Systemic therapy is generally preferred over topical therapy to treat possible subclinical upper genital tract infections, particularly in women at high risk for preterm delivery. 1
Important Clinical Pitfalls
Do not use metronidazole gel intravaginally during the first trimester - existing data do not support the use of topical metronidazole agents during pregnancy for this indication. 1
Avoid clindamycin vaginal cream in later pregnancy - evidence from three trials shows increased adverse events (prematurity and neonatal infections) after use of clindamycin cream, particularly in newborns. 1
Clindamycin cream is oil-based and may weaken latex condoms and diaphragms. 1
Patients should avoid alcohol during metronidazole treatment and for 24 hours afterward due to potential disulfiram-like reaction. 3
Special Considerations
If prolonged maternal therapy is required, theoretically there is risk of neonatal bleeding by inhibiting vitamin K synthesis; consider treating mother and neonate with phytomenadione (vitamin K). 2
If a single 2g oral dose is used during lactation, stopping breastfeeding for 12-24 hours after the dose is recommended. 2
Treatment of male sex partners is not recommended for bacterial vaginosis as it does not influence treatment response or reduce recurrence rates. 1, 3
Follow-up visits are unnecessary if symptoms resolve, but for high-risk pregnant women, a follow-up evaluation one month after treatment completion may be considered. 1