Side Effects of Vaginal Metronidazole
Vaginal metronidazole is significantly better tolerated than oral formulations, with minimal systemic side effects due to achieving less than 2% of the serum concentrations seen with oral dosing. 1, 2
Common Local Side Effects
The most frequently reported adverse events from vaginal metronidazole gel include:
- Vaginal discharge (12% of patients) - the most common local side effect 2
- Symptomatic Candida cervicitis/vaginitis (10%) - yeast overgrowth following treatment 2
- Vulvar/vaginal irritative symptoms (9%) - including burning, itching, or discomfort 2
- Pelvic discomfort (3%) 2
Systemic Side Effects (Less Common)
Despite minimal systemic absorption, some patients experience:
- Gastrointestinal complaints (7%) - significantly lower than the 51.8% seen with oral metronidazole 2, 3
- Headache (5%) 2
- Nausea and/or vomiting (4%) - compared to 30.4% with oral administration 2, 4
- Unusual/metallic taste (2%) - dramatically reduced from 17.9% with oral therapy 2, 4
- Dizziness (2%) 2
- Diarrhea/loose stools (1%) 2
Comparative Safety Profile
The intravaginal route demonstrates a markedly superior side effect profile compared to oral metronidazole:
- Nausea occurs in only 10.2% of vaginal users versus 30.4% with oral administration (p<0.001) 4
- Abdominal pain affects 16.8% intravaginally versus 31.9% orally (p<0.01) 4
- Metallic taste occurs in 8.8% intravaginally versus 17.9% orally (p<0.05) 4
- Overall adverse event rate is significantly lower with vaginal administration (p=0.023) 4
Serious Adverse Events
- No deaths or serious adverse events were reported in clinical trials involving 800 non-pregnant women 2
- Only 2 of 505 patients (0.4%) discontinued therapy due to drug-related adverse events: one due to moderate abdominal cramping and loose stools, another due to mild vaginal burning 2
- Both discontinuation symptoms resolved after stopping the medication 2
Important Clinical Considerations
Alcohol avoidance: Patients must avoid alcohol during treatment and for 24 hours after completion to prevent disulfiram-like reactions 1
Contraceptive interaction: The gel formulation does not contain oil (unlike clindamycin cream) and does not weaken latex condoms or diaphragms 1
Pregnancy safety: Metronidazole vaginal gel can be used during the second and third trimesters, though it is contraindicated in the first trimester 1, 5
Rare or Theoretical Side Effects
Based on experience with other metronidazole formulations, the following have been reported but are extremely uncommon with vaginal administration: