What are the common side effects of topical vaginal Flagyl (metronidazole)?

Common Side Effects of Topical Vaginal Metronidazole

The most common side effects of topical vaginal metronidazole gel are vaginal discharge (12%), symptomatic Candida vaginitis (10%), and vulvovaginal irritative symptoms (9%), with gastrointestinal complaints being significantly less frequent than with oral metronidazole. 1

Most Frequent Local Side Effects

Based on FDA-approved labeling from clinical trials of 505 non-pregnant women, the following local reactions occur most commonly: 1

• Vaginal discharge occurs in 12% of patients 1
• Symptomatic Candida cervicitis/vaginitis develops in 10% of patients, representing a secondary yeast infection triggered by disruption of normal vaginal flora 2, 1
• Vulvovaginal irritative symptoms (burning, itching, irritation) affect 9% of patients 1
• Pelvic discomfort occurs in 3% of patients 1

Gastrointestinal Side Effects

Topical vaginal metronidazole produces substantially fewer gastrointestinal complaints compared to oral formulations: 3

• Gastrointestinal discomfort affects 7% of patients 1
• Nausea and/or vomiting occurs in 4% of patients 1
• Unusual/metallic taste affects 2% of patients 1
• Diarrhea/loose stools occurs in 1% of patients 1
• Decreased appetite affects 1% of patients 1

Research demonstrates that only 32.7% of patients using vaginal metronidazole gel report gastrointestinal complaints, compared to 51.8% with oral metronidazole (P = 0.04), representing a significant clinical advantage of the topical route. 3

Neurologic Side Effects

• Headache occurs in 5% of patients 1
• Dizziness affects 2% of patients 1
• Depression occurs in less than 1% of patients 1

Other Notable Side Effects

• Unspecified cramping occurs in 1% of patients 1
• Darkened urine may occur, though this is typically benign 1
• Generalized itching or rash occurs in less than 1% of patients 1

Critical Clinical Consideration: Secondary Yeast Infections

The 10% incidence of symptomatic Candida vaginitis following metronidazole treatment represents a predictable consequence of disrupting the normal vaginal microbiome. 2, 1

• When metronidazole eliminates anaerobic bacteria, it creates conditions favorable for yeast overgrowth 2
• Patients should be counseled about symptoms of yeast infection (pruritus, white discharge, vulvar burning) before starting treatment 2
• Women with a history of recurrent yeast infections are at higher risk 2
• If yeast infection develops, topical azole medications (clotrimazole, miconazole) are more effective than nystatin for treatment 2

Safety Profile and Discontinuation Rate

• Only 2 out of 505 patients (0.4%) discontinued therapy due to drug-related adverse events in pivotal trials 1
• One patient discontinued due to moderate abdominal cramping and loose stools 1
• One patient discontinued due to mild vaginal burning 1
• Both patients' symptoms resolved after discontinuation 1
• Overall, 39% of patients reported at least one adverse event judged possibly related to treatment, but the vast majority were mild and did not require discontinuation 1

Comparison to Oral Metronidazole

The topical vaginal formulation provides minimal systemic exposure compared to oral metronidazole, which explains the reduced frequency and severity of systemic side effects, particularly gastrointestinal complaints. 1, 3 However, the possibility of systemic reactions cannot be entirely excluded given that some drug absorption does occur. 1