Imidazole derivatives (antiprotozoal / antibacterial)
ATC code: J01XD01 (Metronidazole)
Brand names
Flagyl, Metrogel
Reduced under anaerobic conditions by ferredoxin-dependent systems in bacteria and protozoa to active nitro radicals that damage DNA. Active against obligate anaerobes (Bacteroides, Clostridium, Fusobacterium), protozoa (Giardia, Entamoeba, Trichomonas), and Helicobacter pylori. Used in H. pylori eradication regimens, anaerobic infections, pseudomembranous colitis, and amebiasis. Inhibits CYP2C9 – raising warfarin exposure. Causes a disulfiram-like reaction with ethanol (tachycardia, flushing, nausea).
First line
First-line for bacterial vaginosis per CDC STI 2021 and . Oral 500 mg twice daily for 7 days or intravaginal 0.75 % gel 5 g once daily for 5 days. Alternative — clindamycin. Partner treatment is not indicated in BV (BV is not strictly an STI).
First line
Component of Helicobacter pylori eradication regimens per Maastricht VI/Florence Consensus 2022. In bismuth quadruple therapy: metronidazole 500 mg four times daily with tetracycline, bismuth, and PPI. Efficacy decreases with metronidazole resistance (above 20 % of strains in Russia).
First line
First-line for trichomoniasis in men and women per CDC STI Treatment Guidelines 2021 and . Preferred regimen in women: 500 mg twice daily for 7 days. Single 2 g dose is less effective in women (CDC downgraded in 2021); still acceptable in men. Mandatory simultaneous partner treatment. Sexual contact no sooner than 7 days after both partners complete therapy.
Not recommended
Metronidazole is not used in viral URI. The drug does not act on viruses or aerobic flora and is not mentioned in international URI guidelines. Common Russian prescriptions for «antibiotic-associated dysbiosis» or in «frequently ill children» are not justified by evidence.
Metronidazole inhibits acetaldehyde dehydrogenase. With alcohol – disulfiram-like reaction: flushing, nausea, vomiting, tachycardia. Full alcohol abstinence during treatment and 48 hours after. Counsel patient before starting therapy.
Source: FDA: Flagyl (metronidazole) prescribing information (2020)
4 pairs found. Sorted from critical to minor.
Mechanism
Metronidazole stereospecifically inhibits CYP2C9, the enzyme that metabolizes S-warfarin (the more potent enantiomer). Warfarin concentration rises and INR climbs substantially (often by 2–4 units) as early as days 3–5 of the course. Cases of INR above 10 and major bleeding have been reported (Stockley's Drug Interactions; Drug Interaction Database).
Management
Pre-emptively reduce warfarin dose by 25–35 % before starting metronidazole. Check INR on days 3 and 7 of the course and again 7–10 days after completion. For high bleeding risk (age ≥ 75, ≥ 3, recent bleeding), choose an alternative antibiotic where possible or pre-transition to a DOAC.
Sources
Mechanism
Метронидазол – мощный ингибитор CYP2C9, основного фермента метаболизма S-варфарина. МНО может удвоиться за 5–7 дней.
Management
Снизить дозу варфарина на 25–35% при старте курса метронидазола. МНО на 4-й и 7-й день.
Mechanism
A target combination in triple/quadruple Helicobacter pylori eradication regimens (Maastricht VI / Florence Consensus 2022, Kyoto Global Consensus, Russian Ministry of Health 2024 guidelines). No direct pharmacokinetic interaction – the two drugs act synergistically against H. pylori.
Management
Standard regimen: omeprazole 20 mg twice daily + amoxicillin 1000 mg twice daily + metronidazole (or clarithromycin) 500 mg twice daily for 14 days.
Sources
Mechanism
No direct pharmacokinetic interaction. Concurrent use at standard doses is safe.
Management
No dose adjustment is required.
Sources
FDA categories were retired in 2015. Manufacturer label contraindicates first-trimester use; theoretical teratogenicity is not confirmed in large cohort studies. Used in the second and third trimesters on indication. In trichomoniasis and BV during pregnancy, metronidazole is given without interruption to avoid adverse obstetric outcomes.
Transfers into milk. Per LactMed — short courses are compatible with breastfeeding; for a single 2 g dose, defer feeds for 12–24 hours.
metronidazole is evaluated for the following indications with varying evidence strength: Helicobacter pylori infection (evidence tier A), Bacterial vaginosis (evidence tier A), Trichomoniasis (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of metronidazole (≥ 1 in 100): Nausea, vomiting, Metallic taste, Dry mouth, Headache, Diarrhea, Dark urine (from metabolites). See the Safety section for uncommon and serious reactions.
FDA categories were retired in 2015. Manufacturer label contraindicates first-trimester use; theoretical teratogenicity is not confirmed in large cohort studies. Used in the second and third trimesters on indication. In trichomoniasis and BV during pregnancy, metronidazole is given without interruption to avoid adverse obstetric outcomes.
Transfers into milk. Per LactMed — short courses are compatible with breastfeeding; for a single 2 g dose, defer feeds for 12–24 hours.
metronidazole is contraindicated in: First trimester of pregnancy; Severe CNS disease (epilepsy); Prior leukopenia; Severe hepatic impairment; Hypersensitivity to nitroimidazoles. Full list in the Safety section.