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 — . 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.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
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)
8 pairs found. Sorted from critical to minor.
Mechanism
Metronidazole prolongs the QT interval. Combined with amiodarone, torsades de pointes has been reported, especially with hypokalaemia.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antibiotics without QT effect: a cephalosporin, amoxicillin-clavulanate, or fosfomycin. For anaerobic infection requiring metronidazole: ECG before start and at day 2.
Mechanism
Metronidazole stereospecifically inhibits CYP2C9, the clearance route for S-warfarin. INR may double within 3–7 days of co-administration.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
For short metronidazole courses, empirically reduce warfarin by 20–30% and check INR 3–4 days after starting and 7 days after stopping the antibiotic. For prolonged therapy, titrate warfarin to INR.
Sources
Mechanism
Metronidazole stereospecifically inhibits CYP2C9, the clearance route for S-warfarin (the more active stereoisomer). INR may double within 3–7 days of co-administration.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.
Management
For short metronidazole courses (5–7 days), empirically reduce warfarin by 20–30% and check INR 3–4 days after starting and 7 days after stopping the antibiotic. For prolonged metronidazole therapy, titrate warfarin to INR.
Mechanism
Metronidazole does not block CYP3A4 but increases myopathy risk with statins (mechanism not fully established; reported in post-marketing data). The effect is rare.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Symptoms usually appear 2–6 weeks after starting the combination.
Management
For short metronidazole courses (5–7 days), no special adjustment. In patients with myopathy risk factors, check creatine kinase on muscle symptoms. For prolonged metronidazole therapy, temporarily reduce atorvastatin.
Mechanism
Target combination in triple and quadruple Helicobacter pylori eradication (Maastricht VI/Florence Consensus 2022, Kyoto Global Consensus). Synergistic antibacterial action.
Symptoms
Possible combination side effects: metallic taste (from metronidazole), nausea, diarrhoea. In some patients, disulfiram-like reaction with alcohol on metronidazole.
Management
Standard combination in H. pylori eradication (amoxicillin 1000 mg twice daily + metronidazole 500 mg three times daily + PPI or bismuth for 10–14 days). Exclude alcohol throughout the course and for 48 hours after metronidazole. If metronidazole is intolerated, alternatives: tetracycline or levofloxacin.
Sources
Mechanism
Calcium carbonate as an antacid may theoretically reduce metronidazole absorption, but no clinically significant effect on antibacterial efficacy has been described.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
For short metronidazole courses (5–10 days), no specific adjustment needed. In Helicobacter pylori eradication (with bismuth or a PPI), the combination is standard.
Mechanism
Metronidazole does not induce CYP3A4 and does not affect hepatic ethinylestradiol metabolism. The historical theory of reduced COC efficacy is rejected by meta-analyses.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
Additional contraception during short metronidazole courses is not needed. Exclude alcohol throughout the course and for 48 hours after due to a disulfiram-like reaction.
Mechanism
No direct pharmacokinetic interaction. Co-administration at standard doses is safe.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. Paracetamol remains the analgesic and antipyretic of choice on metronidazole.
Sources
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Direct links to regulator labels. Open in a new tab.
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.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
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 category B. 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.