Imidazole derivatives (antiprotozoal / antibacterial)
Brand names: Flagyl, Metrogel
Updated · Methodology
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).
Sources
ICD-10: N76 · ICD-11: GA02
First line
Component of Helicobacter pylori eradication regimens per Maastricht VI/Florence Consensus 2022. In bismuth quadruple therapy: metronidazole 250–500 mg three to four times daily with tetracycline, bismuth, and PPI. Efficacy decreases with metronidazole resistance (above 20 % of strains in Russia).
Sources
ICD-10: B98.0 · ICD-11: DA42.1
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.
Sources
ICD-10: A59 · ICD-11: 1A92
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.
Sources
ICD-10: J00 · ICD-11: CA00
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).
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 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)
9 pairs found. Sorted from critical to minor.
Mechanism
The disulfiram label attributes the interaction to a possible synergistic effect of the two drugs that causes an acute psychotic reaction and confusion. Psychotic reactions have been reported in patients with alcohol dependence who took metronidazole together with disulfiram.
Symptoms
Confusion and acute psychotic reactions in a patient who takes disulfiram or has recently taken it.
Management
The combination is contraindicated in the disulfiram label and in the US Food and Drug Administration () labels for disulfiram and metronidazole. Do not start disulfiram in a patient who is taking metronidazole or has recently taken it (disulfiram label). Do not give metronidazole to a patient who has taken disulfiram within the last two weeks (metronidazole FDA label). The Spanish metronidazole label also says the combination must be avoided (metronidazole label).
Sources
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.
Sources
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 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
The metronidazole and duloxetine documents do not mention each other, neither the Spanish SmPCs nor the US Food and Drug Administration () labels. No kinetic pathway is described: duloxetine is cleared through CYP1A2 and CYP2D6 (duloxetine SmPC) and does not inhibit CYP2C9 or CYP3A (FDA duloxetine label), while the metronidazole SmPC lists interactions with warfarin, lithium, ciclosporin, phenytoin, 5-fluorouracil and busulfan but none with antidepressants. Metronidazole's own clearance is slowed by inhibitors of hepatic microsomal enzymes such as cimetidine (FDA metronidazole label), and duloxetine is not one of them. The documents give metronidazole no serotonergic activity, and the metronidazole warning about QT prolongation with QT-prolonging drugs does not apply to duloxetine: in the duloxetine SmPC approved by the European Medicines Agency () the rate-corrected QT interval of patients on duloxetine did not differ from placebo, and the FDA duloxetine label found no QT prolongation even at doses above the maximum. The only overlap is the liver: duloxetine has caused severe liver enzyme elevation, hepatitis and jaundice, and its SmPC asks for caution with other medicines associated with liver injury (EMA duloxetine SmPC). The metronidazole SmPC lists enzyme elevation, cholestatic or mixed hepatitis, hepatocellular damage and cases of liver failure among its adverse reactions and describes rapid, sometimes fatal hepatotoxicity in Cockayne syndrome.
Symptoms
The documents describe no symptoms specific to the interaction. Watch for the signs of liver injury that each document lists for its own drug: abdominal pain, enlarged liver, rising transaminases, jaundice (US Food and Drug Administration () duloxetine label and European Medicines Agency () duloxetine SmPC), raised liver enzymes and hepatitis with jaundice (metronidazole SmPC, section 4.8). In Cockayne syndrome, liver failure with metronidazole has developed as early as 2 days after the start of treatment (FDA metronidazole label).
Management
By the documents, neither drug needs a dose change because of the other: the metronidazole and duloxetine documents do not mention the pair and describe no kinetic interaction. The only instruction concerns the liver: duloxetine is used with caution in patients taking other medicines associated with liver injury (duloxetine SmPC approved by the European Medicines Agency, ), and metronidazole's own SmPC places it among such medicines (section 4.8). So during a combined course, watch for signs of liver injury, and if jaundice or other evidence of clinically significant liver dysfunction appears, stop duloxetine and do not resume it unless another cause is established (US Food and Drug Administration () duloxetine label). In Cockayne syndrome metronidazole is contraindicated (FDA metronidazole label); the Spanish metronidazole SmPC allows it only when benefit outweighs risk and no alternative exists, with liver function tests before, during and after treatment and withdrawal if values rise markedly. Duloxetine is contraindicated in liver disease causing hepatic impairment (EMA duloxetine SmPC), and that restriction applies regardless of metronidazole. No electrocardiogram is needed for the combination: by its own documents duloxetine does not prolong the QT interval.
Sources
Mechanism
There is no interaction that calls for action. Amoxicillin and metronidazole are cleared by different routes, share no relevant transporters, and the interaction sections of their labels do not pit them against each other. The combination is prescribed on purpose in more than one setting: Helicobacter pylori eradication, odontogenic infection and abscess, mixed intra-abdominal and pelvic infection, where amoxicillin covers aerobes and metronidazole anaerobes.
Symptoms
What shows up with this pair are each drug's own effects, mostly gastrointestinal: nausea, metallic taste and diarrhoea. Watery diarrhoea starting during the course or weeks later calls for ruling out Clostridioides difficile infection, a risk that belongs to antibiotics in general.
Management
The regimen runs as prescribed, for the intended duration. What does matter is alcohol: the metronidazole label asks for alcoholic drinks to be avoided during treatment because of a disulfiram-like effect with dizziness and vomiting, and that warning holds for a few days after the course. The rest of the regimen depends on the indication: in H. pylori eradication the third component is a proton pump inhibitor or bismuth.
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
Verbatim lines from the interaction sections, in the language of the label
«Psychotic Reaction with Disulfiram: Use of oral metronidazole is associated with psychotic reactions in alcoholic patients who were using disulfiram concurrently. Do not administer metronidazole to…»FDA, section 4 · Open on DailyMed
«Disulfiram: La administración simultánea de disulfiram puede causar estados de confusión o incluso reacciones psicóticas. Debe evitarse la combinación de ambos agentes.»AEMPS, section 4.5 · Open on CIMA
«Litio: Se debe tener precaución cuando se administre metronidazol simultáneamente con sales de litio, ya que durante el tratamiento con metronidazol se han observado concentraciones plasmáticas de…»AEMPS, section 4.5 · Open on CIMA
«Amiodarona: Se han notificado casos de prolongación del intervalo QT y torsade de pointes con la administración conjunta de metronidazol y amiodarona. Puede ser apropiado controlar el intervalo QT en…»AEMPS, section 4.5 · Open on CIMA
«Derivados de la cumarina: El tratamiento concomitante con metronidazol puede potenciar el efecto anticoagulante de estos y aumentar el riesgo de hemorragia como consecuencia de la disminución de la…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. When…»FDA, section 7 · Open on DailyMed
«Ciclosporina: Durante el tratamiento simultáneo con ciclosporina y metronidazol existe el riesgo de aumento de las concentraciones plasmáticas de ciclosporina. Se requiere una monitorización…»AEMPS, section 4.5 · Open on CIMA
«Micofenolato de mofetilo: Las sustancias que alteran la flora gastrointestinal (p. ej., antibióticos) pueden reducir la biodisponibilidad oral del ácido micofenólico. Durante el tratamiento…»AEMPS, section 4.5 · Open on CIMA
«Tacrolimus: La administración conjunta con metronidazol puede aumentar las concentraciones sanguíneas de tacrolimus. El mecanismo propuesto es la inhibición del metabolismo hepático del tacrolimus a…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Metronidazole has been reported to potentiate the anticoagulant effect of warfarin and other oral coumarin anticoagulants, resulting in a prolongation of prothrombin time. When…»FDA, section 7 · Open on DailyMed
«Medicamentos anticonceptivos: Algunos antibióticos pueden, en algunos casos excepcionales, disminuir el efecto de las píldoras anticonceptivas interfiriendo con la hidrólisis bacteriana de los…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos anticonceptivos: Algunos antibióticos pueden, en algunos casos excepcionales, disminuir el efecto de las píldoras anticonceptivas interfiriendo con la hidrólisis bacteriana de los…»AEMPS, section 4.5 · Open on CIMA
«Barbitúricos: Fenobarbital puede aumentar el metabolismo hepático de metronidazol, reduciendo su vida media plasmática a 3 horas.»AEMPS, section 4.5 · Open on CIMA
«Carbamazepina: Metronidazol puede inhibir el metabolismo de carbamazepina y aumentar, como consecuencia, las concentraciones plasmáticas.»AEMPS, section 4.5 · Open on CIMA
«Fluorouracilo: Metronidazol inhibe el metabolismo del fluorouracilo administrado simultáneamente, es decir, aumenta la concentración plasmática de fluorouracilo.»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: Lithium»FDA, section 7 · Open on DailyMed
«Drug Interactions: Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT)…»FDA, section 7 · Open on DailyMed
«Barbitúricos: Fenobarbital puede aumentar el metabolismo hepático de metronidazol, reduciendo su vida media plasmática a 3 horas.»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in…»FDA, section 7 · Open on DailyMed
«Fenitoína: Metronidazol inhibe el metabolismo de la fenitoína administrada simultáneamente, es decir, se incrementa la concentración plasmática de fenitoína. Por otro lado, la eficacia del…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions: The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in…»FDA, section 7 · Open on DailyMed
«Drug Interactions: Drugs that Prolong the QT interval»FDA, section 7 · Open on DailyMed
«Medicamentos anticonceptivos: Algunos antibióticos pueden, en algunos casos excepcionales, disminuir el efecto de las píldoras anticonceptivas interfiriendo con la hidrólisis bacteriana de los…»AEMPS, section 4.5 · Open on CIMA
«CONTRAINDICATIONS: Patients who are receiving or have recently received metronidazole, paraldehyde, alcohol, or alcohol-containing preparations, e.g., cough syrups, tonics and the like, should not be…»FDA, section 4 · Open on DailyMed
«Inhibidores de CYP3A4/AEMPS, section 4.5 · Open on CIMA
«Interacciones que aumentan los niveles de litio: Antibióticos (nitroimidazoles (ej. Metronidazol)): el uso concomitante puede aumentar las concentraciones séricas de litio debido a la reducción del…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Diuretics, NSAID, renin-angiotensin system antagonists, or metronidazole may increase lithium serum concentrations. Recommend frequent monitoring of serum lithium concentration and…»FDA, section 7 · Open on DailyMed
«Inhibidores enzimáticos: pueden potenciar el efecto anticoagulante, con riesgo de hemorragias, debido a una inhibición de su metabolismo hepático, cuando se administra conjuntamente con: alopurinol…»AEMPS, section 4.5 · Open on CIMA
«Becloforte contiene una pequeña cantidad de etanol. Existe un teórico potencial de interacción en pacientes particularmente sensibles que estén tomando disulfiram o metronidazol.»AEMPS, section 4.5 · Open on CIMA
«Norfloxacino y metronidazol: No se ha observado interacción significativa en la administración concomitante de micofenolato de mofetilo con norfloxacino o con metronidazol en voluntarios sanos. Sin…»AEMPS, section 4.5 · Open on CIMA
«Otros estudios de interacciones: También se han realizado estudios de interacción administrando pantoprazol de forma concomitante con antibióticos (claritromicina, metronidazol y amoxicilina). No se…»AEMPS, section 4.5 · Open on CIMA
«Drug Interactions:: sulbactam metronidazole»FDA, section 7 · Open on DailyMed
«CYP450 Interactions: CYP2C9 amiodarone, capecitabine, cotrimoxazole, etravirine, fluconazole, fluvastatin, fluvoxamine, metronidazole, miconazole, oxandrolone, sulfinpyrazone, tigecycline…»FDA, section 7 · Open on DailyMed
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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.
Avoid alcohol during therapy and for 48 hours after the last dose — disulfiram-like reaction: nausea, vomiting, tachycardia, hypotension.
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.
Direct links to regulator labels. Open in a new tab.
Moxifloxacin, Norfloxacin, Trimethoprim, Amoxicillin + Clavulanic Acid, Amoxicillin, Cefuroxime axetil, Co-trimoxazole, Fosfomycin