Drug reference

Metronidazole

Nitroimidazole · Antibiotic

Also known as Metronidazole Benzoate

START

Confirm anaerobic/protozoal infection. Baseline CBC, LFTs. Rule out Cockayne syndrome. Counsel on absolute alcohol avoidance during and 3 days after therapy. Obtain pregnancy test if applicable.

TYPICAL MAX

4 g/day IV; 2 g single oral dose. Do not exceed 4 g/day (neurotoxicity risk).

STOP IF

Signs of peripheral neuropathy (numbness, tingling, burning), encephalopathy (ataxia, confusion, seizures), severe rash, jaundice/hepatotoxicity, pregnancy

WATCH

CNS symptoms (neuropathy, encephalopathy — especially with courses >10 days), LFTs (prolonged therapy), INR if on warfarin, alcohol compliance

CDSCO approvedSchedule HJan AushadhiATC P01AB01

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 23min · absorption onset
PEAK: 1.5h · 1-2 h (oral)
t½: 7h · 6-8 h (normal); 18-24 h (severe hepatic)
DURATION: 8h · 6-8 h (q6-8h dosing)

EXCRETION

60-80% renal (parent + metabolites); 6-15% fecal; dialyzable

route + CYP

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

FDA PLLR: Use with caution. Animal studies showed no teratogenicity but limited human data. Avoid high-dose or prolonged use in first trimester. For trichomoniasis, defer treatment to second trimester if possible. Metronidazole crosses placenta.

FDA category + note

Top interactionssee all 12 →

Eikenella CorrodensContraindicatedTextbookHarrison 22e · p1054
LopinavirContraindicatedTextbookG&G 14e · p1245-1266
AlcoholContraindicatedDatabaseKimi deep-research + Cla · p948
DisulfiramContraindicatedDatabaseKimi deep-research + Cla

Available in India

82 branded formulations and 736 fixed-dose combinations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Metronidazole is a nitroimidazole antimicrobial that is selectively taken up by anaerobic organisms and certain protozoa. Within the cell, its nitro group is reduced by low-redox-potential electron transport proteins (ferredoxin, flavodoxin) to form highly reactive cytotoxic radical anions. These radicals damage microbial DNA by causing strand breakage, helix destabilization, and inhibition of nucleic acid synthesis. The drug is active only against anaerobic and microaerophilic organisms because oxygen competes with the nitro group for electrons, preventing the reduction necessary for activation.

Indications

Amebiasis (Entamoeba histolytica) — intestinal and extraintestinalTrichomoniasis (Trichomonas vaginalis)Giardiasis (Giardia lamblia/intestinalis)Anaerobic bacterial infections (Bacteroides fragilis, Clostridium, Fusobacterium, Peptostreptococcus)Bacterial vaginosis (Gardnerella vaginalis, anaerobes)C. difficile infection (oral formulation only — first-line for mild-moderate)Peptic ulcer disease (H. pylori eradication — combination therapy)Brain abscess, intra-abdominal infections, diabetic foot infections (anaerobic coverage)

Dosing

Adult: Amebiasis: 500-750 mg PO TID x 5-10 days. Trichomoniasis: 2 g PO single dose OR 500 mg BID x 7 days. Giardiasis: 250 mg PO TID x 5-7 days. Anaerobic infections: 500 mg IV q6-8h. C. difficile: 500 mg PO QID x 10-14 days. Bacterial vaginosis: 500 mg PO BID x 7 days. H. pylori: 500 mg PO BID (with PPI, clarithromycin, amoxicillin).
Pediatric: Amebiasis: 35-50 mg/kg/day PO divided TID (max 750 mg/dose) x 5-10 days. Giardiasis: 15 mg/kg/day PO divided TID x 5-7 days. Anaerobic: 30 mg/kg/day IV divided q6h (max 4 g/day). C. difficile (≥10 kg): 10 mg/kg PO QID (max 500 mg/dose).
Renal adjustment: CrCl <10: reduce dose by 50%. Hemodialysis: supplemental dose post-dialysis (metronidazole and metabolites are dialyzable). CRRT: standard dose.
Hepatic adjustment: Severe hepatic impairment: reduce dose by 50%. Monitor for CNS toxicity (encephalopathy, peripheral neuropathy).
Geriatric: No specific adjustment; monitor for CNS effects and adjust for renal function.
Max dose: 4 g/day (IV); 2 g single dose (oral); 750 mg/dose

Pharmacokinetics

Onset

Rapid bactericidal activity against anaerobes; clinical response within 48-72 hours.

Peak effect

Oral: peak plasma at 1-2 hours. IV: immediate distribution.

Duration

6-8 hours (supports q6-8h dosing).

Half-life

6-8 hours (range 6-10 hours; prolonged in severe hepatic impairment to 18-24 hours).

Bioavailability

>90% (oral; comparable to IV).

Protein binding

~10-20% (low).

Metabolism

Hepatic via oxidation, hydroxylation, glucuronidation. Major metabolite: hydroxymetronidazole (active). CYP2C9 substrate; CYP3A4 inhibitor (weak).

Excretion

Urine: ~60-80% (parent + metabolites) within 24 hours. Feces: 6-15%. Dialyzable.

Contraindications

Hypersensitivity to metronidazole or other nitroimidazoles (tinidazole, secnidazole)
Disulfiram use within past 14 days (psychotic reactions)
Alcohol consumption during and for at least 3 days after therapy (disulfiram-like reaction)
Cockayne syndrome (severe irreversible hepatotoxicity/acute liver failure)
First trimester of pregnancy (for trichomoniasis — relative)

Side effects

Common

Nausea, vomiting, abdominal pain, metallic tasteHeadache, dizzinessDark/reddish-brown urine (harmless metabolite — patient reassurance needed)AnorexiaDry mouth

Serious

Peripheral neuropathy (dose-related, cumulative; may be irreversible with prolonged use)
Encephalopathy (ataxia, dizziness, dysarthria, seizures — reversible on discontinuation)
Seizures
Aseptic meningitis
Severe hepatotoxicity (acute liver failure in Cockayne syndrome)
Severe cutaneous adverse reactions (SJS, TEN, DRESS)
Bone marrow suppression (leukopenia, neutropenia)
Disulfiram-like reaction with alcohol (severe nausea, vomiting, flushing, abdominal cramps, headache)

Pregnancy & lactation

Pregnancy

Lactation

Excreted in breast milk (concentrations similar to plasma). AAP recommends temporary discontinuation of breastfeeding during therapy and for 12-24 hours after last dose (milk can be pumped and discarded). Infant may develop loose stools, candidiasis, or blood dyscrasias.

Drug interactions

Eikenella Corrodens

Contraindicated

Textbook

ineffective treatment

Eikenella corrodens is resistant to metronidazole but sensitive to trimethoprim-sulfamethoxazole and fluoroquinolones. Amoxicillin-clavulanate, ampicillin-sulbactam, and cefoxitin are good choices for human bite infections.

Source: Harrison 22e · p1054

Lopinavir

Contraindicated

Textbook

Disulfiram-like reaction.

Should not be administered with metronidazole.

Source: G&G 14e · p1245-1266

Alcohol

Contraindicated

Database

Disulfiram-like reaction: metronidazole inhibits aldehyde dehydrogenase (ALDH), causing accumulation of acetaldehyde. Severe nausea, vomiting, flushing, abdominal cramps, headache, hypotension.

Absolute alcohol avoidance during therapy and for at least 3 days after last dose. This includes alcohol-containing medications, mouthwashes, and cough syrups. Patient counseling mandatory.

Source: Kimi deep-research + Cla · p948

Disulfiram

Contraindicated

Database

Psychotic reactions (acute confusional state, paranoid delusions) have occurred in patients taking metronidazole concurrently with disulfiram or within 14 days of disulfiram.

Do not administer metronidazole to patients who have taken disulfiram within the past 14 days. Wait at least 2 weeks after stopping disulfiram before starting metronidazole.

Source: Kimi deep-research + Cla

Carbamazepine

Severe

Textbook-cited

Loss of therapeutic efficacy of metronidazole.

Avoid concurrent use or increase dose with monitoring

Source: KDT 7e · p949

Phenobarbital

Severe

Textbook-cited

Loss of therapeutic efficacy of metronidazole

Avoid concurrent use or increase dose with monitoring