Metronidazole is an antibiotic used for infections caused by anaerobic bacteria and by certain parasites (trichomoniasis, amoebiasis). During treatment and for up to 3 days after, do not drink alcohol — it causes an unpleasant reaction (cramps, nausea, vomiting, flushing).
Also known as: Flagyl
Combining Lithium with Metronidazole increases serum Lithium concentrations, with a risk of toxicity.
In patients stabilised on relatively high lithium doses, short-term metronidazole therapy has been associated with elevation of serum lithium and, in a few cases, signs of lithium toxicity; the metronidazole label recommends obtaining serum lithium and creatinine levels a few days after starting metronidazole, to detect any increase that may precede clinical symptoms of lithium intoxication. The lithium label includes metronidazole among the drugs that can raise lithium levels, with a recommendation for frequent monitoring and dose adjustment.
Lithium + metronidazole: can raise lithium levels and cause toxicity. Check lithium and creatinine a few days after starting metronidazole.
Metronidazole may increase serum Lithium concentrations; the mechanism involves reduced renal excretion.
Confusion, tremor or vomiting after starting Metronidazole require level testing and reassessment.
Confusion, tremor or vomiting after starting Metronidazole require level testing and reassessment.
Monitor Lithium levels and watch for signs of toxicity during Metronidazole use.
DailyMed/FDA (NIH/NLM) — approved Lithium label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0e6b0a2d-b79c-44d8-b785-5267df9e8f72 ; approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5784eeb-6b99-4e8a-847b-b0d1090ed48a — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Metronidazole inhibits Warfarin metabolism, potentiating its anticoagulant effect, with a raised INR and bleeding risk.
Metronidazole is a potent inhibitor of CYP2C9, the enzyme that metabolises active S-warfarin, and has been associated with marked INR elevations and bleeding, including severe cases. The effect can appear within days of starting the antibiotic. The warfarin label lists metronidazole among the drugs that potentiate its effect. The INR should be monitored frequently during and after treatment, a warfarin dose reduction should be considered, and bleeding signs watched for; in patients with a borderline INR the interaction can be particularly dangerous.
Metronidazole inhibits CYP2C9 and can markedly raise the INR. Monitor the INR during and after the antibiotic and consider a warfarin dose reduction.
Metronidazole inhibits the hepatic enzymes (CYP2C9/CYP3A4) that metabolize oral anticoagulants, raising Warfarin levels and prolonging prothrombin time.
Monitor the INR frequently and watch for bleeding signs.
Active bleeding, an elevated INR or new bruising require urgent evaluation.
Adjust the warfarin dose based on the INR and reinforce bleeding surveillance during and after the combination.
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d5784eeb-6b99-4e8a-847b-b0d1090ed48a ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Phenytoin + metronidazole: metronidazole inhibits phenytoin metabolism, increasing its serum levels and the toxicity risk (QUADRO 2).
Metronidazole inhibits CYP2C9, the enzyme that metabolises phenytoin, potentially increasing its plasma concentrations and the risk of toxicity. QUADRO 2 of Annex 7 records this interaction in the phenytoin section. Early toxicity signs include nystagmus, ataxia, dysarthria, drowsiness and, in severe cases, paradoxical seizures. The risk is higher in patients on near-maximum phenytoin doses, the elderly or those with hypoalbuminaemia (more free drug). Monitor phenytoin levels and neurological signs during metronidazole treatment; consider reducing the phenytoin dose and using an alternative antibiotic when possible.
Metronidazole + phenytoin: metronidazole inhibits phenytoin metabolism — toxicity risk (nystagmus, ataxia); monitor levels and clinical signs.
Metronidazole inhibits the enzymes that metabolise phenytoin — increased phenytoin serum level (QUADRO 2, Phenytoin: "Drugs that inhibit phenytoin metabolism... Metronidazole").
Watch for signs of phenytoin toxicity (nystagmus, ataxia, diplopia, somnolence).
Nystagmus, ataxia, diplopia (phenytoin toxicity) during metronidazole.
Monitor phenytoin levels during metronidazole; consider dose reduction.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Phenytoin)
Disulfiram + metronidazole: confusion and psychoses have been reported in patients taking disulfiram and metronidazole (mechanism unknown) (QUADRO 2).
The combination of metronidazole with disulfiram has been associated with acute psychotic reactions, confusion and delirium, even at usual doses; the mechanism is not fully understood but probably involves interference with amine metabolism. QUADRO 2 of Annex 7 records this interaction in the disulfiram section. The guidance is to avoid the combination, respecting a minimum interval of about 14 days between stopping one drug and starting the other. If metronidazole is essential in a patient on disulfiram, consider an alternative antibiotic; watch for neuropsychiatric symptoms (confusion, hallucinations, agitation).
Metronidazole + disulfiram: risk of acute psychotic reaction and confusion; avoid — minimum interval of 14 days.
The disulfiram + metronidazole combination has been associated with psychotic/confusional reactions — QUADRO 2 records confusion and psychoses, with unknown mechanism (QUADRO 2, Disulfiram: "Metronidazole: confusion and psychoses have been reported in patients taking disulfiram and metronidazole").
Monitor mental state during concomitant therapy.
Acute confusion, psychosis in a patient taking disulfiram + metronidazole.
Avoid the combination; if metronidazole is required, watch the mental state.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 7, QUADRO 2 (Disulfiram)
Taking with food reduces GI irritation without significantly affecting absorption.
Take with food to improve GI tolerance.
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cc3fd98-d579-432e-a4b5-b6d5586991a6
Metronidazole inhibits acetaldehyde dehydrogenase: alcohol causes a disulfiram-like reaction (flushing, nausea, vomiting, tachycardia, headache).
Do not consume alcohol during treatment and for 48–72 hours after the last dose.
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cc3fd98-d579-432e-a4b5-b6d5586991a6
Metronidazole can cause encephalopathy, seizures and peripheral neuropathy, especially at high doses or with prolonged use.
Stop if neurological symptoms appear; use with caution in CNS disease.
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cc3fd98-d579-432e-a4b5-b6d5586991a6
Metronidazole is metabolised in the liver; in severe liver disease elimination is reduced and accumulation can cause neurotoxicity.
Reduce the dose and monitor for neurotoxicity signs (paraesthesia, ataxia).
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cc3fd98-d579-432e-a4b5-b6d5586991a6
Dose-dependent toxicity; avoid in non-neoplastic indications in hepatic impairment.
Reduce the dose and avoid in non-neoplastic indications.
Prontuário Terapêutico do INFARMED (11th ed., 2012) — Annex 3, Drugs and hepatic impairment: Dose-dependent toxicity; avoid in non-neoplastic indications in hepatic impairment.
Metronidazole crosses the placenta; data show no clear increase in malformations, but use in the 1st trimester is cautious.
Avoid in the 1st trimester; use short courses when clearly indicated.
Excreted into breast milk; avoid breastfeeding during treatment and for 12–24 h after the last dose.
No specific additional contraception.
DailyMed/FDA (NIH/NLM) — approved Metronidazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5cc3fd98-d579-432e-a4b5-b6d5586991a6
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Antibiotic and antiprotozoal agent with bactericidal activity against anaerobes and against Trichomonas, Giardia and Entamoeba. Plasma concentrations are proportional to the dose: 250, 500 and 2,000 mg produce peaks of 6, 12 and 40 mcg/ml, respectively.
Prodrug: the nitro group is reduced intracellularly in anaerobic microorganisms, generating reactive intermediates that damage DNA and inhibit nucleic acid synthesis.
Well absorbed after oral administration, with peak plasma concentrations between 1 and 2 hours. Less than 20% is bound to plasma proteins. It appears in cerebrospinal fluid, saliva and breast milk at concentrations similar to plasma.
The major route of elimination of metronidazole and its metabolites is urine (60 to 80% of the dose), with faecal excretion of 6 to 15%. The metabolites result mainly from side-chain oxidation and glucuronide conjugation; unchanged drug accounts for about 20% of the total. The hydroxy metabolite retains antimicrobial activity.
The mean elimination half-life in healthy subjects is about 8 hours.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
