Metronidazole
Metronidazole is a nitroimidazole antimicrobial active against anaerobic bacteria and protozoa, used for trichomoniasis, bacterial vaginosis, giardiasis, amoebiasis, C. difficile infection and H. pylori eradication. Launched as Flagyl, it is now a widely available generic on the WHO essential list.
- Chemical formula
- C6H9N3O3
- CAS number
- 443-48-1
- ATC code
- P01AB01
- Molecular weight
- 171.16 g/mol
- Drug class
- Nitroimidazole antimicrobial
- Also known as
- Flagyl, Metronidazol, Metronidazolum
What is it?
Metronidazole is a synthetic nitroimidazole discovered at Rhône-Poulenc in the late 1950s and launched as Flagyl in 1960, initially as a treatment for Trichomonas vaginalis. Its activity against anaerobic bacteria was recognised a few years later when a patient's gum infection cleared during trichomoniasis treatment, which opened the door to its use in surgical, dental and intra-abdominal infections. The molecule is small (171 g/mol), inexpensive and available as tablets, suspension, injection, vaginal and topical preparations. It is on the WHO Model List of Essential Medicines and remains a first-line drug for several protozoal diseases worldwide.
Mechanism of action
Metronidazole is a prodrug that enters cells by passive diffusion. In anaerobic bacteria and protozoa, low-redox-potential electron carriers such as ferredoxin reduce its nitro group, generating nitroso and hydroxylamine radicals. These intermediates bind to DNA, break the strands and destabilise the helix, so replication stops and the cell dies. The reduction also creates a concentration gradient that draws more drug into the organism. Aerobic and facultative cells in the presence of oxygen cannot reduce the nitro group effectively, which gives the drug its selective toxicity. The effect is bactericidal and largely independent of the organism's growth phase.
Pharmacokinetics
Oral bioavailability approaches 100%, with peak plasma concentrations about 1 to 2 hours after a dose. Protein binding is low (under 20%) and the drug distributes widely, reaching therapeutic concentrations in abscesses, bile, bone, cerebrospinal fluid, saliva, breast milk and vaginal secretions. Hepatic metabolism, mainly through CYP2A6 and side-chain oxidation, produces a hydroxy metabolite with 30 to 65% of the parent's activity. The elimination half-life is about 8 hours, prolonged in severe hepatic impairment. Around 60 to 80% of a dose is excreted in urine, often colouring it dark brown.
Indications
Metronidazole is indicated for trichomoniasis, bacterial vaginosis, giardiasis, intestinal and extra-intestinal amoebiasis and infections caused by anaerobic bacteria such as Bacteroides, Clostridium, Fusobacterium and Peptostreptococcus. These include intra-abdominal and pelvic infections, brain abscess, aspiration pneumonia, osteomyelitis and dental infections. It is part of triple and quadruple regimens for Helicobacter pylori, a treatment option for Clostridioides difficile infection, and is used for surgical prophylaxis in colorectal procedures and for rosacea in topical form. According to clinical guidelines, it should be reserved for confirmed or strongly suspected anaerobic or protozoal disease.
Safety profile
Common adverse effects are nausea, metallic taste, loss of appetite, headache and dark urine. A disulfiram-like reaction with alcohol (flushing, vomiting, tachycardia) can occur and alcohol should be avoided during treatment and for 48 hours afterwards. Peripheral neuropathy, and rarely seizures, encephalopathy or optic neuropathy, are associated with prolonged or repeated high-dose courses; new numbness or tingling warrants stopping the drug and consulting a doctor. Metronidazole potentiates warfarin, raises lithium levels and is contraindicated with disulfiram. Carcinogenicity in rodents has not been confirmed in humans, but unnecessary long courses are avoided as a precaution.
Products containing this ingredient
Frequently asked questions
How long does the disulfiram-like reaction risk last after metronidazole? ▾
The interaction is usually described as lasting for the duration of treatment and at least 48 hours after the last dose, because the drug and its active metabolite take about two days to clear. Some prescribing information advises 72 hours. The reaction includes flushing, headache, nausea, vomiting and palpitations and can be triggered by alcohol in medicines and mouthwash as well as drinks. If symptoms occur after accidental intake, contact a doctor or pharmacist.
Is metronidazole an antibiotic or an antiparasitic? ▾
Both. Metronidazole is classified as an antiprotozoal (ATC P01AB01) and as an antibacterial (J01XD01) because the same mechanism of nitro-group reduction works in anaerobic bacteria and in protozoa such as Trichomonas, Giardia and Entamoeba. It has no useful activity against aerobic bacteria, fungi or viruses, so it is often combined with other agents for mixed infections.
Why does metronidazole cause a metallic taste? ▾
The drug and its metabolites are secreted into saliva, where they stimulate taste receptors and produce the characteristic metallic or bitter taste. It affects a large proportion of patients, is harmless and resolves within days of stopping. Taking doses with food, chewing sugar-free gum or rinsing the mouth helps. Dark or reddish-brown urine from the metabolites is a similarly benign effect.
Can metronidazole be used in pregnancy? ▾
Metronidazole crosses the placenta, but large cohort studies and meta-analyses have not shown an increased rate of birth defects, and guidelines accept its use for symptomatic bacterial vaginosis and trichomoniasis in pregnancy. Many prescribers avoid the single 2g dose during the first trimester and prefer a 7-day course. As with any medicine in pregnancy, the decision should be made with the treating doctor.
What is the risk of neuropathy with metronidazole? ▾
Peripheral neuropathy is uncommon with standard 7 to 10 day courses but becomes more likely with cumulative doses above roughly 40g or treatment longer than 4 weeks, as in Crohn's disease or chronic osteomyelitis. Symptoms are numbness, tingling or burning in the feet and hands. According to the prescribing information, the drug should be stopped if these appear; most patients improve after discontinuation, although recovery may take months.
Does metronidazole interact with warfarin? ▾
Yes. Metronidazole inhibits the metabolism of S-warfarin and can raise the INR within days, increasing bleeding risk. According to the prescribing information, anticoagulated patients need an INR check within the first week of co-treatment and possibly a temporary warfarin dose reduction. The same caution applies to other coumarin anticoagulants such as acenocoumarol and phenprocoumon.
Sources
This page is compiled from the official prescribing information for Metronidazole. The links below open a search for that active ingredient in each register, so you always reach the current version of the label rather than a cached copy.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.