Metronidazole, marketed under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication.[3] It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.[3] It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis.[3] It is an option for a first episode of mild-to-moderate Clostridium difficile colitis if vancomycin or fidaxomicin is unavailable.[3][4] Metronidazole is available by mouth, as a cream, and intravenously.[3]

Common side effects include nausea, a metallic taste, loss of appetite, and headaches.[3] Occasionally seizures or allergies to the medication may occur.[3] Some state that metronidazole should not be used in early pregnancy while others state doses for trichomoniasis are safe.[5] It should not be used when breastfeeding.[5]

Metronidazole began to be commercially used in 1960 in France.[6] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[7] It is available in most areas of the world.[8] The pills are relatively inexpensive, costing between 0.01 and 0.10 USD each.[9][10] In the United States it is about 26 USD for ten days of treatment.[3]

Medical uses

A tube of metronidazole

Metronidazole is primarily used to treat: bacterial vaginosis, pelvic inflammatory disease (along with other antibacterials like ceftriaxone), pseudomembranous colitis, aspiration pneumonia, rosacea (topical), fungating wounds (topical), intra-abdominal infections, lung abscess, periodontitis, amoebiasis, oral infections, giardiasis, trichomoniasis, and infections caused by susceptible anaerobic organisms such as Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, and Prevotella species.[11] It is also often used to eradicate Helicobacter pylori along with other drugs and to prevent infection in people recovering from surgery.[11]

Metronidazole is bitter and so the liquid suspension contains metronidazole benzoate. This requires hydrolysis in the stomach and so maybe unsuitable in people with diarrhoea or feeding-tubes in the duodenum or jejunum.[12]

Bacterial vaginosis

Drugs of choice for the treatment of bacterial vaginosis include metronidazole and clindamycin. The treatment of choice for bacterial vaginosis in nonpregnant women include metronidazole oral twice daily for seven days, or metronidazole gel intravaginally once daily for five days, or clindamycin intravaginally at bedtime for seven days. For pregnant women, the treatment of choice is metronidazole oral three times a day for seven days. Data does not report routine treatment of male sexual partners.[13]


The 5-nitroimidazole drugs (metronidazole and tinidazole) are the mainstay of treatment for infection with Trichomonas vaginalis. Treatment for both the infected patient and the patient's sexual partner is recommended, even if asymptomatic. Therapy other than 5-nitroimidazole drugs is also an option, but cure rates are much lower.[14]


Oral metronidazole is a treatment option for giardiasis, however, the increasing incidence of nitroimidazole resistance is leading to the increased use of other compound classes.[15]


In the case of Dracunculus (guinea worm), metronidazole just eases worm extraction rather than killing the worm.[3]

C. difficile colitis

Initial antibiotic therapy for less-severe Clostridium difficile colitis (pseudomembranous colitis) consists of metronidazole, vancomycin, or fidaxomicin by mouth.[4] In 2017 the IDSA generally recommended vancomycin and fidazomicin over metronidazole.[4] Vancomycin by mouth has been shown to be more effective in treating people with severe C. difficile colitis.[16]

E. histolytica

Invasive colitis and extraintestinal disease including liver abscesses, pleuropulmonary infections, and brain abscesses can result from infection with Entamoeba histolytica. Metronidazole is widely used in patients with these infections.[medical citation needed]

Preterm births

Metronidazole has also been used in women to prevent preterm birth associated with bacterial vaginosis, amongst other risk factors including the presence of cervicovaginal fetal fibronectin (fFN). Metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women (selected by history and a positive fFN test) and, conversely, the incidence of preterm delivery was found to be higher in women treated with metronidazole.[17]

Adverse effects

Common adverse drug reactions (≥1% of those treated with the drug) associated with systemic metronidazole therapy include: nausea, diarrhea, weight loss, abdominal pain, vomiting, headache, dizziness, and metallic taste in the mouth. Intravenous administration is commonly associated with thrombophlebitis. Infrequent adverse effects include: hypersensitivity reactions (rash, itch, flushing, fever), headache, dizziness, vomiting, glossitis, stomatitis, dark urine, and paraesthesia.[11] High doses and long-term systemic treatment with metronidazole are associated with the development of leucopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity.[11] Common adverse drug reaction associated with topical metronidazole therapy include local redness, dryness and skin irritation; and eye watering (if applied near eyes).[11] Metronidazole has been associated with cancer in animal studies.[18]

Metronidazole may cause mood swings[citation needed]. Some evidence from studies in rats indicates the possibility it may contribute to serotonin syndrome, although no case reports documenting this have been published to date.[19][20]

Mutagenesis and carcinogenesis

Metronidazole is listed by the US National Toxicology Program (NTP) as reasonably anticipated to be a human carcinogen.[21] Although some of the testing methods have been questioned, oral exposure has been shown to cause cancer in experimental animals and has also demonstrated some mutagenic effects in bacterial cultures.[21][22] The relationship between exposure to metronidazole and human cancer is unclear.[21][23] One study [24][full citation needed] found an excess in lung cancer among women (even after adjusting for smoking), while other studies [25][full citation needed] found either no increased risk, or a statistically insignificant risk.[21] [26] Metronidazole is listed as a possible carcinogen according to the WHO International Agency for Research on Cancer.[27] A study in those with Crohn's disease also found chromosomal abnormalities in circulating lymphocytes in people treated with metronidazole.[22]

Stevens–Johnson syndrome

Metronidazole alone rarely causes Stevens–Johnson syndrome, but is reported to occur at high rates when combined with mebendazole.[28]

Drug interactions


Consuming alcohol while taking metronidazole has long been thought to have a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia, and shortness of breath.[29] Consumption of alcohol is typically advised against by patients during systemic metronidazole therapy and for at least 48 hours after completion of treatment.[11] However, some studies call into question the mechanism of the interaction of alcohol and metronidazole,[30][31][32] and a possible central toxic serotonin reaction for the alcohol intolerance is suggested.[19] Metronidazole is also generally thought to inhibit the liver metabolism of propylene glycol (found in some foods, medicines, and in many electronic cigarette e-liquids), thus propylene glycol may potentially have similar interaction effects with metronidazole.[citation needed]

Other drug interactions

It also inhibits CYP2C9, so may interact with medications metabolised by these enzymes (e.g. lomitapide, warfarin).[1]

Mechanism of action

Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by disrupting the DNA of microbial cells.[1] This function only occurs when metronidazole is partially reduced, and because this reduction usually happens only in anaerobic cells, it has relatively little effect upon human cells or aerobic bacteria.[33]


2-Methylimidazole (1) may be prepared via the Debus-Radziszewski imidazole synthesis, or from ethylenediamine and acetic acid, followed by treatment with lime, then Raney nickel. 2-Methylimidazole is nitrated to give 2-methyl-4(5)-nitroimidazole (2), which is in turn alkylated with ethylene oxide or 2-chloroethanol to give metronidazole (3):[34][35][36]

Synthesis of metronidazole.png

Veterinary use

Metronidazole is widely used to treat infections of Giardia in dogs, cats, and other companion animals, although it does not reliably clear infection with this organism and is being supplanted by fenbendazole for this purpose in dogs and cats.[37] It is also used for the management of chronic inflammatory bowel disease in cats and dogs.[38] Another common usage is the treatment of systemic and/or gastrointestinal clostridial infections in horses. Metronidazole is used in the aquarium hobby to treat ornamental fish and as a broad-spectrum treatment for bacterial and protozoan infections in reptiles and amphibians. In general, the veterinary community may use metronidazole for any potentially susceptible anaerobic infection. The U.S. Food and Drug Administration suggests it only be used when necessary because it has been shown to be carcinogenic in mice and rats, as well as the microbes for which it is prescribed, and resistance can develop.[39][40]


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