Metronidazole (INN) (IPA: ) is a nitroimidazole anti-infective drug used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. It is marketed by Sanofi-Aventis under the trade name Flagyl, and also by various generic manufacturers. Metronidazole is also used in the treament of the dermatological condition rosacea, where it is marketed by Galderma under the trade names Rozex and MetroGel.

Mode of action

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Metronidazole is selectively taken up by anaerobic bacteria and sensitive protozoal organisms because of the ability of these organisms to reduce metronidazole to its active form intracellularly. The nitro group of metronidazole is chemically reduced by ferredoxin (or ferredoxin-linked metabolic process) and the products are responsible for disrupting the DNA helical structure, thus inhibiting nucleic acid synthesis.

Indications

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Systemic metronidazole is indicated for the treatment of:

• Bacterial vaginosis due to Trichomonas vaginalis infection in both symptomatic patients as well as their asymptomatic sexual contacts; and due to Gardnerella or Mycoplasma hominis infection in symptomatic patients
• Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin, levofloxacin, or ceftriaxone
• Amoebic dysentery due to Entamoeba histolytica should be treated alone or in conjunction with iodoquinol or diloxanide furoate
• Hepatic abscess due to Entamoeba histolytica
• Anaerobic bacterial infections such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in intraabdominal abscess, peritonitis, empyema, pneumonia, aspiration pneumonia, lung abscess, diabetic foot ulcer, meningitis and brain abscess, bone and joint infections, septicemia, endometritis, tubo-ovarian abscess, or endocarditis
• Pseudomembranous colitis due to Clostridium difficile
• Helicobacter pylori eradication therapy (as part of a multi-drug regimen in peptic ulcer disease)
• Surgical prophylaxis for those undergoing potentially contaminated colorectal surgery and may be combined with neomycin
• Acute gingivitis and other dental infections (TGA approved, non-Food and Drug Administration (FDA) approved)
• Crohn's disease with colonic or perianal involvement (non-FDA approved)

Topical metronidazole is indicated for the treatment of rosacea, and has been used in the treatment of malodorous fungating wounds.Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3

Prevention of 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). A randomised controlled trial demonstrated that metronidazole was ineffective in preventing preterm delivery in high-risk pregnant women and, conversely, the incidence of preterm delivery was actually higher in women treated with metronidazole.Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, et al. A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG 2006;113(1):65-74. PMID 16398774

Adverse effects

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Common adverse drug reactions (≥1% of patients) associated with systemic metronidazole therapy include: nausea, diarrhoea, and/or metallic taste. 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/or paraesthesia.

High doses and/or long-term systemic treatment with metronidazole is associated with the development of furry black tongue, leukopenia, neutropenia, increased risk of peripheral neuropathy and/or CNS toxicity.

Metronidazole is listed by the International Agency for Research on Cancer (IARC) as a potential human carcinogen. Although some of the testing methods have been questioned, it has been shown to cause cancer in experimental animals.National Toxicology Program. Metronidazole. In: Report on carcinogens. 11th ed. Research Triangle Park (NC): U.S. Department of Health and Human Services. 2005 Aug 26; cited 2006 Jun 20. Available from: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf Nevertheless, it appears to have a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweighs the risk.

Common adverse drug reactions associated with topical metronidazole therapy include local redness, dryness, and/or skin irritation; and eye watering (if applied near eyes).

Interaction with alcohol

Co-administration of metronidazole and ethanol (alcohol) results, rarely, in a disulfiram-like reaction (nausea, vomiting, flushing, tachycardia). Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 24 hours after completion of treatment. However, the occurrence of this reaction in the clinical setting has recently been questioned by some authors.Williams CS, Woodcock KR. Do ethanol and metronidazole interact to produce a disulfiram-like reaction? Ann Pharmacother 2000;34(2):255-7. PMID 10676835Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP. Lack of disulfiram-like reaction with metronidazole and ethanol. Ann Pharmacother 2002;36(6):971-4. PMID 12022894

References

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External links

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Information from Pfizer website (PDF) ^*

Nitroimidazole antibiotics | Antiprotozoal agents | Dermatological preparations

Metronidazol | Métronidazole | Metronidazolo | Metronidazol | 甲硝唑