Metronidazole
Metronidazole (INN) (pronounced /mɛtrəˈnaɪdəzoʊl/) is a nitroimidazole anti-infective medication used mainly in the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. It is marketed by Pfizer under the trade name Flagyl in the US, while Sanofi-Aventis markets metronidazole globally under the same tradename, Flagyl, and also by various generic manufacturers, who sell it at a lower price. Metronidazole is also used as a gel preparation in the treatment of the dermatological conditions such as rosacea (Rozex and MetroGel by Galderma) and fungating tumours (Anabact, Cambridge Healthcare Supplies).
Metronidazole is a prodrug. It is converted in anaerobic organisms by the redox enzyme pyruvate-ferredoxin oxidoreductase. The nitro group of metronidazole is chemically reduced by ferredoxin (or a ferredoxin-linked metabolic process) and the products are responsible for disrupting the DNA helical structure, thus inhibiting nucleic acid synthesis.
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.
Indications
Systemic metronidazole is indicated for the treatment of:
- Vaginitis due to Trichomonas vaginalis (protozoal) infection in both symptomatic patients as well as their asymptomatic sexual contacts - always consult the GP and contact all previous partners
- Bacterial vaginosis, commonly associated with overgrowth of Gardnerella species and coinfective anerobes (Mobiluncus, Bacteroides), in symptomatic patients
- Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin, levofloxacin, or ceftriaxone
- Protozoal infections due to Entamoeba histolytica (Amoebic dysentery or Hepatic abscesses), and Giardia lamblia (Giardiasis) should be treated alone or in conjunction with iodoquinol or diloxanide furoate
- Anaerobic bacterial infections such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in intra-abdominal 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
- 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)- believed to be more effective in combination with ciprofloxacin
- With amphotericin B and certain other drugs, it is used as an adjunct in the attempted treatment of primary amoebic meningoencephalitis caused by Naegleria fowleri infection
Topical metronidazole is indicated for the treatment of rosacea, and in the treatment of malodorous fungating wounds.[1]
Prevention of preterm births
Latest paper studying Metronidazole found "Metronidazole therapy before 32 weeks was associated with an increased risk of preterm birth" "Changes in the vaginal flora may explain the increased risk of preterm birth seen with vaginal clindamycin or oral metronidazole therapy." ref: Carey JC, Klebanoff MA.Is a change in the vaginal flora associated with an increased risk of preterm birth?Am J Obstet Gynecol. 2005 Apr;192(4):1341-6.
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.[2]
Lamont has argued that Metronidazole is not the right antibiotic to administer in these circumstances and was often administered too late to be of use. Clindamycin administered early in the second trimester to women who test positive for bacterial vaginosis seems to be more effective.[3]
Adverse effects
Common adverse drug reactions (≥1% of patients) associated with systemic metronidazole therapy include: nausea, diarrhea, and/or 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/or paraesthesia.[1]
High doses and/or long-term systemic treatment with metronidazole is associated with the development of black hairy tongue, leukopenia, neutropenia, increased risk of peripheral neuropathy and/or CNS toxicity.[1]
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.[4] Nevertheless, it appears to have a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweigh 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).[1]
Interaction with alcohol
Consuming ethanol (alcohol) while using metronidazole causes a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia (accelerated heart rate), and shortness of breath.[5] Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 48 hours after completion of treatment.[1] However, the mechanism of this reaction in the clinical setting has recently been questioned by some authors,[6][7] and a possible central toxic serotonin reaction for the alcohol intolerance suggested.[8]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Rossi, Simone(ed). (2006). Rossi S. ed.. Australian Medicines Handbook 2006. Australian Medicines Handbook Pty Ltd, Adelaide. ISBN 0-9757919-2-3. OCLC 224831213.
- ↑ Shennan A, Crawshaw S, Briley A, Hawken J, Seed P, Jones G, et al. (2006). "A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study". BJOG 113 (1): 65–74. doi:10.1111/j.1471-0528.2005.00788.x. PMID 16398774.
- ↑ Lamont RF (2005). "Can antibiotics prevent preterm birth—the pro and con debate". BJOG 112(suppl): 67–73. doi:10.1111/j.1471-0528.2005.00589.x. PMID 15715599.
- ↑ National Toxicology Program. Metronidazole. In: Report on carcinogens. 11th ed. Research Triangle Park (NC): U.S. Department of Health and Human Services. [updated 2005 Aug 26; cited 2006 Jun 20]. Available from: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf
- ↑ Stephen J Cina, Roger A Russell, Sandra E Conradi (1996). "Sudden death due to metronidazole/ethanol interaction". American Journal of Forensic Medical Pathology 17 (4): 343–346. doi:10.1097/00000433-199612000-00013.
- ↑ Williams CS, Woodcock KR (2000). "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?". Ann Pharmacother 34 (2): 255–7. doi:10.1345/aph.19118. PMID 10676835.
- ↑ Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP (2002). "Lack of disulfiram-like reaction with metronidazole and ethanol". Ann Pharmacother 36 (6): 971–4. doi:10.1345/aph.1A066. PMID 12022894.
- ↑ Karamanakos PN, Pappas P, Boumba VA, et al (2007). "Pharmaceutical agents known to produce disulfiram-like reaction: effects on hepatic ethanol metabolism and brain monoamines". Int. J. Toxicol. 26 (5): 423–32. doi:10.1080/10915810701583010. PMID 17963129.
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