Metronidazole
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Metronidazole
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| Systematic (IUPAC) name | |
| 2-(2- methyl- 5-nitro- 1H- imidazol- 1-yl) ethanol | |
| Identifiers | |
| CAS number | |
| ATC code | A01 , D06, G01, J01, P01, QP51 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C6H9N3O3 |
| Mol. mass | 171.15 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 100% (oral) 59–94% (rectal) |
| Metabolism | Hepatic |
| Half life | 6–7 hours |
| Excretion | Renal (60-80%), biliary (6–15%) |
| Therapeutic considerations | |
| Pregnancy cat. |
B2 (Au) |
| Legal status | |
| Routes | Oral, topical, rectal, IV, vaginal |
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).
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[edit] Treatment
Metronidazole is selectively taken up by anaerobic bacteria and sensitive protozoa.
[edit] Indications
Systemic metronidazole is indicated for the treatment of:
[edit] Bacterial
- 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
- 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
[edit] Protozoal
- Vaginitis due to Trichomonas vaginalis infection[1] in both symptomatic patients as well as their asymptomatic sexual contacts - always consult the GP and contact all previous partners
- 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
- 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 to the bowl
[edit] Nonspecific
- Prophylaxis for those undergoing potentially contaminated colorectal surgery or appendectomies 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
- Topical metronidazole is indicated for the treatment of rosacea, and in the treatment of malodorous fungating wounds.[2]
[edit] Prevention of preterm births
Latest paper studying Metronidazole found "Metronidazole therapy before 32 weeks was associated with an increased risk of preterm birth", possibly as a result of "changes in the vaginal flora... seen with vaginal clindamycin or oral metronidazole therapy." [3]
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.[4].
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.[5]
[edit] 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.[2]
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.[2]
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.[6]. Yet, metronidazole was shown to be safe in humans.[7] Available from: http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s112metr.pdf It appears to have a fairly low potential for cancer risk and under most circumstances the benefits of treatment outweigh the risk. Metronidazole is banned in the EU for veterinary use in the feed of animals. [8]
Common adverse drug reactions associated with topical metronidazole therapy include local redness, dryness, and/or skin irritation; and eye watering (if applied near eyes).[2]
[edit] Interaction with alcohol
Consuming ethanol (alcohol) while using metronidazole has long been thought to have a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the skin, tachycardia (accelerated heart rate), and shortness of breath,[9] however there are studies calling that notion into question. [1] Consumption of alcohol should be avoided by patients during systemic metronidazole therapy and for at least 48 hours after completion of treatment.[2] However, the mechanism of this reaction in the clinical setting has recently been questioned by some authors,[10][11] and a possible central toxic serotonin reaction for the alcohol intolerance suggested.[12]
[edit] Stevens-Johnson Syndrome with Mebendazole
Metronidazole alone rarely causes Stevens-Johnson syndrome but is reported to occur at high rates when combined with Mebendazole.[13]
[edit] References
- ^ Cudmore SL, Delgaty KL, Hayward-McClelland SF, Petrin DP, Garber GE (October 2004). "Treatment of infections caused by metronidazole-resistant Trichomonas vaginalis". Clin. Microbiol. Rev. 17 (4): 783–93, table of contents. doi:. PMID 15489348. PMC: 523556. http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=15489348.
- ^ a b c d e Rossi, Simone(ed). (2006). Rossi S. ed. Australian Medicines Handbook 2006. Australian Medicines Handbook Pty Ltd, Adelaide. ISBN 0-9757919-2-3. OCLC 224831213.
- ^ Carey JC, Klebanoff MA. (April 2005). "Is a change in the vaginal flora associated with an increased risk of preterm birth?". Am J Obstet Gynecol. 192 (4): 1341–6. doi:.
- ^ 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:. PMID 16398774.
- ^ Lamont RF (2005). "Can antibiotics prevent preterm birth—the pro and con debate". BJOG 112(suppl): 67–73. doi:. 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]
- ^ www.pfizer.com/pfizer/download/uspi_flagyl_375.pdf
- ^ http://www.emea.europa.eu/pdfs/vet/mrls/017396en.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:.
- ^ Williams CS, Woodcock KR (2000). "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?". Ann Pharmacother 34 (2): 255–7. doi:. PMID 10676835."the authors of all the reports presumed the metronidazole-ethanol reaction to be an established pharmacologic fact. None provided evidence that could justify their conclusions"
- ^ 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:. 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:. PMID 17963129.
- ^ Chen KT, Twu SJ, Chang HJ, Lin RS. (2003). "Outbreak of Stevens-Johnson syndrome/toxic epidermal necrolysis associated with mebendazole and metronidazole use among Filipino laborers in Taiwan." Am J Public Health 93(3): 489-492, PMID 12604501, Full text at PMC: 1447769.
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