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metronidazole (Flagyl, MetroGel)

Tradename: Flagyl. Indications: - bacterial infections caused by anaerobic bacteria (anaerobic infections) - intra-abdominal infections - antibiotic-associated pseudomembranous colitis - diverticulosis - bacterial peritonitis - abdominal abscess - hepatic abscess - fistulas & abscesses associated with Crohn's disease - urogenital infections - tubo-ovarian abscess - pelvic inflammatory disease - endometritis - brain abscess [7] - endocarditis - lower respiratory tract infection - periodontitis - skin or soft tissue infections - diabetic foot infection [7] - infectious arthritis [7] - protozoan infections - Trichomonas vaginalis - Giardia lamblia - Entamoeba histolytica - Balantidium coli - Dracunculus medinensis - topical agent for treatment of rosacea - intravaginal agent for treatment of bacterial vaginosis - used in combination with other agents for treatment of Helicobacter pylori gastritis - empiric treatment for fever of unknown origin [7] - prophylaxis for perioperative infection - gynecologic surgery [7] -postoperative infection [7] Contraindications: - use in combination with beta lactam/beta-lactamase inhibitor combination (i.e. Zosyn, Unasyn, Augmentin) Caution: avoid during pregnancy. Dosage: 1) Trichomonas: a) 2 g PO single dose b) 250 mg PO TID for 7 days 2) Giardia: 250 mg PO TID for 5 days 3) Clostridium difficile: 250-500 mg PO TID for 10 days 4) Entamoeba histolytica: 750 mg PO TID for 10 days 5) anaerobic infection: a) 30 mg/kg/day PO/IV divided every 6-8 hours b) max: 4 g/day Tabs: 250 & 500 mg. Topical agent (MetroGel, Metrocream) 0.75%: apply BID Vaginal: applicator BID or QHS Topical: 0.75% (gel: 30 g, ointment: 45 g) Vaginal: 0.75% (70 g) with 5 g applicator Powder for injection: 500 mg/100 mL (as HCl) Dosage adjustment in renal failure: creatinine clearance dosage 10-50 mL/min 100% < 10 mL/min* 50% * dose after hemodialysis Antimicrobial activity: Anaerobes - Bacteroides fragilis - Bacteroides melaninogenicus - Clostridium difficile - Clostridium species - Peptostreptococcus species Pharmacokinetics: 1) well absorbed orally 2) peak serum concentration in 1-2 hours 3) well distributed in most fluids & tissues, including abscesses & bone 4) good penetration into CSF 5) crosses placenta & appears in breast milk 6) protein binding < 20% 7) metabolized by the liver (30-60%) 8) 20% eliminated unchanged in the urine 9) 1/2life is 7-9 hours, increased with liver failure (7-21 hours ESRD) 10) dose must be reduced in severe liver disease Adverse effects: 1) common (> 10%) - nausea/vomiting, dizziness, headache, diarrhea, loss of appetite 2) less common (1-10%) - peripheral neuropathy, seizures 3) uncommon (< 1%) - ataxia, hypersensitivity, leukopenia, pancreatitis, thrombophlebitis, vaginal candidiasis, taste disturbance, dry mouth, furry tongue, dark urine 4) other - metallic taste with rapid IV infusion - mental status changes (rare) - colitis (rare) - 2-fold increased risk of miscarriage [8] Drug interactions: 1) inhibits cyt P450 2C9 & 3A4 [6] -> may increase levels of drugs metabolized by cyt P450 2C9 & 3A4 (including warfarin) 2) agents that increase metabolism of metronidazole a) phenobarbital b) hydantoin 3) severe disulfiram-like reaction with alcohol 4) cimetidine decreases metabolism of metronidazole 5) metronidizole may diminish clearance of phenytoin, quinidine, cisapride & lithium [6] Mechanism of action: - reduced by microbial nitro-reductase to form reactive intermediate that disrupts bacterial DNA & RNA synthesis

Interactions

drug interactions

Related

cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)

General

antiprotozoal agent nitroimidazole

Properties

MISC-INFO: elimination route LIVER KIDNEY protein-binding <20% 1/2life 7-9 HOURS pregnancy-category B <1st trimester> safety in lactation ? elimination by hemodialysis + peritoneal dialysis +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 166
  3. Sanford Guide to antimicrobial therapy 1997
  4. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  5. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  6. Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
  7. Deprecated Reference
  8. Muanda FT, Sheehy O, Berard A Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ 2017 May 1;189:E625-33 PMID: 28461374 http://www.cmaj.ca/content/189/17/E625.full.pdf+html

Component-of

bismuth subcitrate/metronidazole/tetracycline bismuth subsalicylate/metronidazole/tetracycline brilliant green/cellulose/metronidazole Helidac kit (triple therapy) metronidazole/subsalicylate/tetracycline (Pylera) metronidazole/tetracycline