metronidazole (Flagyl, MetroGel)
Jump to navigation
Jump to search
Introduction
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
- brain abscess[7]
- endocarditis
- lower respiratory tract infection
- periodontitis
- skin or soft tissue infections
- infectious arthritis[7]
- intra-abdominal infections
- protozoan infections
- 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
Contraindications
- use in combination with beta lactam/beta-lactamase inhibitor combination (i.e. Zosyn, Unasyn, Augmentin)
Caution: avoid during pregnancy.
Dosage
- Trichomonas:
- Giardia: 250 mg PO TID for 5 days
- Clostridium difficile: 250-500 mg PO TID for 10 days
- Entamoeba histolytica: 750 mg PO TID for 10 days
- anaerobic infection:
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
Table
| creatinine clearance | dosage |
|---|---|
| 10-50 mL/min | 100% |
| < 10 mL/min* | 50% |
* dose after hemodialysis
Pharmacokinetics
- well absorbed orally
- peak serum concentration in 1-2 hours
- well distributed in most fluids & tissues, including abscesses & bone
- good penetration into CSF
- crosses placenta & appears in breast milk
- protein binding < 20%
- metabolized by the liver (30-60%)
- 20% eliminated unchanged in the urine
- 1/2life is 7-9 hours, increased with liver failure (7-21 hours ESRD)
- dose must be reduced in severe liver disease
elimination via liver
elimination via kidney
protein binding = <20 %
1/2life = 7-9 hours
elimination by hemodialysis = +
elimination by peritoneal dialysis = +
Antimicrobial activity
- Bacteroides fragilis
- Bacteroides melaninogenicus
- Clostridium difficile
- Clostridium species
- Peptostreptococcus species
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncommon (< 1%)
- ataxia, hypersensitivity, leukopenia, pancreatitis, thrombophlebitis, vaginal candidiasis, taste disturbance, dry mouth, furry tongue, dark urine
- other
- metallic taste with rapid IV infusion
- mental status changes (rare)
- colitis (rare)
- 2-fold increased risk of miscarriage[8]
Drug interactions
- inhibits cyt P450 2C9 & 3A4[6]
- may increase levels of drugs metabolized by cyt P450 2C9 & 3A4 (including warfarin)
- agents that increase metabolism of metronidazole
- severe disulfiram-like reaction with alcohol
- cimetidine decreases metabolism of metronidazole
- 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
More general terms
Additional terms
Component of
- brilliant green/cellulose/metronidazole
- bismuth subcitrate/metronidazole/tetracycline
- bismuth subsalicylate/metronidazole/tetracycline
- metronidazole/tetracycline
- Helidac kit (triple therapy)
- metronidazole/subsalicylate/tetracycline (Pylera)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 166
- ↑ Sanford Guide to antimicrobial therapy 1997
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 6.0 6.1 6.2 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Deprecated Reference
- ↑ 8.0 8.1 Muanda FT, Sheehy O, Berard A Use of antibiotics during pregnancy and risk of spontaneous abortion. CMAJ 2017 May 1;189:E625-33 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28461374 <Internet> http://www.cmaj.ca/content/189/17/E625.full.pdf+html