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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Metronidazole

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
12-07-2010

Zambia Specific Information

  • Available formulation in Zambia: Injection: 500 mg in 100 ml vial. Oral liquid: 200 mg (as benzoate)/5 ml. Tablet: 200-500 mg.
  • C. difficile: metronidazole 800 mg q8h x 10 d (withdraw offending antibiotic if possible)
  • Amoebic dysentery (E. histolytica): metronidazole 800 mg q8h x 10 d
  • Giardiasis (G. lamblia): metronidazole 400 mg q8h x 10 d
  • Pyogenic liver abscess: metronidazole 400 mg PO q8h plus benzylpenicillin and gentamicin
  • Amoebic liver abscess: metronidazole 400 mg PO q8h
  • Dental abscess and/or severe gingivitis in PCN allergic pts: metronidazole 200 mg q8h (plus erythromycin)
  • Trichomoniasis: metronidazole 2000 mg x 1 or 250 mg tid x 7d if pregnant.

REFERENCES

Zambia Information Author: Paul A. Pham, Pharm. D.

INDICATIONS

FDA

  • Anaerobic infections: Intra-abdominal infections; skin and skin structure infections and bone and joint infections 
  • Bacterial septicemia; endocarditis (caused by Bacteroides spp.).
  • Gynecologic infections (endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection) caused by anaerobes
  • Lower respiratory tract infections (in combination with another agent with activity against microaerophilic Streptococcus).
  • Adjunct treatment for gastritis and duodenal ulcer associated with Helicobacter pylori.
  • CNS infections (meningitis and brain abscess).
  • Treatment of acute intestinal amebiasis and amebic liver abscess.
  •  Treatment of symptomatic and asymptomatic Periodontal disease.trichomoniasis.
  •  Bacterial vaginosis(vaginal gel) 
  •    Rosacea (topical gel)
NON-FDA APPROVED USES

  • Colitis, antibiotic-associated (treatment).
  • Periodontal disease. 
  • Elective colorectal surgery prophylaxis (classified as contaminated or potentially contaminated)
  • Treatment of giardiasis and dracunculiasis

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
Flagyl and genericMetronidazole Pfizer and generic manufacturersoral
tablet
250 mg
 $0.48
      oral
cap
375 mg
 $5.24
      oral
tablet
500 mg
$0.72 
      IV
vial
500 mg
 $2.58
Metrocream; Metrolotion MetronidazoleGalderma topical
cream
0.75% (45 g)
$249.40 
      topical
lotion
0.75% (70 g)
$281.40/2oz 
MetroGel (Vaginal) Metronidazole Prasco topical
gel
0.75% (70 g)
$36.00 
MetroGel  and generic Metronidazole Galderma; Tarotopical
gel
0.75% (1.5 oz)
$71.15
      topical
gel
1% (60 g)
$193.20
Flagyl ER MetronidazolePfizeroral
extended release tab
750 mg
$12.70

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • Susceptible anaerobic infections: 250-500 mg PO 3 times daily or 500 mg IV q6h (manufacturer's recommendation) or consider 0.5-1 gm PO or IV q12h (based on PK data).
  • C. difficile colitis: 500 mg PO 3 times daily or 250 mg PO 4 times per day x 10-14 d.
  • Bacterial vaginosis: 500 mg twice-daily PO x 7d or Flagyl ER 750 mg PO once-daily x 7d.
  • Trichomoniasis: single 2 gm x 1 dose or 500 mg PO twice-daily x 7 d (alternative).
  • Amebiasis: 750 mg PO 3 times daily x 5-10 d.
  • Giardiasis: 250 mg PO t3 times daily x 5-10 d.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Usual dose.

DOSING IN HEMODIALYSIS

Usual regimen.

DOSING IN PERITONEAL DIALYSIS

Usual regimen.

DOSING IN HEMOFILTRATION

No data. Usual dose likely.

ADVERSE DRUG REACTIONS

COMMON

  • GI intolerance
  • Metallic taste
  • Headache
  • Dark urine (harmless)
OCCASIONAL

  • Peripheral neuropathy (with prolonged use-usually reversible)
  • Phlebitis at injection sites
  • Disulfiram-like reaction with alcohol
  • Insomnia
  • Stomatitis
RARE

  • Seizures
  • Encephalopathy, aseptic meningitis, optic neuropathy, dysarthria
  • Stevens-Johnson Syndrome

DRUG INTERACTIONS

Alcohol (including drugs co-formulated with alcohol) should be avoided, and disulfiram should be discontinued 2 wks prior to use of metronidazole. Nausea, vomiting, headache, abdominal cramps, and flushing can occur. Acute of psychosis or confusional state have been reported.

Drug-to-Drug Interactions

Drug-to-Drug Interaction

DrugEffect of InteractionRecommendations/Comments
Ritonavir  Alcohol content in the RTV liquid formulation may cause a disulfiram-like reaction Avoid co-administration.
Lopinavir/ritonavir  Alcohol content in the LPV/r liquid formulation may cause a disulfiram-like reaction Avoid co-administration.
Tipranavir  Alcohol content in the TPV caps formulation may cause a disulfiram-like reaction. Avoid co-administration.
Barbiturates May decrease metronidazole serum concentrations. Monitor for clinical response to metronidazole with co-administration.
Lithium Lithium serum concentrations may be increased. Monitor lithium serum concentrations closely with co-administration.
Phenytoin Phenytoin serum concentrations may be increased. Monitor phenytoin serum concentrations with co-administration.
Warfarin INR may be increased. Monitor INR closely with co-administration.

SPECTRUM

Trichomonas vaginalis; Giardia lambia; Entamoeba histolytica. Active against virtually all anaerobes with exception of actinomyces, Propionibacterium acnes, and Lactobacillus spp.

Detailed Spectrum of Activity

RESISTANCE

  • H. pylori resistance rate up to 20-30%. High metronidazole doses (1.5g/d) may overcome resistance.

PHARMACOLOGY

Pharmacology

COMMENTS

Metronidazole is gold standard anti-anaerobic agent. Active against virtually all anaerobes with exception of actinomyces, Propionibacterium acnes, and Lactobacillus spp. Additional antibiotic coverage needed for combined aerobes/anaerobes infections (metronidazole only active against anaerobes). First line agent for giardiasis, trichomoniasis, and amebiasis. Oral vancomycin and metronidazole are equivalent in the treatment of mild C. difficile colitis with comparable rates of response and relapse, but most experts recommend oral vancomycin in moderate to severe disease.

REFERENCES

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