Zambian HIV Guidelines:: Metronidazole

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	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>

Metronidazole

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
03-18-2008

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

Intra-abdominal infections; skin and skin structure infections; bone and joint infections.
Bacterial septicemia; endocarditis (caused by Bacteroides spp.).
Gynecologic infections (endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection).
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 giardiasis, dracunculiasis, trichomoniasis, and amebiasis.
Periodontal disease.
Elective colorectal surgery (classified as contaminated or potentially contaminated.)
Bacterial vaginosis.

NON-FDA APPROVED USES

Colitis, antibiotic-associated (treatment).

FORMS

brand name	generic	Mfg	brand forms	cost*
Flagyl	Metronidazole	Pfizer and generic manufacturers	oral tablet 250 mg	$0.47
			oral tablet/cap 375 mg	$1.70
			oral tablet 500 mg	$1.14
			IV vial 500 mg	$2.08
Metrocream	Metronidazole	Galderma	topical cream 0.75% (45 g)	$70.37
MetroGel (Vaginal)	Metronidazole	3M Pharmaceuticals	topical gel 0.75% (70 g)	$79.26
MetroGel	Metronidazole	Galderma	topical gel 0.75% (1.5 oz)	$66.57
Flagyl ER	Metronidazole	Pfizer	oral extended release tab 750 mg	$10.96

*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 tid 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 tid or 250 mg PO qid x 10-14 d.
Bacterial vaginosis: 500 mg bid PO x 7d or Flagyl ER 750 mg PO once daily x 7d.
Trichomoniasis: single 2 gm x 1 dose or 500 mg PO bid x 7 d (alternative).
Amebiasis: 750 mg PO tid x 5-10 d.
Giardiasis: 250 mg PO tid 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

DRUG INTERACTIONS

Phenytoin: phenytoin levels may be increased.
Ethanol: nausea, vomiting, headache, abdominal cramps, and flushing. Acute of psychosis or confusional state may also occur (avoid co-administration). Alcohol should be avoided and disulfiram should be discontinued 2 wks prior to use of metronidazole.
Warfarin: INR may be increased.
Barbiturates: may decrease metronidazole levels.
RTV liquid: due to the alcohol content in the RTV liquid formulation, a disulfiram-like reaction may occur (avoid co-administration).
LPV/r liquid: disulfiram-like reaction may occur due to the alcohol content in the LPV/r liquid formulation (avoid co-administration).
TPV capsule: due to the alcohol content in the TPV capsule formulation, a disulfiram-like reaction may occur (avoid co-administration).
Disulfiram: contraindicated
Lithium: lithium levels may be increased.

SPECTRUM

Trichomonas vaginalis; Giardia lambia; Entamoeba histolytica

Detailed Spectrum of Activity

PHARMACOLOGY

Pharmacology

COMMENTS

Metronidazole is the 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 C. difficile- associated colitis with comparable rates of response and relapse, but most experts recommend oral vancomycin in severe disease.

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