Metronidazole

Metronidazole

[1 vial $2.46]

ADMINISTRATION ROUTES:

  • IV, PO

ALTERNATIVE NAMES:

  • Flagyl, Metronidazole, Trichozole

ICU INDICATIONS:

  1. treatment of infections caused by susceptible organisms
  2. empirical cover where anaerobes are suspected to be causative

PRESENTATION AND ADMINISTRATION:

  • PO Tablets:
    Trichozole 200mg tablets (white), Trichozole 400mg tablets (yellow)
  • Suspension: Flagyl-S oral suspension 200mg/5ml
    Note: use suspension for NG administration
  • IV:
    Infusion minibag 500mg in 100ml solution
    Administer over 20-30 minutes
    Dilution is not generally recommended.
    For patients maintained on IV fluids, metronidazole infusion may be diluted to 1 in 5 or greater with appropriate volumes of the following solutions:
    Normal saline, 5% glucose, Glucose and sodium chloride, or the above with KCl 20-40mmol per 1000ml.
    Protect from direct sunlight.
    Prolonged exposure to light will cause darkening or solution.
    Precipitation may occur if refrigerated.
    Do not use solution is it is cloudy, coloured or precipitate is visible.

DOSAGE:

  • IV:
    500mg 8 hourly
  • PO:
    400mg 8 hourly

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

  • Dose in renal impairment [GFR (ml/min)]
    <20: normal dose every 12 hours
    21-30: dose as in normal renal function
    >31-70: dose as in normal renal function
  • Dose in renal replacement therapy
    CAPD: normal dose every 12 hours
    HD: dose as in normal renal function
    CVVHDF: dose as in normal renal function

DOSAGE IN PAEDIATRICS:

  • IV:
    15mg/kg stat then 7.5mg/kg 8 hourly

CLINICAL PHARMACOLOGY:

  • Metronidazole is a synthetic antibacterial compound. Metronidazole is active in vitro against most obligate anaerobes, but does not appear to possess any clinically relevant activity against facultative anaerobes or obligate aerobes.
    Against susceptible organisms, metronidazole is generally bactericidal at concentrations equal to or slightly higher than the minimal inhibitory concentrations.
    Metronidazole has been shown to have in vitro and clinical activity against the following organisms: Anaerobic Gram-Negative Bacilli, including:
    Bacteroides species including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B vulgatus) and Fusobacterium species.
    Anaerobic Gram-Positive Bacilli, including:
    Clostridium
    species and susceptible strains of Eubacterium.
    Anaerobic Gram-Positive Cocci, including:
    Peptococcus species and Peptostreptococcus species.

CONTRAINDICATIONS:

  1. hypersensitivity to metronidazole or other nitroimidazole derivatives

WARNINGS

  • Carcinogenicity
    Metronidazole has been shown to be carcinogenic in mice and rats
  • Convulsive Seizures and Peripheral Neuropathy
    Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with metronidazole.

PRECAUTIONS

  • General
    Patients with severe hepatic disease metabolize metronidazole slowly, with resultant accumulation of metronidazole and its metabolites in the plasma. Accordingly, for such patients, doses below those usually recommended should be administered cautiously.
  • Laboratory Tests:
    No tests in addition to routine ICU tests are required.
  • Drug/Laboratory Test Interactions:
    Metronidazole may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed.

IMPORTANT DRUG INTERACTIONS FOR THE ICU

  • Metronidazole has been reported to potentiate the anticoagulant effect of warfarin, resulting in a prolongation of prothrombin time. This possible drug interaction should be considered when metronidazole is prescribed for patients on this type of anticoagulant therapy.
  • The simultaneous administration of drugs that induce microsomal liver enzymes, such as phenytoin or phenobarbital, may accelerate the elimination of metronidazole, resulting in reduced plasma levels; impaired clearance of phenytoin has also been reported.
    Psychotic reactions have been reported in alcoholic patients who are using metronidazole and disulfiram concurrently. Metronidazole should not be given to patients who have taken disulfiram within the last 2 weeks.

ADVERSE REACTIONS

  • Gastrointestinal:
    Nausea, vomiting, abdominal discomfort, diarrhea, and an unpleasant metallic taste.
  • Hematopoietic:
    Reversible neutropenia (leukopenia).
  • Dermatologic:
    Erythematous rash and pruritus.
  • Central Nervous System:
    Headache, dizziness, syncope, ataxia, and confusion.
  • Local Reactions:
    Thrombophlebitis after IV infusion. This reaction can be minimized or avoided by avoiding prolonged use of indwelling IV catheters.
  • Other:
    Fever. Instances of a darkened urine have also been reported, and this manifestation has been the subject of a special investigation. Although the pigment which is probably responsible for this phenomenon has not been positively identified, it is almost certainly a metabolite of metronidazole and seems to have no clinical significance.

Critical Care Drug Manual

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