Metronidazole
ADMINISTRATION ROUTES:
IV, PO
ALTERNATIVE NAMES:
Flagyl, Trichozole
ICU INDICATIONS:
- Treatment of infections caused by susceptible organisms, including parasites
- Empirical cover where anaerobic organisms are suspected to be causative
PRESENTATION AND ADMINISTRATION:
PO:
Tablets:
Trichozole 200 mg tablets (white), Trichozole 400 mg tablets (yellow)
Suspension:
Flagyl-S oral suspension 200 mg/5 mL
Note: use suspension for NG administration
Suppository:
Flagyl suppository 500 mg
IV:
Infusion minibag 500 mg in 100 mL 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% dextrose, dextrose and sodium chloride
or the above with KCl 20-40 mmol per 1000 mL.
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:
500 mg TDS
PO:
400 mg TDS
Amoebiasis may require use up to 800 mg TDS. Consult Infectious Diseases service for advice
PR:
1 gm TDS
Convert to oral as early as possible. If rectal administration required beyond 3 days, reduce dose to 1 gm BD
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment
| GFR (ml/min) | DOSE |
|---|---|
| <20 | normal dose BD |
| 21-30 | dose as in normal renal function |
| >31-70 | dose as in normal renal function |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | normal dose BD |
| HD | dose as in normal renal function |
| CVVHDF | dose as in normal renal function |
DOSAGE IN PAEDIATRICS:
IV:
15 mg/kg stat then 7.5 mg/kg TDS
CLINICAL PHARMACOLOGY:
Metronidazole is a synthetic antibacterial compound. It 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:
- Bacteroides species including the Bacteroides fragilis group (B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B vulgatus) and Fusobacterium species
Anaerobic Gram-Positive Bacilli:
- Clostridium species
- Eubacterium
Anaerobic Gram-Positive Cocci:
- Peptococcus species
- Peptostreptococcus species
Parasites:
- Trichomonas vaginlais (causing urogenital trichomoniasis)
- Entamoeba histolytica (cuasing amoebiasis or amoebic dysentery)
CONTRAINDICATIONS:
- 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 characterised mainly by numbness or paraesthesia of an extremity, have been reported in patients treated with metronidazole
PRECAUTIONS:
General:
Patients with severe hepatic disease metabolise 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 IN 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, diarrhoea, and an unpleasant metallic taste
Haematopoietic:
Reversible neutropaenia (leukopaenia)
Dermatologic:
Erythematous rash and pruritus
Central Nervous System:
Headache, dizziness, syncope, ataxia, and confusion
Local Reactions:
Thrombophlebitis after IV infusion. This reaction can be minimised 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.