Chemicals / Complex Chemical Agents/ Chemical:

Metronidazole (with special reference to Hedgehogs, Elephants, Lagomorphs, Ferrets and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Antibiotic agent active against anaerobic bacteria and against protozoa. (B263)

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Names and Formulae
Type Nitroimidazole antimicrobial agent. (B201.1.w1)Antiprotozoal, anthelmintic and antibiotic. (W324)
Alternative Names "Flagyl, Metizol; Metric 21; Protostat; 2-Methyl-5-nitroimidazole-1-ethanol; 1-(beta-ethylol)-2-methyl-5-nitro-3-azapyrrole; 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole; 2-methyl-1-(2-hydroxyethyl)-5-nitroimidazole; acromona; anagiardil; atrivyl; bayer 5360; Bexon; Clont; CONT; danizol; deflamon-wirkstoff; efloran; elyzol; entizol; Eumin; flagemona; flagesol; flagil; flegyl; giatricol; giniflavir; 1-(beta-hydroxyethyl)-2-methyl-5-nitroimidazole; 1-hydroxyethyl-2-methyl-5-nitroimidazole; 1-(2-hydroxy-1-ethyl)-2-methyl-5-nitroimidazole; Klion; meronidal; 2-methyl-3-(2-hydroxyethyl)-4-nitroimidazole; metronidaz; metronidazol; metronidazolo; monagyl; Nalox; neo-tric; NIDA; novonidazol; orvagil; rp 8823; sanatrichom; sc 10295; takimetol; trichazol; trichex; trichocide; trichomol; trichomonacid 'pharmachim'; trichopal; trichopol; tricocet; tricom; tricowas b; trikacide; trikamon; trikojol; trikozol; trivazol; trimeks; vagilen; vagimid; vertisal; Flagyl 375; 2-Methyl-5-nitro-1-imidazoleethanol; Gineflavir; Methyl-5-nitroimidazole-1-ethanol; Metryl; Satric; Metrogel; Metrogyl; Metrozine; Rozex; METRONIDAZOLE USP." (W324)
Chemical Formula C6H9N3O3 (W324)
Chemical Structure (B135.54.w54)
Molecular Weight 171.1554. (W324)
Related Chemicals --

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Physical Properties / Chemistry
Appearance
  • White to pale-yellow crystalline powder or crystals. (B263, W324)
Melting point --
Boiling point --
Density --
Water solubility
  • <0.1 g/100 mL at 20C. (W324)
  • Metronidazole base: sparingly soluble. (B263)
  • Metronidazole hydrochloride: very soluble. (B263)
Other solubility
  • Metronidazole base: sparingly soluble in alcohol. (B263)
Acid/Base

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Pharmacology & General Information
Pharmacology
  • Against anaerobic bacteria: mode of action is not properly understood. Following take-up by anaerobic bacteria it is reduced to a polar compound which is believed to disrupt DNA and nucleic acid synthesis. (B263)
    • Chemically reduced by ferredoxin or ferredoxin-linked metabolic processes, with the reduction products apparently reacting with various intracellular macromolecules to give the bactericidal effect. (B135.54.w54)
  • Against protozoa including amoebae and Trichomonas spp.: mechanism of action is not understood. (B263)
  • Known to have some inhibitive actions on cell-mediated immunity. (B263)
  • Radiosensitising effect on tumour cells may involve interaction with free radicals; it appears to be dependant on relative hypoxia in the tumour cells. (B135.54.w54)
Storage / Stability
  • Store both tablets and powder for injection below 30C; protect from light. (B263)
  • Store injection at room temperature, protect from freezing; protect from light. (B263)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26)

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Therapeutic Information

Uses/Indications
Activity
  • Bactericidal against most Gram-negative and many Gram-positive anaerobic bacteria. (B135.54.w54, B201.1.w1)
  • Active against most obligate anaerobic bacteria such as Bacteroides spp. (including Bacteroides fragilis), Fusobacterium spp., Veillonella spp., Clostridium spp., Peptococcus and Peptostreptococcus. (B263)
  • Active against Serpulina (Treponema) hyodysenteriae. (B201.1.w1)
  • Active against protozoa including amoebae such as Entamoeba histolica (mainly against trophozoites rather than encysted forms), Trichomonas spp, Balantidium coli, Giardia. (B135.54.w54, B263)
  • Radiosensitising effect on tumour cells. (B135.54.w54)
Appropriate Use
  • Dogs and cats: used in treatment of enteric and systemic anaerobic bacterial infections. (B263); including for gingivitis and empyema. B201.1.w1
  • Dogs and cats: used in the treatment of Giardia, Trichomoniasis and Balantidium coli infections. (B201.1.w1, B263)
  • Horses: used for the treatment of anaerobic bacterial infections. (B263)
  • Topical irrigation of wounds (using injectable solution). (B201.1.w1)
  • In the treatment of hepatic encephalopathy (controls blood-ammonia concentrations by activity against urease-positive anaerobes producing ammonia in the intestines). B201.1.w1
Limitations
  • Actinomyces spp. are frequently resistant to metronidazole. (B263)
  • Activity against aerobic bacteria is negligible therefore concurrent use of a drug with activity against aerobic bacteria is commonly required to treat mixed (aerobic/anaerobic) infections. (B201.1.w1)
  • No apparent significant effect against facultative anaerobes. B135.54.w54
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Following oral administration this drug is well absorbed. (B201.1.w1, B263)
  • Peak levels about one hour after administration. (B263)

Bioavailability:

  • Dogs high but variable (50-100%); enhanced by administration with food. (B263)
  • Horse 57-100% average about 80%.
  • Humans: absorption delayed by administration with food. (B263)
Distribution
  • Lipophilic; widely distributed by diffusion. (B135.54.w54, B263)
  • Distributed to most tissues and fluids including bone, abscesses and necrotic tissue, , central nervous system and cerebrospinal fluid, seminal fluid, milk. (B135.54.w54, B201.1.w1, B263)
  • Concentration within cells rapidly approaches extracellular concentration. B135.54.w54
Plasma Protein binding / Storage
  • Humans: less than 205 plasma protein-bound. (B263)
Elimination Route
  • Mainly metabolised in the liver using several pathways. (B263)
  • Elimination of both unchanged drug and of metabolites occurs in the faeces and urine. (B263)
Elimination half-life / Clearance Rate Plasma clearance is decreased in individuals with impaired hepatic function. B135.54.w54

Elimination half-life:

  • Humans: 6-8 hours. (B263)
  • Dogs: 4-5 hours. (B263)
  • Horses: 2.9-4.3 hours. (B263)
Drug Interactions
  • Use of metronidazole in patients taking anticoagulant such as warfarin may result in an increased prothrombin time: concurrent use should be avoided if possible and if such use is necessary, monitoring should be intensified. (B263)
  • Rate of metronidazole metabolisation may be increased and therefore blood levels decreased if used concurrently with phenobarbital or phenytoin. (B263)
  • Rate of metronidazole metabolisation may be decreased if used concurrently with cimetidine; likelihood of dose-related side-effects may be increased. (B263)
  • Intake of alcohol in an individual receiving metronidazole may induce a disulfiram-like reaction with nausea, vomiting, cramps etc. (B263)
  • Reported physical incompatibility of metronidazole ready-to-use solutions for injection with (or data conflicts): aztreonam, cefamandole naftate, dopamine hydrochloride. (B263)
  • Reported physical compatibility of metronidazole ready-to-use solutions for injection with: amikacin sulphate, aminophylline, carbenicilin disodium, cefazolin sodium, cefotaxime sodium, cefoxitin sodium, cefuroxime sodium, cephalothin sodium, chloramphenicol sodium succinate, clindamycin phosphate, disopyramide phosphate, gentamicin sulphate, heparin sodium, hydrocortisone sodium succinate, hydromorphone hydrochloride, magnesium sulphate, meperidine hydrochloride, morphine sulphate, moxalactam disodium, multielectrolyte concentrate, multivitamins, netilmicin sulphate, penicillin G sodium, tobramycin sulphate. (B263)

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Administration
Formulations available
  • Metronidazole base as tablets and as a solution for intravenous injection.(B263)
  • Metronidazole hydrochloride as injectable powder for reconstitution. (B263)
Doses / Administration Routes / Frequencies In the treatment of trichomoniasis or giardiosis:
  • Dogs, cats, birds: 20 mg/kg daily, orally or subcutaneous injection. (B201.1.w1)

In the treatment of hepatic encephalopathy:

  • Dog: 10-15 mg/kg oral two to three times daily. (B201.1.w1)
  • Cat: 7.5 mg/kg oral twice daily. (B201.1.w1)

Erinaceus europaeus - West European Hedgehog:

  • 40 mg/kg subcutaneous once daily. (D93)
  • Metronidazole 25 mg/tablet / Spiramycin 46.9 mg/tablet: 1/2 tablet per kg oral once daily. For dental disease. (D93)

Atelerix albiventris - Four-toed hedgehog:

  • 25 mg/kg oral every 12 hours. For parasitic infections. (J204.59.w1)

"Hedgehog" (species not distinguished between Erinaceus europaeus - West European Hedgehog or Erinaceus europaeus - West European Hedgehog):

  • 25 mg/kg orally every 12 hours for five days. For flagellates. (B267)
  • 25 mg/kg oral, twice daily for five days. For protozoal infections. (B150.w1)
  • 25 mg/kg oral twice daily. For flagellate infections. (J34.24.w1)

Elephants:

The following information is taken with permission directly from the Elephant Care International website (W580.Aug2005.w23):

Elephants:

a) 15 mg/kg per rectum (Gulland and Carwardine, 1987)

Elephant References:

a) Gulland,F.M. and Carwardine,P.C. 1987. Plasma metronidazole levels in an Indian elephant (Elephas maximus) after rectal administration. Veterinary Record 120:440 
Summary: A female Asian elephant was treated for a mixed aerobic and anaerobic tusk sulcus infection with 15/kg metronidazole administered rectally once daily for 10 days using 1 gram suppositories. Plasma metronidazole levels of 4.4, 7.7, and 6.6 ug/ml  were achieved at three, six, and 24 hours respectively. These levels are similar to those obtained in man following therapeutic use of metronidazole suppositories. Plasma minimum inhibitory concentrations of metronidazole for the majority of human pathogens including Bacteriods species, Fusobacter species, and Clostridia species are in the range of 0.3 to 3 ug/ml. After seven days of antibiotic therapy and daily flushing of the gingival sulcus with dilute hydrogen peroxide through a 4FG plastic urinary catheter, clinical recovery was achieved. No digestive disturbances were noted.

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 10 - 20 mg/kg orally every 12 hours, or 40 mg/kg orally every 24 hours. (B546)
  • 20 mg/kg orally every 12 hours. (B548.w8)
  • 40 mg/kg orally every 24 hours for three days. (B548.w8)
  • 20 mg/kg orally twice daily. "Treatment of choice for enterotoxaemia." (B600.4.w4)
  • 20 - 30 mg/kg orally every 12 hours. (B601.15.w15)
  • 20 mg/kg orally every 12 hours. (B602.41.w41)
  • 20 mg/kg orally every 12 hours. Against anaerobes. (B603.5.w5)
    • Note: tablets are very bitter. Liquid formulations are available, however, many rabbits do not like the "cherry" flavoured liquid. (B603.5.w5)

Ferrets - Mustela putorius fero - Ferret:

  • 50 mg/kg orally once daily or 10 - 25 mg/kg orally twice daily. "Used for anaerobic infections. Neurotoxicity seen in dogs. May be used with chloromycin." (B626.App.w22)
  • 15 - 20 mg/kg orally every 12 hours. (B602.41.w41, B631.21.w21) "Used to treat many GI infections including Helicobacter. Very bad taste, should be heavily flavoured." (B631.21.w21)
  • 10 - 20 mg/kg orally once or twice daily. Note: extremely bitter. Compliance depends on masking of the flavour. (J213.3.w1)
  • Treatment of protozoal infection: 
    • 20 mg/kg orally every 12 hours. (B602.41.w41, B631.21.w21)
    • 20 mg/kg orally once or twice daily for 5 - 10 days. (B626.App.w22)
    • 15 - 25 mg/kg orally twice daily for 14 days. Note: the bitter taste may result in salivation or vomiting. (J213.3.w1)

Great Apes

  • 30-50 mg/kg every 24 hours (or divided and given every eight hours) for 5 - 10 days. For the treatment of protozoal infections. (B336.39.w39)
  • Adult Pan troglodytes - Chimpanzee: 25 mg/kg orally twice daily. (W768.Jun2012.w1)
  • Primates: 50 mg/kg orally twice daily. In the treatment of respiratory infections with suspected involvement of anaerobic organisms, also in treatment of hepatitis, enteritis/gastrointestinal upset, and in the treatment of protozoal infections. Note: unpleasant taste, therefore can be difficult to administer. (D425.3.15.w3o)
  • Primates: 30 - 50 mg/kg orally twice daily for ten days. In the treatment of protozoal infections. (D425.3.15.w3o)
Monitoring parameters --

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Withdrawal period / Withholding time
Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in individuals known to be sensitive to metronidazole or to nitroimidazole derivatives. (B263)
  • Use is not recommended in severely debilitated animals. (B263)
  • Use is not recommended in pregnant or nursing animals. (B263)
  • Use with caution in individuals with hepatic dysfunction; if use is necessary, consideration should be given to reducing the dose to 25-50% of normal. (B263)
  • Use with care in patients with renal impairment. (B201.1.w1)
  • Avoid use in pregnancy unless the benefits to the mother outweigh the potential risks to the fetuses, particularly early in gestation. (B263)
Adverse Effects / Side Effects / Warnings
  • Dogs: neurological disorders, lethargy, weakness, neutropaenia, hepatotoxicity, haematuria, anorexia, nausea, vomiting, diarrhoea. (B263)
Operator Warnings
  • Impervious gloves should be worn when applying topical treatment. (B201.1.w1)
Overdose / Acute Toxicity
  • Dogs and cats: anorexia and/or vomiting, depression, mydriasis, nystagmus, ataxia, head-tilt, proprioceptive deficits, knuckling at the joints, disorientation, tremors, seizures, bradycardia, rigidity and stiffness. (B263); reversible neurological depression, ataxia and hepatic impairment. B201.1.w1

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity
  • Dogs and cats: chronic (long-term) moderate to high dose therapy may result in neurological side-effects as described for acute toxicity. (B263)
Reproductive effects --
Teratogenic effects
  • Implicated as a teratogen in some laboratory animals. (B263)
  • Cats and dogs: no data available. (B263)
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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