Metronidazole
Dosage & Administration Guidelines
| Species | Route | Dose | Frequency | Duration & Clinical Notes |
|---|---|---|---|---|
| Dog | PO | 10-25 mg/kg | q12h | Duration: 5-7 days for giardiasis; 7-10 days for anaerobic infections; for IBD, may be used for 2-4 weeks Notes: For IBD, lower doses (10 mg/kg q12h) may be used to minimize neurological side effects. For hepatic encephalopathy, 7.5 mg/kg q8h. |
| Cat | PO | 10-25 mg/kg | q12h | Duration: 5-7 days for giardiasis; 7-10 days for anaerobic infections; for IBD, may be used for 2-4 weeks Notes: Cats are more sensitive to neurological side effects; use lower end of dose range. For IBD, 10 mg/kg q12h. |
| Horse | PO | 15-25 mg/kg | q12h | Duration: 5-10 days Notes: Oral bioavailability is variable; consider IV for severe infections. For EPM, not first-line; use with other antiprotozoals. |
| Cattle | PO | 10-25 mg/kg | q12h | Duration: 5-7 days Notes: Not approved in many countries for food animals; extra-label use requires veterinary oversight and extended withdrawal times. |
| Sheep/Goat | PO | 10-20 mg/kg | q12h | Duration: 5-7 days Notes: Use with caution; monitor for neurological signs. |
| Rabbit | PO | 20 mg/kg | q12h | Duration: 5-7 days Notes: May cause anorexia; monitor food intake. |
| Bird (e.g., pigeon) | PO | 25-50 mg/kg | q12h | Duration: 5-7 days Notes: For trichomoniasis (canker), use 50 mg/kg q12h. |
| Reptiles | PO | 20-50 mg/kg | q24-48h | Duration: 5-10 days Notes: Dosing interval may be extended due to slower metabolism in reptiles. |
Clinical Indications & Species Uses
- Treatment of infections caused by susceptible anaerobic bacteria and protozoa
- Anaerobic bacterial infections
- Giardiasis
- Trichomoniasis
- Inflammatory bowel disease (IBD)
- Periodontal disease
- Hepatic encephalopathy (adjunctive therapy)
- Anaerobic bacterial infections
- Giardiasis
- Trichomoniasis
- Inflammatory bowel disease (IBD)
- Chronic diarrhea
- Anaerobic bacterial infections
- Clostridial infections
- Potomac horse fever (Neorickettsia risticii) - adjunctive
- Protozoal myeloencephalitis (EPM) - not first-line
- Anaerobic bacterial infections
- Bovine trichomoniasis (Trichomonas foetus) - not approved in many countries
- Giardiasis (off-label)
- Anaerobic bacterial infections
- Giardiasis (off-label)
- Trichomoniasis (off-label)
- Anaerobic bacterial infections
- Giardiasis
- Trichomoniasis
- Mucoid enteropathy (adjunctive)
- Anaerobic bacterial infections
- Giardiasis
- Trichomoniasis (e.g., canker in pigeons)
- Reptiles: Anaerobic infections, protozoal infections; Ferrets: Giardiasis, IBD; Small mammals: Giardiasis, anaerobic infections
Pharmacology & Mechanism of Action
Drug Class: Nitroimidazole antibiotic | Pharmacological Group: Antibacterial, Antiprotozoal
Mechanism of Action: Metronidazole is a prodrug that is selectively reduced by anaerobic microorganisms and sensitive protozoa. The nitro group of metronidazole is reduced by ferredoxin-like electron transport proteins unique to anaerobic organisms, producing reactive cytotoxic intermediates that disrupt DNA helical structure, inhibit nucleic acid synthesis, and cause DNA strand breakage. This leads to rapid bactericidal and antiprotozoal activity against susceptible organisms.
Pharmacodynamics: Metronidazole is effective against a wide range of anaerobic bacteria (e.g., Bacteroides, Fusobacterium, Clostridium) and protozoa (e.g., Giardia, Trichomonas, Entamoeba). It is bactericidal at concentrations equal to or slightly above the minimum inhibitory concentration (MIC). It has no activity against aerobic bacteria or facultative anaerobes. The drug also has immunomodulatory effects, including inhibition of cell-mediated immunity, which may contribute to its efficacy in inflammatory bowel disease.
β‘ Pharmacokinetics Summary
Available Formulations & Strengths
Contraindications & Clinical Warnings
- Hypersensitivity to metronidazole or other nitroimidazoles
- Pregnancy (especially first trimester) unless benefits outweigh risks
- Lactation (use with caution; drug is excreted in milk)
- Severe hepatic disease (metabolized by liver)
- Concurrent use with alcohol or propylene glycol (disulfiram-like reaction)
- Use with caution in patients with hepatic dysfunction; dose adjustment may be necessary.
- Use with caution in patients with neurological disorders; may exacerbate seizures.
- Cats are more sensitive to neurological adverse effects; monitor for signs of toxicity.
- Prolonged use may cause peripheral neuropathy.
- In food animals, observe withdrawal times; extra-label use requires veterinary oversight.
- Do not use in pregnant animals unless clearly needed.
- May cause anorexia, nausea, or vomiting; administer with food to reduce GI upset.
Adverse Effects & Reactions
Common:
- Anorexia
- Nausea
- Vomiting
- Diarrhea
- Hypersalivation (especially cats due to bitter taste)
Serious / Severe:
- Neurological signs: ataxia, nystagmus, head tilt, seizures, tremors, weakness
- Peripheral neuropathy (with prolonged use)
- Hepatotoxicity (rare)
- Bone marrow suppression (rare)
Rare:
- Allergic reactions (urticaria, anaphylaxis)
- Pancreatitis
- Disulfiram-like reaction with alcohol
Key Drug Interactions
| Interacting Drug / Class | Clinical Effect & Mechanism | Severity |
|---|---|---|
| Warfarin and other anticoagulants | Metronidazole may potentiate the anticoagulant effect by inhibiting hepatic metabolism of warfarin. | High |
| Phenobarbital and other CYP450 inducers | May increase metabolism of metronidazole, reducing its efficacy. | Moderate |
| Cimetidine | May decrease hepatic metabolism of metronidazole, increasing risk of toxicity. | Moderate |
| Alcohol or propylene glycol | Disulfiram-like reaction (nausea, vomiting, flushing, tachycardia). | High |
| Cyclosporine | Metronidazole may increase cyclosporine levels; monitor for toxicity. | Moderate |
| Lithium | Metronidazole may increase lithium levels; monitor for toxicity. | Moderate |
Overdose & Toxicity Management
Signs of Toxicity:
- Nausea
- Vomiting
- Ataxia
- Tremors
- Seizures
- Peripheral neuropathy
- Hepatotoxicity
- Bone marrow suppression
Emergency Treatment Protocol: There is no specific antidote. Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide IV fluids, anticonvulsants (e.g., diazepam) for seizures, and supportive care. Monitor hepatic and renal function. In severe cases, hemodialysis may be considered.
Food Animal Withdrawal Times
Withdrawal times are not established for all species; these are general recommendations. For extra-label use in food animals, consult FARAD (Food Animal Residue Avoidance Databank) for specific withdrawal times. In cattle, a withdrawal time of at least 10 days for meat and 4 days for milk is often recommended, but may vary by formulation and country.
Storage, Handling & Regulatory Information
Storage Temperature: Store at room temperature (20-25Β°C) in a tight, light-resistant container.
Light Sensitivity: Light-sensitive β protect from direct exposure.
Handling & Special Conditions: Protect from light and moisture. Do not freeze oral suspension. Keep out of reach of children and animals.
Dispensing Status: Prescription Required (Rx Only)
Approval Status: Metronidazole is not FDA-approved for veterinary use in the US, but it is commonly used extra-label in dogs, cats, and other species. It is approved for human use.
Extra-Label (Off-Label) Use: In the US, extra-label use of metronidazole in food animals is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) with veterinary supervision, provided there is no approved animal drug product available and withdrawal times are extended. It is prohibited in lactating dairy cows if the drug is not approved for that species and a milk withdrawal time has not been established.
Clinical Pearls & Practice Notes
References & Literature
- π Plumb's Veterinary Drug Handbook
- π Papich Veterinary Pharmacology and Therapeutics
- π Compendium of Veterinary Products (CVP)