Isoniazid — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	5-10 mg/kg	q12h or q24h	Duration: 6-12 months (often in combination with rifampin and/or other agents) Notes: Administer on an empty stomach. Monitor liver enzymes and neurologic status.
Cat	PO	5-10 mg/kg	q12h or q24h	Duration: 6-12 months (often in combination therapy) Notes: Cats may be more prone to hepatotoxicity; monitor closely.
Horse	PO	5-10 mg/kg	q24h	Duration: 6-12 months (combination therapy) Notes: Limited data; use with caution.
Cattle	PO	10-20 mg/kg	q24h	Duration: Variable; often not recommended due to regulatory and zoonotic concerns Notes: Extra-label use; withdrawal times must be observed. Culling is often preferred.
Small Ruminants	PO	10-20 mg/kg	q24h	Duration: Variable; not commonly used Notes: Extra-label use; withdrawal times must be observed.
Rabbit	PO	10-20 mg/kg	q24h	Duration: Variable; experimental Notes: Limited data; monitor for hepatotoxicity.
Birds/Poultry	PO	30-40 mg/kg	q24h	Duration: Variable; not commonly used Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications

Treatment of tuberculosis caused by susceptible mycobacteria
Prophylaxis in animals exposed to tuberculosis

Dog (Canine)

Treatment of tuberculosis (Mycobacterium tuberculosis, M. bovis)
Treatment of atypical mycobacterial infections (e.g., M. avium complex) in combination with other agents

Cat (Feline)

Treatment of tuberculosis (rare)
Treatment of atypical mycobacterial infections (e.g., M. avium complex) in combination with other agents

Horse (Equine)

Treatment of tuberculosis (rare)
Treatment of mycobacterial infections (e.g., M. bovis) in combination therapy

Cattle (Bovine)

Treatment of tuberculosis (M. bovis) - often not recommended due to zoonotic risk and regulatory concerns

Small Ruminants (Sheep / Goat)

Treatment of tuberculosis (rare)

Rabbit & Small Mammals

Treatment of tuberculosis (experimental)

Avian & Poultry

Treatment of tuberculosis (rare)

Exotic & Other Species

Treatment of mycobacterial infections in exotic animals (e.g., primates, elephants) - use with caution

Pharmacology & Mechanism of Action

Drug Class: Antimycobacterial | Pharmacological Group: Nicotinic acid hydrazide derivative

Mechanism of Action: Isoniazid is a prodrug that requires activation by the mycobacterial enzyme KatG catalase-peroxidase. The activated form inhibits the synthesis of mycolic acids, essential components of the mycobacterial cell wall, by targeting the enoyl-acyl carrier protein reductase InhA. This disrupts cell wall integrity, leading to bacterial death. It is bactericidal against actively dividing mycobacteria, particularly Mycobacterium tuberculosis complex, and bacteriostatic against non-dividing organisms.

Pharmacodynamics: Isoniazid is highly specific for mycobacteria, with minimal activity against other bacteria. It exhibits concentration-dependent killing and has a post-antibiotic effect. Resistance develops rapidly when used as monotherapy due to mutations in katG or inhA genes. In veterinary medicine, it is primarily used for the treatment of tuberculosis in various species, often in combination with other antimycobacterial agents to prevent resistance.

⚡ Pharmacokinetics Summary

Absorption: Isoniazid is well absorbed after oral administration in most species. Bioavailability is high (approximately 80-90%) in dogs and humans. Food can decrease absorption, so it is recommended to administer on an empty stomach. In ruminants, oral absorption may be variable due to ruminal degradation.

Distribution: Isoniazid distributes widely throughout the body, including into cerebrospinal fluid, pleural fluid, and caseous lesions. It crosses the placenta and is present in milk. Volume of distribution is approximately 0.6-0.7 L/kg in dogs. It penetrates macrophages and is effective against intracellular organisms.

Metabolism: Isoniazid is metabolized in the liver primarily by N-acetylation (via N-acetyltransferase 2) and hydrolysis to isonicotinic acid and hydrazine. The rate of acetylation varies among species and individuals; dogs are slow acetylators, while cats are intermediate. In ruminants, metabolism may be altered due to ruminal microflora.

Excretion: Metabolites are excreted primarily in the urine (75-95% within 24 hours), with small amounts excreted in feces. Renal excretion of the parent drug is minimal. In animals with renal impairment, dose adjustment may be necessary.

Half-Life: Dog: 1.5-3 hours; Cat: 2-4 hours; Horse: 1-2 hours; Cattle: 2-3 hours (estimated); Humans: 1-4 hours (depending on acetylator status).

Bioavailability: Oral bioavailability is high (80-90%) in dogs and cats, but may be reduced in ruminants due to ruminal degradation. In horses, oral bioavailability is approximately 70-80%.

Protein Binding: Isoniazid has low protein binding, approximately 10-15% in most species.

Available Formulations & Strengths

Oral Tablet 50 mg, 100 mg, 300 mg (PO)

Oral Syrup 10 mg/mL (PO)

Injectable Solution 100 mg/mL (IM)

Contraindications & Clinical Warnings

Contraindications:

Hypersensitivity to isoniazid or any component
Severe hepatic disease
Acute liver disease
History of isoniazid-induced hepatotoxicity
Concurrent use with alcohol (not applicable in animals but caution in handlers)

Warnings & Clinical Precautions:

Use with caution in animals with pre-existing liver disease, renal impairment, or seizure disorders.
Monitor liver function tests (ALT, AST, ALP) and neurologic status periodically during therapy.
Administer pyridoxine (vitamin B6) to prevent peripheral neuropathy, especially in dogs and cats.
Isoniazid may cause false-positive urine glucose tests (with Benedict's reagent).
In food animals, extra-label use is prohibited in some countries; consult regulatory authorities.
Handle with care; isoniazid is a human carcinogen and mutagen; wear gloves when handling tablets.

Adverse Effects & Reactions

Common:

Hepatotoxicity (elevated liver enzymes)
Gastrointestinal upset (vomiting, diarrhea)
Peripheral neuropathy (with high doses or prolonged use)
Lethargy

Serious / Severe:

Severe hepatotoxicity (hepatic necrosis)
Seizures
Peripheral neuritis
Hemolytic anemia
Lupus-like syndrome (rare)

Rare:

Aplastic anemia
Agranulocytosis
Thrombocytopenia
Eosinophilia
Vasculitis
Psychosis (in humans; rare in animals)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Rifampin	Increased risk of hepatotoxicity; may require monitoring of liver enzymes.	High
Phenytoin	Isoniazid inhibits phenytoin metabolism, increasing phenytoin levels and toxicity.	High
Carbamazepine	Isoniazid may increase carbamazepine levels, leading to toxicity.	Moderate
Benzodiazepines	Isoniazid may inhibit the metabolism of diazepam, increasing sedation.	Moderate
Antacids (aluminum-containing)	May decrease absorption of isoniazid; separate administration by 1-2 hours.	Mild
Corticosteroids	May increase the risk of hepatotoxicity and decrease isoniazid efficacy.	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Nausea, vomiting
Dizziness, ataxia
Slurred speech
Seizures (refractory)
Metabolic acidosis
Coma
Respiratory depression
Hepatotoxicity (delayed)

Emergency Treatment Protocol: Immediate decontamination (induction of vomiting if recent ingestion, gastric lavage, activated charcoal). Administer pyridoxine (vitamin B6) intravenously at a dose equal to the amount of isoniazid ingested (if known) or 5-10 g in dogs/cats. Control seizures with diazepam or barbiturates. Correct metabolic acidosis with sodium bicarbonate. Provide supportive care including IV fluids, oxygen, and monitoring of liver and renal function. Hemodialysis may be considered in severe cases.

Food Animal Withdrawal Times

🥩 Meat: 30 days🥛 Milk: 7 days

Withdrawal times are not established for isoniazid in food animals; extra-label use requires extended withdrawal periods. Consult regulatory authorities. In cattle, a meat withdrawal of at least 30 days and milk withdrawal of 7 days is suggested based on pharmacokinetic data, but official withdrawal times are not available.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, excursions permitted to 15-30°C).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and moisture. Keep in tightly closed container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, isoniazid is not FDA-approved for veterinary use; extra-label use is permitted under AMDUCA for non-food animals. For food animals, extra-label use is prohibited if an approved animal drug exists that is effective. In the EU, use in food animals is restricted. Always follow regulatory guidelines.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Isoniazid is a critical drug for the treatment of tuberculosis in animals, but its use is limited by potential hepatotoxicity and the need for prolonged therapy. It should always be used in combination with other antimycobacterial agents (e.g., rifampin, ethambutol) to prevent resistance. Baseline and periodic monitoring of liver enzymes and neurologic status is essential. Pyridoxine supplementation is recommended to prevent peripheral neuropathy. In food animals, the decision to treat tuberculosis must consider zoonotic risks and regulatory implications; often, culling is preferred. For exotic animals, consult a specialist. Due to the risk of human exposure, handle with care and follow biosafety protocols.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)