Zafirlukast

Leukotriene receptor antagonist Anti-inflammatory / antiasthmatic

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.5-2 mg/kg q12h Duration: Variable; often 2-4 weeks to assess response.
Notes: Administer on an empty stomach (1 hour before or 2 hours after meals).
Cat PO 0.5-1 mg/kg q12h Duration: Variable; often 2-4 weeks to assess response.
Notes: Administer on an empty stomach; may be compounded.
Horse PO Not established; anecdotal doses of 0.5-1 mg/kg q12h have been used. q12h Duration: Variable.
Notes: Limited data; not recommended as sole therapy.

Clinical Indications & Species Uses

General Indications
  • Not approved for veterinary use; limited anecdotal use in small animals for respiratory conditions.

Pharmacology & Mechanism of Action

Drug Class: Leukotriene receptor antagonist | Pharmacological Group: Anti-inflammatory / antiasthmatic

Mechanism of Action: Zafirlukast is a selective and competitive antagonist at the cysteinyl leukotriene receptor (CysLT1) in the airways. By blocking the binding of leukotrienes (LTC4, LTD4, LTE4) to these receptors, it inhibits bronchoconstriction, mucus secretion, vascular permeability, and eosinophil recruitment, thereby reducing airway inflammation and bronchospasm.

Pharmacodynamics: Zafirlukast reduces airway edema, smooth muscle contraction, and inflammatory cell infiltration. It improves lung function and reduces symptoms of asthma. In veterinary species, its efficacy is variable and not well established; it may have limited anti-inflammatory effects in some animals.

⚡ Pharmacokinetics Summary

Absorption: Rapidly absorbed after oral administration; peak plasma concentrations occur within 3 hours in humans. Food reduces bioavailability; therefore, it should be given on an empty stomach.
Distribution: Highly protein-bound (99%) in humans; distributes into tissues, but limited data in veterinary species.
Metabolism: Extensively metabolized in the liver via cytochrome P450 (CYP2C9) to inactive metabolites.
Excretion: Excreted primarily in feces (about 90%) and urine (about 10%) in humans.
Half-Life: Approximately 10 hours in humans; not well defined in veterinary species.
Bioavailability: Unknown in veterinary species; in humans, oral bioavailability is reduced by food.
Protein Binding: 99% in humans; likely similar in animals.

Available Formulations & Strengths

Oral Tablet 10 mg, 20 mg (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to zafirlukast or any component.
  • Hepatic impairment (severe).
  • Concurrent use with CYP2C9 inhibitors (e.g., fluconazole) may increase levels.
Warnings & Clinical Precautions:
  • Not approved for veterinary use; use with caution and informed consent.
  • May not be effective in all animals; monitor clinical response.
  • Use with caution in animals with hepatic disease.
  • Do not use in pregnant or lactating animals unless benefits outweigh risks (safety not established).
  • Administer on an empty stomach to maximize absorption.
  • May take several weeks to achieve full effect.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea)
  • Lethargy
  • Decreased appetite

Serious / Severe:

  • Hepatotoxicity (elevated liver enzymes, jaundice)
  • Hypersensitivity reactions (angioedema, urticaria)
  • Churg-Strauss syndrome (in humans, rare)

Rare:

  • Headache (in humans)
  • Dizziness
  • Insomnia

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Aspirin May increase zafirlukast plasma concentrations. Moderate
Erythromycin Decreases zafirlukast plasma concentrations. Moderate
Theophylline Increases theophylline levels; monitor for toxicity. High
Warfarin May increase prothrombin time; monitor coagulation. High
CYP2C9 inhibitors (e.g., fluconazole) May increase zafirlukast levels. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Vomiting
  • Diarrhea
  • Lethargy
  • Hepatotoxicity (with large doses)

Emergency Treatment Protocol: No specific antidote. Induce emesis if recent ingestion and animal is stable. Administer activated charcoal to reduce absorption. Provide symptomatic and supportive care, including IV fluids and monitoring of liver enzymes.

Food Animal Withdrawal Times

Not approved for food animals; no withdrawal times established. Do not use in animals intended for food.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F).

Handling & Special Conditions: Protect from moisture; keep in original container.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not approved for veterinary use; approved for human use (Accolate).

Extra-Label (Off-Label) Use: In the US, extra-label use in animals is permitted under AMDUCA only with a valid veterinarian-client-patient relationship and for non-food animals. Not approved for veterinary species.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Zafirlukast is a leukotriene receptor antagonist used primarily in human asthma. In veterinary medicine, its use is anecdotal and not well-supported by clinical trials. It may be considered as an adjunctive therapy for inflammatory airway disease in dogs and cats, but response is variable. It is not a bronchodilator and should not be used for acute bronchospasm. Always administer on an empty stomach. Monitor liver enzymes periodically during therapy. Due to lack of safety data, use with caution in pregnant or lactating animals. For food animals, it is prohibited due to lack of withdrawal times.

References & Literature

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