Accolate (Zafirlukast): 10 mg & 20 mg Tablets

LEUKOTRIENE-RECEPTOR ANTAGONIST

Highlights of Prescribing Information

  • Leukotriene-receptor antagonist used primarily for feline asthma; appears to have very limited efficacy
  • Not for treatment of acute bronchospasm
  • Well tolerated
  • Dose on an empty stomach

What Is Drug Used For?

While zafirlukast potentially could be useful in treating feline asthma, including allowing dose reductions of corticosteroid therapy, its efficacy has been disappointing to this point and most do not recommend its use. Potentially, it could be of benefit in allergy-mediated (where leukotrienes play a role) dermatologic conditions, such as atopy in dogs, but evidence has been that it is not very effective.

Pharmacology / Actions

Zafirlukast selectively and competitively inhibits leukotriene receptors, specifically receptors for leukotriene D4 and E4 (LTD4 and LTE4). Additionally, it competes for receptors with some components of slow-reacting substance of anaphylaxis (SRS-A). These substances have all been implicated in the inflammatory and bronchoconstrictive aspects of bronchial asthma.

Pharmacokinetics

No specific veterinary data was located. In humans, zafirlukast is rapidly absorbed after oral administration. Food may impair the absorption of the drug, therefore, give on an empty stomach. Peak plasma levels occur about 3 hours after dosing. Zafirlukast is highly bound to plasma proteins (>99%). The drug is extensively metabolized; less than 10% of a dose is excreted in the urine, the rest in the feces. Half lives in humans average about 10 hours.

Before you take Drug

Contraindications / Precautions / Warnings

Zafirlukast is contraindicated in patients hypersensitive to it.

Zafirlukast is not indicated for, and is ineffective for treating bronchospasm associated with acute asthma attacks.

Patients with significantly decreased hepatic function may have reduced clearances (and increased plasma levels) of zafirlukast.

Adverse Effects

Veterinary experience is very limited and no adverse effects have been reported thus far. In humans, the adverse effect profile seems to be minimal; headache was noted most often, but incidence is not much different than placebo.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.)

Zafirlukast is excreted in milk, but it is probably safe to administer to nursing veterinary patients.

Overdosage / Acute Toxicity

In dogs, doses of up to 500 mg/kg were tolerated without mortality.

Drug Interactions

The following drug interactions have either been reported or are theoretical in humans or animals receiving zafirlukast and may be of significance in veterinary patients:

■ ASPIRIN: May significantly increase zafirlukast plasma levels

■ ERYTHROMYCIN: May decrease the bioavailability of zafirlukast

■ THEOPHYLLINE: May decrease plasma levels of zafirlukast

■ WARFARIN: Zafirlukast may significantly increase the prothrombin time of patients taking warfarin.

Laboratory Considerations

None were noted

How to use Drug

Drug dosage for dogs:

a) For adjunctive treatment of atopic dermatitis: 20 mg (total dose) PO twice daily; only moderate success ()

Drug dosage for cats:

a) For adjunctive treatment of feline bronchial asthma: 1-2 mg/kg PO once to twice daily ()

Monitoring

■ Clinical efficacy

Client Information

■ Preferably give on an empty stomach.

■ Give this medication even if animal appears well; do not use to treat acute asthma clinical signs.

■ Because experience in veterinary medicine is minimal, report any untoward effects to the veterinarian.

Chemistry / Synonyms

A leukotriene-receptor antagonist, zafirlukast occurs as a white to pale yellow, fine amorphous powder. It is practically insoluble in water.

Zafirlukast may also be known as: ICI-204219, Accolate, Accoleit, Aeronix, Azimax, Olmoran, Resma, Vanticon, Zafarismal, Zafirst, or Zuvair.

Storage / Stability

Zafirlukast tablets should be stored at room temperature and protected from light and moisture. The manufacturer states that the tablets should be dispensed only in the original, unopened container.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this

drug as a class 4 substance. See the appendix for more information.

Human-Labeled Products:

Zafirlukast Tablets (film-coated): 10 mg & 20 mg; Accolate* (Astra-Zeneca); (Rx)

 

Selections from the book: “Plumb’s Veterinary Drug Handbook. Sixth Edition”. 2008