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Zafirlukast (Monograph)

Brand name: Accolate
Drug class: Leukotriene Modifiers
- Leukotriene-receptor Antagonists
ATC class: R03DC01
VA class: RE109
Chemical name: [3-[[2-Methoxy-4-[[[(2-methylphenyl)-sulfonyl]amino]carbonyl]phenyl]methyl]-1H-indol-5-yl-carbamic acid cyclopentyl ester
Molecular formula: C31H33N3O6S
CAS number: 107753-78-6

Medically reviewed by on Apr 15, 2024. Written by ASHP.


Antiasthmatic agent; leukotriene-receptor antagonist.

Uses for Zafirlukast


Prevention and long-term symptomatic management of asthma.

In patients with mild persistent asthma, low-dose orally inhaled corticosteroids considered first-line agents for long-term control. Alternative agents, including certain leukotriene modifiers (i.e., zafirlukast, montelukast), may be used but are less effective than inhaled corticosteroids and are not preferred as initial therapy.

In patients with moderate persistent asthma, low-dose inhaled corticosteroids with a long-acting inhaled β2-agonist bronchodilator (e.g., salmeterol, formoterol) or monotherapy with medium-dose inhaled corticosteroids preferred. However, the National Asthma Education and Prevention Program (NAEPP) recommends that beneficial effects of long-acting inhaled β2-agonists be weighed carefully against increased risk of severe asthma exacerbations and asthma-related deaths associated with daily use of such agents.

Alternative agents, including certain leukotriene modifiers (i.e., zafirlukast, montelukast), can be added to a low dosage of inhaled corticosteroid for treatment of moderate persistent asthma, but these options are less effective. Considerations favoring combination with orally inhaled corticosteroids include intolerance to long-acting β2-adrenergic agonists, marked preference for oral therapy, and demonstration of superior responsiveness to these leukotriene modifiers.

In adults and children ≥5 years of age with severe persistent asthma, NAEPP and the Global Initiative for Asthma (GINA) state that maintenance therapy with inhaled corticosteroids at medium to high dosages and adjunctive therapy with a long-acting inhaled β2-agonist is preferred. Alternatives to a long-acting inhaled β2-agonist in such patients receiving medium-dose inhaled corticosteroids include certain leukotriene modifiers (i.e., zafirlukast, montelukast), but these agents are generally not preferred.

Therapy with zafirlukast may be especially useful in patients who are unable or unwilling to comply with therapy using inhaled drugs (e.g., children).

Not recommended for relief of acute bronchospasm; however, may continue therapy during acute asthma exacerbations. (See Acute Asthma under Cautions.)

Allergic Rhinitis

Has been used for symptomatic management of seasonal allergic rhinitis [off-label].

Exercise-induced Bronchospasm

Has been used for prevention of exercise-induced bronchospasm [off-label].

Leukotriene modifiers not included as first-line agents or as alternative agents to orally inhaled β2-adrenergic agonists in current guidelines.

Zafirlukast Dosage and Administration


Oral Administration

Administer twice daily on an empty stomach (i.e., at least 1 hour before or two hours after meals).


Pediatric Patients


Children 5–11 years of age: 10 mg twice daily.

Children ≥12 years of age: 20 mg twice daily.



20 mg twice daily.

Special Populations

Hepatic Impairment

Clearance may be decreased. Dosage reduction may be necessary; however, the manufacturer currently makes no specific recommendations for dosage adjustment. Not evaluated in patients with hepatitis or in long-term studies in patients with cirrhosis. (See Special Populations under Absorption and under Elimination in Pharmacokinetics and see Hepatic Impairment.)

Renal Impairment

Dosage adjustment not required.

Geriatric Patients

Dosage adjustment not required. (See Special Populations under Absorption and under Elimination in Pharmacokinetics.)

Cautions for Zafirlukast


Known hypersensitivity to zafirlukast or any ingredient in the formulation.



Hepatic Effects

Hepatic dysfunction, including increases in liver enzyme concentrations, hepatitis, and/or hyperbilirubinemia, reported. Zafirlukast-induced hepatotoxicity usually is reversible following discontinuance of the drug.

Serious and potentially fatal hepatotoxicity, including fulminant hepatitis and liver failure, reported rarely.

Monitor closely for signs and symptoms of hepatic impairment; consider performing liver function tests (e.g., serum AST and ALT) periodically. Advise patients to immediately contact their clinician if they notice signs and symptoms of liver dysfunction.

Discontinue therapy if signs and/or symptoms suggestive of liver dysfunction occur; immediately perform liver function tests (i.e., serum ALT) and manage patient accordingly.

Do not reinitiate therapy if results of liver function tests are consistent with hepatic dysfunction or if zafirlukast was discontinued because of hepatic dysfunction when no other attributable cause could be identified.

Acute Asthma

Do not use for relief of acute bronchospasm (including status asthmaticus); zafirlukast can be continued during acute exacerbations of asthma, but it will not provide immediate symptomatic relief. Patients who experience exacerbations of asthma should continue their usual regimen of inhaled β2–adrenergic agonists for prophylaxis and have a short-acting orally inhaled β2-adrenergic agonist available for rescue.


Concomitant use with warfarin results in a clinically important increase in PT. (See Specific Drugs under Interactions.)

Sensitivity Reactions

Eosinophilia and Churg-Strauss Syndrome

Systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome reported rarely in patients receiving leukotriene modifiers; these events usually associated with reduction (tapered dosage) or withdrawal of oral or high-dose inhaled corticosteroid therapy.

Be alert to the development of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy; causal relationship not established.

General Precautions

Concomitant Corticosteroid Therapy

Do not abruptly substitute zafirlukast for oral or inhaled corticosteroids. Orally inhaled corticosteroid requirements may be reduced during zafirlukast therapy; undertake only gradual (e.g., at 2-week intervals) reduction of corticosteroid dosage.

Neuropsychiatric Effects

Neuropsychiatric events reported with zafirlukast during postmarketing experience. Data from placebo-controlled trials with leukotriene modifiers indicate that suicidal ideation occurred in 0.01% of 9929 patients treated with montelukast and in none of those receiving other leukotriene modifiers; no completed suicide occurred during therapy with any leukotriene modifier. FDA concluded that some neuropsychiatric events reported with zafirlukast (e.g., depression, insomnia) appear consistent with a drug-induced effect.

Be alert to the potential for neuropsychiatric events in patients receiving the drug. Instruct patients to contact their clinician if behavior or mood changes occur. Carefully evaluate the risks and benefits of continuing zafirlukast therapy in patients who develop neuropsychiatric symptoms.

Specific Populations


Category B.

ACOG generally recommends use of leukotriene receptor antagonists (i.e., zafirlukast, montelukast) as alternatives to a long-acting β2-agonist in pregnant women with moderate persistent asthma who are inadequately controlled with low to medium dosages of an inhaled corticosteroid. (See Asthma under Uses.)


Distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety demonstrated in children 5–11 years of age; efficacy extrapolated from demonstrated efficacy in adults with asthma and the likelihood that the disease course, pathophysiology, and drug’s effect are similar between the two populations.

Safety and efficacy not established in children <5 years of age.

Increased systemic exposure and AUC, reflecting decreased clearance in children relative to adults.

Effect on growth in pediatric patients not evaluated in clinical studies to date.

Geriatric Use

Possible increased incidence of infection (e.g., pharyngitis, rhinitis) compared with younger adults.

Hepatic Impairment

Decreased clearance; dosage reduction may be necessary. (See Special Populations under Absorption and under Elimination in Pharmacokinetics.)

Common Adverse Effects

Headache, infection, nausea, diarrhea.

Drug Interactions

Metabolized by CYP2C9.

Inhibits CYP3A4 and CYP2C9.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP2C9 and CYP3A4 substrates: Potential pharmacokinetic interaction (increased plasma substrate concentrations).

Specific Drugs




Anticonvulsants (e.g., carbamazepine, phenytoin)

Possible increased plasma anticonvulsant concentrations

Monitor for adverse effects


Increased plasma zafirlukast concentrations

Monitor for alterations in clinical response and/or adverse effects

Astemizole (no longer commercially available in the US)

Possible increased plasma astemizole concentrations

Calcium-channel blocking agents, dihydropyridine (nicardipine, nifedipine)

Possible increased plasma concentrations of dihydropyridine calcium-channel blocking agents

Monitor for alterations in clinical response and/or adverse effects

Cisapride (commercially available in US only under limited-access protocol)

Possible increased cisapride concentrations

Monitor for alterations in clinical response and/or adverse effects

Contraceptives, oral (fixed dose estrogen-progestin combination)

Pharmacokinetic interactions unlikely

Contraceptive efficacy not affected by concomitant administration


Possible increased plasma cyclosporine concentrations

Monitor for alterations in clinical response and/or adverse effects


Decreased plasma zafirlukast concentrations

Monitor for alterations in clinical response and/or adverse effects

Terfenadine (no longer commercially available in US)

Decreased plasma concentrations of zafirlukast

No alteration in terfenadine pharmacokinetics; no effect on QTc interval


Rarely, increased theophylline concentrations when zafirlukast is added to existing theophylline regimen

Decreased plasma zafirlukast concentrations when administered with liquid theophylline preparation

No alterations in pharmacokinetics of theophylline administered orally in pediatric patients

Monitor for alterations in clinical response and/or adverse effects


Possible increased plasma tolbutamide concentrations

Monitor for adverse effects


Increased AUC and half-life of S-warfarin; possible increased PT

Monitor PT frequently and adjust warfarin dose accordingly

Zafirlukast Pharmacokinetics



Rapidly absorbed following oral administration; peak plasma concentrations attained within 3 hours.

Steady-state plasma concentrations are proportional to dose.

Children 5–11 years of age: Increased peak plasma concentrations, AUC, and systemic exposure.


Improvement in asthma symptoms and/or lung function test results and decreased use of β-agonist bronchodilators are evident within 3–14 days.


Food decreases rate and extent of absorption; high-fat or high-protein meal decreases mean bioavailability by approximately 40%.

Special Populations

In patients with hepatic impairment (stable alcoholic cirrhosis), peak plasma concentration and AUC increased 50–60%.

Asthmatic patients ≥65 years of age: Increased peak plasma concentration and AUC.



Not fully characterized.

Minimally crosses the placenta and blood-brain barrier in animals (rats, mice); not known whether zafirlukast crosses the placenta in humans.

Distributed into human milk.

Plasma Protein Binding

>99% (mainly albumin).



Extensively metabolized in the liver principally via CYP2C9.

Elimination Route

Excreted principally in feces (about 90%) via biliary excretion as unchanged drug and metabolites.


Adults: 8–16 hours.

Special Populations

Clearance is reduced in children 5–11 years of age and adults >65 years of age.

Clearance is reduced in patients with hepatic impairment.

Pharmacokinetics not affected by gender, race, or renal function.





20–25°C; protect from light and moisture.


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names



Tablets, film-coated

10 mg



20 mg



AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 24, 2012. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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