Zafirlukast: Overview and Practice Questions (2025)

Zafirlukast is an important medication in the management of asthma and allergic rhinitis. As a leukotriene receptor antagonist, it offers a unique approach to controlling respiratory symptoms by targeting specific inflammatory pathways.

This article provides a detailed overview of zafirlukast, including its mechanism of action, clinical applications, dosing, and important considerations for patients and healthcare providers.

What is Zafirlukast?

Zafirlukast (Accolate) is an oral medication classified as a leukotriene receptor antagonist, commonly used in the long-term management of asthma. It works by blocking leukotrienes—chemical substances in the body that cause inflammation, bronchoconstriction, and mucus production in the airways.

By inhibiting these effects, zafirlukast helps prevent asthma symptoms such as wheezing, shortness of breath, and chest tightness. It is not intended for quick relief of acute asthma attacks but rather as a maintenance therapy to reduce the frequency and severity of episodes.

Mechanism of Action

Zafirlukast works by blocking the action of leukotrienes, which are inflammatory molecules produced by the immune system. Specifically, it antagonizes the cysteinyl leukotriene receptor (CysLT1), preventing leukotrienes from binding to their receptors in the airways. This action helps reduce several key features of asthma:

• Bronchoconstriction: Prevents the narrowing of airways
• Inflammation: Reduces swelling and irritation in the respiratory tract
• Mucus production: Decreases excessive mucus secretion
• Vascular permeability: Limits fluid leakage into tissues

Note: By interrupting this inflammatory cascade, zafirlukast helps maintain more open airways and reduces the frequency and severity of asthma symptoms.

Clinical Uses of Zafirlukast

Primary Indications

Zafirlukast is primarily prescribed for:

• Chronic asthma management in adults and children 5 years and older
• Prevention of exercise-induced bronchospasm
• Allergic rhinitis (though this is less common)

Role in Asthma Treatment

According to asthma treatment guidelines, zafirlukast is typically considered as:

• An alternative to low-dose inhaled corticosteroids for mild persistent asthma
• An add-on therapy to inhaled corticosteroids for patients with inadequate control
• A suitable option for patients who cannot or prefer not to use inhaled medications

Dosing and Administration

Standard Dosing

• Adults and adolescents 12 years and older: 20 mg twice daily
• Children 5-11 years: 10 mg twice daily

Important Administration Guidelines

Zafirlukast should be taken on an empty stomach, either 1 hour before or 2 hours after meals. Food can significantly reduce the absorption of the medication, potentially decreasing its effectiveness. The medication should be taken at the same time each day to maintain consistent blood levels.

Effectiveness and Clinical Benefits

Clinical studies have demonstrated that zafirlukast can provide several benefits for asthma patients:

• Improved lung function: Increases in forced expiratory volume (FEV1)
• Reduced symptoms: Fewer episodes of wheezing, coughing, and shortness of breath
• Decreased rescue medication use: Less frequent need for quick-relief inhalers
• Better quality of life: Improved sleep and daily activities
• Reduced asthma exacerbations: Fewer severe episodes requiring emergency treatment

Note: The medication typically begins to show effects within a few days, with maximum benefits often achieved after several weeks of consistent use.

Side Effects and Adverse Reactions

Common Side Effects

Most patients tolerate zafirlukast well, but some may experience:

• Headache
• Nausea
• Diarrhea
• Abdominal pain
• Dizziness
• Fatigue

Serious Adverse Effects

While rare, more serious side effects can occur:

• Liver toxicity: Elevated liver enzymes or hepatitis
• Churg-Strauss syndrome: A rare vasculitic condition
• Neuropsychiatric events: Mood changes, depression, or suicidal thoughts
• Severe allergic reactions: Rash, swelling, or difficulty breathing

Drug Interactions

Zafirlukast can interact with several medications:

Significant Interactions

• Warfarin: Zafirlukast can increase warfarin levels, requiring careful monitoring of blood clotting times
• Theophylline: May decrease zafirlukast effectiveness
• Aspirin: Can increase zafirlukast blood levels
• Erythromycin: May reduce zafirlukast absorption

CYP2C9 Considerations

Zafirlukast is metabolized by the CYP2C9 enzyme system and can inhibit this pathway, potentially affecting other medications metabolized by the same system.

Special Populations

• Pregnancy and Breastfeeding: Zafirlukast is classified as Pregnancy Category B, meaning animal studies have not shown risk to the fetus, but human studies are limited. It should be used during pregnancy only when clearly needed. The medication is excreted in breast milk, so breastfeeding mothers should discuss risks and benefits with their healthcare provider.
• Elderly Patients: Older adults may be more sensitive to the effects of zafirlukast and may require dose adjustments based on kidney and liver function.
• Pediatric Use: The safety and effectiveness of zafirlukast in children under 5 years of age have not been established.

Monitoring and Follow-up

Patients taking zafirlukast should undergo regular monitoring:

• Liver function tests: Periodic monitoring, especially during the first few months of treatment
• Asthma control assessment: Regular evaluation of symptoms and lung function
• Medication adherence: Ensuring consistent daily dosing
• Side effect monitoring: Watching for signs of adverse reactions

Advantages and Limitations

Advantages

• Oral administration (convenient for patients who have difficulty with inhalers)
• Once or twice daily dosing
• Can be used as monotherapy or add-on treatment
• Alternative for patients with steroid concerns
• Effective for exercise-induced bronchospasm

Limitations

• Not for acute asthma attacks
• Slower onset of action compared to bronchodilators
• Food restrictions affect dosing convenience
• Potential for drug interactions
• Less effective than inhaled corticosteroids for most patients

Patient Education Points

Patients prescribed zafirlukast should understand:

• The importance of taking the medication consistently, even when feeling well
• Proper timing relative to meals
• It will not provide immediate relief during an asthma attack
• The need to continue rescue medications as prescribed
• When to contact their healthcare provider (worsening symptoms, side effects)
• The importance of regular follow-up appointments

Zafirlukast Practice Questions

1. What is the generic name of Accolate?
Zafirlukast.

2. What is the brand name of zafirlukast?
Accolate.

3. What is the pharmacologic class of zafirlukast?
Leukotriene modifier.

4. What is the therapeutic class of zafirlukast?
Anti-inflammatory drug used for asthma prophylaxis.

5. What is the primary use of zafirlukast?
Prevention and long-term treatment of persistent asthma.

6. Can zafirlukast be used for acute asthma attacks?
No, zafirlukast is not effective for reversing bronchospasm in acute asthma attacks.

7. How is zafirlukast administered?
It is taken orally (PO).

8. When should zafirlukast be taken in relation to meals?
It should be taken 1 hour before or 2 hours after meals.

9. What are the common side effects of zafirlukast?
Headache, dizziness, abdominal pain, muscle pain (myalgia), and fatigue (asthenia).

10. What are the serious adverse effects of zafirlukast?
Liver toxicity, hepatitis, elevated hepatic enzymes, and rare development of Churg-Strauss Syndrome.

11. What are the signs of Churg-Strauss Syndrome that may develop with zafirlukast?
Vasculitis, migratory lung infiltrates, and eosinophilia during steroid tapering.

12. What is the mechanism of action of zafirlukast?
It blocks cysteinyl leukotriene receptors, preventing bronchoconstriction, airway inflammation, and mucus production.

13. What role do leukotrienes play in asthma?
They are inflammatory mediators that cause bronchoconstriction, edema, and increased mucus secretion.

14. What is the pregnancy category of zafirlukast?
Category B.

15. What age group is zafirlukast approved for?
Children 5 years and older.

16. What is the peak onset time of zafirlukast’s therapeutic effect?
Peak action may begin as early as Day 1, but full effect may take up to 2 weeks.

17. How is zafirlukast eliminated from the body?
Primarily via feces, with about 10% excreted in the urine.

18. What are contraindications for zafirlukast use?
Hypersensitivity to the drug or its inactive ingredients, breastfeeding, acute asthma symptoms, and severe hepatic disease.

19. What condition requires caution when using zafirlukast?
Liver disease, age over 65, and patients taking warfarin.

20. What drugs interact with zafirlukast?
Theophyllines, warfarin, erythromycin, and clarithromycin.

21. Why should food be avoided with zafirlukast?
Food decreases its bioavailability by approximately 40%.

22. What are some behavioral side effects of zafirlukast?
Mood changes, depression, and suicidal ideation.

23. What are the respiratory-related side effects of zafirlukast?
Cough, nasal congestion, pharyngitis, and throat pain.

24. What is a key care consideration when monitoring patients on zafirlukast?
Watch for neuropsychiatric symptoms and consider discontinuing if symptoms appear.

25. What is a major benefit of zafirlukast in asthma treatment?
It reduces the frequency of asthma symptoms and prevents exercise-induced bronchospasm.

26. What conditions can zafirlukast help prevent besides asthma?
It may be used for prophylaxis of allergic rhinitis.

27. Why is zafirlukast not suitable for treating an asthma attack?
It lacks rapid bronchodilatory action needed to relieve acute symptoms.

28. What happens if zafirlukast is taken with alcohol?
It may increase the risk of liver toxicity.

29. How does zafirlukast affect mucus production?
It decreases mucus secretion by blocking leukotriene action.

30. Which drugs are in the same class as zafirlukast?
Montelukast (Singulair) and Zileuton (Zyflo CR).

31. What is the interaction between zafirlukast and warfarin or aspirin?
Zafirlukast may increase the risk of bleeding when taken with warfarin or aspirin due to effects on clotting factors.

32. How does zafirlukast interact with theophylline?
Zafirlukast inhibits the metabolism of theophylline, potentially increasing theophylline serum levels and toxicity risk.

33. How does food affect the bioavailability of zafirlukast?
Food decreases the bioavailability of zafirlukast by approximately 40%, so it should be taken on an empty stomach.

34. What is the recommended action if a zafirlukast overdose is suspected?
Supportive care should be initiated; treatment typically involves monitoring and symptom management, as there is no specific antidote.

35. Why should zafirlukast not be used during acute asthma attacks?
Zafirlukast lacks rapid bronchodilatory effects and is not effective for immediate symptom relief.

36. When should zafirlukast be administered in relation to meals?
It should be taken at least 1 hour before or 2 hours after eating to ensure optimal absorption.

37. What levels should be monitored when zafirlukast is used concurrently with warfarin or aspirin?
PT/INR levels should be monitored to detect changes in bleeding risk.

38. Why is it important to monitor liver function in patients taking zafirlukast?
Zafirlukast can cause liver toxicity; elevated liver enzymes or symptoms like jaundice require immediate medical attention.

39. What behavioral changes should patients taking zafirlukast report to their healthcare provider?
Patients should report mood swings, depression, agitation, or suicidal thoughts.

40. Which medications should not be relied on for treating acute asthma symptoms?
Anticholinergics, LABAs, mast cell stabilizers, and corticosteroids are not intended for acute symptom relief.

41. What instructions should be given about quick-relief vs long-term asthma inhalers?
Quick-relief inhalers are used at the first sign of symptoms; long-term inhalers are used daily for asthma control.

42. What should patients do after using an inhaled corticosteroid or long-acting inhaler?
They should rinse their mouth and spit to prevent oral thrush.

43. Why should patients keep a log of asthma attack durations?
Tracking attack frequency and duration helps healthcare providers evaluate treatment effectiveness and make adjustments.

44. What urinary symptom should be monitored in patients using zafirlukast?
Patients should report urinary retention to their provider.

45. What should a patient know about correct inhaler administration?
They should be taught inhaler technique, including spacing between puffs and shaking or loading the device as needed.

46. How long should a patient wait between inhaler puffs of the same medication?
Patients should wait 2–3 minutes between puffs to allow for optimal drug delivery.

47. How long should a patient wait before using a second inhaled medication?
A 5-minute wait is recommended between different aerosol medications.

48. What pre-use step is essential when using an MDI inhaler?
Shake the inhaler well before use, or load the device correctly if using powder or tablets.

49. What respiratory assessments should be performed in patients on zafirlukast?
Monitor respiratory rate, lung sounds, and peak expiratory flow rate to assess therapy effectiveness.

50. What vital signs should be monitored during zafirlukast therapy?
Monitor heart rate, respiratory rate, and oxygen saturation to evaluate respiratory function and detect side effects.

51. What safety information should patients carry with them?
Patients should carry medical ID noting their asthma diagnosis, allergies, and current medications.

52. What is the purpose of using a peak flow meter with zafirlukast therapy?
It helps monitor pulmonary function and detect early signs of asthma worsening.

53. What nonpharmacologic measures can support zafirlukast therapy?
Encourage hydration, small frequent meals, rest between activities, and reduced exposure to allergens.

54. Why is it important to monitor sleep and eating patterns during zafirlukast therapy?
Disruptions may indicate poorly controlled asthma or adverse drug effects requiring intervention.

55. What is the function of a spacer with an MDI inhaler?
A spacer improves medication delivery to the lungs and reduces deposition in the throat.

56. What types of medications should patients avoid when on zafirlukast?
Avoid drugs that could increase side effects, such as hepatotoxic agents or interacting bronchodilators.

57. What should patients know about their dosage schedule?
They must follow the prescribed fixed or PRN dosing exactly to maintain effective asthma control.

58. What should patients be advised about dosing limits?
They should not exceed the prescribed dose of zafirlukast, as overdose may increase the risk of side effects.

59. What is the mechanism of action of zafirlukast in asthma management?  
Zafirlukast blocks leukotriene receptors, preventing leukotriene-mediated bronchoconstriction, inflammation, and mucus production.

60. What class of medication is zafirlukast classified under?  
Zafirlukast is classified as a leukotriene receptor antagonist used for asthma prophylaxis.

61. What symptoms of asthma does zafirlukast help alleviate over time?  
Zafirlukast reduces wheezing, shortness of breath, coughing, and chest tightness in chronic asthma.

62. Can zafirlukast be used to treat exercise-induced bronchospasm?  
Yes, zafirlukast can help prevent exercise-induced bronchospasm when taken regularly.

63. At what age is zafirlukast approved for use in children?  
Zafirlukast is approved for use in children aged 5 years and older.

64. What pregnancy category is zafirlukast classified as?  
Zafirlukast is classified as Pregnancy Category B.

65. What are the common gastrointestinal side effects of zafirlukast?  
Common gastrointestinal side effects include nausea, vomiting, abdominal pain, and dyspepsia.

66. Why should patients with liver dysfunction avoid zafirlukast?  
Zafirlukast may cause liver enzyme elevation and hepatic injury, which poses a risk in patients with liver impairment.

67. What respiratory tract symptoms are listed as side effects of zafirlukast?  
Pharyngitis, rhinitis, and cough are potential respiratory side effects of zafirlukast.

68. Why is zafirlukast not suitable for treating acute asthma attacks?  
It lacks the rapid onset of action needed to relieve acute bronchospasm.

69. What is Churg-Strauss syndrome, and how is it related to zafirlukast?  
Churg-Strauss syndrome is a rare vasculitis that can emerge when systemic steroids are withdrawn in patients on zafirlukast.

70. What warning should be given regarding mood and behavior changes with zafirlukast?  
Patients should be warned of potential neuropsychiatric effects such as agitation, hallucinations, or suicidal ideation.

71. What is the onset of therapeutic effect for zafirlukast in asthma control?  
Improvement may be seen as early as Day 1, but full benefits usually occur after 1 to 2 weeks of therapy.

72. How is zafirlukast eliminated from the body?  
Zafirlukast is primarily excreted in the feces, with about 10% eliminated in the urine.

73. What patient teaching is important regarding zafirlukast and meals?  
Patients should be taught to take zafirlukast on an empty stomach, 1 hour before or 2 hours after meals.

74. What symptoms may indicate liver problems while taking zafirlukast?  
Symptoms such as jaundice, dark urine, fatigue, or upper right abdominal pain may signal liver issues.

75. How does zafirlukast compare to montelukast in terms of class?  
Both are leukotriene receptor antagonists used to manage chronic asthma.

76. What is a rare but serious hematologic side effect of zafirlukast?  
Agranulocytosis or eosinophilia can rarely occur, especially in association with Churg-Strauss syndrome.

77. What monitoring is recommended if zafirlukast is used with warfarin?  
Frequent PT/INR monitoring is required due to potential interaction affecting coagulation.

78. Why should zafirlukast not be combined with alcohol?  
Alcohol may increase the risk of liver toxicity when taken with zafirlukast.

79. What is the recommended dosing frequency for zafirlukast?  
Zafirlukast is typically taken twice daily on a consistent schedule to maintain therapeutic levels.

80. What should a patient do if they miss a dose of zafirlukast?  
The patient should take the missed dose as soon as possible, but skip it if it’s almost time for the next dose—never double up.

81. How should zafirlukast be stored?  
Zafirlukast should be stored at room temperature, away from moisture, heat, and direct light.

82. What form does zafirlukast come in for administration?  
Zafirlukast is available in oral tablet form.

83. Why should patients avoid using NSAIDs while on zafirlukast?  
NSAIDs, such as aspirin, may increase the risk of bleeding and alter drug metabolism.

84. What should be assessed before starting zafirlukast therapy?  
Liver function tests should be evaluated before initiating therapy due to potential hepatotoxicity.

85. What should patients be taught regarding zafirlukast and symptom tracking?  
Patients should keep a log of asthma symptoms and triggers to evaluate medication effectiveness.

86. What is the role of zafirlukast in allergic rhinitis?  
Zafirlukast may be used prophylactically to help manage symptoms of seasonal allergic rhinitis.

87. What signs of hypersensitivity should prompt immediate discontinuation of zafirlukast?  
Rash, swelling, itching, or difficulty breathing may indicate an allergic reaction requiring immediate medical attention.

88. What class of drugs should not be used as a substitute for zafirlukast in chronic asthma?  
Short-acting beta-agonists (SABAs) should not replace zafirlukast for long-term control.

89. What effect does zafirlukast have on airway inflammation?  
Zafirlukast reduces airway inflammation by inhibiting leukotriene-mediated responses.

90. Why must zafirlukast be taken regularly, even when symptoms improve?  
Regular use maintains therapeutic levels to prevent asthma exacerbations and inflammation.

91. How does zafirlukast affect mucus production in asthma?  
Zafirlukast decreases mucus production by reducing leukotriene-induced inflammation in the airways.

92. What monitoring is important for patients on long-term zafirlukast therapy?  
Periodic liver function tests and assessment of respiratory status are essential.

93. Can zafirlukast be used with corticosteroids?  
Yes, zafirlukast may be used in conjunction with inhaled corticosteroids for improved asthma control.

94. What effect does food have on the absorption of zafirlukast?  
Food decreases the bioavailability of zafirlukast by approximately 40%.

95. What enzyme pathway metabolizes zafirlukast?  
Zafirlukast is metabolized by the liver via the cytochrome P450 enzyme system.

96. What condition may worsen with the sudden withdrawal of steroids in patients taking zafirlukast?  
Churg-Strauss syndrome may emerge during steroid tapering in patients taking zafirlukast.

97. How should zafirlukast be timed in relation to other inhalers?  
It should be taken separately from inhaled medications and not used as a replacement for quick-relief inhalers.

98. What is the most serious hepatic side effect associated with zafirlukast?  
Symptomatic hepatitis with hyperbilirubinemia or jaundice is a serious potential side effect.

99. How does zafirlukast improve asthma symptoms over time?  
By consistently blocking leukotrienes, it reduces bronchial inflammation, swelling, and constriction.

100. What should patients understand about zafirlukast and emergency situations?  
Zafirlukast is not a rescue medication and should not be relied upon during acute asthma attacks.

Final Thoughts

Zafirlukast represents an important treatment option in the management of asthma and represents the benefits of targeting specific inflammatory pathways. While it may not be the first-line treatment for all patients, it offers valuable alternatives for those who cannot tolerate or prefer not to use inhaled medications.

Success with zafirlukast requires proper patient selection, appropriate dosing, careful monitoring, and good patient education. As with all asthma medications, treatment should be individualized based on patient factors, disease severity, and response to therapy.

Healthcare providers should consider zafirlukast as part of a comprehensive asthma management plan, always keeping in mind the need for regular assessment and adjustment of therapy based on patient response and changing clinical circumstances.