Usage
- Zafirlukast is prescribed for the prophylaxis and chronic treatment of asthma in adults and children aged 5 years and older. It is also sometimes used to treat allergic rhinitis and exercise-induced asthma.
- Pharmacological classification: Leukotriene receptor antagonist (LTRA).
- Mechanism of action: Zafirlukast selectively and competitively blocks the cysteinyl leukotriene receptor CysLT1. Cysteinyl leukotrienes (LTC4, LTD4, LTE4) are potent bronchoconstrictors, increase vascular permeability, and promote mucus secretion. By blocking their action, zafirlukast helps prevent asthma symptoms.
Alternate Names
How It Works
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Pharmacodynamics: Zafirlukast antagonizes the effects of cysteinyl leukotrienes, resulting in bronchodilation, decreased vascular permeability, and reduced mucus secretion.
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Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration, with peak plasma concentrations (Cmax) reached in about 3 hours. Food reduces bioavailability by approximately 40%.
- Distribution: Highly protein-bound (99%), primarily to albumin. Volume of distribution is about 70 L.
- Metabolism: Primarily metabolized in the liver via CYP2C9, CYP2C19 and CYP3A4 enzymes.
- Elimination: Excreted primarily in feces (more than 90%) with less than 10% excreted in urine. Elimination half-life is approximately 10 hours.
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Mode of action: Binds to the CysLT1 receptor, preventing leukotrienes from binding and initiating their effects.
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Receptor binding: CysLT1 receptor antagonist.
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Elimination pathways: Primarily hepatic metabolism followed by fecal excretion.
Dosage
Standard Dosage
Adults:
- 20 mg orally twice daily, taken at least 1 hour before or 2 hours after meals.
Children:
- 5-11 years: 10 mg orally twice daily, taken at least 1 hour before or 2 hours after meals.
- 12 years and older: 20 mg orally twice daily, taken at least 1 hour before or 2 hours after meals.
- Younger than 5 years: Safety and efficacy not established.
Special Cases:
- Elderly Patients: May have decreased hepatic clearance, but dose adjustment is not routinely recommended. Monitor for side effects.
- Patients with Renal Impairment: Dose adjustment is not necessary.
- Patients with Hepatic Dysfunction: Contraindicated in patients with hepatic impairment, including cirrhosis.
- Patients with Comorbid Conditions: Caution is advised in patients taking other medications metabolized by CYP enzymes, particularly warfarin.
Clinical Use Cases
Zafirlukast is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest). A short-acting beta-agonist should be used for acute asthma attacks.
Dosage Adjustments:
No specific dosage adjustments are routinely recommended for renal impairment or geriatric patients. However, careful monitoring is advised.
Side Effects
Common Side Effects
- Headache
- Infection (particularly upper respiratory tract infections)
- Nausea
- Diarrhea
- Abdominal pain
- Dizziness
- Insomnia
Rare but Serious Side Effects
- Hepatotoxicity (e.g., hepatitis, hepatic failure)
- Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis)
- Hypersensitivity reactions (e.g., angioedema, urticaria)
- Neuropsychiatric events (e.g., depression, hallucinations, suicidal ideation)
Long-Term Effects
Chronic complications from prolonged use are rare but may include hepatic dysfunction.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate intervention include severe hepatotoxicity, Churg-Strauss syndrome, and hypersensitivity reactions.
Contraindications
- Hypersensitivity to zafirlukast.
- Hepatic impairment, including cirrhosis.
Drug Interactions
Zafirlukast can interact with several medications, including:
- Warfarin: Increased risk of bleeding. Close monitoring of INR is required.
- Theophylline: Zafirlukast may increase theophylline levels.
- Aspirin: High-dose aspirin may increase zafirlukast plasma concentration.
- Erythromycin: Decreases zafirlukast levels and efficacy.
- CYP3A4 substrates: May increase levels of other drugs metabolized by CYP3A4 (e.g., simvastatin, lovastatin).
- CYP2C9 substrates: May increase levels of other drugs metabolized by CYP2C9 (e.g., warfarin, tolbutamide).
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B. Zafirlukast should be used during pregnancy only if clearly needed. Weigh the benefits against potential risks.
- Breastfeeding: Zafirlukast is excreted in breast milk. Breastfeeding is not recommended while taking zafirlukast.
Drug Profile Summary
- Mechanism of Action: CysLT1 receptor antagonist, preventing bronchoconstriction, mucus secretion, and vascular permeability.
- Side Effects: Headache, infection, nausea, diarrhea, abdominal pain, dizziness, insomnia; rarely hepatotoxicity, Churg-Strauss syndrome, neuropsychiatric events.
- Contraindications: Hypersensitivity, hepatic impairment.
- Drug Interactions: Warfarin, theophylline, aspirin, erythromycin, CYP3A4 substrates, CYP2C9 substrates.
- Pregnancy & Breastfeeding: Category B; breastfeeding not recommended.
- Dosage: Adults: 20 mg BID; Children 5-11 years: 10 mg BID; 12 years and older: 20 mg BID. Take on an empty stomach.
- Monitoring Parameters: Liver function tests (LFTs), INR if co-administered with warfarin, signs and symptoms of hepatic or neuropsychiatric events.
Popular Combinations
Zafirlukast is sometimes used in combination with inhaled corticosteroids for patients with moderate to severe persistent asthma who do not achieve adequate control with inhaled corticosteroids alone.
Precautions
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Zafirlukast?
A: Adults and children 12 years and older: 20 mg twice daily. Children 5-11 years: 10 mg twice daily. Take on an empty stomach.
Q2: How does Zafirlukast work?
A: It’s a leukotriene receptor antagonist that blocks the action of leukotrienes, substances that cause airway inflammation and bronchoconstriction in asthma.
Q3: What are the common side effects of Zafirlukast?
A: Headache, infection, nausea, diarrhea, abdominal pain, dizziness, and insomnia are common side effects.
Q4: Can Zafirlukast be used to treat an acute asthma attack?
A: No. It is for long-term control and prevention of asthma symptoms, not for acute relief. Use a short-acting bronchodilator (like albuterol) for acute attacks.
Q5: Are there any serious side effects I should be aware of?
A: Yes, although rare, serious side effects can include liver damage, Churg-Strauss syndrome, severe allergic reactions, and neuropsychiatric events (depression, suicidal ideation, etc.).
Q6: What are the contraindications for Zafirlukast?
A: Zafirlukast is contraindicated in patients with known hypersensitivity to the drug and in those with hepatic impairment, including cirrhosis.
Q7: Does Zafirlukast interact with other medications?
A: Yes, significant interactions can occur with warfarin, theophylline, aspirin, erythromycin, and other drugs metabolized by CYP2C9 and CYP3A4.
Q8: Can Zafirlukast be taken during pregnancy or while breastfeeding?
A: It’s a pregnancy category B drug, meaning it should only be used if clearly needed during pregnancy. It is not recommended during breastfeeding.
Q9: What should patients be monitored for while taking Zafirlukast?
A: Monitor liver function tests periodically, observe for any signs of neuropsychiatric effects, and monitor INR if co-administered with warfarin.
Q10: How long does it take for Zafirlukast to become effective?
A: It may take 2-6 weeks for optimal efficacy to be achieved. Patients should continue taking the medication as prescribed even if they do not experience immediate relief.
