(za FIR loo kast)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Accolate: 10 mg, 20 mg
Generic: 10 mg, 20 mg
Brand Names: U.S.
- Leukotriene-Receptor Antagonist
Zafirlukast is a selectively and competitive leukotriene-receptor antagonist (LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.
Vdss: ~70 L
Extensively hepatic via CYP2C9
Feces (~90%); Urine (~10%)
Clearance: Children 5 to 6 years: 9.2 L/hour; Children 7 to 11 years: 11.4 L/hour; Adults: 20 L/hour
Onset of Action
Asthma symptom improvement: Peak effect: 2 to 6 weeks
Time to Peak
Children: 2 to 2.5 hours
Adults: 3 hours
Duration of Action
Asthma symptom improvement: 12 hours
~10 hours (range: 8 to 16 hours)
>99%, primarily to albumin
Special Populations: Hepatic Function Impairment
Approximately 50% to 60% greater Cmax and AUC compared with healthy subjects.
Special Populations: Elderly
In patients older than 65 years of age, there are about 2- to 3-fold greater Cmax and AUC compared with young adults.
Use: Labeled Indications
Asthma: Prophylaxis and chronic treatment of asthma in adults and children 5 years and older.
Off Label Uses
Data from controlled, double-blind trials are conflicting regarding the use of zafirlukast as monotherapy or in combination with antihistamines for the management of chronic urticaria refractory to antihistamine monotherapy. Zafirlukast in combination with antihistamines may be more effective in patients with autoimmune (positive autologous serum skin test [ASST]) chronic urticaria.
Based on clinical practice guidelines from the American Academy of Allergy, Asthma and Immunology (AAAAI); the American College of Allergy, Asthma, and Immunology (ACAAI); the Joint Council of Allergy, Asthma and Immunology (JCAAI); and the World Allergy Organization for the diagnosis and management of acute and chronic urticaria, a leukotriene receptor antagonist may be added to antihistamine therapy in patients who do not respond to antihistamines.
Hypersensitivity to zafirlukast or any component of the formulation; hepatic impairment (including hepatic cirrhosis)
Canadian labeling: Additional contraindications (not in U.S. labeling): Patients in whom zafirlukast was discontinued due to treatment related hepatotoxicity
Asthma: Oral: 20 mg twice daily
Chronic urticaria (off-label use): Oral: 20 mg twice daily (Bagenstose, 2004)
Refer to adult dosing.
Children 5 to 11 years: 10 mg twice daily
Children ≥12 years and Adolescents: Refer to adult dosing.
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
Use is contraindicated.
Oral: Administer at least 1 hour before or 2 hours after a meal.
Store tablets at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light and moisture; dispense in original airtight container.
Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination
Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy
Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy
Ceritinib: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Concurrent use of ceritinib with a CYP2C9 substrate that has a narrow therapeutic index (e.g., warfarin, phenytoin) should be avoided when possible. Monitor therapy
CYP2C9 Inducers (Moderate): May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Consider therapy modification
CYP2C9 Substrates (High risk with Inhibitors): CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates (High risk with Inhibitors). Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP2C9 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy
Enzalutamide: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP2C9 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP2C9 substrate should be performed with caution and close monitoring. Consider therapy modification
Erythromycin (Systemic): May decrease the serum concentration of Zafirlukast. Monitor therapy
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination
Lumacaftor: May decrease the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Lumacaftor may increase the serum concentration of CYP2C9 Substrates (High Risk with Inhibitors or Inducers). Monitor therapy
MiFEPRIStone: May increase the serum concentration of CYP2C9 Substrates (High risk with Inhibitors). Management: Use CYP2C9 substrates at the lowest recommended dose, and monitor closely for adverse effects, during and in the 2 weeks following mifepristone treatment. Consider therapy modification
Rifapentine: May decrease the serum concentration of CYP2C9 Substrates (High risk with Inducers). Monitor therapy
Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy
Theophylline Derivatives: May decrease the serum concentration of Zafirlukast. Zafirlukast may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Zafirlukast may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Incidences reported in children ≥12 years and adults unless otherwise specified.
>10%: Central nervous system: Headache (13%; children 5 to 11 years: 5%)
1% to 10%:
Central nervous system: Dizziness (2%), pain (2%)
Gastrointestinal: Nausea (3%), diarrhea (3%), abdominal pain (2%; children 5 to 11 years: 3%), vomiting (2%), dyspepsia (1%)
Hepatic: Increased serum ALT (2%)
Infection: Infection (4%)
Neuromuscular & skeletal: Back pain (2%), myalgia (2%), weakness (2%)
Miscellaneous: Fever (2%)
<1% (Limited to important or life-threatening): Agranulocytosis, angioedema, arthralgia, bruise, depression, edema, eosinophilia (systemic), eosinophilic pneumonitis, hemorrhage, hepatic failure, hepatitis, hyperbilirubinemia, hypersensitivity reaction, insomnia, malaise, pruritus, skin rash, urticaria, vasculitis (with clinical features of eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss]; rare)
Concerns related to adverse effects:
• Eosinophilia and vasculitis: In rare cases, patients may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss), a condition which is often treated with systemic corticosteroid therapy. Healthcare providers should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between zafirlukast and these underlying conditions has not been established.
• Hepatotoxicity: Serious hepatic adverse events (including hepatitis, hyperbilirubinemia, and hepatic failure) have been reported with use; female patients may be at greater risk. Periodic testing of liver function may be considered (early detection coupled with therapy discontinuation is generally believed to improve the likelihood of recovery). Advise patients to be alert for and to immediately report symptoms (eg, anorexia, right upper quadrant abdominal pain, nausea). If hepatic dysfunction is suspected (due to clinical signs/symptoms), discontinue use immediately and measure liver function tests (particularly ALT); resolution observed in most but not all cases upon discontinuation of therapy. Do not resume or restart if hepatic function studies indicate dysfunction. Use in patients with hepatic impairment (including hepatic cirrhosis) is contraindicated.
• Infections: An increased proportion of patients >55 years of age reported infections as compared to placebo-treated patients. These infections were mostly mild or moderate in intensity and predominantly affected the respiratory tract. Infections occurred equally in both sexes, were dose-proportional to total milligrams of zafirlukast exposure, and were associated with coadministration of inhaled corticosteroids.
• Neuropsychiatric events: Postmarketing reports of behavioral changes (ie, depression, insomnia) have been noted. Instruct patients to report neuropsychiatric symptoms/events during therapy.
Concurrent drug therapy issues:
• Warfarin: Concomitant use with warfarin results in a clinically significant increase in INR; closely monitor INR with concurrent use.
• Elderly: Clearance is decreased in elderly patients; Cmax and AUC are increased approximately two- to threefold in adults ≥65 years compared to younger adults; however, no dosage adjustments are recommended in this age group.
• Reversal of bronchospasm: Not approved for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus; therapy can be continued during acute exacerbations of asthma.
Monitor for improvements in air flow; monitor closely for sign/symptoms of hepatic injury; periodic monitoring of LFTs may be considered (not proved to prevent serious injury, but early detection may enhance recovery)
Pregnancy Risk Factor
Adverse events were not observed in animal reproduction studies except with doses that were also maternally toxic. Based on limited data, an increased risk of teratogenic effects has not been observed with zafirlukast use in pregnancy (Bakhireva, 2007). Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Zafirlukast may be considered for use in women who had a favorable response prior to becoming pregnant; however, initiating a leukotriene receptor antagonist during pregnancy is an alternative (but not preferred) treatment option for mild persistent asthma (NAEPP, 2005).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, abdominal pain, nausea, or diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), insomnia, flu-like symptoms, chills, severe pharyngitis, burning or numbness feeling, shortness of breath, excessive weight gain, swelling of arms or legs, abnormal heartbeat, mood changes, depression, behavioral changes, angina, or sinusitis (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: leukotriene modifiers
Other brands: Accolate