Accolate Generic Name & Formulations
Accolate 10 mg tablets, white, round, biconvex, film-coated tablets debossed with "P" on one side and "10" on the other, are supplied in opaque
- bottles of 60 tablets
ACCOLATE 20 mg tablets, white, round, biconvex, film-coated tablets debossed with "P" on one side and "20" on the other, are supplied in opaque
- bottles of 60 tablets
Accolate tablets should be stored at controlled room temperature, 20-25° C (68-77° F).
Protect from light and moisture.
Accolate is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.
Accolate Dosage and Administration
Adults and Children
Hepatic impairment including hepatic cirrhosis.
Accolate is contraindicated in patients with hepatic impairment including hepatic cirrhosis.
Cases of life-threatening hepatic failure have been reported in patients treated with zafirlukast. Cases of liver injury without other attributable cause have been reported from post-marketing adverse event surveillance of patients who have received the recommended dose of zafirlukast (40 mg/day). In most, but not all post-marketing reports, the patient’s symptoms abated and the liver enzymes returned to normal or near normal after stopping zafirlukast. In rare cases, patients have either presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death. In extremely rare post-marketing cases, no clinical symptoms or signs suggestive of liver dysfunction were reported to precede the latter observations.
Accolate Boxed Warnings
Cases of life-threatening hepatic failure have been reported in patients treated with zafirlukast.
Zafirlukast should be discontinued if liver dysfunction is suspected based upon clinical signs or symptoms.
Immediately obtain liver function tests (in particular serum ALT) and manage the patient accordingly.
If liver function tests are consistent with hepatic dysfunction, zafirlukast should not be resumed.
Patients in whom zafirlukast was withdrawn because of hepatic dysfunction where no other attributable cause is identified should not be re-exposed to zafirlukast.
Zafirlukast is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus.
Therapy with zafirlukast can be continued during acute exacerbations of asthma.
Patients with asthma on zafirlukast may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy.
Be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients.
These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy.
The possibility that zafirlukast may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established.
Neuropsychiatric events have been reported in patients taking zafirlukast.
Be alert for neuropsychiatric events.
Advise patients to notify their prescriber if these changes occur.
Carefully evaluate the risks and benefits of continuing treatment with zafirlukast if such events occur.
There are no adequate and well-controlled trials in pregnant women. Zafirlukast should be used during pregnancy only if clearly needed.
Nursing Mother Considerations
Zafirlukast is excreted in breast milk. Zafirlukast should not be administered to mothers who are breast-feeding.
The safety and effectiveness of zafirlukast for pediatric patients less than 5 years of age has not been established. The effect of Accolate on growth in children has not been determined.
Based on cross-study comparison, the clearance of zafirlukast is reduced in patients ≥65 years of age such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients.
A total of 8094 patients were exposed to zafirlukast in North American and European short-term placebo-controlled clinical trials. Of these, 243 patients were elderly (≥65 years). No overall difference in adverse events was seen in the elderly patients, except for an increase in the frequency of infections among zafirlukast-treated elderly patients compared to placebo-treated elderly patients (7.0% vs. 2.9%). The infections were not severe, occurred mostly in the lower respiratory tract, and did not necessitate withdrawal of therapy.
Zafirlukast is rapidly absorbed following oral administration. Peak plasma concentrations are generally achieved 3 hours after oral administration.
In two separate studies, one using a high fat and the other a high protein meal, administration of zafirlukast with food reduced the mean bioavailability by ~40%.
Zafirlukast is <99% bound to plasma proteins, predominantly albumin.
Following oral administration of radiolabeled zafirlukast, urinary excretion accounts for ~10% of the dose and the remainder is excreted in feces.
The mean terminal half-life of zafirlukast is ~10 hours in both normal adult patients and patients with asthma.
Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT) by ~35%. Patients on oral warfarin anticoagulant therapy and Accolate should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly.
Coadministration of zafirlukast with a single dose of a liquid theophylline preparation resulted in decreased mean plasma concentrations of zafirlukast by ~30%, but no effect on plasma theophylline concentrations was observed.
Rare cases of patients experiencing increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity after the addition of Accolate to an existing theophylline regimen have been reported.
Coadministration of a single dose of zafirlukast with erythromycin resulted in decreased mean plasma concentrations of zafirlukast by ~40% due to a decrease in zafirlukast bioavailability.
Coadministration of zafirlukast with aspirin resulted in mean increased plasma concentrations of zafirlukast by ~45%.
Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by ~58%. The clinical significance of this interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors.
Accolate Adverse Reactions
Adults and Children ≥12 years of age
Most common (≥1%)
headache, infection, nausea, diarrhea, pain (generalized), asthenia, abdominal pain, accidental injury, dizziness, myalgia, fever, back pain, vomiting, SGPT elevation, dyspepsia.
Pediatric patients 5 to 11 years of age
Most common (≥2%)
headache, abdominal pain
Accolate Clinical Trials
Three US double-blind, randomized, placebo-controlled, 13-week clinical trials in 1380 adults and children ≥12 years of age with mild to moderate asthma demonstrated that zafirlukast improved daytime asthma symptoms, nighttime awakenings, mornings with asthma symptoms, rescue beta2-agonist use, FEV1, and morning peak expiratory flow rate.
had a mean baseline FEV1 of approximately 75% of predicted normal
mean baseline beta2-agonist requirement of approximately 4-5 puffs of albuterol per day.
The results of the largest of the trials are shown below.
Mean Change from Baseline at Study End Point:
Daytime Asthma symptom score (0-3 scale)
- Zafirlukast 20 mg twice daily (N=514) = -0.44*
- Placebo = -0.25
Nightime Awakenings (number per week)
- Zafirlukast 20 mg twice daily (N=514) = -1.27*
- Placebo = -0.43
Mornings with Asthma Symptoms (days per week)
- Zafirlukast 20 mg twice daily (N=514) = -1.32*
- Placebo = -0.75
Rescue β2 -agonist use (puffs per day)
- Zafirlukast 20 mg twice daily (N=514) = -1.15*
- Placebo = -0.24
- Zafirlukast 20 mg twice daily (N=514) = +0.15*
- Placebo = +0.05
Morning PEFR (L/min)
- Zafirlukast 20 mg twice daily (N=514) = +22.06*
- Placebo = +7.63
Evening PEFR (L/min)
- Zafirlukast 20 mg twice daily (N=514) = +13.12*
- Placebo = +10.14
* P <0.05, compared to placebo
In a second and smaller study, the effect of zafirlukast on most efficacy parameters was comparable to the active control (inhaled cromolyn sodium 1600 mcg four times per day) and superior to placebo at end point for decreasing rescue beta2-agonist use.
In these trials, improvement in asthma symptoms occurred within one week of initiating treatment with zafirlukast. The role of zafirlukast in the management of patients with more severe asthma, patients receiving antiasthma therapy other than as-needed, inhaled beta2-agonists, or as an oral or inhaled corticosteroid-sparing agent remains to be fully characterized.
Accolate Patient Counseling
Hepatic dysfunction is a rare side effect of zafirlukast. If patients experience symptoms of hepatic dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia), they should contact their physician immediately. Liver failure resulting in liver transplantation and death has occurred in those taking zafirlukast.
Inform patients that zafirlukast is indicated for the chronic treatment of asthma and should be taken regularly as prescribed, even during symptom-free periods.
Inform patients that zafirlukast is not a bronchodilator and should not be used to treat acute episodes of asthma. When taking zafirlukast, do not decrease the dose or stop taking any other anti-asthma medications unless instructed by a physician.
Inform patients to notify their physician if they experience neuropsychiatric events while using zafirlukast.
Do not take zafirlukast in female patients who are breast-feeding. Alternative anti-asthma medication should be considered in this patient population.
The bioavailability of zafirlukast may be decreased when taken with food. Inform patients that zafirlukast should be taken at least 1 hour before or 2 hours after meals.