Drugs Details

Drugs Info of Accolate
Drugs Details
  • Drugs Type  : FDA
  • Date : 9th Jul 2015 03:40 am
  • Brand Name : Accolate
  • Generic Name : zafirlukast (Pronunciation: za FIR loo kast)
Descriptions

Zafirlukast is a synthetic, selective peptide leukotriene receptor antagonist (LTRA), with the chemical name 4(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3ylmethyl)-3-methoxy-N-o-tolylsulfonylbenzamide. The molecular weight of zafirlukast is 575.7 and the structural formula is:

 

ACCOLATE® (zafirlukast) Structural Formula Illustration

 

The empirical formula is: C31H33N3O6S

Zafirlukast, a fine white to pale yellow amorphous powder, is practically insoluble in water. It is slightly soluble in methanol and freely soluble in tetrahydrofuran, dimethylsulfoxide, and acetone.

ACCOLATE is supplied as 10 and 20 mg tablets for oral administration.

Inactive Ingredients: Film-coated tablets containing croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.

 

What are the possible side effects of zafirlukast (Accolate)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • worsening asthma symptoms;
  • new or worsening cough, fever, trouble breathing;
  • mood or behavior changes, anxiety, depression, sleep problems (insomnia);
  • skin rash, bruising, severe tingling, numbness, pain, muscle weakness; or
  • nausea, pain in your upper stomach, loss of appetite, flu symptoms, itching, dark...

Read All Potential Side Effects and See Pictures of Accolate »

What are the precautions when taking zafirlukast (Accolate)?

Before taking zafirlukast, tell your doctor or pharmacist if you are allergic to it; or to other leukotriene blockers (e.g., montelukast); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems.

Caution is advised when using this drug in the elderly because they may be more sensitive to the side effects of the drug, especially headache, diarrhea and nausea.

This medication should be used during pregnancy only if clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk....

Read All Potential Precautions of Accolate »

Indications

ACCOLATE is indicated for the prophylaxis and chronic treatment of asthmain adults and children 5 years of age and older.

Dosage Administration

Because food can reduce the bioavailability of zafirlukast, ACCOLATE should be taken at least 1 hour before or 2 hours after meals.

Adults and Children 12 years of age and older

The recommended dose of ACCOLATE in adults and children 12 years and older is 20 mg twice daily.

Pediatric Patients 5 through 11 years of age

The recommended dose of ACCOLATE in children 5 through 11 years of age is 10 mg twice daily.

Elderly Patients

Based on cross-study comparisons, the clearance of zafirlukast is reduced in elderly patients (65 years of age and older), such that Cmax and AUC are approximately twice those of younger adults. In clinical trials, a dose of 20 mg twice daily was not associated with an increase in the overall incidence of adverse events or withdrawals because of adverse events in elderly patients.

Patients with Hepatic Impairment

ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis (see CONTRAINDICATIONS). The clearance of zafirlukast is reduced in patients with stable alcoholic cirrhosis such that the Cmax and AUC are approximately 50 - 60% greater than those of normal adults. ACCOLATE has not been evaluated in patients with hepatitis or in long-term studies of patients with cirrhosis.

Patients with Renal Impairment

Dosage adjustment is not required for patients with renal impairment.

How Supplied

ACCOLATE 10 mg Tablets, (NDC 0310-0401) white, unflavored, round, biconvex, film-coated, mini-tablets identified with “ACCOLATE 10” debossed on one side are supplied in opaque HDPE bottles of 60 tablets.

ACCOLATE 20 mg Tablets, (NDC 0310-0402) white, round, biconvex, coated tablets identified with “ACCOLATE 20” debossed on one side are supplied in opaque HDPE bottles of 60 tablets.

Store at controlled room temperature, 20-25°C (6877°F) [see USP]. Protect from light and moisture. Dispense in the original air-tight container.

Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850. Rev . 02/2011

Side Effects

Adults and Children 12 years of age and older

The safety database for ACCOLATE consists of more than 4000 healthy volunteers and patients who received ACCOLATE, of which 1723 were asthmatics enrolled in trials of 13 weeks duration or longer. A total of 671 patients received ACCOLATE for 1 year or longer. The majority of the patients were 18 years of age or older; however, 222 patients between the age of 12 and 18 years received ACCOLATE.

A comparison of adverse events reported by ≥ 1% of zafirlukast-treated patients, and at rates numerically greater than in placebo-treated patients, is shown for all trials in the table below.

 

ADVERSE EVENT ACCOLATE
N=4058
PLACEBO
N=2032
Headache 12.9% 11.7%
Infection 3.5% 3.4%
Nausea 3.1% 2.0%
Diarrhea 2.8% 2.1%
Pain (generalized) 1.9% 1.7%
Asthenia 1.8% 1.6%
Abdominal Pain 1.8% 1.1%
Accidental Injury 1.6% 1.5%
Dizziness 1.6% 1.5%
Myalgia 1.6% 1.5%
Fever 1.6% 1.1%
Back Pain 1.5% 1.2%
Vomiting 1.5% 1.1%
SGPT Elevation 1.5% 1.1%
Dyspepsia 1.3% 1.2%

 

The frequency of less common adverse events was comparable between ACCOLATE and placebo.

Rarely, elevations of one or more liver enzymes have occurred in patients receiving ACCOLATE in controlled clinical trials. In clinical trials, most of these have been observed at doses four times higher than the recommended dose. The following hepatic events (which have occurred predominantly in females) have been reported from postmarketing adverse event surveillance of patients who have received the recommended dose of ACCOLATE (40 mg/day): cases of symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; and rarely, hyperbilirubinemia without other elevated liver function tests. In most, but not all postmarketing reports, the patient's symptoms abated and the liver enzymes returned to normal or near normal after stopping ACCOLATE. In rare cases, patients have presented with fulminant hepatitis or progressed to hepatic failure, liver transplantation and death (see WARNINGS, Hepatotoxicity and PATIENT INFORMATION).

In clinical trials, an increased proportion of zafirlukast patients over the age of 55 years reported infections as compared to placebo-treated patients. A similar finding was not observed in other age groups studied. 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. The clinical significance of this finding is unknown.

In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitisconsistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should 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 ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (seePRECAUTIONS, Eosinophilic Conditions).

Neuropsychiatric adverse events, including insomnia and depression, have been reported in association with ACCOLATE therapy (see PRECAUTIONS,Neuropsychiatric Events). Hypersensitivity reactions, including urticaria,angioedema and rashes, with or without blistering, have also been reported in association with ACCOLATE therapy. Additionally, there have been reports of patients experiencing agranulocytosis, bleeding, bruising, or edema,arthralgia, myalgia, malaise, and pruritus in association with ACCOLATE therapy.

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. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown and not predicted by available in vitro metabolism data and the results of two clinical drug interaction studies (see CLINICAL PHARMACOLOGY and PRECAUTIONS: DRUG INTERACTIONS).

Pediatric Patients 5 through 11 years of age

ACCOLATE has been evaluated for safety in 788 pediatric patients 5 through 11 years of age. Cumulatively, 313 pediatric patients were treated with ACCOLATE 10 mg twice daily or higher for at least 6 months, and 113 of them were treated for one year or longer in clinical trials. The safety profile of ACCOLATE 10 mg twice daily-versus placebo in the 4- and 6-week double-blind trials was generally similar to that observed in the adult clinical trials with ACCOLATE 20 mg twice daily.

In pediatric patients receiving ACCOLATE in multi-dose clinical trials, the following events occurred with a frequency of ≥ 2% and more frequently than in pediatric patients who received placebo, regardless of causality assessment: headache (4.5 vs. 4.2%) and abdominal pain (2.8 vs. 2.3%).

The post-marketing experience in this age group is similar to that seen in adults, including hepatic dysfunction, which may lead to liver failure.

Interactions

In a drug interaction study in 16 healthy male volunteers, coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin resulted in a significant increase in the mean AUC (+ 63%) and half-life (+36%) of S-warfarin. The mean prothrombin time (PT) increased by approximately 35%. This interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system. Patients on oral warfarin anticoagulant therapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see WARNINGS, Concomitant Warfarin Administration). No formal drug-drug interaction studies with ACCOLATE and other drugs known to be metabolized by the cytochrome P450 2C9 isoenzyme (eg, tolbutamide, phenytoin, carbamazepine) have been conducted; however, care should be exercised when ACCOLATE is coadministered with these drugs.

In a drug interaction study in 11 asthmatic patients, coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state resulted in decreased mean plasma levels of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability.

Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline.

Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmatic patients, 18 to 44 years of age, resulted in decreased mean plasma levels of zafirlukast by approximately 30%, but no effect on plasma theophylline levels 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. The mechanism of the interaction between ACCOLATE and theophylline in these patients is unknown (see ADVERSE REACTIONS).

Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma levels of zafirlukast by approximately 45%.

In a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, 40 mg twice daily of zafirlukast had no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy.

No formal drug-drug interaction studies between ACCOLATE and marketed drugs known to be metabolized by the P450 3A4 (CYP3A4) isoenzyme (eg, dihydropyridine calcium-channel blockers, cyclosporin, cisapride) have been conducted. As ACCOLATE is known to be an inhibitor of CYP3A4 in vitro , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with ACCOLATE.

Warnings

Hepatotoxicity

Cases of life-threatening hepatic failure have been reported in patients treated with ACCOLATE. 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 ACCOLATE (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 ACCOLATE. 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.

Physicians may consider the value of liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug enhances the likelihood for recovery.

Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue,lethargy, pruritus, jaundice, flu-like symptoms, and anorexia) and to contact their physician immediately if they occur. Ongoing clinical assessment of patients should govern physician interventions, including diagnostic evaluations and treatment.

If liver dysfunction is suspected based upon clinical signs or symptoms (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, anorexia, and enlarged liver), ACCOLATE should be discontinued. Liver function tests, in particular serum ALT, should be measured immediately and the patient managed accordingly. If liver function tests are consistent with hepatic dysfunction, ACCOLATE therapy should not be resumed. Patients in whom ACCOLATE was withdrawn because of hepatic dysfunction where no other attributable cause is identified should not be re-exposed to ACCOLATE (see PRECAUTIONS, PATIENT INFORMATION andADVERSE REACTIONS).

Bronchospasm

ACCOLATE is not indicated for use in the reversal of bronchospasm in acuteasthma attacks, including status asthmaticus. Therapy with ACCOLATE can be continued during acute exacerbations of asthma.

Concomitant Warfarin Administration

Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT). Patients on oral warfarin anticoagulanttherapy and ACCOLATE should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see PRECAUTIONS:DRUG INTERACTIONS).

Precautions

Information for Patients

Patients should be told that a rare side effect of ACCOLATE is hepatic dysfunction, and to contact their physician immediately if they experience symptoms of hepatic dysfunction (eg. right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia). Liver failure resulting in liver transplantation and death has occurred in patients taking zafirlukast (see WARNINGS, Hepatotoxicity andADVERSE REACTIONS).

ACCOLATE is indicated for the chronic treatment of asthma and should be taken regularly as prescribed, even during symptom-free periods. ACCOLATE is not a bronchodilator and should not be used to treat acute episodes of asthma. Patients receiving ACCOLATE should be instructed not to decrease the dose or stop taking any other antiasthma medications unless instructed by a physician. Patients should be instructed to notify their physician if neuropsychiatric events occur while using ACCOLATE (seePRECAUTIONS, Neuropsychiatric Events). Women who are breast-feeding should be instructed not to take ACCOLATE (see PRECAUTIONS,Nursing Mothers). Alternative antiasthma medication should be considered in such patients.

The bioavailability of ACCOLATE may be decreased when taken with food. Patients should be instructed to take ACCOLATE at least 1 hour before or 2 hours after meals.

Eosinophilic Conditions

In rare cases, patients with asthma on ACCOLATE may present with systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitisconsistent with Churg-Strauss syndrome, a condition which is often treated with systemic steroid therapy. Physicians should 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 ACCOLATE may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established (seeADVERSE REACTIONS).

Neuropsychiatric Events

Neuropsychiatric events have been reported in adult, adolescent and pediatric patients taking ACCOLATE. Post-marketing reports with ACCOLATE include insomnia and depression. The clinical details of some post-marketing reports involving ACCOLATE appear consistent with a drug-induced effect. Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with ACCOLATE if such events occur (see ADVERSE REACTIONS).

Carcinogenesis, Mutagenesis, Impairment of Fertility

In two-year carcinogenicity studies, zafirlukast was administered at dietary doses of 10, 100, and 300 mg/kg to mice and 40, 400, and 2000 mg/kg to rats. Male mice at an oral dose of 300 mg/kg/day (approximately 30 times the maximum recommended daily oral dose in adults and in children on a mg/m² basis) showed an increased incidence of hepatocellular adenomas; female mice at this dose showed a greater incidence of whole body histocytic sarcomas. Male and female rats at an oral dose of 2000 mg/kg/day (resulting in approximately 160 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma area-under the curve [AUC] values) of zafirlukast showed an increased incidence of urinary bladder transitional cell papillomas. Zafirlukast was not tumorigenic at oral doses up to 100 mg/kg (approximately 10 times the maximum recommended daily oral dose in adults and in children on a mg/m² basis) in mice and at oral doses up to 400 mg/kg (resulting in approximately 140 times the exposure to drug plus metabolites from the maximum recommended daily oral dose in adults and in children based on a comparison of the plasma AUC values) in rats. The clinical significance of these findings for the long-term use of ACCOLATE is unknown.

Zafirlukast showed no evidence of mutagenic potential in the reverse microbial assay, in 2 forward point mutation (CHO-HGPRT and mouse lymphoma) assays or in two assays for chromosomal aberrations (the in vitrohuman peripheral blood lymphocyte clastogenic assay and the in vivo ratbone marrow micronucleus assay).

No evidence of impairment of fertility and reproduction was seen in male and female rats treated with zafirlukast at oral doses up to 2000 mg/kg (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m² basis).

Pregnancy Category B

No teratogenicity was observed at oral doses up to 1600 mg/kg/day in mice (approximately 160 times the maximum recommended daily oral dose in adults on a mg/m² basis), up to 2000 mg/kg/day in rats (approximately 410 times the maximum recommended daily oral dose in adults on a mg/m² basis) and up to 2000 mg/kg/day in cynomolgus monkeys (which resulted in approximately 20 times the exposure to drug plus metabolites compared to that from the maximum recommended daily oral dose in adults based on comparison of the AUC values). At an oral dose of 2000 mg/kg/day in rats, maternal toxicity and deaths were seen with increased incidence of early fetal resorption. Spontaneous abortions occurred in cynomolgus monkeys at the maternally toxic oral dose of 2000 mg/kg/day. There are no adequate and well-controlled trials in pregnant women. Because animal reproductive studies are not always predictive of human response, ACCOLATE should be used during pregnancy only if clearly needed.

Nursing Mothers

Zafirlukast is excreted in breast milk. Following repeated 40 mg twice-a-day dosing in healthy women, average steady-state concentrations of zafirlukast in breast milk were 50 ng/mL compared to 255 ng/mL in plasma. Because of the potential for tumorigenicity shown for zafirlukast in mouse and rat studies and the enhanced sensitivity of neonatal rats and dogs to the adverse effects of zafirlukast, ACCOLATE should not be administered to mothers who are breast-feeding.

Pediatric Use

The safety of ACCOLATE at doses of 10 mg twice daily has been demonstrated in 205 pediatric patients 5 through 11 years of age in placebo-controlled trials lasting up to six weeks and with 179 patients in this age range participating in 52 weeks of treatment in an open label extension.

The effectiveness of ACCOLATE for the prophylaxis and chronic treatment of asthma in pediatric patients 5 through 11 years of age is based on an extrapolation of the demonstrated efficacy of ACCOLATE in adults with asthma and the likelihood that the disease course, and pathophysiology and the drug's effect are substantially similar between the two populations. The recommended dose for the patients 5 through 11 years of age is based upon a cross-study comparison of the pharmacokinetics of zafirlukast in adults and pediatric subjects, and on the safety profile of zafirlukast in both adult and pediatric patients at doses equal to or higher than the recommended dose.

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.

Geriatric Use

Based on cross-study comparison, the clearance of zafirlukast is reduced in patients 65 years of age and older such that Cmax and AUC are approximately 2- to 3-fold greater than those of younger patients (seeDOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY).

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 (age 65 years and older). 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.

An open-label, uncontrolled, 4-week trial of 3759 asthma patients compared the safety and efficacy of ACCOLATE 20 mg given twice daily in three patient age groups, adolescents (12-17 years), adults (18-65 years), and elderly (greater than 65 years). A higher percentage of elderly patients (n=384) reported adverse events when compared to adults and adolescents. These elderly patients showed less improvement in efficacy measures. In the elderly patients, adverse events occurring in greater than 1% of the population included headache (4.7%), diarrhea and nausea (1.8%), and pharyngitis(1.3%). The elderly reported the lowest percentage of infections of all three age groups in this study.

OverDose

No deaths occurred at oral zafirlukast doses of 2000 mg/kg in mice (approximately 210 times the maximum recommended daily oral dose in adults and children on a mg/m² basis), 2000 mg/kg in rats (approximately 420 times the maximum recommended daily oral dose in adults and children on a mg/m² basis), and 500 mg/kg in dogs (approximately 350 times the maximum recommended daily oral dose in adults and children on a mg/m² basis).

Overdosage with ACCOLATE has been reported in four patients surviving reported doses as high as 200 mg. The predominant symptoms reported following ACCOLATE overdose were rash and upset stomach. There were no acute toxic effects in humans that could be consistently ascribed to the administration of ACCOLATE. It is reasonable to employ the usual supportive measures in the event of an overdose; eg, remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive therapy, if required.

ContrainDications

ACCOLATE is contraindicated in patients who are hypersensitive to zafirlukast or any of its inactive ingredients.

ACCOLATE is contraindicated in patients with hepatic impairment including hepatic cirrhosis.

Clinical Pharamacology

Mechanism of Action

Zafirlukast is a selective and competitive receptor antagonist of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance ofanaphylaxis (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. Patients with asthma were found in one study to be 25-100 times more sensitive to the bronchoconstricting activity of inhaled LTD4 than nonasthmatic subjects.

In vitro studies demonstrated that zafirlukast antagonized the contractile activity of three leukotrienes (LTC4, LTD4 and LTE4) in conducting airway smooth muscle from laboratory animals and humans. Zafirlukast prevented intradermal LTD4-induced increases in cutaneous vascular permeability and inhibited inhaled LTD4-induced influx of eosinophils into animal lungs. Inhalational challenge studies in sensitized sheep showed that zafirlukast suppressed the airway responses to antigen; this included both the early- and late-phase response and the nonspecific hyperresponsiveness.

In humans, zafirlukast inhibited bronchoconstriction caused by several kinds of inhalational challenges. Pretreatment with single oral doses of zafirlukast inhibited the bronchoconstriction caused by sulfur dioxide and cold air in patients with asthma. Pretreatment with single doses of zafirlukast attenuated the early- and late-phase reaction caused by inhalation of various antigens such as grass, cat dander, ragweed, and mixed antigens in patients with asthma. Zafirlukast also attenuated the increase in bronchial hyperresponsiveness to inhaled histamine that followed inhaled allergen challenge.

Clinical Pharmacokinetics and Bioavailability

Absorption

Zafirlukast is rapidly absorbed following oral administration. Peak plasma concentrations are generally achieved 3 hours after oral administration. The absolute bioavailability of zafirlukast is unknown. 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 approximately 40%.

Distribution

Zafirlukast is more than 99% bound to plasma proteins, predominantly albumin. The degree of binding was independent of concentration in the clinically relevant range. The apparent steady-state volume of distribution (Vss/F) is approximately 70 L, suggesting moderate distribution into tissues. Studies in rats using radiolabeled zafirlukast indicate minimal distribution across the blood-brain barrier.

Metabolism

Zafirlukast is extensively metabolized. The most common metabolic products are hydroxylated metabolites which are excreted in the feces. The metabolites of zafirlukast identified in plasma are at least 90 times less potent as LTD4 receptor antagonists than zafirlukast in a standard in vitro test of activity. In vitro studies using human liver microsomes showed that the hydroxylated metabolites of zafirlukast excreted in the feces are formed through the cytochrome P450 2C9 (CYP2C9) pathway. Additional in vitrostudies utilizing human liver microsomes show that zafirlukast inhibits the cytochrome P450 CYP3A4 and CYP2C9 isoenzymes at concentrations close to the clinically achieved total plasma concentrations (see DRUG INTERACTIONS).

Excretion

The apparent oral clearance (CL/f) of zafirlukast is approximately 20 L/h. Studies in the rat and dog suggest that biliary excretion is the primary route of excretion. Following oral administration of radiolabeled zafirlukast to volunteers, urinary excretion accounts for approximately 10% of the dose and the remainder is excreted in feces. Zafirlukast is not detected in urine.

In the pivotal bioequivalence study, the mean terminal half-life of zafirlukast is approximately 10 hours in both normal adult subjects and patients with asthma. In other studies, the mean plasma half-life of zafirlukast ranged from approximately 8 to 16 hours in both normal subjects and patients with asthma. The pharmacokinetics of zafirlukast are approximately linear over the range from 5 mg to 80 mg. Steady-state plasma concentrations of zafirlukast are proportional to the dose and predictable from single-dose pharmacokinetic data. Accumulation of zafirlukast in the plasma following twice-daily dosing is approximately 45%.

The pharmacokinetic parameters of zafirlukast 20 mg administered as a single dose to 36 male volunteers are shown with the table below.

Mean (% Coefficient of Variation) pharmacokinetic parameters of zafirlukast following single 20 mg oral dose administration to male volunteers (n=36) 

CMAX NG/ML TMAX* H AUC NG• H/ML T½ H CL/F L/H
326 (31.0) 2 (0.5 - 5.0) 1137 (34) 13.3 (75.6) 19.4 (32)
* Median and range

 

Special Populations

Gender: The pharmacokinetics of zafirlukast are similar in males and females. Weight-adjusted apparent oral clearance does not differ due to gender.

Race: No differences in the pharmacokinetics of zafirlukast due to race have been observed.

Elderly: The apparent oral clearance of zafirlukast decreases with age. In patients above 65 years of age, there is an approximately 2-3 fold greater Cmax and AUC compared to young adult patients.

Children: Following administration of a single 20 mg dose of zafirlukast to 20 boys and girls between 7 and 11 years of age, and in a second study, to 29 boys and girls between 5 and 6 years of age, the following pharmacokinetic parameters were obtained:

 

PARAMETER CHILDREN AGE 5-6 YEARS MEAN 
(% COEFFICIENT OF VARIATION)
CHILDREN AGE 7-11 YEARS MEAN
(% COEFFICIENT OF VARIATION)
Cmax (ng/mL) 756 (39%) 601 (45%)
AUC (ng•h/mL) 2458 (34%) 2027 (38%)
tmax (h) 2.1 (61%) 2.5 (55%)
CL/f (L/h) 9.2 (37%) 11.4 (42%)

 

Weight unadjusted apparent clearance was 11.4 L/h (42%) in the 7-11 year old children and 9.2 L/h (37%) in the 5-6 year old children, which resulted in greater systemic drug exposures than that obtained in adults for an identical dose. To maintain similar exposure levels in children compared to adults, a dose of 10 mg twice daily is recommended in children 5-11 years of age (seeDOSAGE AND ADMINISTRATION).

Zafirlukast disposition was unchanged after multiple dosing (20 mg twice daily) in children and the degree of accumulation in plasma was similar to that observed in adults.

Hepatic Insufficiency: In a study of patients with hepatic impairment (biopsy-proven cirrhosis), there was a reduced clearance of zafirlukast resulting in a 50-60% greater Cmax and AUC compared to normal subjects.

Renal Insufficiency: Based on a cross-study comparison, there are no apparent differences in the pharmacokinetics of zafirlukast between renallyimpaired patients and normal subjects.

Drug-Drug Interactions

The following drug interaction studies have been conducted with zafirlukast (see PRECAUTIONS: DRUG INTERACTIONS).

  • Coadministration of multiple doses of zafirlukast (160 mg/day) to steady-state with a single 25 mg dose of warfarin (a substrate of CYP2C9) resulted in a significant increase in the mean AUC (+63%) and half-life (+36%) of S-warfarin. The mean prothrombin time increased by approximately 35%. The pharmacokinetics of zafirlukast were unaffected by coadministration with warfarin.
  • Coadministration of zafirlukast (80 mg/day) at steady-state with a single dose of a liquid theophylline preparation (6 mg/kg) in 13 asthmaticpatients, 18 to 44 years of age, resulted in decreased mean plasma concentrations of zafirlukast by approximately 30%, but no effect on plasma theophylline concentrations was observed.
  • Coadministration of zafirlukast (20 mg/day) or placebo at steady-state with a single dose of sustained release theophylline preparation (16 mg/kg) in 16 healthy boys and girls (6 through 11 years of age) resulted in no significant differences in the pharmacokinetic parameters of theophylline.
  • Coadministration of zafirlukast dosed at 40 mg twice daily in a single-blind, parallel-group, 3-week study in 39 healthy female subjects taking oral contraceptives, resulted in no significant effect on ethinyl estradiol plasma concentrations or contraceptive efficacy.
  • Coadministration of zafirlukast (40 mg/day) with aspirin (650 mg four times daily) resulted in mean increased plasma concentrations of zafirlukast by approximately 45%.
  • Coadministration of a single dose of zafirlukast (40 mg) with erythromycin (500 mg three times daily for 5 days) to steady-state in 11 asthmatic patients resulted in decreased mean plasma concentrations of zafirlukast by approximately 40% due to a decrease in zafirlukast bioavailability.

Clinical Studies

Three U.S. double-blind, randomized, placebo-controlled, 13-week clinical trials in 1380 adults and children 12 years of age and older with mild-tomoderate asthma demonstrated that ACCOLATE improved daytime asthma symptoms, nighttime awakenings, mornings with asthma symptoms, rescue beta2-agonist use, FEV1, and morning peak expiratory flow rate. In these studies, the patients had a mean baseline FEV1 of approximately 75% of predicted normal and a mean baseline beta2-agonist requirement of approximately 4-5 puffs of albuterol per day. The results of the largest of the trials are shown in the table below.

Mean Change from Baseline at Study End Point 

  ACCOLATE 20 MG TWICE DAILY
N=514
PLACEBO
N=248
Daytime Asthma symptom score (0-3 scale) -0.44* -0.25
Nightime Awakenings (number per week) -1.27* -0.43
Mornings with Asthma Symptoms (days per week) -1.32* -0.75
Rescue β2-agonist use (puffs per day) -1.15* -0.24
FEV1 (L) +0.15* +0.05
Morning PEFR (L/min) +22.06* +7.63
Evening PEFR (L/min) +13.12 +10.14
*p < 0.05, compared to placebo

 

In a second and smaller study, the effect of ACCOLATE 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 (figure below).

Mean β2 -agonist use (puffs/day)

View Enlarged Table

 

In these trials, improvement in asthma symptoms occurred within one week of initiating treatment with ACCOLATE. The role of ACCOLATE 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.

Patient Information

ACCOLATE® 
(ak-o-late)
(zafirlukast) Tablets

Read the Patient Information leaflet before you start taking ACCOLATE and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

What is ACCOLATE?

ACCOLATE is a prescription medicine used to help prevent asthma attacks and for the long-term treatment of asthma symptoms in adults and children 5 years and older.

It is not known if ACCOLATE is safe and effective when used in children under 5 years old. The effect of ACCOLATE on growth in children has not been determined.

Do not take ACCOLATE if you need relief right away for a sudden asthma attack. If you get an asthma attack, you should follow the instructions your healthcare provider gave you for treating asthma attacks.

Who should not take ACCOLATE?

Do not take ACCOLATE if you:

  • are allergic to zafirlukast or any of the ingredients in ACCOLATE. See the end of this leaflet for a complete list of ingredients in ACCOLATE.
  • have problems with your liver.

What should I tell my healthcare provider before taking ACCOLATE?

Before you take ACCOLATE, tell your healthcare provider if you:

  • have liver problems
  • have any other medical conditions
  • are pregnant or plan to become pregnant. It is not known if ACCOLATE will harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed. ACCOLATE can pass into your milk; it is not known whether ACCOLATE may harm your baby. Women who are breastfeeding should not take ACCOLATE.

Tell your healthcare provider about all the medicines you take,including prescription and non-prescription medicines, vitamins, and herbalsupplements.

ACCOLATE may affect the way other medicines work, and other medicines may affect how ACCOLATE works.

Especially tell your healthcare provider if you take:

  • warfarin sodium (Coumadin, Jantoven)
  • erythromycin (ERYC, ERY-TAB, PCE)
  • theophylline (Elixophyllin, Theo-24, Theochron, Theolair, Uniphyl)

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take ACCOLATE?

  • Take ACCOLATE exactly as your healthcare provider tells you to take it.
  • Take ACCOLATE regularly, even if you do not have asthma symptoms. Do not change your dose or stop taking ACCOLATE without talking to your healthcare provider.
  • Do not stop taking or change the dose of your other asthma medicines unless your healthcare provider tells you to.
  • Take your prescribed dose of ACCOLATE by mouth at least 1 hour before or 2 hours after meals.
  • ACCOLATE does not treat the symptoms of a sudden asthma attack. Always have a short-acting beta2-agonist medicine (rescue inhaler) with you to treat sudden symptoms. If you do not have a rescue inhaler medicine, talk to your healthcare provider to have one prescribed for you.
  • If you take too much ACCOLATE, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of ACCOLATE? ACCOLATE may cause serious side effects, including:

  • Severe liver problems. In some cases, these liver problems can lead to liver failure, the need for a liver transplant or death. Tell your healthcare provider right away if you have:
  • pain or tenderness in the right upper side of your stomach area (abdomen)
  • nausea
  • tiredness
  • itchiness
  • yellowing of your skin or the whites of your eyes
  • flu-like symptoms
  • loss of appetite
  • dark (tea colored) urine
  • Inflammation of your blood vessels. Rarely, this can happen in people with asthma who take ACCOLATE. This usually, but not always, happens in people who also take a steroid medicine by mouth that is being stopped or the dose is being lowered. Tell your healthcare provider right away if you have:
    • a feeling of pins and needles or numbness of your arms or legs
    • flu like symptoms
    • rash
    • pain and swelling of your sinuses
  • Changes in behaviour or mood. Tell your healthcare provider if you have changes in your behaviour, problems sleeping or feel very sad.
  • Hypersensitivity reactions. Tell your healthcare provider if you have severe itching, breathing problems, skin rash, skin blisters, or skin redness, or swelling.

The most common side effects of ACCOLATE in people 12 years and older include:

  • headache
  • infection
  • nausea
  • diarrhea
  • pain (generalized)

The most common side effects of ACCOLATE in children 5 to 11 years include:

  • headache
  • stomach pain

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all of the possible side effects of ACCOLATE. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1800-FDA-1088.

You may also report side effects to AstraZeneca at 1800-236-9933.

How should I store ACCOLATE?

  • Store ACCOLATE at 68°F to 77°F (20°C -25°C).
  • Keep ACCOLATE tablets dry.
  • Keep ACCOLATE in a tight closed container and keep ACCOLATE out of the light.
  • Keep ACCOLATE and all medicines out of the reach of children.

General information about the safe and effective use of ACCOLATE.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ACCOLATE for a condition for which it was not prescribed. Do not give ACCOLATE to other people, even if they have the same symptoms that you have. It may harm them.

This Patient Information leaflet summarizes the most important information about ACCOLATE. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about ACCOLATE that is written for healthcare professionals.

For more information, go to www.accolate.com or call AstraZeneca Information Center at 1-800-236-9933, Monday through Friday, 8 a.m. – 6 p.m. Eastern Standard Time, excluding holidays.

What are the ingredients in ACCOLATE?

Active ingredient: zafirlukast

Inactive ingredients: croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, povidone, hypromellose, and titanium dioxide.

What do ACCOLATE tablets look like?

  • the 10 mg tablet is white and round with “ACCOLATE 10” marked on one side.
  • the 20 mg tablet is white and round with “ACCOLATE 20” marked on one side.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ZAFIRLUKAST - ORAL

 

(ZA-fir-LOO-kast)

 

COMMON BRAND NAME(S): Accolate

 

USES: Zafirlukast is used to prevent asthma symptoms and to decrease the number of asthma attacks in people 5 and older. It helps make breathing easier by reducing swelling (inflammation) in the airways. Regular use of this medication can help control your asthma, improve your ability to exercise, and decrease the number of times you need to use your rescue inhaler.

This medication works by blocking the activity of natural substances (leukotrienes) that may cause or worsen asthma. This medication does not work immediately and is not used to treat sudden asthma attacks.

 

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used for hay fever and to prevent breathing problems while exercising.

 

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking zafirlukast and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Take this medication by mouth, usually twice a day or as directed by your doctor. Zafirlukast should be taken on an empty stomach at least 1 hour before or 2 hours after meals. Your dosage is based on your age, medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day.

Do not increase or decrease your dose or stop using this medication without consulting your doctor. Continue to take other medications for asthma as directed by your doctor. This medication works over time and is not meant to relieve sudden attacks of asthma. Therefore, if an asthma attack occurs, use your quick-relief inhaler as prescribed.

It may take 1 to 2 weeks before you feel the full benefit of this medication. Inform your doctor if your condition (e.g., asthma symptoms, number of times you use your rescue inhaler) persists or worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Headache, sore throat, trouble sleeping, malaise, and nausea may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

This drug may rarely cause serious (possibly fatal) liver disease. Seek immediate medical attention if you notice any of the following unlikely but very serious side effects: severe stomach/abdominal pain, persistent nausea/vomiting, unusual tiredness, yellowing of the eyes/skin, dark urine.

If your doctor determines that you have experienced liver problems from this medication, do not take it again.

Tell your doctor immediately if any of these rare but very serious side effects occur: mental/mood changes (e.g., agitation, aggression, hallucinations, abnormal dreams, depression, suicidal thoughts/suicide), worsening shortness of breath, tingling of the hands/feet, muscle/joint aches, coughing up blood, swelling of the hands/feet, chest pain, easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat).

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Accolate (zafirlukast) Side Effects Center for a complete guide to possible side effects

Learn More »
 

PRECAUTIONS: Before taking zafirlukast, tell your doctor or pharmacist if you are allergic to it; or to other leukotriene blockers (e.g., montelukast); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver problems.

Caution is advised when using this drug in the elderly because they may be more sensitive to the side effects of the drug, especially headache, diarrhea and nausea.

This medication should be used during pregnancy only if clearly needed. Discuss the risks and benefits with your doctor.

This medication passes into breast milk. Breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Other medications can affect the removal of zafirlukast from your body, which may affect how zafirlukast works. Examples include macrolide antibiotics (such as erythromycin), among others.

This medication can slow down the removal of other medications from your body, which may affect how they work. Examples of affected drugs include theophylline, warfarin, among others.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., liver function tests) may be performed from time to time to check for side effects. Consult your doctor for more details.

Learn to use a peak flow meter, use it daily, and promptly report worsening asthma (such as readings in the yellow or red range or increased use of quick-relief inhalers).

Avoid allergens, irritants, smoking, and other factors that make asthma worse.

Most people with asthma should receive a flu shot annually. Discuss with your doctor.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

 

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Accolate

Generic Name: zafirlukast (Pronunciation: za FIR loo kast)

  • What is zafirlukast (Accolate)?
  • What are the possible side effects of zafirlukast (Accolate)?
  • What is the most important information I should know about zafirlukast (Accolate)?
  • What should I discuss with my healthcare provider before taking zafirlukast (Accolate)?
  • How should I take zafirlukast (Accolate)?
  • What happens if I miss a dose (Accolate)?
  • What happens if I overdose (Accolate)?
  • What should I avoid while taking zafirlukast (Accolate)?
  • What other drugs will affect zafirlukast (Accolate)?
  • Where can I get more information?

What is zafirlukast (Accolate)?

 

Zafirlukast is a leukotriene (loo-koe-TRY-een) inhibitor. Leukotrienes are chemicals your body releases when you breathe in an allergen (such as pollen). These chemicals cause swelling in your lungs and tightening of the muscles around your airways, which can result in asthma symptoms.

Zafirlukast is used to for chronic treatment of asthma, and to prevent asthma attacks in adults and children as young as 5 years old.

Do not give this medication to a child without a doctor's advice.

Zafirlukast may also be used for purposes not listed in this medication guide.

Accolate 10 mg

round, white, imprinted with ACCOLATE 10, ZENECA

What are the possible side effects of zafirlukast (Accolate)?

 

Get emergency medical help if you have any of thesesigns of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • worsening asthma symptoms;
  • new or worsening cough, fever, trouble breathing;
  • mood or behavior changes, anxiety, depression, sleep problems (insomnia);
  • skin rash, bruising, severe tingling, numbness, pain, muscle weakness; or
  • nausea, pain in your upper stomach, loss of appetite, flu symptoms, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

  • headache;
  • diarrhea, stomach pain;
  • weakness;
  • dizziness;
  • muscle pain; or
  • sore throat, cold symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Accolate (zafirlukast) Side Effects Center for a complete guide to possible side effects

Learn More »
 

What is the most important information I should know about zafirlukast (Accolate)?

 

Zafirlukast will not work fast enough to treat an asthma attack that has already begun. Use only a fast-acting inhalation medicine to treat an asthma attack. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.

It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after several weeks of treatment.

Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.

Patient Detailed How Take

What should I discuss with my healthcare provider before taking zafirlukast (Accolate)?

 

You should not use this medication if you are allergic to zafirlukast, or if you have liver disease (including cirrhosis).

To make sure you can safely take zafirlukast, tell your doctor if you have liver disease.

The chewable tablet form of this medication may contain up to 0.842 milligrams of phenylalanine. Talk to your doctor before using this form of zafirlukast if you have phenylketonuria (PKU).

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Zafirlukast can pass into breast milk and may harm a nursing baby. Do not breast-feed while you are taking zafirlukast.

How should I take zafirlukast (Accolate)?

 

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Zafirlukast is usually taken twice daily. Follow your doctor's instructions.

Take zafirlukast on an empty stomach, at least 1 hour before or 2 hours after a meal.

Zafirlukast will not work fast enough to treat an asthma attack that has already begun. Use only a fast-acting inhalation medicine to treat an asthma attack. Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks.

It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after several weeks of treatment.

Asthma is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice, even if you have no asthma symptoms.

Call your doctor right away if you feel that this medicine is not working as well as usual, or if it makes your condition worse. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor.

Store at room temperature away from moisture and heat.

Patient Detailed Avoid Taking

What happens if I miss a dose (Accolate)?

 

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Accolate)?

 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include skin rash and upset stomach.

What should I avoid while taking zafirlukast (Accolate)?

 

Avoid situations or activities that may trigger an asthma attack.

What other drugs will affect zafirlukast (Accolate)?

 

Tell your doctor about all other medicines you use, especially:

  • aspirin;
  • a blood thinner such as warfarin (Coumadin, Jantoven);
  • tolbutamide (Orinase);
  • erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole);
  • theophylline (Elixophyllin, Theo-24, Theochron, Uniphyl);
  • carbamazepine (Carbatrol, Equetro, Tegretol); or
  • phenytoin (Dilantin).

This list is not complete and other drugs may interact with zafirlukast. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

 

Your pharmacist can provide more information about zafirlukast.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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