Accolate

Name: Accolate

Is it available as a generic drug?

Yes, it is available as a generic drug.

Is this medication safe to use during pregnancy or while breastfeeding?

  • Safe use of Accolate for prevention and medical treatment for asthma during pregnancy has not been established. Doctors or other health care professionals may prescribe it during pregnancy if it is felt that its benefits outweigh the potential unknown risks.
  • It is secreted into breast milk and should not be used by women who are breastfeeding.

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Reviewed on 3/16/2017 References Reference: FDA Prescribing Information

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What happens if I overdose?

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

Accolate (zafirlukast) side effects

Get emergency medical help if you have signs of an allergic reaction: hives, blisters, severe itching; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • depressed mood, unusual thoughts or behavior;

  • severe sinus pain or congestion;

  • numbness or tingly feeling in your arms or legs;

  • worsening or no improvement in your asthma symptoms;

  • liver problems--nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

  • high levels of certain white blood cells--skin rash, bruising, severe tingling, pain, muscle weakness, new or worsening cough, fever, trouble breathing.

Common side effects may include:

  • nausea, diarrhea, stomach pain;

  • headache; or

  • cold symptoms such as stuffy nose, sneezing, sore throat.

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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Zafirlukast

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

10 mg

Accolate

AstraZeneca

20 mg

Accolate

AstraZeneca

Commonly used brand name(s)

In the U.S.

  • Accolate

Available Dosage Forms:

  • Tablet

Therapeutic Class: Anti-Inflammatory

Pharmacologic Class: Leukotriene Pathway Inhibitor

Proper Use of Accolate

Zafirlukast is used to prevent asthma attacks. It is not used to relieve an attack that has already started. For relief of an asthma attack that has already started, you should use an inhaled medicine that works quickly. If you do not have another medicine to use for an attack or if you have any questions about this, check with your doctor.

Use this medicine only as directed by your doctor. Do not use more of it and do not use it more often than your doctor ordered. Also, do not stop taking this medicine without telling your doctor. To do so may increase the chance of side effects.

This medicine usually comes with patient information leaflet. It is very important that you read and understand this information. Be sure to ask your doctor about anything you do not understand.

Food may change the amount of zafirlukast that is absorbed. It should be taken on an empty stomach, 1 hour before or 2 hours after a meal.

To work properly, zafirlukast must be taken every day at regularly spaced times, even if your asthma seems better.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (tablets):
    • For asthma:
      • Adults and children 12 years of age and older—20 milligrams (mg) two times a day.
      • Children 5 to 11 years of age—10 mg two times a day.
      • Children younger than 5 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

What are some other side effects of Accolate?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Belly pain.
  • Upset stomach.
  • Loose stools (diarrhea).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

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, Information for Patients and ADVERSE REACTIONS).

Bronchospasm:

Accolate is not indicated for use in the reversal of bronchospasm in acute asthma 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 anticoagulant therapy and Accolate should have their prothrombin times monitored closely and anticoagulant dose adjusted accordingly (see PRECAUTIONS, Drug Interactions).

Dosage and 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.

Getting the most from your treatment

  • Try to keep your regular appointments with your doctor. This is so your doctor can check on your progress. Also, your doctor may want you to have blood tests from time to time to check on the way your liver is working.
  • Zafirlukast will not give you immediate relief if you are having an asthma attack. Your doctor will prescribe a reliever inhaler for you to use if this happens. Make sure that you keep it with you all the time in case you need to use it.
  • If you find that your asthma symptoms are getting worse, or that you need to use the reliever inhaler more regularly than usual, please contact your doctor or nurse for advice straightaway.
  • Do not smoke. Smoking causes severe irritation and damage to the lungs. It will make your condition worse and will reduce the beneficial effects of your medication.
  • If you buy any medicines, check with a pharmacist that they are suitable for you to take. Some anti-inflammatory painkillers and aspirin can make asthma symptoms worse in some people.

Indications

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

How supplied

ACCOLATE 10 mg Tablets, (NDC 0310-0401) white, unflavored, round, biconvex, film-coated, minitablets 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 (68-77°F) [see USP]. Protect from light and moisture. Dispense in the original air-tight container.

Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850. Revised: Nov 2013

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 PRECAUTIONS, 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 vasculitis consistent 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 (see PRECAUTIONS, 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.

Accolate Interactions

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • warfarin (Coumadin, Jantoven)
  • theophylline (Theo-24)
  • erythromycin (Ery-Tab, Erythrocin)
  • fluconazole (Diflucan)
  • aspirin

This is not a complete list of Accolate drug interactions. Ask your doctor or pharmacist for more information.

Inform MD

Before using Accolate, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

  • Are allergic to Accolate or to any of its ingredients
  • Have or have had any liver disease including cirrhosis
  • Are pregnant or plan to become pregnant
  • Are breastfeeding or plan to breastfeed

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

     

    Pharmacology

    Mechanism of Action

    Inhibits bronchoconstriction as competitive receptor antagonist of leukotrienes D4 & E4; receptor occupation and cysteinyl leukotriene production has been associated with the pathophysiology of ashtma

    Pharmacokinetics

    Half-Life: 8-16 hr

    Onset: 3-14 days

    Peak plasma concentration: 326 ng/mL (healthy subjects); 568 ng/mL (asthmatics)

    Peak plasm time: 3 hr (healthy subjects); 3.5 hr (asthmatics)

    Clearance: 20 L/hr; significantly decreased in cirrhosis and age 65 yr

    Protein bound: 99%

    Vd: 70 L

    Bioavailability: Reduced 40% with food

    Metabolism: Hepatic CYP2C9

    Excretion: Feces (90%); urine (10%)

    Enzymes inhibited: Hepatic CYP2C9, CYP3A4

    Zafirlukast Pregnancy Warnings

    No teratogenicity was observed at oral doses up to 1600 mg/kg/day in mice, up to 2000 mg/kg/day in rats and up to 2000 mg/kg/day in cynomolgus monkeys. 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. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

    Use is not recommended unless clearly needed. AU TGA pregnancy category: B1 US FDA pregnancy category: B

    (web3)