Accolate

Name: Accolate

Zafirlukast Dosage

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Zafirlukast will not work fast enough to treat an asthma attack. Use only a fast acting inhalation medicine for an asthma attack. Tell your doctor if it seems like your asthma medications don't work as well.

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

Your dose needs may change if you have surgery, are ill, are under stress, or have recently had an asthma attack. Do not change your medication dose or schedule without your doctor's advice.

Keep using this medicine as directed, even if you have no asthma symptoms.

Asthma is sometimes 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. Every person with asthma should remain under the care of a doctor.

If you also use a steroid medication, do not stop using it suddenly or you may have unpleasant withdrawal symptoms. Talk with your doctor about tapering your steroid dose before stopping completely.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

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

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 side effects can this medication cause?

Zafirlukast may cause side effects. Tell your doctor if this symptom is severe or does not go away.

  • headache

Some side effects can be serious. If you experience any of the following symptoms or those listed in the SPECIAL PRECAUTIONS section, call your doctor immediately.

  • nausea
  • loss of appetite
  • pain in the right upper part of your stomach
  • excessive tiredness
  • lack of energy
  • itching
  • yellowing of the skin or eyes
  • flu-like symptoms
  • rash
  • swelling of the eyes, face, lips, tongue, or throat
  • difficulty breathing or swallowing
  • hoarseness
  • pain, burning, numbness, or tingling in the hands or feet

Zafirlukast may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

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

You should not use this medicine if you have liver disease (including cirrhosis).

Zafirlukast will not work fast enough to treat an asthma attack. Use only a fast acting inhalation medicine for an asthma attack. Tell your doctor if it seems like your asthma medications don't work as well.

Do not give this medicine to a child younger than 5 years without a doctor's advice.

Before Using Accolate

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of zafirlukast in children. However, safety and efficacy have not been established in children younger than 5 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of zafirlukast in the elderly. However, elderly patients are more likely to have lower respiratory tract infections and unwanted side effects, which may require caution and an adjustment in the dose for elderly patients receiving zafirlukast.

Pregnancy

Pregnancy Category Explanation
All Trimesters B Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Erythromycin
  • Terfenadine
  • Theophylline
  • Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Asthma attack, acute—Should not be used to control acute asthma.
  • Churg-Strauss syndrome (a rare blood condition)—Use with caution. May make this condition worse.
  • Liver disease (including cirrhosis)—Should not be used in patients with this condition.

How is this medicine (Accolate) best taken?

Use Accolate as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take even during sign-free periods.
  • Take on an empty stomach. Take 1 hour before or 2 hours after meals.
  • Take this medicine at the same time of day.
  • To gain the most benefit, do not miss doses.
  • Keep taking Accolate as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Adverse Reactions

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.

Accolate

PLACEBO

Adverse Event

N=4058

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, Information for Patients).

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.

Clinical pharmacology

Mechanism Of Action

Zafirlukast is a selective and competitive receptor antagonist 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. 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 vitro studies 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. Steadystate 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 tmax1 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)
1. 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 (see DOSAGE 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 renally-impaired 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 asthmatic patients, 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.
  • Coadministration of zafirlukast with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 58% (90% CI:28, 95). The clinical significance of this interaction is unknown. Zafirlukast exposure is likely to be increased by other moderate and strong CYP2C9 inhibitors. Coadministration of zafirlukast with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast.

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-to-moderate 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) -0.441 -0.25
Nightime Awakenings (number per week) -1.271 -0.43
Mornings with Asthma Symptoms (days per week) -1.321 -0.75
Rescue β2-agonist use (puffs per day) -1.151 -0.24
FEV1 (L) +0.151 +0.05
Morning PEFR (L/min) +22.061 +7.63
Evening PEFR (L/min) +13.12 +10.14
1. 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).

 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 nonprescription medicines, vitamins, and herbal supplements.

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)
  • fluconazole (Diflucan)

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 1-800-FDA-1088.

You may also report side effects to AstraZeneca at 1-800-236-9933.

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.

Accolate Precautions

Serious side effects have been reported with Accolate including the following:

  • Liver dysfuntion. Tell your healthcare provider right away if you have some or all of the following symptoms: abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, or loss of appetite.
  • Behavior and mood-related changes. Tell your doctor right away if you have mood-related changes.
  • Increase in certain white blood cells (eosinophils) and possible inflamed blood vessels throughout the body (systemic vasculitis). 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. 

If you have asthma and aspirin makes your asthma symptoms worse, continue to avoid taking aspirin or other medicines called non-steroidal anti-inflammatory drugs (NSAIDs) while taking Accolate.

Avoid taking Accolate if you have liver disease including cirrhosis.

Do not taking Accolate if you are allergic to Accolate or to any of its ingredients.

Accolate and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

Accolate has been detected in human breast milk. Because of the potential for serious harm in nursing infants from Accolate, a decision should be made whether to discontinue nursing or to discontinue Accolate, taking into account the importance of the medication to the mother.

Pregnancy & Lactation

Pregnancy Category: B

Lactation: Excreted in breast milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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.

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Read the Accolate User Reviews »

© Accolate Patient Information is supplied by Cerner Multum, Inc. and Accolate Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

For Healthcare Professionals

Applies to zafirlukast: oral tablet

General

The most commons adverse effects may be associated with headache or gastrointestinal disturbances. These symptoms are usually mild.[Ref]

Nervous system

Very common (10% or more): Headache (up to 12.9%)
Common (1% to 10%): Dizziness (1.6%)
Frequency not reported: Neuropathy, neuropsychiatric events[Ref]

Gastrointestinal

Common (1% to 10%): Nausea (up to 3.1%), diarrhea (up to 2.8%), abdominal pain (up to 2.8%), vomiting (up to 1.5%), dyspepsia (1.3%)[Ref]

Hepatic

In most of the postmarketing reports, the patient's symptoms abated and the liver enzymes returned to normal or near normal after stopping this drug.[Ref]

Common (1% to 10%): SGPT elevation (1.5%), AST (1.4%)
Rare (less than 0.1%): Hyperbilirubinemia without other elevated liver function tests; fulminant hepatitis or progressed to hepatic failure, liver transplantation and death
Postmarketing reports: Symptomatic hepatitis (with or without hyperbilirubinemia) without other attributable cause; hepatic dysfunction[Ref]

Musculoskeletal

Common (1% to 10%): Myalgia (1.6%), back pain (1.5%)
Frequency not reported: Arthralgia[Ref]

Other

Common (1% to 10%): Generalized pain (1.9%), asthenia (up to 1.8%), accidental injury (1.6%), fever (1.4%)
Rare (less than 0.1%): Increased theophylline levels with or without clinical signs or symptoms of theophylline toxicity when this drug was added to an existing theophylline regime.
Frequency not reported: Edema, malaise[Ref]

Respiratory

Common (1% to 10%): Respiratory tract infection (3.5%)[Ref]

Infections were usually mild or moderate, predominantly affecting the respiratory tract and not necessitating withdrawal from the therapy.
In clinical trials, an increased proportion of patients over the age of 55 years reported these infections. Infections occurred equally in both sexes and were associated with coadministration of inhaled corticosteroids.[Ref]

Cardiovascular

Rare (less than 0.1%): Bleeding disorders including menorrhagia, thrombocytopenia[Ref]

Dermatologic

Rare (less than 0.1%): Alopecia
Frequency not reported: Bruising, pruritus[Ref]

Hematologic

Rare (0.01% to 0.1%): Granulomatosis
Very rare (less than 0.01%): Agranulocytosis[Ref]

Immunologic

Systemic eosinophilia may also involve various body systems including vasculitic rash, worsening pulmonary symptoms, cardiac complications or neuropathy.[Ref]

Rare (less than 0.1%): Systemic eosinophilia, eosinophilic pneumonia, or clinical features of vasculitis consistent with Churg-Strauss syndrome[Ref]

Hypersensitivity

Frequency not reported: Urticaria, angioedema, rashes (with or without blistering)[Ref]

Psychiatric

Frequency not reported: Insomnia, depression[Ref]

Some side effects of Accolate may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Zafirlukast Levels and Effects while Breastfeeding

Summary of Use during Lactation

No published information is available on the use of zafirlukast during breastfeeding; however, manufacturer's data indicate that the dose in milk is low. If zafirlukast is required by the mother, it is not a reason to discontinue breastfeeding. Because there is no published experience with zafirlukast during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Zafirlukast has been used in children as young as 12 months of age.[1]

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

The manufacturer reports that after administration of zafirlukast 40 mg twice daily to lactating women (number not reported), average steady-state milk concentrations were 50 mcg/L.[2] Using these data, a fully breastfed infant would be expected to receive about 0.6% of the maternal weight-adjusted dosage.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Beclomethasone, Cromolyn, Terbutaline, Theophylline

References

1. Berlin CM, Briggs GG. Drugs and chemicals in human milk. Semin Fetal Neonatal Med. 2005;10:149-59. PMID: 15701580

2. Anon. Accolate Package Insert. AstraZeneca Pharmaceuticals. Wilmington DE. 2011.

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