Accolate

Get emergency medical help if you have any of these 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.

Zafirlukast is an oral leukotriene receptor antagonist used for treating asthma. Leukotrienes are a group of chemicals manufactured in the body from arachidonic acid. Release of leukotrienes within the body, for example, by allergic reactions, promotes inflammation in many diseases such as asthma, a disease in which inflammation occurs in the lungs. Zafirlukast blocks the binding of leukotriene types D4 (LTD4), and E4 (LTE4) and the promotion of inflammation.

The most common health side effects include:

• Headache
• Dizziness
• Nausea
• Diarrhea
• Abdominal pain
• Sore throat
• Respiratory infections
• Rhinitis

Other health side effects and adverse effects include:

• Fever
• Vasculitis
• Eosinophilia
• Bleeding
• Liver failure
• Back pain

• Accolate is the brand name available for this medication.

Before taking zafirlukast,

• tell your doctor and pharmacist if you are allergic to zafirlukast or any other medications.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants ('blood thinners') such as warfarin (Coumadin); aspirin or aspirin-containing products; calcium channel blockers such as amlodipine (Norvasc, in Caduet), diltiazem (Cardizem, Tiazac), felodipine (Plendil), isradipine (Dynacirc), nicardipine (Cardene), nifedipine (Adalat, Procardia, others), nimodipine (Nimotop), nisoldipine (Sular), or verapamil (Calan, Covera, Isoptin, Verelan); carbamazepine (Equetro, Tegretol); cisapride (Propulsid) (not available in the U.S.); cyclosporine (Neoral, Sandimmune); erythromycin (E.E.S, Erythrocin); phenytoin (Dilantin); theophylline (Theo-Dur, others); and tolbutamide. Other medications may also interact with zafirlukast, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• tell your doctor if you have or have ever had liver disease.
• tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking zafirlukast, call your doctor.
• do not breastfeed while you are taking zafirlukast.
• you should know that your mental health may change in unexpected ways while you are taking zafirlukast. You should call your doctor right away if you experience any of the following symptoms: agitation, aggressive behavior, anxiety, irritability, unusual dreams, hallucinations (seeing things or hearing voices that do not exist), depression, difficulty falling asleep or staying sleep, restlessness, suicidal behavior (thinking about harming or killing yourself or planning or trying to do so), or tremor (uncontrollable shaking of a part of the body). Your doctor will decide if you should continue taking zafirlukast.

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

Symptoms of overdose may include:

• nausea
• rash

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

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

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

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

To make sure zafirlukast is safe for you, tell your doctor if you have:

• a history of liver disease;

• if you also take erythromycin or theophylline; or

• if you also take a blood thinner (warfarin, Coumadin, Jantoven).

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).

Zafirlukast is not expected to harm 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. You should not breast-feed while using this medicine.

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.

Avoid situations or activities that may trigger an asthma attack.

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak plasma concentrations attained within 3 hours.1 45 52

Steady-state plasma concentrations are proportional to dose.a

Children 5–11 years of age: Increased peak plasma concentrations, AUC, and systemic exposure.1

Onset

Improvement in asthma symptoms and/or lung function test results and decreased use of β-agonist bronchodilators are evident within 3–14 days.1 14 17 22 25 45 52 53

Food

Food decreases rate and extent of absorption; high-fat or high-protein meal decreases mean bioavailability by approximately 40%.1 45 52 53

Special Populations

In patients with hepatic impairment (stable alcoholic cirrhosis), peak plasma concentration and AUC increased 50–60%.1 45

Asthmatic patients ≥65 years of age: Increased peak plasma concentration and AUC.1 45 52

Distribution

Extent

Not fully characterized.1 45

Minimally crosses the placenta and blood-brain barrier in animals (rats, mice); not known whether zafirlukast crosses the placenta in humans.1 52

Distributed into human milk.1 45 52

Plasma Protein Binding

>99% (mainly albumin).1 45 52

Elimination

Metabolism

Extensively metabolized in the liver principally via CYP2C9.1 45

Elimination Route

Excreted principally in feces (about 90%) via biliary excretion as unchanged drug and metabolites.1 45 52

Half-life

Adults: 8–16 hours.1 45

Special Populations

Clearance is reduced in children 5–11 years of age and adults >65 years of age.1

Clearance is reduced in patients with hepatic impairment.1

Pharmacokinetics not affected by gender, race, or renal function.1

• Risk of hepatotoxicity; importance of patients immediately informing their clinicians if right upper quadrant pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, or anorexia occurs.1

• Importance of taking zafirlukast at regular intervals, when asymptomatic as well as during periods of worsening asthma.1

• Importance of contacting clinician if asthma is not well controlled; seek medical attention if short-acting, inhaled β2-adrenergic bronchodilators are needed more often than usual or if more than the maximum number of inhalations for a 24-hour period are needed.1

• Importance of not using zafirlukast for the relief of acute bronchospasm.1 Patients should be provided with and instructed in the use of a short-acting, inhaled β2-adrenergic bronchodilator as supplemental therapy for acute asthma symptoms.1

• Importance of not discontinuing or reducing the dosage of other antiasthmatic agents unless instructed to do so by the clinician.1 44 45

• If patient experiences exacerbations of asthma after exercise, necessity of continuing the usual regimen of inhaled β2-adrenergic agonist for prophylaxis and of having a short-acting, orally inhaled β2-adrenergic agonist available for rescue.1

• Importance of informing clinicians if behavior or mood changes occur.1 81

• Importance of informing clinicians of existing or concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

Zafirlukast is used to help control the symptoms of asthma and improve lung function. However, this medicine should not be used to relieve an asthma attack that has already started.

This medicine is available only with your doctor's prescription.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Call your doctor right away if your breathing problems get worse, if your rescue inhaler does not work as well, or if you need to use your rescue inhaler more often.
• Liver problems have happened with Accolate. Sometimes, this has been very bad and has led to the need for a liver transplant or death. Liver problems may happen in people with or without liver disease. Talk with the doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• If you are taking warfarin, talk with your doctor. You may need to have your blood work checked more closely while you are taking it with this medicine.
• If you are 65 or older, use Accolate with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

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.

Accolate 10 mg Tablets, (NDC 49884-589-02) white, round, biconvex, film-coated tablets debossed with “P” on one side and “10” on the other, are supplied in opaque HDPE bottles of 60 tablets.

Accolate 20 mg Tablets, (NDC 49884-590-02) white, round, biconvex, film-coated tablets debossed with “P” on one side and “20” on the other, 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.

Accolate is a registered trademark of Par Pharmaceutical, Inc.

Manufactured by:

Par Pharmaceutical Companies, Inc.

Chestnut Ridge, NY 10977 U.S.A.

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 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: o a feeling of pins and needles or numbness of your arms or legs o flu like symptoms o rash o 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 Par Pharmaceutical, Inc. at 1-800-828-9393.

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.parpharm.com, or call 1-800-828-9393.

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

• Astrazeneca

Dosage Forms & Strengths

tablets

• 10mg
• 20mg

Asthma

Indicated for chronic asthma treatment and prophylaxis

20 mg PO twice daily

Administration

Take at least 1 hour before or 2 hours after meals

Take at regular intervals

Hepatic Impairment

Contraindicated

Renal Impairment

Dose adjustment not necessary

Dosage Forms & Strengths

tablets

• 10mg
• 20mg

Asthma

<5 years: Safety and efficacy not established

5-12 years: 10 mg PO twice daily

>12 years: 20 mg PO twice daily

Administration

Take at least 1 hour before or 2 hours after meals

Take at regular intervals

Hepatic Impairment

Contraindicated

Renal Impairment

Dose adjustment not necessary

Clearance reduced in patients aged 65 yr or older (Cmax and AUC 2- to 3-fold higher than in younger patients)

Potential for increased incidence of adverse effects; use caution

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.

Avoid situations or activities that may trigger an asthma attack.