Prescription Drug Information: ACCOLATE (Page 3 of 4)

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 (see DOSAGE 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.

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 on ACCOLATE therapy 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. These events usually, but not always, have been associated with the reduction of oral steroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between ACCOLATE and these underlying conditions has not been 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.

OVERDOSAGE

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.

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: 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, white, unflavored, round, biconvex, film-coated, mini-tablets identified with “ACCOLATE 10” debossed on one side.

ACCOLATE 20 mg Tablets, white, round, biconvex, coated tablets identified with “ACCOLATE 20” debossed on one side are supplied.

They are supplied by State of Florida DOH Central Pharmacy as follows:

NDC Strength Quantity/Form Color Source Prod. Code
53808-0203-1 20 mg 30 Tablets in a Blister Pack WHITE 0310-0402

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 trademark of the AstraZeneca group of companies.

© AstraZeneca 2001, 2004, 2007, 2009

Manufactured for:

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

By: IPR Pharmaceuticals, Inc.

Canovanas, PR 00729

This Product was Repackaged By:

State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2024. All Rights Reserved.