DrugindexOnline^{2nd edition}

Pronouncation: (zah-fur-LOO-cast)
Class: Leukotriene receptor antagonist

Trade Names:
Accolate
- Tablets 10 mg
- Tablets 20 mg

Mechanism of Action

Pharmacology

Inhibits 3 leukotriene receptor types. Leukotrienes have been associated with the longer, inflammatory component of asthma.

Pharmacokinetics

Absorption

Rapidly absorbed. T _max is 3 hr. Bioavailability is unknown. Administration with food reduced the mean bioavailability about 40%.

Distribution

At least 99% bound to proteins (predominantly albumin). Vd is 70 L. Minimal distribution across blood-brain barrier.

Metabolism

Extensively metabolized. Most common metabolic products are hydroxylated metabolites, which are excreted in feces. These metabolites are formed through the cytochrome P450 2C9 pathway. Inhibits CYP3A4 and CYP2C9 isoenzymes.

Elimination

Oral Cl is about 20 L/hr. Biliary route is primary route of excretion. Urinary excretion accounts for about 10% of the dose, while the rest is excreted in feces. The terminal t _½ is about 10 hr. The plasma t _½ is about 8 to 16 hr.

Special Populations

Hepatic Function Impairment

Approximately 50% to 60% greater C _max and AUC compared with healthy subjects.

Elderly

Oral Cl decreases with age. In patients older than 65 yr of age, there are about 2- to 3-fold greater C _max and AUC compared with young adults.

Indications and Usage

Prophylaxis and chronic treatment of asthma in adults and children 5 yr of age and older.

Contraindications

Standard considerations.

Dosage and Administration

Adults and Children 12 yr of age or older

PO 20 mg bid.

Children 5 to 11 yr of age

PO 10 mg bid.

General Advice

• Not to be used for the acute treatment of bronchospasm or asthma symptoms.
• May be used alone or in combination with bronchodilators and inhaled or systemic corticosteroids.
• Administer prescribed dose 1 hr before or 2 hr after meals.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F). Protect from light and moisture.

Drug Interactions

Aspirin

Increased zafirlukast plasma levels.

Erythromycin, theophylline

Lowered zafirlukast plasma concentrations.

Warfarin

Zafirlukast potentiates the hypoprothrombinemic effect of warfarin. Significant increase in the PT may result.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (13%); dizziness (2%).

GI

Nausea, diarrhea (3%); vomiting (2%); dyspepsia (1%).

Hematologic

Agranulocytosis.

Hepatic

ALT elevations (2%).

Hypersensitivity

Hypersensitivity (including urticaria, angioedema, rashes).

Musculoskeletal

Myalgia (2%).

Miscellaneous

Infection (4%); pain, asthenia, abdominal pain, accidental injury, fever, back pain (2%).

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy in children younger than 5 yr of age not established.

Elderly

Drug Cl decreases with age.

Acute asthma

Zafirlukast is not effective in treating acute asthmatic symptoms, but it can be continued during these times.

Infections

Elderly patients experienced an increased frequency of infections (primarily respiratory) compared with placebo-treated patients. These appeared to be associated with coadministration of inhaled corticosteroids.

Overdosage

Symptoms

Rash, upset stomach.

Patient Information

• Explain name, dose, action, and potential side effects of drug.
• Advise patient to take each dose on an empty stomach, either 1 hr before or 2 hr after meals.
• Advise patient to continue taking other medications for asthma as prescribed by health care provider.
• Warn patient that drug is an asthma controller and is not to be used to treat an acute asthma attack. Advise patient to continue to take zafirlukast during an acute attack but to use rescue medication (bronchodilator) to obtain rapid relief of asthma symptoms.
• Instruct patient not to stop the medication once symptoms have been controlled. Continued daily use is necessary to control symptoms.
• Advise patient not to change the dose or stop using unless advised by health care provider.
• Instruct patient not to exceed prescribed dose. Advise patient to contact health care provider if this medication no longer seems to control asthma symptoms.
• Advise patient to discontinue therapy and contact health care provider immediately if any of the following occur: persistent nausea; unexplained fatigue; excessive sleepiness or drowsiness; stomach pain; flu-like symptoms; itching; yellowing of skin or eyes; appetite loss.
• Advise patient to carry Medi-Alert card indicating asthma.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding.
• Caution patient not to take any prescription or OTC medications, dietary supplements, or herbal preparations unless advised by health care provider.
• Advise patient that follow-up visits will be required to monitor therapy and to keep appointments.