No

Leukotriene Receptor Antagonist

Prophylaxis and chronic treatment of asthma in adults and children greater than or equal to 7 years of age

B

Clinical effects on the fetus: At 2,000 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 a maternally toxic dose of 2,000 mg/kg/day orally. There are no adequate and well controlled trials in pregnant women.

Breast-feeding/lactation: Zafirlukast is excreted in breast milk; do not administer to nursing women

Hypersensitivity to zafirlukast or any of its inactive ingredients

The clearance of zafirlukast is reduced in patients with stable alcoholic cirrhosis such that the C_max and AUC are approximately 50% to 60% greater than those of normal adults.

An increased proportion of zafirlukast patients >55 years old reported infections as compared to placebo-treated patients. 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.

Although the frequency of hepatic transaminase elevations was comparable between zafirlukast and placebo-treated patients, a single case of symptomatic hepatitis and hyperbilirubinemia, without other attributable cause, occurred in patient who had received 40 mg/day of zafirlukast for 100 days. In this patient, the liver enzymes returned to normal within 3 months of stopping zafirlukast.

>10%: Central nervous system: Headache (12.9%)

1% to 10%:

Central nervous system: Dizziness, pain, fever

Gastrointestinal: Nausea, diarrhea, abdominal pain, vomiting, dyspepsia

Neuromuscular & skeletal: Myalgia, weakness

There is no experience to date with zafirlukast overdose in humans

Use supportive treatment measures

CYP2C9 enzyme substrate; CYP2C9 and 3A3/4 enzyme inhibitor

Erythromycin: Coadministration of a single dose of zafirlukast with erythromycin to steady state results in decreased mean plasma levels of zafirlukast by 40% due to a decrease in zafirlukast bioavailability.

Terfenadine: Coadministration of zafirlukast with terfenadine to steady state results in a decrease in the mean C_max (66%) and AUC (54%) of zafirlukast. No effect of zafirlukast on terfenadine plasma concentrations or EKG parameters was seen.

Theophylline: Coadministration of zafirlukast at steady state with a single dose of liquid theophylline preparations results in decreased mean plasma levels of zafirlukast by 30%, but no effects on plasma theophylline levels were observed.

Increased effect: Aspirin: Coadministration of zafirlukast with aspirin results in mean increased plasma levels of zafirlukast by 45%

Increased toxicity: Warfarin: Coadministration of zafirlukast with warfarin results in a clinically significant increase in prothrombin time (PT). Closely monitor prothrombin times of patients on oral warfarin anticoagulant therapy and zafirlukast, and adjust anticoagulant dose accordingly.

Store tablets at controlled room temperature (20°C to 25°C; 68°F to 77°F); protect from light and moisture; dispense in original airtight container

Zafirlukast is a selectively and competitive leukotriene-receptor antagonist (LTRA) 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.

Absorption: Food reduces bioavailability by 40%

Protein binding: >99%, predominantly albumin

Metabolism: extensively metabolized by liver via cytochrome P-450 2C9 enzyme pathway.

Half-life: 10 hours

Time to peak serum concentration: 3 hours

Elimination: Urinary excretion (10%) and feces

Oral:

Children 7-11 years: 10 mg twice daily

Adults: 20 mg twice daily

Elderly: The mean dose (mg/kg) normalized AUC and C_max increase and plasma clearance decreases with increasing age. In patients >65 years of age, there is an 2-3 fold greater C_max and AUC compared to younger adults.

Dosing adjustment in renal impairment: There are no apparent differences in the pharmacokinetics between renally impaired patients and normal subjects.

Dosing adjustment in hepatic impairment: In patients with hepatic impairment (ie, biopsy-proven cirrhosis), there is a 50% to 60% greater C_max and AUC compared to normal subjects.

May cause dizziness

None reported

No information available to require special precautions

No effects or complications reported

Do not use during acute bronchospasm. Take regularly as prescribed, even during symptom-free periods. Do not take more than recommended or discontinue use without consulting prescriber. Do not stop taking other antiasthmatic medications unless instructed by prescriber. Avoid aspirin or aspirin-containing medications unless approved by prescriber. You may experience headache, drowsiness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); gastric upset, nausea, or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report persistent CNS or GI symptoms; muscle or back pain; weakness, fever, chills; yellowing of skin or eyes; dark urine, or pale stool; skin rash; or worsening of condition. Breast-feeding precautions: Do not breast-feed.

Tablet: 10 mg, 20 mg