Zafirlukast Medicine - Information, Side effects and uses of Zafirlukast Pharmacokinetics

Zafirlukast is indicated in patients with chronic asthma to improve daytime asthma symptoms, forced expiratory volume in 1 second (FEV 1), and morning peak expiratory flow rates, and to decrease nighttime awakenings, mornings with asthma symptoms, and use of a rescue beta 2 agonist.

When used daily with an as-needed, inhaled beta 2 agonist in patients with mild-to-moderate asthma, zafirlukast significantly reduces asthma symptoms and use of an as-needed, inhaled beta 2 agonist as compared with use of an as-needed, inhaled beta 2 agonist alone. Only patients with mild-to-moderate asthma have been treated with zafirlukast in clinical trials; therefore, its use in the management of patients with more severe asthma and in those receiving antiasthma therapy other than as-needed, inhaled beta 2 agonists remains to be studied, as does use of zafirlukast as an oral or inhaled corticosteroid-sparing agent.

Zafirlukast is not indicated for the treatment of bronchospasm in acute asthma attacks, including status asthmaticus; however, use of zafirlukast can be continued during an acute exacerbation.

Zafirlukast - Mechanism of action/Effect:

Zafirlukast is a selective and competitive receptor antagonist of the cysteinyl leukotrienes D 4 and E 4.

The cysteinyl leukotrienes, originally described as slow-reacting substances of anaphylaxis, produce airway edema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, all of which are associated with the pathophysiology of asthma .

In humans, pretreatment with single oral doses of zafirlukast inhibited bronchoconstriction caused by sulfur dioxide and cold air and reduced the early- and late-phase reaction in patients with asthma caused by inhalation of various antigens, such as grass, cat dander, and ragweed. Zafirlukast reduced the increase in bronchial hyperresponsiveness to inhaled histamine that followed inhaled allergen challenge.

Precaution and Warning while taking Zafirlukast

• Zafirlukast was not mutagenic in reverse or forward point mutation assays or in human and rat assays for chromosomal abnormalities.
• Appropriate studies on the relationship of age to the effects of zafirlukast have not been performed in the pediatric population. Safety and efficacy in children up to 7 years of age have not been established.
• Pregnancy - Adequate and well-controlled studies have not been done in humans.
• In clinical trials, a greater incidence of mild or moderate infections, predominantly affecting the respiratory tract, occurred in patients older than 55 years of age treated with zafirlukast, as compared with other age groups and placebo-treated patients. The number of infections was proportional to the amount, in milligrams, of zafirlukast administered and was associated with concurrent use of inhaled corticosteroids. The clinical significance of this finding is unknown.
• Zafirlukast is distributed into human breast milk. Steady-state concentrations of zafirlukast in breast milk and plasma were 50 and 255 nanograms per mL, respectively, after administration of 40 mg two times a day. Because of the potential for tumorigenicity and adverse effects in the neonate shown in animal studies, use of zafirlukast during breast-feeding is not recommended.
• In patients 65 years of age and older, the clearance of zafirlukast is reduced, resulting in peak plasma concentration and area under the plasma concentration-time curve (AUC) values that are approximately two to three times greater than those of younger patients. However, the recommended dose of 20 mg two times a day did not result in increased adverse effects or withdrawal from the study in elderly patients during clinical trials when compared with patients younger than 65 years of age.

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