Leukotrienes are inflammatory molecules released by mast cells in response to inhaled allergens. Cysteinyl leukotrienes bind to receptors on airway smooth muscle and macrophages and activate a number of airway effects, ultimately resulting in bronchoconstriction and inflammation associated with asthma, as well as the pathophysiologic effects associated with allergic rhinitis. Leukotriene receptor antagonists (LTRAs) prevent binding of cysteinyl leukotrienes to active receptors. Currently available LTRAs include montelukast and zafirlukast, with montelukast FDA-approved for prevention and chronic management of asthma in adults and children 12 months of age and older, seasonal allergic rhinitis in adults and children 2 years of age and older, perennial allergic rhinitis in adults and children 6 months of age and older, and prevention of exercise-induced bronchoconstriction in adults and children 6 years of age and older. Zafirlukast is only FDA-approved for use in preventing and managing chronic asthma in adults and children 5 years of age and older.

The Expert Panel created by the National Heart, Lung and Blood Institute considers LTRAs to be alternative, not preferred, treatment options. The GINA guidelines consider LTRAs to be an option for children greater than 5 years of age, adolescents, and adults at all levels of severity, although clinical benefit is not as significant as that seen with low-dose inhaled corticosteroids. In adult patients, LTRAs may be used as an alternative therapy for mild persistent asthma; however, when used as monotherapy, LTRAs are less effective than low-dose inhaled corticosteroids and may contribute to loss of asthma control if substituted in patients already maintained on inhaled corticosteroid therapy. LTRAs may also be utilized as add-on treatment in patients not adequately controlled on low-dose inhaled corticosteroids and may contribute to inhaled corticosteroid dosage reductions in adults with moderate persistent or severe asthma. However, most studies have shown that long-acting inhaled beta2-agonists are more effective than LTRAs as add-on therapy. In pediatric asthma patients, GINA guidelines state that LTRAs provide partial protection against exercise-induced bronchoconstriction and provide moderate clinical improvement with reduced exacerbations when used as adjunctive therapy in patients inadequately controlled with low-dose inhaled corticosteroids. In moderate persistent asthma, however, increasing inhaled corticosteroid doses is more effective than adding LTRAs to existing therapy, and in moderate-to-severe persistent asthma, the addition of montelukast has not been shown to decrease the use of inhaled corticosteroids.