Singulair: FDA approves new indication for montelukast

Key Points

MERCKLeukotriene receptor antagonist approved for prevention of exercise-induced bronchoconstriction

This agent is a selective, orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotriene (CysL) T₁ receptor, thus inhibiting leukotriene-mediated effects such as airway edema, smooth muscle contraction, and altered cellular activity associated with inflammation. Montelukast was previously approved for the prophylaxis and chronic treatment of asthma in adult and pediatric patients (aged ≥12 months), for the relief of seasonal allergic rhinitis in adult and pediatric patients (aged ≥2 years), and for the relief of perennial allergic rhinitis in adult and pediatric patients (aged ≥6 months). This agent was approved on April 13, 2007, for the prevention of exercise-induced bronchoconstriction in patients aged ≥15 years.

Efficacy. The efficacy of montelukast for the prevention of exercise-induced bronchoconstriction was assessed in 3 randomized, double-blind, placebo-controlled, crossover studies (Studies A, B, and C) that enrolled a total of 160 patients aged ≥15 years. A single 10-mg dose of montelukast or placebo was administered 2 hours before exercise, and exercise-challenge testing was conducted at 2 hours, 8.5 or 12 hours, and 24 hours after dose administration. The primary efficacy end point was the mean maximum percent decrease in forced expiratory volume in 1 second (FEV₁) after exercise challenge. In Study A, patients treated with montelukast demonstrated a statistically significant improvement in FEV₁. At the 2-hour exercise challenge, montelukast-treated patients demonstrated a mean maximum decrease in FEV₁ of 13% versus 22% among placebo-treated patients (treatment difference, –9%; 95% CI, –12% to –5%). At the 8.5-hour exercise challenge, montelukast-treated patients demonstrated a mean maximum decrease in FEV₁ of 12% versus 17% among placebo-treated patients (treatment difference, –5%; 95% CI, –9% to –2%). At the 24-hour exercise challenge, montelukast-treated patients demonstrated a mean maximum decrease in FEV₁ of 10% versus 14% among placebo-treated patients (treatment difference, –4%; 95% CI, –7% to –1%). These results are representative of the results from Studies B and C, as well.

Dosing. For the prevention of exercise-induced bronchoconstriction, patients should take one 10-mg tablet ≥2 hours before exercise. An additional dose should not be taken within 24 hours. If patients are already taking montelukast daily for another indication, they should not take an additional dose for the prevention of exercise-induced bronchoconstriction. Patients should have a short-acting beta-agonist available for rescue therapy.