Long-term safety profile

With prolonged treatment, the adverse-event profile in both adults with asthma (treatment for up to 2 years) and children aged 6 to 14 years with asthma (treatment for up to 1 year or longer) did not significantly change.

Additional safety information

• SINGULAIR should not be used as rescue medication to treat acute asthma attacks. Patients should be advised to have appropriate rescue medication available.
• Neuropsychiatric events have been reported in patients taking SINGULAIR. These events included agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, dream abnormalities, hallucinations, insomnia, irritability, restlessness, somnambulism, suicidal thinking and behavior (including suicide), and tremor. The clinical details of some postmarketing reports appear consistent with a drug-induced effect. Patients should be advised to report any neuropsychiatric events.
• While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, SINGULAIR should not be abruptly substituted for inhaled or oral corticosteroids.
• Patients receiving SINGULAIR should not decrease the dose or stop taking any other antiasthma medications unless instructed by a physician.
• Patients with known aspirin sensitivity should continue to avoid aspirin or nonsteroidal antiinflammatory agents while taking SINGULAIR.
• Systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, has been reported. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy.
• Parents or guardians of patients with phenylketonuria should be informed that the 4-mg and 5-mg chewable tablets contain phenylalanine, a component of aspartame.
• SINGULAIR is contraindicated in patients with hypersensitivity to any component of this product.

Linear growth rate in pediatric patients

In a 56-week study of children aged 6 to 8 with asthma
Children taking SINGULAIR had growth rates similar to children taking placebo

Change in height (cm) from randomization visit by scheduled week (treatment group mean + standard error of the mean)

Growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year, for the treatment groups taking SINGULAIR, placebo, and beclomethasone were 5.67 (5.46, 5.88), 5.64 (5.42, 5.86), and 4.86 (4.64, 5.08), respectively (Study III).

The standard errors of the treatment group means in change in height are too small to be visible on the plot.

Study Designs

Study I: A 6-week, double-blind, placebo-controlled study of 172 pediatric patients aged 12 to 23 months, 124 of whom were treated with SINGULAIR.

Study II: SINGULAIR has been evaluated for safety in 573 pediatric patients aged 2 to 5 years in single- and multiple-dose studies.

Study III: A 56-week, multicenter, double-blind, randomized, active- and placebo-controlled parallel-group study of 360 pediatric patients aged 6 to 8 years with mild asthma. Patients were randomized to receive SINGULAIR 5 mg once daily, beclomethasone dipropionate (168 mcg twice daily with a spacer device; total daily dose=336 mcg). or placebo. The study compared the effect on linear growth of SINGULAIR vs placebo and beclomethasone, respectively. For each subject, a growth rate was defined as the slope of a linear regression line fit to the height measurements over 56 weeks.