Acute Asthma: SINGULAIR is not indicated for use in the reversal of bronchospasm in acute asthma attacks, including status asthmaticus. Patients should be advised to have appropriate rescue medication available. Therapy with SINGULAIR can be continued during acute exacerbations of asthma. Patients who have exacerbations of asthma after exercise should have available for rescue a short-acting inhaled β-agonist.
Concomitant Corticosteroid Use: While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, SINGULAIR should not be abruptly substituted for inhaled or oral corticosteroids.
Aspirin Sensitivity: Patients with known aspirin sensitivity should continue avoidance of aspirin or non-steroidal anti-inflammatory agents while taking SINGULAIR. Although SINGULAIR is effective in improving airway function in asthmatics with documented aspirin sensitivity, it has not been shown to truncate bronchoconstrictor response to aspirin and other non-steroidal anti-inflammatory drugs in aspirin-sensitive asthmatic patients (see Pharmacology: Pharmacodynamics: Clinical Studies: Asthma under Actions).
Neuropsychiatric Events: Neuropsychiatric events have been reported in adult, adolescent, and pediatric patients taking SINGULAIR. Post-marketing reports with SINGULAIR use include agitation, aggressive behavior or hostility, anxiousness, depression, disorientation, disturbance in attention, dream abnormalities, hallucinations, insomnia, irritability, memory impairment, restlessness, somnambulism, suicidal thinking and behavior (including suicide), tic, and tremor. The clinical details of some post-marketing reports involving SINGULAIR appear consistent with a drug-induced effect.
Patients and prescribers should be alert for neuropsychiatric events. Patients should be instructed to notify their prescriber if these changes occur. Prescribers should carefully evaluate the risks and benefits of continuing treatment with SINGULAIR if such events occur (see Post-Marketing Experience under Adverse Reactions).
Eosinophilic Conditions: Patients with asthma on therapy with SINGULAIR may present with systemic eosinophilia, sometimes presenting with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition which is often treated with systemic corticosteroid therapy. These events have been sometimes associated with the reduction of oral corticosteroid therapy. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal association between SINGULAIR and these underlying conditions has not been established (see Post-Marketing Experience under Adverse Reactions).
Phenylketonuria: Phenylketonuric patients should be informed that the 4-mg and 5-mg chewable tablets contain phenylalanine (a component of aspartame), 0.674 and 0.842 mg per 4-mg and 5-mg chewable tablet, respectively.
Use in Specific Populations: Hepatic Insufficiency: No dosage adjustment is required in patients with mild-to-moderate hepatic insufficiency (see Pharmacology: Pharmacokinetics under Actions).
Renal Insufficiency: No dosage adjustment is recommended in patients with renal insufficiency (see Pharmacology: Pharmacokinetics under Actions).
Use in Children: Safety and efficacy of SINGULAIR have been established in adequate and well-controlled studies in pediatric patients with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults (see Clinical Trials Experience under Adverse Reactions, Pharmacology: Pharmacokinetics: Special Populations and Pharmacodynamics: Clinical Studies: Asthma and Exercise-Induced Bronchoconstriction (EIB) under Actions).
The efficacy of SINGULAIR for the treatment of seasonal allergic rhinitis in pediatric patients 2 to 14 years of age and for the treatment of perennial allergic rhinitis in pediatric patients 6 months to 14 years of age is supported by extrapolation from the demonstrated efficacy in patients 15 years of age and older with allergic rhinitis as well as the assumption that the disease course, pathophysiology and the drug's effect are substantially similar among these populations.
The safety of SINGULAIR 4-mg chewable tablets in pediatric patients 2 to 5 years of age with asthma has been demonstrated by adequate and well-controlled data (see Clinical Trials Experience under Adverse Reactions). Efficacy of SINGULAIR in this age group is extrapolated from the demonstrated efficacy in patients 6 years of age and older with asthma and is based on similar pharmacokinetic data, as well as the assumption that the disease course, pathophysiology and the drug's effect are substantially similar among these populations. Efficacy in this age group is supported by exploratory efficacy assessments from a large, well-controlled safety study conducted in patients 2 to 5 years of age.
The safety of SINGULAIR 4-mg oral granules in pediatric patients 12 to 23 months of age with asthma has been demonstrated in an analysis of 172 pediatric patients, 124 of whom were treated with SINGULAIR, in a 6-week, double-blind, placebo-controlled study (see Clinical Trials Experience under Adverse Reactions). Efficacy of SINGULAIR in this age group is extrapolated from the demonstrated efficacy in patients 6 years of age and older with asthma based on similar mean systemic exposure (AUC), and that the disease course, pathophysiology and the drug's effect are substantially similar among these populations, supported by efficacy data from a safety trial in which efficacy was an exploratory assessment.
The safety of SINGULAIR 4-mg and 5-mg chewable tablets in pediatric patients aged 2 to 14 years with allergic rhinitis is supported by data from studies conducted in pediatric patients aged 2 to 14 years with asthma. A safety study in pediatric patients 2 to 14 years of age with seasonal allergic rhinitis demonstrated a similar safety profile (see Clinical Trials Experience under Adverse Reactions). The safety of SINGULAIR 4-mg oral granules in pediatric patients as young as 6 months of age with perennial allergic rhinitis is supported by extrapolation from safety data obtained from studies conducted in pediatric patients 6 months to 23 months of age with asthma and from pharmacokinetic data comparing systemic exposures in patients 6 months to 23 months of age to systemic exposures in adults.
The safety and effectiveness in pediatric patients below the age of 12 months with asthma, 6 months with perennial allergic rhinitis, and 6 years with exercise-induced bronchoconstriction have not been established.
Growth Rate in Pediatric Patients: A 56-week, multi-center, double-blind, randomized, active- and placebo-controlled parallel group study was conducted to assess the effect of SINGULAIR on growth rate in 360 patients with mild asthma, aged 6 to 8 years. Treatment groups included SINGULAIR 5 mg once daily, placebo, and beclomethasone dipropionate administered as 168 mcg twice daily with a spacer device. For each subject, a growth rate was defined as the slope of a linear regression line fit to the height measurements over 56 weeks. The primary comparison was the difference in growth rates between SINGULAIR and placebo groups. Growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year, for the SINGULAIR, placebo, and beclomethasone treatment groups were 5.67 (5.46, 5.88), 5.64 (5.42, 5.86), and 4.86 (4.64, 5.08), respectively. The differences in growth rates, expressed as least-squares (LS) mean (95% CI) in cm/year, for SINGULAIR minus placebo, beclomethasone minus placebo, and SINGULAIR minus beclomethasone treatment groups were 0.03 (-0.26, 0.31), -0.78 (-1.06, -0.49); and 0.81 (0.53, 1.09), respectively. Growth rate (expressed as mean change in height over time) for each treatment group is shown in FIGURE 2. (See Figure 2.)
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Use in Elderly: Of the total number of subjects in clinical studies of montelukast, 3.5% were 65 years of age and over, and 0.4% were 75 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. The pharmacokinetic profile and the oral bioavailability of a single 10-mg oral dose of montelukast are similar in elderly and younger adults. The plasma half-life of montelukast is slightly longer in the elderly. No dosage adjustment in the elderly is required.