Introduction            

Montelukast, a selective antagonist of the cysteinyl leukotriene receptor-1, is effectively used for treatment of chronic asthma, especially exercise-induced bronchoconstriction. This pooled analysis summarized the safety data in adult and paediatric patients who received montelukast in controlled clinical trials.

Aim

To analyze safety data of montelukast from double-blind, randomized, placebo-controlled trials in paediatric and adults with chronic asthma

Patient Profile

• 3722 patients (aged >6 years) with chronic asthma were enrolled in the Phase IIb and III trials

Method

Study Design

• Pooled analysis of safety data of montelukast derived from 11 multicentre, randomized, placebo-controlled, double-blind Phase IIb and III trials in patients with chronic asthma (10 trials in adults and one in children) and five long-term extension studies (four trials in adults with exposures up to 4.1 years, and one in children with exposures up to 1.8 years)
• Paediatric patients received either montelukast 5-mg tablet or a placebo once daily in the evening
• Among adult patients, montelukast was administered at dosages of 2 - 200 mg/day in 2 studies and a dosage of 10 mg or placebo once daily in the evening in the remaining 8 studies. In one of the studies, beclomethasone or a placebo inhaler were administered

Safety Endpoints

• Tolerability (clinical and laboratory assessments)
• Clinical adverse events

Results

Safety

• Overall data from the studies showed that long-term treatment with montelukast was well tolerated
• Montelukast-treated patients demonstrated a similar incidence of clinical and laboratory adverse events as those receiving placebo
• Upper respiratory tract infection, asthma and headache were most commonly noted clinical adverse events; the adverse event of asthma often led to study discontinuations
• The paediatric patients on montelukast treatment or on placebo showed similar occurrence of at least one clinical adverse event (75.6% vs. 75.1%) and individual adverse events (48.9% vs. 48.8%)
• Fewer patients on montelukast reported rhinorrhea versus those on beclomethasone (difference: 11.8%) during the paediatric extension study
• Individual laboratory adverse events did not differ between treatment groups in the paediatric trial
• During the paediatric extension study, adverse laboratory events occurred in 12.1% patients in the montelukast group and 8.1% in the inhaled corticosteroid group
• Discontinuations due to clinical adverse events were 1.5% in placebo- and 2.5% in montelukast-treated paediatric patients
• A higher percentage of adults on placebo had at least one clinical adverse event as compared to montelukast (difference 4.8%) or beclomethasone (difference 7.6%)
• Individual adverse events were similar between montelukast, placebo and beclomethasone groups; however, asthma was higher in placebo versus montelukast (difference 5.6%)
• The incidence of laboratory adverse events was similar among adults
• Discontinuations due to clinical adverse events in adults was highest in the placebo group (4.0%), followed by montelukast- (2.3%) and beclomethasone-treated patients (0.4%)
• No dose-related adverse effects of montelukast were observed in patients treated with high dosages
• None of the patients reported vasculitis or Churg-Strauss syndrome
• Montelukast tolerability profile observed in clinical trials was reflected in the post-marketing safety experience

Conclusion

• Montelukast treatment exhibited a favourable tolerability profile similar to placebo, during both short-term and long-term administration, in randomized controlled trials, and comparative extension studies of up to 1.8 years duration in children with chronic asthma (6-14 years of age) and up to 4 years duration in adult patients (15-85 years of age)
• This data established the safety of montelukast administered even at doses substantially higher than the recommended clinical doses in children and adults

Clin Exp Allergy 2001; 31: 77-87