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Spotlight on Montelukast in Asthma in Children 2 to 14 Years of Age

  • Adis Spotlight
  • Published:
American Journal of Respiratory Medicine

Abstract

Montelukast is a cysteinyl leukotriene receptor antagonist which is used as a preventive treatment for persistent asthma in patients ≥2 years of age.

In children aged 6 to 14 years montelukast (5 mg/day) treatment resulted in a significant increase in FEV1 (forced expiratory volume in 1 second, primary clinical outcome) during an 8-week randomized, double-blind trial. Moreover, significant improvements were observed for a range of secondary endpoints assessing symptoms, exacerbation rates, β-agonist usage and quality of life.

Concomitant administration of montelukast (5 mg/day) and inhaled budesonide (200μg twice daily) resulted in a trend towards an increase in FEV1 (p = 0.06, primary endpoint) and a statistically significant reduction in both as-needed β2-agonist usage and the percentage of days with asthma exacerbations compared with budesonide plus placebo. No significant differences were observed in asthma-related quality of life between the two groups.

During clinical trials both improvements in lung function and reductions in as-needed β2-agonist usage were generally observed within 1 day after initiation of therapy in children 2 to 14 years of age with persistent asthma.

Data from a randomized, nonblind trial in 6- to 11-year-old children and a 6-month extension to this trial suggest that both compliance to therapy and patient satisfaction are greater for montelukast than for either inhaled cromolyn sodium (sodium cromoglycate) or inhaled beclomethasone. In addition, patients and parents preferred oral montelukast over cromolyn sodium.

In 2- to 5-year-old children with persistent asthma, montelukast (4 mg/day) treatment resulted in significant improvements in a range of outcomes, such as as-needed β2-agonist usage, symptom scores and percentage of days with asthma symptoms, as assessed during a randomized, double-blind trial primarily designed to assess tolerability.

Data from small randomized, double-blind trials suggest that montelukast reduces exercise-induced bronchoconstriction in 6- to 14-year-old children.

Montelukast is generally well tolerated. The frequency of adverse events in montelukast-treated children of all ages was comparable to that in patients receiving placebo.

Conclusion: Oral montelukast has shown efficacy as a preventive treatment for asthma during clinical trials in children aged 2 to 14 years. The drug offers benefits over more standard therapies such as inhaled cromolyn sodium and nedocromil in terms of compliance and convenience. In addition, the drug offers significant benefits when added to inhaled corticosteroids (according to secondary endpoints). Montelukast offers an effective, well tolerated and convenient treatment option for children with asthma.

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References

  1. Sterk PJ. Rationale for leukotriene receptor antagonists as controller therapy for asthma. Eur Respir Rev 1999 Jun; 9 (Rev. 65): 7–12

    Google Scholar 

  2. Holgate ST, Sampson AP. Antileukotriene therapy: future directions. Am J Respir Crit Care Med 2000; 161: S147–53

    PubMed  CAS  Google Scholar 

  3. Leff AR. Role of leukotrienes in bronchial hyperresponsiveness and cellular responses in airways. Am J Respir Crit Care Med 2000; 161: S125–32

    PubMed  CAS  Google Scholar 

  4. Drazen JM. Leukotrienes as mediators of airway obstruction. Am J Respir Crit Care Med 1998; 158: S193–200

    PubMed  CAS  Google Scholar 

  5. Wenzel SE. Inflammation, leukotrienes and the pathogenesis of the late asthmatic response. Clin Exp Allergy 1999; 29: 1–3

    Article  PubMed  CAS  Google Scholar 

  6. Rachelefsky G. Childhood asthma and allergic rhinitis: the role of leukotrienes. J Pediatr 1997; 131(3): 348–55

    Article  PubMed  CAS  Google Scholar 

  7. Devillier P, Baccard N, Advenier C. Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part II: clinical studies with leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma. Pharmacol Res 1999; 40(1): 15–29

    Article  PubMed  CAS  Google Scholar 

  8. Devillier P, Baccard N, Advenier C. Leukotrienes, leukotriene receptor antagonists and leukotriene synthesis inhibitors in asthma: an update. Part I: synthesis, receptors and role of leukotrienes in asthma. Pharmacol Res 1999; 40(1): 3–13

    Article  PubMed  CAS  Google Scholar 

  9. Bisgaard H. Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma. Allergy 2001 May; 56Suppl. 66: 7–11

    Article  PubMed  Google Scholar 

  10. Jones TR, Labelle M, Belley M, et al. Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist [published erratum appears in Can J Physiol Pharmacol 1995 Jun;73(6):747]. Can J Physiol Pharmacol 1995; 73: 191–201

    Article  PubMed  CAS  Google Scholar 

  11. Lynch KR, O’Neill GP, Liu Q, et al. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature 1999; 399: 789–93

    Article  PubMed  CAS  Google Scholar 

  12. Bisgaard H, Nielsen KG. Bronchoprotection with a leukotriene receptor antagonist in asthmatic preschool children. Am J Respir Crit Care Med 2000 Jul; 162(1): 187–90

    PubMed  CAS  Google Scholar 

  13. Bisgaard H, Loland L, Oj JA. NO in exhaled air of asthmatic children is reduced by the leukotriene receptor antagonist montelukast. Am J Respir Crit Care Med 1999 Oct; 160(4): 1227–31

    PubMed  CAS  Google Scholar 

  14. Bratton DL, Lanz MJ, Miyazawa N, et al. Exhaled nitric oxide before and after montelukast sodium therapy in school-age children with chronic asthma: a preliminary study. Pediatr Pulmonol 1999 Dec; 28(6): 402–7

    Article  PubMed  CAS  Google Scholar 

  15. Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics 2001 Sep; 108(3): e48

    Article  PubMed  CAS  Google Scholar 

  16. Knorr B, Matz J, Bernstein JA, et al. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast Study Group. JAMA 1998 Apr 15; 279(15): 1181–6

    Article  PubMed  CAS  Google Scholar 

  17. Simons FE, Villa JR, Lee BW, et al. Montelukast added to budesonide in children with persistent asthma: A randomized, double-blind, crossover study. J Pediatr 2001 May; 138(5): 694–8

    Article  PubMed  CAS  Google Scholar 

  18. Volovitz B, Tabachnik E, Nussinovitch M, et al. Montelukast, a leukotriene receptor antagonist, reduces the concentration of leukotrienes in the respiratory tract of children with persistent asthma. J Allergy Clin Immunol 1999 Dec; 104(6): 1162–7

    Article  PubMed  CAS  Google Scholar 

  19. Merck and Co. Inc. Singulair (montelukast) prescribing information. Rahway (NJ): Merck and Co. Inc., 2001

  20. Knorr B, Larson P, Nguyen HH, et al. Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults. J Clin Pharmacol 1999 Aug; 39(8): 786–93

    Article  PubMed  CAS  Google Scholar 

  21. Knorr B, Nguyen HH, Kearns GL, et al. Montelukast dose selection in children ages 2 to 5 years: comparison of population pharmacokinetics between children and adults. J Clin Pharmacol 2001 Jun; 41: 612–9

    Article  PubMed  CAS  Google Scholar 

  22. Balani SK, Xu X, Pratha V, et al. Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene, receptor antagonist, in human plasma and bile. Drug Metab Dispos 1997; 25: 1282–7

    PubMed  CAS  Google Scholar 

  23. Chiba M, Xu X, Nishime JA. Hepatic microsomal metabolism of montelukast, a potent leukotriene D4receptor antagonist, in humans. Drug Metab Dispos 1997; 25: 1022–31

    PubMed  CAS  Google Scholar 

  24. Knorr B, Holland S, Rogers JD, et al. Montelukast adult (10-mg film-coated tablet) and pediatric (5-mg chewable tablet) dose selections. J Allergy Clin Immunol 2000 Sep; 106 (3 Suppl.): S171–8

    Article  PubMed  CAS  Google Scholar 

  25. Malmstrom K, Schwartz J, Reiss TF, et al. Effect of montelukast on single-dose theophylline pharmacokinetics. Am J Ther 1998; 5: 189–95

    Article  PubMed  CAS  Google Scholar 

  26. Van Hecken A, Depre M, Verbesselt R, et al. Effect of montelukast on the pharmacokinetics and pharmacodynamics of warfarin in healthy volunteers. J Clin Pharmacol 1999; 39(5): 495–500

    PubMed  Google Scholar 

  27. Depré M, Van Hecken A, Verbesselt R, et al. Effect of multiple doses of montelukast, a CysLT1 receptor antagonist, on digoxin pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999; 39(9): 941–4

    Article  PubMed  Google Scholar 

  28. Holland S, Gertz B, DeSmet M, et al. Montelukast (MON) has no effect on terfenadine (T) pharmacokinetics (PK) or QTc [abstract PIII-99]. Clin Pharmacol Ther 1998; 63: 232

    Google Scholar 

  29. Schwartz J, Larson P, Ebel D, et al. Lack of impact of a leukotriene (LT) D4 receptor antagonist, montelukast (M), on ethinyl estradiol (EE) and norethindrone (NET) serum concentrations [abstract]. 98th Annual Meeting American Society for Clinical Pharmacology and Therapeutics; 1997; San Diego, 162

  30. Holland S, Shahane A, Rogers JD, et al. Metabolism of montelukast is increased by multiple doses of phenobarbital [abstract PIII-99]. Clin Pharmacol Ther 1998; 63: 231

    Google Scholar 

  31. Williams B, Noonan G, Reiss TF, et al. Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin Exp Allergy 2001 Jun; 31(6): 845–54

    Article  PubMed  CAS  Google Scholar 

  32. Volovitz B, Dueñas-Meza E, Chmielewska-Szewczyk DA, et al. Comparison of oral montelukast and inhaled cromolyn with respect to preference, satisfaction, and adherence: a multicenter, randomized, open-label, crossover study in children with mild to moderate persistent asthma. Curr Ther Res Clin Exp 2000; 61(7): 490–506

    Article  CAS  Google Scholar 

  33. Kemp JP, Dockhorn RJ, Shapiro GG, et al. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr 1998; 133: 424–8

    Article  PubMed  CAS  Google Scholar 

  34. Capristo AF, del Giudice MM, Maiello N, et al. Montelukast for the treatment of exercise induced asthma in children, mid term study [abstract P362]. European Respiratory Society annual congress; 1999 Oct 9–13; Madrid

  35. Becker A, Kumar R, Stewart L, et al. Chronobiology of exercise-induced bronchoconstriction in pediatric asthma: response to montelukast [abstract]. Am J Respir Crit Care Med 2000 Mar; 161 Suppl. Pt 2: 194

    Google Scholar 

  36. Storms W, Michele TM, Knorr B, et al. Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged >6 years. Clin Exp Allergy 2001 Jan; 31(1): 77–87

    Article  PubMed  CAS  Google Scholar 

  37. Merck Sharp & Dohme Limited. Singulair (Montelukast) prescribing information 4mg. Hoddesdon: Merck Sharp & Dohme, 2001

    Google Scholar 

  38. Merck Sharp & Dohme Limited. Singulair (Montelukast) prescribing information 10mg and 5mg. Hoddesdon: Merck Sharp & Dohme, 2001

    Google Scholar 

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Acknowledgements

The full text article in Pediatric Drugs 2002; 4 (2): 123–139 was reviewed by: J. Haughney, Alison Lea Medical Centre, Calderwood, East Kilbride, UK; M.E. Krawiec, Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA; D. Ng, Department of Paediatrics, Kwong Wab Hospital, Kowloon, Hong Kong; E. Simons, Department of Pediatrics & Child Health, University of Manitoba, Winnipeg, Manitoba, Canada; B. Volovitz, Asthma Research and Education, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel.

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  1. Adis International Inc., 860 Town Center Drive, Langhorne, Pennsylvania, 19047, USA

    Richard B. R. Muijsers & Stuart Noble

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  1. Richard B. R. Muijsers
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  2. Stuart Noble
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Correspondence to Richard B. R. Muijsers.

Additional information

This Spotlight is derived from abstract and summary text of an Adis Drug Evaluation originally published in full in Pediatric Drugs 2002; 4 (2): 123–139

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Muijsers, R.B.R., Noble, S. Spotlight on Montelukast in Asthma in Children 2 to 14 Years of Age. Am J Respir Med 1, 225–228 (2002). https://doi.org/10.1007/BF03256612

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