Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged ≥ 6 years

Storms, William W.; Michele, Theresa; Knorr, Barbara; Noonan, Gertrude; Shapiro, G.G.; Zhang, J.; Shingo, Sumiko; Reiss, Theodore F.

doi:10.1046/j.1365-2222.2001.00969.x

Cited by 79 publications

(63 citation statements)

References 20 publications

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“…Montelukast is an orally bioavailable cysteinyl leukotriene (LT) receptor antagonist that is effective, safe, well tolerated, and approved by the U.S. Food and Drug Administration for preventive therapy for the inflammatory component in asthma and allergic rhinitis in children 2 years and older (21)(22)(23)(24), with no demonstrable development of tolerance in long-term studies (25,26). We have recently found that the cloned human cysteinyl LT receptors 1 and 2 (LT1-R, LT2-R) (27,28) have increased expression in the tonsillar tissues of children with SA (29).…”

mentioning

confidence: 99%

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Goldbart

Goldman

Veling

et al. 2005

Am J Respir Crit Care Med

284

157

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Background: Children with mild sleep-disordered breathing (SDB), who may not be recommended for adenotonsillectomy, frequently exhibit neurocognitive and behavioral morbidity, and may benefit from alternative therapeutic interventions, such as leukotriene modifier therapy. Methods: Twenty-four children with SDB completed an open-label intervention study for 16 weeks with daily montelukast therapy. Sleep studies and adenoid size estimates from lateral X-ray films of the neck were obtained before and after treatment. In a parallel study, adenoid and tonsillar tissues from children with obstructive sleep apnea or recurrent throat infections were subjected to quantitative polymerase chain reaction, immunohistochemistry, and Western blotting for gene and protein expression of leukotriene receptors LT1-R and LT2-R, and for concentrations of LTB4 and LTC4/D4/E4. Results: Montelukast treatment induced significant reductions in adenoid size and respiratory-related sleep disturbances, which were absent in 16 children with SDB who did not receive treatment. LT1-R and LT2-R mRNA was similarly abundant in adenoid tissues, but increased LT1-R and LT2-R protein expression and higher levels of LTB4 and LTC4/D4/E4 emerged in children with obstructive sleep apnea. Conclusions: Oral therapy with a leukotriene modifier appears to be associated with improved breathing during sleep. Double-blind, placebo-controlled trials will be needed to corroborate current findings and solidly establish antiinflammatory strategies, such as leukotriene modifiers, as therapeutic alternatives in children with SDB too mild to justify referral for adenotonsillectomy.

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mentioning

confidence: 99%

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Goldbart

Goldman

Veling

et al. 2005

Am J Respir Crit Care Med

284

157

View full text Add to dashboard Cite

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“…46 Less serious side effects of montelukast occur uncommonly, but may include pharyngitis, dizziness, nausea, headache, diarrhea, fever, abdominal pain and rash. 33,36,[41][42][43][44] The incidence of adverse events associated with montelukast is comparable to those of other standard therapies for asthma in childhood and in some studies montelukast was equivalent to placebo. 40 Although FDA approval for montelukast has been obtained for children $2 years of age, safety data to date suggest that this agent may also be used for younger patients between the ages of 6 months and 2 years.…”

Section: Safetymentioning

confidence: 95%

“…33,[36][37][38][39][40][41][42][43][44][45] Serious adverse events, such as worsening asthma, appear to be rare 46 and all reported patients with drug overdoses recovered without sequelae. 46 Less serious side effects of montelukast occur uncommonly, but may include pharyngitis, dizziness, nausea, headache, diarrhea, fever, abdominal pain and rash.…”

Section: Safetymentioning

confidence: 99%

Montelukast Sodium: Administration to Children to Control Intermittent Asthma

2010

Clinical Medicine Reviews in Therapeutics

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The prototype cysteinyl leukotriene receptor antagonist, montelukast, is generally considered to have a niche application in the chemotherapy of exercise-induced asthma. It has also been used as add-on therapy in patients whose asthma is poorly controlled with inhaled corticosteroid monotherapy, or with the combination of a long-acting β(2)-agonist and an inhaled corticosteroid. Recently, however, montelukast has been reported to possess secondary anti-inflammatory properties, apparently unrelated to conventional antagonism of cysteinyl leukotriene receptors. These novel activities enable montelukast to target eosinophils, monocytes, and, in particular, the corticosteroid-insensitive neutrophil, suggesting that this agent may have a broader spectrum of anti-inflammatory activities than originally thought. If so, montelukast is potentially useful in the chemotherapy of intermittent asthma because most exacerbations of this condition involve respiratory virus infection-triggered inflammatory mechanisms which, to a large extent, involve airway epithelial cell/neutrophil interactions. The primary objective of this review is to evaluate the role of montelukast in the treatment of intermittent asthma in children.

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“…18,19 Indeed, nasal and oropharyngeal mucosal inflammation are present in adult patients with SDB, 20-23 and C-reactive protein, a systemic marker for inflammation, was reported recently to be increased in the serum of children with SDB and to correlate with the severity of their respiratory disturbance during sleep. 24 Thus, systemic anti-inflammatory agents with relatively safe therapeutic profiles for use in children could serve as an alternative intervention to nasal CPAP, especially when residual SDB is mild.Montelukast is an orally bioavailable cysteinyl-leukotriene receptor antagonist that is effective, safe, well tolerated, and Food and Drug Administration approved for preventive therapy of the inflammatory component in asthma and allergic rhinitis in children 2 years and older, [25][26][27][28] with no demonstrable development of tolerance in long-term studies. 29,30 We recently found that the cloned human cysteinyl leukotriene receptors 1 and 2 31,32 have increased expression in the tonsillar tissues of children with SDB 33 and that 12 to 16 weeks of treatment with montelukast leads to significant improvements in SDB.…”

mentioning

confidence: 99%

“…Montelukast is an orally bioavailable cysteinyl-leukotriene receptor antagonist that is effective, safe, well tolerated, and Food and Drug Administration approved for preventive therapy of the inflammatory component in asthma and allergic rhinitis in children 2 years and older, [25][26][27][28] with no demonstrable development of tolerance in long-term studies. 29,30 We recently found that the cloned human cysteinyl leukotriene receptors 1 and 2 31,32 have increased expression in the tonsillar tissues of children with SDB 33 and that 12 to 16 weeks of treatment with montelukast leads to significant improvements in SDB.…”

mentioning

confidence: 99%

Intranasal Steroids and Oral Leukotriene Modifier Therapy in Residual Sleep-Disordered Breathing After Tonsillectomy and Adenoidectomy in Children

2006

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Financial Disclosure: Drs Kheirandish and Gozal are the recipients of an investigator-initiated grant from Astra Zeneca Ltd for an unrelated research project on the effect of intranasal budesonide in mild sleepdisordered breathing in children. Dr Gozal serves on the national speaker bureau of Merck. ABSTRACTOBJECTIVE. Tonsillectomy and adenoidectomy (T&A) is the primary therapeutic approach for sleep-disordered breathing (SDB) in children. However, residual mild SDB will be found in more than one third of these patients after T&A. We hypothesized that combined therapy with the leukotriene receptor antagonist montelukast and intranasal budesonide would result in normalization of residual SDB after T&A.METHODS. During the period of October 2002 to February 2005, children who underwent T&A for SDB underwent a routine postoperative (second) overnight polysomnographic evaluation (PSG) 10 to 14 weeks after T&A surgery. In children with residual apnea hypopnea index (AHI) Ͼ1 and Ͻ5/hour of total sleep time (TST), treatment with montelukast and intranasal budesonide aqueous solution was administered for a period of 12 weeks (M/B group), at which time a third PSG was performed. Children who had residual SDB and did not receive M/B therapy from their treating physicians were recruited as control subjects.RESULTS. Twenty-two children received M/B, and 14 children served as control subjects. Mean age, gender distribution, ethnicity, and BMI were similar in the 2 treatment groups. The mean AHI at the second PSG was 3.9 Ϯ 1.2/hour of TST and 3.6 Ϯ 1.4/hour of TST in M/B-treated and control patients, respectively. Similar nadir arterial oxygen saturation (87.3 Ϯ 1.2%) and respiratory arousal index (4.6 Ϯ 0.7/hour of TST) were recorded for both groups. However, the M/B group demonstrated significant improvements in AHI (0.3 Ϯ 0.3/hour of TST), in nadir arterial oxygen saturation (92.5 Ϯ 3.0%), and in respiratory arousal index (0.8 Ϯ 0.7/hour of TST) on the third PSG, whereas no significant changes occurred over time in control subjects.CONCLUSIONS. Combined anti-inflammatory therapy that consists of oral montelukast and intranasal budesonide effectively improves and/or normalizes respiratory and sleep disturbances in children with residual SDB after T&A. O BSTRUCTIVE SLEEP APNEA and sleep-disordered breathing (SDB) is a common and highly prevalent disorder in the pediatric age range that affects 2% to 3% of all children. 1 When left untreated, SDB is associated with substantial morbidity, primarily affecting neurobehavioral and cardiovascular systems. 2-9 Thus, because in otherwise normal children SDB is attributed primarily to adenotonsillar hypertrophy, 10,11 tonsillectomy and adenoidectomy (T&A) is currently the most common treatment for children with SDB. 12 However, although a recent meta-analysis of the published literature suggested a relatively high success rate for T&A, averaging ϳ85%, 13 the overall short-term cure rates for this surgical procedure in otherwise healthy children may not be as favorable as previously an...

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Clinical safety and tolerability of montelukast, a leukotriene receptor antagonist, in controlled clinical trials in patients aged ≥ 6 years

Abstract: These data indicate a tolerability profile for montelukast similar to placebo during both short-term and long-term administration, even at doses substantially higher than the recommended clinical dose of 10 mg once daily for adults and 5 mg once daily for children aged 6-14 years.

Cited by 79 publications

References 20 publications

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Leukotriene Modifier Therapy for Mild Sleep-disordered Breathing in Children

Montelukast Sodium: Administration to Children to Control Intermittent Asthma

Intranasal Steroids and Oral Leukotriene Modifier Therapy in Residual Sleep-Disordered Breathing After Tonsillectomy and Adenoidectomy in Children

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