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Pharmacology 2014Montelukast, a leucotriene receptor antagonist, binds the cysteinyl leucotriene type 1 receptor. Montelukast is commonly prescribed to asthma patients as add-on therapy... (Review)
Review
BACKGROUND
Montelukast, a leucotriene receptor antagonist, binds the cysteinyl leucotriene type 1 receptor. Montelukast is commonly prescribed to asthma patients as add-on therapy to inhaled corticosteroids. Several clinical trials emphasized that montelukast can be considered a safe drug. However, recent evidence reconsidered the benefit/risk ratio of the use of montelukast for both paediatric and adult patients.
SUMMARY
The present review analyzed the previous published case reports regarding montelukast-induced adverse drug reactions (ADRs). They included agitation, anxiety, depression, sleep disturbance, hallucinations, suicidal thinking and suicidality, tremor, dizziness, drowsiness, neuropathies and seizures. The immune system can be involved, in particular, cases of Churg-Strauss syndrome have been published. Furthermore, it can induce hypersensitivity reactions, including anaphylaxis and eosinophilic infiltration. In addition, hepatobiliary, pancreatic and uropoietic disorders have been observed. Some of these cases are characterized by severe prognosis (i.e. neurological deficit and fatal hepatotoxicity). Key Message: The use of montelukast can be burdened by several ADRs, of which physicians should be aware in their clinical practice. A better understanding of the mechanisms causing ADRs after using montelukast could help researchers and clinicians in defining a risk-reduction strategy aimed to lessen montelukast toxicity. More accurate epidemiological studies, in order to discover risk factors favouring montelukast-associated ADRs, are demanded.
Topics: Acetates; Adult; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Humans; Leukotriene Antagonists; Quinolines; Risk Factors; Sulfides
PubMed: 25196099
DOI: 10.1159/000366164 -
Journal of Clinical Sleep Medicine :... Oct 2022Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and...
STUDY OBJECTIVES
Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma.
METHODS
We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications.
RESULTS
Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters.
CONCLUSIONS
Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma.
CITATION
Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. . 2022;18(10):2377-2385.
Topics: Acetates; Adolescent; Adrenal Cortex Hormones; Anti-Allergic Agents; Asthma; Body Mass Index; Carbon Dioxide; Child; Cyclopropanes; Humans; Oxygen; Pediatric Obesity; Quinolines; Retrospective Studies; Sleep; Sulfides
PubMed: 35801341
DOI: 10.5664/jcsm.10114 -
International Journal of Molecular... Oct 2021Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently...
Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growth-promoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.
Topics: Acetates; Animals; Animals, Newborn; Coculture Techniques; Cyclopropanes; Drug Evaluation, Preclinical; Female; Leukotriene Antagonists; Male; Nerve Regeneration; Neuronal Outgrowth; Quinolines; Rats; Receptors, G-Protein-Coupled; Sulfides
PubMed: 34769111
DOI: 10.3390/ijms222111683 -
Respiratory Medicine Nov 2006Several clinical studies have confirmed the effectiveness of montelukast 10mg orally in adults with both asthma and allergic rhinitis. The objective of this phase IV...
Several clinical studies have confirmed the effectiveness of montelukast 10mg orally in adults with both asthma and allergic rhinitis. The objective of this phase IV study was to investigate the efficacy and safety of montelukast 10mg in adults with both asthma and allergic rhinitis in a real-life setting. Data from 5855 patients (mean age: 42.8+/-15.4 years) were collected and analyzed following treatment for 4-6 weeks. Efficacy was analyzed by comparing baseline values of: general, day- and night-time improvement in asthma symptoms, need for rescue medication or inhaled corticosteroids (ICSs), general and specific improvement in allergic rhinitis symptoms, reduction in rhinitis medication use, and general and specific quality of life (QoL) improvement with values collected at the end of the observation period of 4-6 weeks. Following treatment with 10mg montelukast 86.5% (n=4547) of patients reported a strong or marked improvement in day-time asthma symptoms and 88.5% (n=4367) reported improvement in night-time symptoms. A similarly high proportion of patients had a strong or marked improvement in all symptoms of allergic rhinitis (i.e. sneezing/itching (84%), rhinorrhea (81.7%), nasal congestion (79.3%), watery eyes (78.4%) and red or burning eyes (77.7%). The use of asthma and rhinitis medication was also reduced. 92.3% (n=5685) of all patients intended to continue montelukast therapy. Overall QoL was "very good" or "good" in 85.2% of patients (n=4991) and a "strong" or "marked" improvement in each of the four domains of sleep, work, everyday life and physical activity. Montelukast was well tolerated. Adverse drug reactions occurred in 14 out of 6158 patients. None of the adverse events was serious. Accordingly, montelukast 10mg is a safe and effective treatment for patients with both asthma and allergic rhinitis.
Topics: Acetates; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Asthmatic Agents; Asthma; Cyclopropanes; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Product Surveillance, Postmarketing; Quality of Life; Quinolines; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Sulfides; Treatment Outcome
PubMed: 16626955
DOI: 10.1016/j.rmed.2006.02.026 -
Drug Design, Development and Therapy 2021The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation.
PATIENTS AND METHODS
A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (C), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC), AUC from t = 0 to infinity (AUC), half-life (t), time to C (T), and terminal elimination rate constant (λ), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs).
RESULTS
The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (C, AUC, and AUC ) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00-125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable.
CONCLUSION
The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects.
Topics: Acetates; Administration, Oral; Adolescent; Adult; Asian People; Cross-Over Studies; Cyclopropanes; Drug Compounding; Fasting; Female; Healthy Volunteers; Humans; Male; Middle Aged; Quinolines; Sulfides; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 33727797
DOI: 10.2147/DDDT.S298355 -
Pharmacology Research & Perspectives Oct 2017Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its...
Montelukast, a selective leukotriene receptor antagonist, is recommended in guidelines for the treatment of asthma in both children and adults. However, its effectiveness is debated, and recent studies have reported several adverse events such as neuropsychiatric disorders and allergic granulomatous angiitis. This study aims to obtain more insight into the safety profile of montelukast and to provide prescribing physicians with an overview of relevant adverse drug reactions in both children and adults. We retrospectively studied all adverse drug reactions on montelukast in children and adults reported to the Netherlands Pharmacovigilance Center Lareb and the WHO Global database, VigiBase until 2016. Depression was reported most frequently in the whole population to the global database VigiBase (reporting odds ratio (ROR) 6.93; 95% CI: 6.5-7.4). In the VigiBase , aggression was reported the most in children (ROR, 29.77; 95% CI: 27.5-32.2). Headaches were reported the most frequently to the Dutch database (ROR, 2.26; 95% CI: 1.61-3.19). Furthermore, nightmares are often reported for both children and adults to the Dutch and the global database. Eight patients with allergic granulomatous angiitis were reported to the Dutch database and 563 patients in the VigiBase . These data demonstrate that montelukast is associated with neuropsychiatric adverse drug reactions such as depression and aggression. Especially in children nightmares are reported frequently. Allergic granulomatous angiitis is also reported, a causal relationship has not been established.
Topics: Acetates; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Child; Child, Preschool; Churg-Strauss Syndrome; Cyclopropanes; Databases, Factual; Depression; Dreams; Female; Headache; Humans; Infant; Male; Middle Aged; Netherlands; Pharmacovigilance; Quinolines; Retrospective Studies; Sulfides; Young Adult
PubMed: 28971612
DOI: 10.1002/prp2.341 -
Canadian Respiratory Journal 1999Leukotrienes (LTs), lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past... (Comparative Study)
Comparative Study Review
Leukotrienes (LTs), lipid mediators of inflammation, have proved to be important biochemicals involved in the symptoms and physiological changes of asthma. In the past year and a half, the development of three new drugs that modulate the LT pathway has been completed. The first subclass of these drugs, leukotriene receptor antagonists (LTRA) (zafirlukast and montelukast), blocks the interaction of the cysteinyl form of the LTs with the cell type bearing the receptor. The second subclass, the 5-lipoxygenase (5-LO) inhibitors (zileuton) inhibits the 5-LO enzyme, which prevents the formation of both cysteinyl LTs and LTB4. The LT modulators have shown efficacy in inhibiting the physiological changes occurring after allergen, acetylsalicylic acid and exercise challenge in asthmatics. In addition, they have shown efficacy in improving symptoms, beta-agonist use and forced expiratory volume in 1 s (FEV1) in chronic, 'day-to-day' asthma in patients with mild disease. Comparison studies with low doses of inhaled corticosteroids suggest that LT modulators may have similar effects on symptom scores and beta-agonist use, but have lesser effects on FEV1. Finally, emerging data suggest that these drugs are beneficial in decreasing the dose of inhaled corticosteroids necessary to control more moderate to severe asthma. While long term studies will be helpful in determining the 'disease modifying' effects of these drugs, data suggest that these drugs are useful in the treatment of a broad range of asthmatic patients.
Topics: Acetates; Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-Agonists; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Cyclopropanes; Forced Expiratory Volume; Humans; Hydroxyurea; Indoles; Leukotriene Antagonists; Leukotriene B4; Lipoxygenase Inhibitors; Phenylcarbamates; Quinolines; Receptors, Leukotriene; Sulfides; Sulfonamides; Tosyl Compounds
PubMed: 10322101
DOI: 10.1155/1999/676798 -
Chinese Medical Journal Nov 2021Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis.
BACKGROUND
Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.
METHODS
A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.
RESULTS
Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.
CONCLUSIONS
SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.
PROSPERO REGISTRATION NUMBER
CRD42019133156.
Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Humans; Quinolines; Salmeterol Xinafoate; Sulfides
PubMed: 34784306
DOI: 10.1097/CM9.0000000000001853 -
Scientific Reports Feb 2024Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in...
Preclinical and clinical data indicate that the 5-lipoxygenase pathway becomes activated in cardiovascular diseases suggesting an important role of CysLTs in atherosclerosis and in its ischemic complications. This study aims to investigate the effects of montelukast, a CysLTR-1 antagonist, in a mouse model of myocardial infarction (MI). C57BL/6N female mice were subjected to coronary artery ligation and received montelukast (10 mg/kg/day, intraperitoneal) or vehicle. Montelukast exerted beneficial effects in the infarcted area, decreasing mRNA expression of inflammatory genes, such Il1β and Ccl2 (p < 0.05), at 48 h after MI, and reducing infarct size and preventing ischemic wall thinning (p < 0.05) at 4 weeks. Furthermore, montelukast counteracted maladaptive remodelling of whole heart. Indeed, montelukast reduced LV mass (p < 0.05) and remote wall thickening (p < 0.05), and improved cardiac pumping function, as evidenced by increased global ejection fraction (p < 0.01), and regional contractility in infarcted (p < 0.05) and in remote non-infarcted (p < 0.05) myocardium. Finally, montelukast prevented cardiomyocytes hypertrophy (p < 0.05) in remote myocardium, reducing the phosphorylation of GSK3β, a regulator of hypertrophic pathway (p < 0.05). Our data strongly demonstrate the ability of montelukast to contrast the MI-induced maladaptive conditions, thus sustaining cardiac contractility. The results provide evidences for montelukast "repurposing" in cardiovascular diseases and in particular in myocardial infarction.
Topics: Mice; Animals; Female; Ventricular Remodeling; Mice, Inbred C57BL; Myocardial Infarction; Myocardium; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38337010
DOI: 10.1038/s41598-024-53936-x -
Therapeutic Advances in Respiratory... 2024Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in... (Review)
Review
A review of the therapeutic potential of the cysteinyl leukotriene antagonist Montelukast in the treatment of bronchiolitis obliterans syndrome following lung and hematopoietic-stem cell transplantation and its possible mechanisms.
Lung and hematopoietic stem cell transplantation are therapeutic modalities in chronic pulmonary and hematological diseases, respectively. One of the complications in these patients is the development of bronchiolitis obliterans syndrome (BOS). The efficacy and safety of available treatment strategies in BOS remain a challenge. A few mechanisms have been recognized for BOS in lung transplant and graft--host disease (GVHD) patients involving the TH-1 and TH-2 cells, NF-kappa B, TGF-b, several cytokines and chemokines, and cysteinyl leukotrienes (CysLT). Montelukast is a highly selective CysLT receptor antagonist that has been demonstrated to exert anti-inflammatory and anti-fibrotic effects in abundant experiments. One area of interest for the use of montelukast is lung transplants or GVHD-associated BOS. Herein, we briefly review data regarding the mechanisms involved in BOS development and montelukast administration as a treatment modality for BOS, and finally, the possible relationship between CysLTs antagonism and BOS improvement will be discussed.
Topics: Humans; Leukotriene Antagonists; Bronchiolitis Obliterans; Bronchiolitis Obliterans Syndrome; Lung; Lung Transplantation; Hematopoietic Stem Cell Transplantation; Graft vs Host Disease; Leukotrienes; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38504551
DOI: 10.1177/17534666241232284