Continuing Education ActivityMontelukast is an orally dosed drug (available as a film-coated tablet, chewable tablet, or oral granules) that is FDA-approved for treating chronic asthma and prophylaxis and the prevention of exercise-induced bronchoconstriction. It is also approved to relieve seasonal and perennial allergic rhinitis symptoms. This activity reviews the indications, mechanism of action, pharmacokinetics, administration, dose in adults and specific patient populations, adverse drug reactions, contraindications, warning and precautions, and toxicity of montelukast therapy in the clinical setting as relates to the essential points needed by members of an interprofessional team managing the care of patients with chronic asthma, exercise-induced bronchoconstriction, and allergic rhinitis. Show Objectives:
Access free multiple choice questions on this topic. IndicationsMontelukast is an orally dosed drug (available as a film-coated tablet, chewable tablet, or oral granules) that is FDA-approved for treating the following conditions.
Mechanism of ActionMontelukast (empirical formula C35H35ClNNaO3S) is a highly selective leukotriene receptor antagonist that binds with high affinity to the cysteinyl leukotriene receptor for leukotrienes D4 and E4. These leukotrienes are excreted by various cells, such as mast cells, and are involved in the inflammatory process that may cause asthma and allergic rhinitis signs and symptoms. Leukotriene receptors are found in airway cells, such as macrophages and smooth muscle cells. When bound to leukotriene receptors, montelukast inhibits leukotriene physiologic effects (such as airway edema, smooth muscle contraction, and impairment of normal cellular activity) without exhibiting any agonist activity. In asthmatics, low doses of montelukast (5 mg) induce a significant inhibition of bronchoconstriction caused by leukotriene D4. Furthermore, in a crossover study, montelukast induced inhibition of both early and late phase bronchoconstriction caused by a challenge with antigen in 12 asthmatic patients. Although Most international asthma guidelines advise that children ≤5 years with asthma be treated with daily low- moderate dose inhaled corticosteroids (ICS) as the preferred controller and montelukast as an alternative therapy.[5] In controlled studies, montelukast is reported to significantly reduce beta2-agonist use (p<0.001), asthma symptoms (p=0.001), blood eosinophils (p=0.009) and significantly increase morning peak expiratory flow (p=0.001). These parameters demonstrate that montelukast decreases airway eosinophilic inflammation and improves clinical symptoms. Its efficacy in the treatment of chronic asthma may be due, in part, to the effect on airway inflammation.[6] Pharmacokinetics
AdministrationMontelukast may be taken without regard to food or meals. Patients with phenylketonuria who receive montelukast should be aware that chewable tablets contain phenylalanine. There is no need to adjust doses when montelukast is co-administered with other systemic treatments.
Specific Patient Population Hepatic Insufficiency: No dosage adjustment is needed in patients with mild-to-moderate hepatic insufficiency. According to product labeling, the pharmacokinetics of montelukast in patients with more severe hepatic impairment have not been assessed. Renal Insufficiency: Montelukast and its metabolites are excreted via the bile. The pharmacokinetics of montelukast has not been evaluated in patients with renal insufficiency. Therefore, no dosage adjustment is recommended in these patients. Pregnancy Considerations: Available data from published studies with montelukast use in pregnant women have not established a drug-associated risk of major congenital disabilities. Breastfeeding Considerations: Low levels of montelukast appear in breastmilk. Montelukast has been used in neonates in dosages far greater than the amounts in breastmilk. Amounts ingested by the infant are not expected to cause any adverse effects in breastfed infants. No special precautions are required.[7] Adverse EffectsNeuropsychiatric events have been reported in patients receiving montelukast. These events have been noted in adults, teenagers, and younger patients. They include, among others: anxiety, depression, aggressiveness, agitation, attention and memory impairment, sleeping disorders (insomnia, somnambulism, dream anomalies), seizures, paresthesia, hypoesthesia, as well as suicidal thoughts and behavior.[7][8] During treatment with montelukast, some patients with asthma may develop systemic eosinophilia, sometimes associated with vasculitis, consistent with Churg-Strauss syndrome (rare). This event may be associated with a decrease in oral corticosteroid doses. However, montelukast is the causative agent of these systemic manifestations has not been established. Other adverse effects of montelukast include (among others):
ContraindicationsMontelukast is contraindicated in patients with a history of hypersensitivity to the drug or its components. In addition, for patients with phenylketonuria (PKU), caution should be exercised with phenylalanine-containing formulations. Boxed Warning: Neuropsychiatric Events Neuropsychiatric events have been described with the use of montelukast sodium. These postmarketing reports have been highly variable, including agitation, aggressive behavior, anxiousness, depression, disorientation, disturbance in attention, irritability, memory impairment, obsessive-compulsive symptoms, hallucinations, insomnia, restlessness, suicidal thoughts, and behavior (including suicide). Neuropsychiatric events have been documented in patients with and without a history of psychiatric disorders. Based on risk-benefit considerations, the asthma indication has not been changed.[10] MonitoringPatients taking montelukast should be regularly monitored for mood or behavior changes, including suicidal thinking or behavior. In addition, clinicians should advise their patients to report any neuropsychiatric signs. ToxicityIn clinical studies, montelukast has been used at high doses in adult patients (up to 200 mg daily for 22 weeks and up to 900 mg daily for about a week) without significant adverse effects. Cases of acute overdosage with montelukast have been reported in adults and children with doses as high as 1000 mg. However, clinical and biological signs in such cases were relatively benign and included headaches, thirst, somnolence or hyperactivity, vomiting, and abdominal pain.[11] In case of overdose with montelukast, classical supportive therapies such as gastric lavage, adsorption with activated carbon, clinical monitoring, and, if necessary, supportive therapy may be used. Unfortunately, there is no known antidote for montelukast overdosage. In addition, no data exist concerning the efficiency of hemodialysis and peritoneal dialysis for removing montelukast from the body. Montelukast has no known carcinogenic or mutagenic effects. In addition, no fertility impairment or teratogenic effect has been reported with this molecule. Dose adjustment is not necessary for renal failure or mild-to-moderate hepatic insufficiency. Enhancing Healthcare Team OutcomesMontelukast is an effective prophylactic agent for asthma. However, prescribers, including nurse practitioners, pharmacists, internists, and primary care providers, must be aware that the drug can cause neuropsychiatric alterations in young people, including suicidal thoughts. It is, therefore, necessary to adopt an interprofessional team approach to montelukast therapy. This healthcare team includes clinicians (MDs, DOs, NPs, PAs), nurses, respiratory therapists, and pharmacists, all contributing from their expertise and openly sharing information and patient status among the team. Young patients may need to be closely monitored by a mental health nurse while on treatment.[12] Using this interprofessional paradigm will result in improved outcomes with fewer adverse events. [Level 5] Review QuestionsFigureStructural formula of montelukast. Contributed by Public Domain (Wikipedia) References1.Sánchez G, Buitrago D. Effect of Montelukast 10 mg in Elderly Patients with Mild and Moderate Asthma Compared with Young Adults. Results of a Cohort Study. Open Respir Med J. 2018;12:67-74. [PMC free article: PMC6425064] [PubMed: 30988828] 2.Sun W, Liu HY. Montelukast and Budesonide for Childhood Cough Variant Asthma. J Coll Physicians Surg Pak. 2019 Apr;29(4):345-348. [PubMed: 30925958] 3.de Benedictis FM, Vaccher S, de Benedictis D. Montelukast sodium for exercise-induced asthma. Drugs Today (Barc). 2008 Nov;44(11):845-55. [PubMed: 19180262] 4.Krishnamoorthy M, Mohd Noor N, Mat Lazim N, Abdullah B. Efficacy of Montelukast in Allergic Rhinitis Treatment: A Systematic Review and Meta-Analysis. Drugs. 2020 Nov;80(17):1831-1851. [PubMed: 32915441] 5.Castro-Rodriguez JA, Rodriguez-Martinez CE, Ducharme FM. Daily inhaled corticosteroids or montelukast for preschoolers with asthma or recurrent wheezing: A systematic review. Pediatr Pulmonol. 2018 Dec;53(12):1670-1677. [PubMed: 30394700] 6.Pizzichini E, Leff JA, Reiss TF, Hendeles L, Boulet LP, Wei LX, Efthimiadis AE, Zhang J, Hargreave FE. Montelukast reduces airway eosinophilic inflammation in asthma: a randomized, controlled trial. Eur Respir J. 1999 Jul;14(1):12-8. [PubMed: 10489822] 7.Drugs and Lactation Database (LactMed) [Internet]. National Library of Medicine (US); Bethesda (MD): 2006. Montelukast. 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Cognitive Effects of Montelukast: A Pharmaco-EEG Study. Brain Sci. 2021 Apr 27;11(5) [PMC free article: PMC8145277] [PubMed: 33925326] |