Montelukast is an orally dosed drug (available as a film-coated tablet, chewable tablet, or oral granules) which is FDA-approved for the treatment of chronic asthma and prophylaxis and the prevention of exercise-induced bronchoconstriction. It is also approved for the relief of symptoms of both seasonal and perennial allergic rhinitis.
Montelukast (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 types of cells, such as mast cells, and are involved in the inflammatory process that may cause the signs and symptoms of asthma and allergic rhinitis. 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.
In controlled studies, patients with asthma who were treated with montelukast demonstrated decreased peripheral blood eosinophil count of 9% to 15% when compared with placebo. In seasonal allergic rhinitis patients who received montelukast, the eosinophil count in peripheral blood increased by 0.2%, compared with a 12.5% increase in placebo-group patients.
Montelukast 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.
Montelukast is not suitable for the treatment of acute asthma exacerbations, such as status asthmaticus.
Neuropsychiatric events have been reported in patients receiving montelukast. These events have been noted in adults, teenagers, and younger patients, and 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.
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 the decrease of oral corticosteroid doses. However, the fact that montelukast is the causative agent of these systemic manifestation has not been established.
Other adverse effects of montelukast include (among others):
Montelukast is contraindicated in patients with a history of hypersensitivity to the drug or its components. For patients with phenylketonuria (PKU), caution should be exercised with phenylalanine-containing formulations.
Patients taking montelukast should be regularly monitored for mood or behavior changes, including suicidal thinking or behavior. They should be advised to alert their physician in case of neuropsychiatric signs.
In 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 the occurrence of significant adverse effects. Cases of acute overdosage with montelukast have been reported in both adults and children with doses as high as 1000 mg. However, clinical and biological signs in such cases were relatively benign and included a headache, thirst, somnolence or hyperactivity, vomiting, and abdominal pain.
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:
There is no known antidote for montelukast overdosage. 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. No fertility impairment or teratogenic effect has been reported with this molecule. Dose adjustment is not necessary in case of renal failure or mild-to-moderate hepatic insufficiency.
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|Effects of oral montelukast on airway function in acute asthma: A randomized trial., Chaudhury A,Gaude GS,Hattiholi J,, Lung India : official organ of Indian Chest Society, 2017 Jul-Aug [PubMed PMID: 28671166]|
|Effectiveness of montelukast in overweight and obese atopic asthmatics., Farzan S,Khan S,Elera C,Tsang J,Akerman M,DeVoti J,, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, 2017 Jun 28 [PubMed PMID: 28668546]|