Montelukast

Article Author:
Talel Badri
Article Editor:
Veronica Takov
Updated:
10/9/2019 3:05:24 PM
PubMed Link:
Montelukast

Indications

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.[1][2][3]

Mechanism of Action

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.[4][5][6]

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.

Administration

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.

  • For the treatment of chronic asthma, it is best to administer the dose in the evening. Recommended doses are 10 mg for patients aged 15 years and older, 5 mg for patients aged six to 14 years, and 4 mg for patients 12 months to five-years-old. For patients aged 12 to 23 months, tablets are not indicated, and only oral granules are used. In the absence of clinical data on efficacy and safety in asthma patients under age of 12 months, montelukast is not indicated for this patient population.

Montelukast is not suitable for the treatment of acute asthma exacerbations, such as status asthmaticus.

  • For prophylaxis of exercise-induced bronchoconstriction, montelukast should be administered at least 2 hours before initiating exercise. Recommended doses are 10 mg for patients aged 15 years and older, and 5 mg for patients aged six to 14 years. In the absence of clinical data on efficacy and safety in patients under age of 6 years with exercise-induced bronchoconstriction, montelukast is not indicated for this patient population. Daily doses of montelukast should be separated by at least 24 hours. A regular intake of montelukast for the treatment of chronic asthma does not prevent exercise-induced bronchoconstriction.  
  • In patients with allergic rhinitis, the dose may be taken in the morning or the evening.
  • For seasonal allergic rhinitis recommended doses are 10 mg for patients aged 15 years and older, and 5 mg for patients aged six to 14 years, and 4 mg for patients aged two to five years. In the absence of clinical data on efficacy and safety in patients younger than two years of age with seasonal allergic rhinitis, montelukast is not indicated in that patient population.
  • For perennial allergic rhinitis recommended doses are 10 mg for patients aged 15 years and older, and 5 mg for patients aged six to 14 years, and 4 mg for patients aged six months to five years. For patients aged six months to 23 months, tablets are not indicated, and only oral granules are used. In the absence of clinical data on efficacy and safety in patients younger than two years of age with seasonal allergic rhinitis, montelukast is not indicated for these patients.

Adverse Effects

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.[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 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):

  • Headaches, fever, fatigue
  • Upper respiratory signs (rhinorrhea, pharyngitis, laryngitis, sinusitis, epistaxis)
  • Auricular signs: otitis
  • Lower respiratory signs: a cough, pneumonia, wheezing
  • Ocular signs: conjunctivitis
  • Gastrointestinal signs (nausea, diarrhea, vomiting, abdominal pain, dyspepsia, pancreatitis)
  • Hepato-biliary signs: liver injury (hepatocellular and mixed-pattern), cholestatic hepatitis
  • Infections (influenza, varicella)
  • Dermatologic manifestations (pruritus, eczema and atopic dermatitis, angioedema, urticaria, skin rash, bruising, erythema multiforme, erythema nodosum, toxic epidermal necrolysis and Stevens-Johnson syndrome)
  • Musculoskeletal signs: Arthralgia, myalgia
  • Hypersensitivity manifestations: anaphylaxis, eosinophilic infiltration of the liver
  • Biologic anomalies: thrombocytopenia, increased plasmatic alanine aminotransferase

Contraindications

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.

Monitoring

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.

Toxicity

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.

Enhancing Healthcare Team Outcomes

Montelukast is an effective prophylactic agent for asthma. However, prescirbers including nurse practitioners, pharmacists, internists and primary care providers must be aware that in young people the drug can cause neuropsychiatric alterations including suicidal thoughts. Patients need to be closely monitored by a mental health nurse while on treatment.



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References

[1] Arnold DH,Bowman N,Reiss TF,Hartert TV,Akers WS,Seger DL, Adverse events associated with weight-based, high-dose montelukast exposures in children. Clinical toxicology (Philadelphia, Pa.). 2019 May 6;     [PubMed PMID: 31056949]
[2] 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. The open respiratory medicine journal. 2018;     [PubMed PMID: 30988828]
[3] Sun W,Liu HY, Montelukast and Budesonide for Childhood Cough Variant Asthma. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2019 Apr;     [PubMed PMID: 30925958]
[4] Zhang L,Lasmar LB,Castro-Rodriguez JA, The impact of asthma and its treatment on growth: an evidence-based review. Jornal de pediatria. 2019 Mar - Apr;     [PubMed PMID: 30472355]
[5] Castro-Rodriguez JA,Rodriguez-Martinez CE,Ducharme FM, Daily inhaled corticosteroids or montelukast for preschoolers with asthma or recurrent wheezing: A systematic review. Pediatric pulmonology. 2018 Dec;     [PubMed PMID: 30394700]
[6] Hoffman BC,Rabinovitch N, Urinary Leukotriene E{sub}4{/sub} as a Biomarker of Exposure, Susceptibility, and Risk in Asthma: An Update. Immunology and allergy clinics of North America. 2018 Nov;     [PubMed PMID: 30342582]
[7] Montelukast 2006;     [PubMed PMID: 30000548]
[8] Farah RI,Damkier P,Christiansen A,Henriksen DP, Early Discontinuation of Montelukast Treatment; A Danish Nationwide Utilization Study. Basic     [PubMed PMID: 29438596]