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]

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.

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.

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

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.