Montelukast

Key points

• In healthy adults, montelukast is cleared from the plasma at an average rate of 45 mL per minute.
• Laboratory studies using human liver microsomes indicate that the enzymes CYP3A4, 2C8 and 2C9 are involved in breaking montelukast down in the body.
• In controlled clinical trials, the most frequently reported reactions, each occurring in five percent or more of patients and more often than with placebo, included upper respiratory infection, fever, headache, pharyngitis and cough, listed in descending order of frequency.

How it works

The product characteristics for Singulair classify montelukast’s pharmacotherapeutic group as a leukotriene receptor antagonist. The cysteinyl leukotrienes LTC4, LTD4 and LTE4 are potent inflammatory mediators released from cells including mast cells and eosinophils, and they bind to cysteinyl leukotriene, or CysLT, receptors found in the human airway, including airway smooth muscle cells and airway macrophages, and on other pro-inflammatory cells including eosinophils. These mediators have been correlated with the disease processes behind asthma and allergic rhinitis. In asthma, the effects driven by leukotrienes include narrowing of the airway, increased mucus, altered blood vessel permeability and the recruitment of eosinophils.

Safety specific to Montelukast

Montelukast carries a boxed warning about serious neuropsychiatric events. The FDA prescribing information states, in full:

• “Serious neuropsychiatric (NP) events have been reported with the use of montelukast sodium. The types of events reported were highly variable, and included, but were not limited to, agitation, aggression, depression, sleep disturbances, suicidal thoughts and behavior (including suicide). The mechanisms underlying NP events associated with montelukast sodium use are currently not well understood”
• “Because of the risk of NP events, the benefits of montelukast sodium may not outweigh the risks in some patients, particularly when the symptoms of disease may be mild and adequately treated with alternative therapies. Reserve use of montelukast sodium for patients with allergic rhinitis who have an inadequate response or intolerance to alternative therapies”
• “In patients with asthma or exercise-induced bronchoconstriction, consider the benefits and risks before prescribing montelukast sodium.”
• “Discuss the benefits and risks of montelukast sodium with patients and caregivers when prescribing montelukast sodium. Advise patients and/or caregivers to be alert for changes in behavior or new NP symptoms when taking montelukast sodium. If changes in behavior are observed, or if new NP symptoms or suicidal thoughts and/or behavior occur, advise patients to discontinue montelukast sodium and contact a healthcare provider immediately”

These events have been reported in adult, adolescent and paediatric patients with and without a previous history of psychiatric disorder, mostly during treatment though some were reported after montelukast was stopped.

Montelukast sodium is not indicated for reversing bronchospasm in an acute asthma attack, including status asthmaticus, so patients should be advised to have appropriate rescue medication available.

While the corticosteroid dose may be reduced gradually under medical supervision, montelukast sodium should not be abruptly substituted for inhaled or oral corticosteroids.

Patients with known aspirin sensitivity should continue to avoid aspirin or non-steroidal anti-inflammatory agents while taking montelukast sodium.

Patients with asthma on montelukast therapy may present with systemic eosinophilia, sometimes with clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition often treated with systemic corticosteroid therapy.

Patients with the rare hereditary conditions galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine, according to the product characteristics for Singulair.

When to seek urgent care

• Tell your prescriber and stop montelukast if you or a caregiver notice new or worsening changes in behaviour, new neuropsychiatric symptoms, or suicidal thoughts or behaviour, since patients are advised to discontinue montelukast sodium and contact a healthcare provider immediately if these appear.
• Seek medical attention for a new rash, worsening breathing symptoms, or new heart or nerve symptoms while on montelukast, since physicians are advised to stay alert to eosinophilia, a vasculitic rash, worsening pulmonary symptoms, cardiac complications and neuropathy presenting in patients on this therapy.

Further reading

• MONTELUKAST SODIUM- montelukast tablet
• Singulair 10 mg film-coated tablets