FDA Strengthens Warning About Risk of Neuropsychiatric Events With Montelukast

The FDA recommends that montelukast only be used for allergic rhinitis in patients who have had an inadequate response or intolerance to alternative therapies.

The Food and Drug Administration (FDA) is requiring the addition of a Boxed Warning to the prescribing information for montelukast, following a review of study data and case reports related to neuropsychiatric adverse events.

Montelukast, a leukotriene receptor antagonist, is indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients ≥12 months of age; for prevention of exercise-induced bronchoconstriction in patients ≥6 years of age; and for the relief of symptoms of seasonal allergic rhinitis in patients ≥2 years of age and perennial allergic rhinitis in patients ≥6 months of age. 

While the labeling currently includes warnings regarding the risk of neuropsychiatric events, an extensive review of data, including an evaluation by an expert panel, indicated that the warnings needed to be stronger. Specifically, the agency reviewed cases reported to the FDA Adverse Event Reporting System (FAERS), conducted an observational study using data from the FDA’s Sentinel System, and reviewed observational and animal studies in the published literature.

Data from FAERS showed that between February 1998 (the time of initial approval) and May 2019, there was an increase in neuropsychiatric event reporting beginning in 2008, when the agency initially communicated the possible association between montelukast use and behavior/mood changes, suicidality, and suicide. An evaluation of completed suicides submitted to the FDA revealed 82 cases linked to montelukast; of these, 34 included documentation that contained additional risk factors that may have contributed to the suicide. 

To investigate the association further, the FDA conducted a study using data from the Sentinel Distributed Database. For this analysis, investigators looked at whether montelukast use for asthma increased the risk of hospitalized or treated outpatient depressive disorders, self-harm, and suicides when compared with inhaled corticosteroids (ICS). Results from the study showed that montelukast was not associated with an increased risk of neuropsychiatric events when compared with ICS, however, the agency noted that the study had several limitations that could have affected the results. A review of other observational studies resulted in similar findings. 

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Given the limited data, the FDA recommends healthcare professionals consider the risks and benefits of montelukast when deciding to prescribe the medication and counsel patients about the potential for mental health side effects; some patients have reported side effects even after discontinuing treatment. In addition, the FDA is advising that montelukast only be used for allergic rhinitis in patients who have had an inadequate response or intolerance to alternative therapies.

Adverse events related to montelukast should be reported to the FDA MedWatch program.

For more information visit fda.gov.