Patient Safety Lessons From the Asthma and Allergy Drug Montelukast (SINGULAIR and generics)

Effectively communicating important safety information about drugs is challenging. Even when the Food and Drug Administration (FDA) requires a boxed warning — the agency’s most prominent warning — in a drug’s prescribing information, patients and clinicians may either not be aware or not change their use of the drug.

The serious mental health adverse effects of the asthma and allergy drug montelukast (SINGULAIR and generics), as recently highlighted in the New York Times, is a striking example of this challenge.[1] Initially approved by the FDA in 1998, montelukast was soon thereafter classified as a Do Not Use drug by Public Citizen’s Health Research Group. Montelukast has limited benefits, none of which are unique; it does have unique risks, such as neuropsychiatric adverse events. Nonetheless, each year more than 12 million people in the United States, mostly adults but also about 1.5 million children, fill at least one prescription for montelukast.[2] Unlike inhaled medications for asthma or allergic rhinitis, which are typically taken multiple times a day, montelukast is a pill taken once a day.

In March 2020, the FDA required a boxed warning about the serious mental health adverse effects of montelukast and advised restricted use for allergic rhinitis.[3] The boxed warning states that the “serious neuropsychiatric events” are “highly variable” and include, but are not limited to, “agitation, aggression, depression, sleep disturbances, [and] suicidal thoughts and behavior (including suicide).” Patients who continued the drug and their clinicians were cautioned to be “alert for changes in behavior or new [neuropsychiatric] symptoms.” If symptoms developed, patients were advised to “discontinue [montelukast] and contact a healthcare provider immediately.”[4]

Despite the 2020 boxed warning, between 2018 and 2022 the number of people filling at least one prescription per year for montelukast remained relatively constant. “Prescribing of the drug has remained at high levels,” according to the New York Times, “raising questions about whether the alert reached enough doctors and patients, who often don’t read the fine print on the drug’s tightly folded label, tucked into a bag at the pharmacy.”[5]

Although the reasons for the neuropsychiatric adverse events and their frequency are poorly understood, the effects on children are especially alarming. The newspaper article highlighted the suicide of a child, age 14, who had been taking montelukast since age 7. As of 2019, the FDA had documented 82 suicides of people taking montelukast.[6]

When the FDA requires a new boxed warning for a drug, it should prospectively monitor prescribing trends using information from nationally representative databases or fund independent researchers to do so. It also should explore new and creative ways to communicate information about serious drug adverse effects to clinicians and patients in ways that they notice and pay attention to. Approaches as diverse as communications through social media and greater use of formal risk evaluation and management strategy programs should be considered. A boxed warning for a drug is the first step toward effective communications, not the last step.
 

References

[1] Jewitt C, Mueller B. The F.D.A. warned an asthma drug could induce despair. Many were never told. New York Times. January 9, 2024. https://www.nytimes.com/2024/01/09/health/fda-singulair-asthma-drug-warning.html.Accessed January 29, 2024.

[2] Ibid.

[3] Food and Drug Administration. Drug Safety Communication. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair); advises restricting use for allergic rhinitis. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug. Accessed January 29, 2024.

[4] Montelukast sodium. Prescribing information. Revised March 2022. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=152e553c-4b81-4638-901e-dc44fa533a86&type=display. Accessed January 29, 2024.

[5] Jewitt C, Mueller B. The F.D.A. warned an asthma drug could induce despair. Many were never told. New York Times. January 9, 2024. https://www.nytimes.com/2024/01/09/health/fda-singulair-asthma-drug-warning.html. Accessed January 29, 2024.

[6] Ibid.