A Boxed Warning for Montelukast: The FDA Perspective.
Katherine Clarridge1, Stacy Chin1, Efe Eworuke1
1Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Md.
The Journal of Allergy and Clinical Immunology. in Practice
|March 21, 2021
Summary
The U.S. Food and Drug Administration (FDA) updated montelukast labeling due to neuropsychiatric risks. For allergic rhinitis, montelukast is now reserved for patients with inadequate response to other therapies.
Area of Science:
- Pharmacovigilance
- Drug Safety
- Regulatory Science
Background:
- Postmarketing reports of neuropsychiatric adverse events with montelukast (Singulair) emerged in 2007.
- Previous FDA reviews and labeling updates did not fully resolve concerns about montelukast's neuropsychiatric risks.
- Stakeholder concerns persisted regarding prescriber and patient awareness of these risks.
Purpose of the Study:
- To conduct a comprehensive review of montelukast's neuropsychiatric safety profile.
- To evaluate the need for further regulatory action based on updated safety data and stakeholder input.
- To provide transparency regarding the FDA's decision-making process for labeling changes.
Main Methods:
- Systematic review of clinical trial safety data, postmarketing reports, and published literature.
- New observational study utilizing claims data from the Sentinel Distributed Database.
- Convening a public Advisory Committee meeting in September 2019 to discuss findings and recommendations.
Main Results:
- The FDA required a boxed warning for montelukast.
- The indication for allergic rhinitis was revised to reserve montelukast for patients with inadequate response or intolerance to alternative therapies.
- The asthma indication's labeling remained unchanged based on benefit-risk assessment.
Conclusions:
- Labeling changes for montelukast were implemented to address neuropsychiatric safety concerns, particularly for allergic rhinitis.
- The decision-making process involved comprehensive data review, stakeholder engagement, and benefit-risk considerations.
- Enhanced communication and prescribing guidelines are crucial for safe montelukast use.
