Adverse effects of montelukast examined by FDA's Pediatric Advisory Committee

At its late September meeting, the Pediatric Advisory Committee (PAC) to the US Food and Drug Administration (FDA) said it’s time to remind healthcare professionals that Singulair (montelukast) may have adverse effects on mental and behavioral functions.

The 13-member committee called for clarifications on labels and for a new letter to providers, even though the association to such conditions has not been proven, warnings are on the labels, and a letter has gone out previously.

Montelukast is used most often in association with diagnoses of asthma and allergies in children, according to the FDA.

The FDA’s “Pediatric Postmarketing Pharmacovigilance and Drug Utilization Review,” made available for the meeting, said, “Safety concerns have been raised and addressed by the FDA in the past regarding the increased risk of neuropsychiatric adverse events, including suicide and suicide attempts with the use of montelukast. However, there continues to be a lack of well-designed epidemiologic studies that can lead to the quantification of the suicide/suicide attempt risk level among patients using montelukast.” 

Concerns with montelukast

Over about 18 months ending in September 2013, almost 9 million patients received dispensed prescriptions for the drug from outpatient retail pharmacies. Thirty-eight percent of those patients were aged 16 years or younger, according to the FDA’s review.

The agency said its Adverse Event Reporting System found 140 pediatric serious cases for montelukast, including 4 deaths, during that same time frame ending in September 2013, and neuropsychiatric events were reported for the majority of those cases.

The public testimony phase of the meeting heard from Jan Gilpin, a member of the group Parents United for Pharmaceutical Safety and Accountability, formed in 2009 over concerns that children had developed mental and development issues while on montelukast. Her group and similar ones have hundreds of members, she said. Years ago, she testified, her son developed crippling anxiety while taking the drug and said he wished that he were dead.

Committee members noted that although some of the reports the FDA had gathered indicated relatively acute onset of problems in children, the rates for those conditions are also higher in all children with chronic medical problems including asthma.

PAC calls for clarity in labeling

Kenneth Towbin, MD, chair of the PAC and chief of clinical child and adolescent psychiatry at the National Institute of Mental Health, said there was a uniform wish among committee members for a way to get better information about the frequency of those events, although the committee had no recommendation on how to do that. He said the National Institutes of Health might be the place to think about the problem.

Googling on cell phones in the midst of the discussion, committee members got a different listing of precautions for the drug from reputable medical information sites, but there were references to possible mental effects on several of them.

The committee voted to recommend that the professional label should have the same kind of clarity as the consumer labeling; that the consumer labeling should have the reference to mental effects easier to see and higher in the list of things to be aware of; and that a letter should be sent to make healthcare providers aware of these changes.

Robert (Skip) Nelson, MD, PhD, deputy director of the FDA Office of Pediatric Therapeutics, said the FDA has jurisdiction over safety labeling. “We can work out what authority we have, but we will make every effort to do it,” he said.

The FDA Division of Pharmacovigilance recommended that it continue surveillance on adverse events and the committee agreed.

In May, the FDA Nonprescription Drugs Advisory Committee recommended that the FDA not allow Singulair to be sold over the counter because of fear that persons would not use it wisely.

During the September pediatric meeting, the committee also agreed with the FDA’s recommendations that it continue surveillance for adverse events for about 11 other pediatric drugs and devices.

The labeling and review information is on the FDA’s web page for the September 23, 2014, PAC meeting.

Ms Foxhall is a freelance writer in the Washington, DC, area. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that might have an interest in any part of this article.