ROCKVILLE, Md -- January 13, 2009 -- On March 27, 2008, the US Food and Drug Administration (FDA) announced that it was reviewing safety data that raised concerns about a possible association between the use of montelukast (Singulair) and behaviour/mood changes, suicidality, and suicide.
The FDA requested manufacturers of products indicated for the treatment of asthma and/or allergic rhinitis that act through the leukotriene pathway (montelukast, zafirlukast, zileuton) to submit adverse event data for suicidality adverse events as well as mood and behavioural-related adverse events from all available placebo-controlled clinical trials.
FDA requested that Merck, AstraZeneca, and Cornerstone Therapeutics use the Columbia Classification Algorithm of Suicide Assessment (C-CASA) to classify suicidal events.
Merck submitted results from 41 placebo-controlled clinical trials in patients aged 6 years and older, of which 9,929 were treated with montelukast and 7,780 were treated with a placebo. Of the patients treated with montelukast, 1 adult patient (.01%) had suicidal ideation and there were no completed suicides. No patients in the placebo group had suicidal ideation or suicide.
Astra Zeneca submitted results from 45 placebo-controlled clinical trials in patients aged 5 years and older, of which 7,540 were treated with zafirlukast and 4,659 were treated with a placebo. No patients treated with zafirlukast had suicidal ideation or completed suicide. In the placebo group, 2 patients (.04%) had suicidality (one suicide attempt and one suicidal ideation).
Cornerstone Therapeutics submitted results from 11 placebo-controlled clinical trials in patients aged 12 years and older, of which 1,745 were treated with zileuton and 1,063 were treated with a placebo. No patients treated with zileuton or placebo had suicidal ideation or completed suicide.
Although these data do not suggest that montelukast, zafirlukast, or zileuton are associated with suicide or suicidal behaviour, these clinical trials were not designed specifically to examine neuropsychiatric events. As a result, some events may not have been reported.
The FDA is continuing to review clinical trial data to assess other neuropsychiatric events related to drugs that act through the leukotriene pathway. As a result, FDA has not yet reached a definitive conclusion regarding the clinical trial data on mood and behavioural adverse events associated with montelukast, zafirlukast, and zileuton.
They will communicate their conclusions and any resulting recommendations to the public at the conclusion of the review, which may take months to complete.
Prescribers and patients should continue monitoring for the possibility of neuropsychiatric events associated with these agents.
The FDA urges both healthcare professionals and patients to report side effects from the use of Singulair, Accolate, Zyflo, and Zyflo CR to the FDA's MedWatch Adverse Event Reporting program
· online at www.fda.gov/medwatch/report.htm
· by returning the postage-paid FDA form 3500 available in PDF format at www.fda.gov/medwatch/getforms.htm to 5600 Fishers Lane, Rockville, MD 20852-9787
· faxing the form to 1-800-FDA-0178
· by phone at 1-800-332-1088
SOURCE: US Food and Drug Administration
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