FDA Has Gone From "No Link" In January 2009 To Wanting An Increased Warning About These Neuropsychiatric Events In June 2009
(Posted by Tom Lamb at DrugInjuryWatch.com)
On June 12, 2009 the FDA announced that Singulair (montelukast) as well as some other less popular leukotriene inhibitors — Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton) — must start to include a warning on its package insert, or label, regarding an increased risk of neuropsychiatric events including suicide and depression.
This June 2009 FDA warning about Singulair is seemingly a reversal from an earlier position taken by the FDA in January 2009 when the agency said their review of clinical trials did not suggest Merck's Singulair asthma drug caused suicide or suicidal thoughts.
For some perspective, let's look back in time to see how this Singulair – suicide link has become a very significant emerging drug-safety issue at the FDA.
We start with a March 27, 2008 ABC News report, "Doctors Not Concerned by US FDA Probing Safety of Merck's Singulair":
The Food and Drug Administration (FDA) announced an investigation Wednesday examining a link between suicide and Merck's popular allergy and asthma drug, Singulair.
Concerns over "behavioral issues" with Singulair developed over the past year. Merck periodically updated the drug's labels to include warnings for tremors, depression and anxiety. FDA spokesperson Susan Cruzan said reports of suicides by "three or four" people who were taking Singulair prompted Merck to clarify suicide warnings on labels and patient information sheets in October 2007.
We get some additional background information from a March 27, 2008 article, "FDA Investigates Possible Suicide Link With Montelukast (Singulair)", published online by MedPage Today:
The FDA said it will probably take at least nine months for it to complete a safety review of the popular asthma and allergy drug montelukast (Singulair).
The ongoing investigation is examining a possible association between use of the drug and behavior/mood changes, suicidality (suicidal thoughts and behavior), and suicide, the agency said….
Over the past year, the maker of Singulair, Merck & Co, has updated the prescribing information and patient information for Singulair to include the following post-marketing adverse events: tremor (March 2007), depression (April 2007), suicidality (suicidal thinking and behavior) (October 2007), and anxiousness (February 2008).
From there we move forward to a January 14, 2009 Reuters article, "FDA says Singulair data do not suggest suicide link":
U.S. regulators on Tuesday said their review of clinical trials does not suggest Merck & Co's Singulair asthma drug or similar medicines cause suicide or suicidal thought, although the data were inadequate to draw a firm conclusion….
The agency also studied trials involving two other medicines that work by blocking inflammation-causing proteins called leukotrienes, AstraZeneca Pls's Accolate (zafirlukast) and Zyflo (zileuton) sold by Cornerstone Therapeutics Inc.
"Although these data do not suggest that [Singulair (montelukast), Accolate (zafirlukast) or Zyflo and Zyflo CR (zileuton)] are associated with suicide or suicidal behavior, these clinical trials were not designed specifically to examine neuropsychiatric events," the FDA said. "As a result, some events may not have been reported."
Concerns about a possible suicidal link have arrested sales growth of Singulair, Merck's biggest product with annual sales of almost $4.5 billion.
Then came the June 2009 announcement from FDA that there may be a link between Singulair and suicide. From a June 12, 2009 MedPage Today article, "FDA: Leukotriene Inhibitors Associated with Suicide, Depression":
Leukotriene inhibitors must include a warning regarding increased risk of neuropsychiatric events including suicide and depression, according to the FDA.
The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.
Upon completing a review of the agents in April, the FDA found reports of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicide, suicidal ideation, and tremor associated with use of the drugs.
The FDA based its review on postmarket reports and clinical trial data submitted by the manufacturers of the drugs….
The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.
Now that the association between Singulair and neuropsychiatric events such as suicide and depression has been announced by the FDA, we expect there to be additional case reports about Singulair users experiencing these serious side effects.
As always, we encourage people with personal knowledge about serious side effects from Singulair use to submit a MedWatch report to the FDA. We also welcome Comments, here, from people who want to share with others their side-effect experiences, or that of a family member, while using Singulair.
P.S. Merck Statement in Response to the FDA's June 12, 2009 Communication with Updated Information on Leukotriene Inhibitors, Including SINGULAIR® (montelukast sodium) — June 12, 2009 press release from Merck & Co., Inc. (6/24/09)
P.S. On August 28, 2009 the FDA and the manufacturers of Singulair, Accolate, Zyflo and Zyflo CR announced an update to the Precautions section of the prescribing information to include information about neuropsychiatric events reported in patients using these products. (8/28/09)
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