The U.S. Food and Drug Administration said it was investigating the possibility of an increased risk of mood changes and suicidal behavior among those who take the highly popular asthma drug Singulair.
Singulair is the number one-selling drug among people aged 17 and younger. Last year, it posted sales of $4.3 billion, making it Merck & Co.’s top-selling product, according to the Associated Press.
In issuing its statement, the FDA stressed that asthma patients should not stop taking Singulair without talking to their doctor first.
Both Merck and the FDA noted that the two have been working together over the past year to determine the scope of the problem and to make appropriate labeling changes to reflect the potential risk of mood changes and suicidal behavior among Singulair users.
“Suicide has been reported to us only in post-marketing experience in anecdotal reports that come to the company,” George Philip, head of Merck’s Singulair development program, told Bloomberg News. The company declined to say how many suicides have been reported, saying only that it is a “very small number” relative to the amount of people taking the drug.
The company also released a statement that detailed the ongoing review.
“Merck voluntarily updated the worldwide product label for Singulair in October 2007 to include ‘suicidal thinking and behavior’ and included similar changes to the patient product information,” the company said in its statement. “These actions were based on a very limited number of post-marketing adverse event reports that Merck has received. Since that time, Merck has worked with the U.S. Food and Drug Administration to provide further clarity in the product label as well as to further communicate this information to physicians.”
Over the past year, Merck has updated prescribing information for the drug to include information on several adverse events including tremor, depression, suicidality (suicidal thinking and behavior) and anxiousness, according to the FDA. And Merck plans to convey recent labeling changes in face-to-face meetings with prescribers and also in patient leaflets.
The FDA has asked Merck to look at Singulair study data for more information about suicidality and suicide. The agency itself is reviewing post-marketing reports of adverse events.
In its statement, Merck detailed the nature of those adverse events. “In a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, placebo-controlled clinical trials — which included over 11,000 adults and children in over 40 studies who were treated with Singulair — there were no reports of suicidal thoughts or actions and no completed suicides in the patients who received Singulair,” the statement read. “Additionally, in a cumulative analysis recently provided to the FDA of Merck’s randomized, double-blind, clinical trials that compared Singulair with other active agents to treat asthma [which included over 3,900 adults and children who were treated with Singulair and over 3,400 who were treated with other asthma therapies], there was one patient who attempted suicide who received Singulair, and there were three patients who attempted suicide who received other asthma therapies [including inhaled corticosteroids and long-acting beta-agonists].”
The FDA noted it was also looking into whether other related drugs, such as Accolate, Zyflo and Zyflo CR need to be investigated as well.
“Due to the complexity of the analyses,” the FDA said, it anticipates that it may take up to nine months to complete the ongoing evaluations.
Experts pointed out that, in the meantime, asthma sufferers need to determine with their doctors whether Singulair is the best choice of treatment for them.
Some patients had complained of nightmares after starting on Singulair.
“The physician really needs to review whether there are symptoms that have developed since patients started taking the medication, if there’s an underlying depression that was there before medication started,” added Dr. Rauno Joks, chief of the division of allergy and immunology at SUNY (State University of New York) Downstate in New York City. “Also, seasonal allergies in and of themselves can cause fatigue and lethargy, which makes it harder to assess, because those are some of the symptoms you have with depression.”
Joks said he had seen headaches develop as a side effect of Singulair, but not psychiatric problems.
The drug, a leukotriene receptor antagonist that targets part of the body’s inflammatory process, is prescribed to treat asthma and the symptoms of allergic rhinitis, as well as to prevent exercise-induced asthma.