March 27, 2008 -- The FDA today announced that it is working with the drug company Merck to investigate a possible link between Merck's asthma and allergy drug Singulair and behavior/mood changes, suicidality (suicidal thinking and behavior), and suicide.
The FDA's investigation may take nine months. As of now, there's no proof that Singulair directly affects suicide risk.
Meanwhile, the FDA calls Singulair "effective" and advises patients with questions not to stop taking Singulair before talking to their doctor.
The FDA also asks health care professionals and caregivers to monitor patients taking Singulair for suicidality and changes in behavior and mood.
Singulair is used to treat asthma and the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose) and to prevent exercise-induced asthma. It's in a class of drugs called leukotriene receptor antagonists.
Other leukotriene modifying medications include the asthma drugsAccolate, Zyflo, and Zyflo CR. The FDA is reviewing postmarketing reports it has received of behavior/mood changes, suicidality, and suicide in patients who took Accolate, Zyflo, and Zyflo CR and will assess whether further investigation is warranted.
Singulair Time Line
The FDA notes that over the past year, Merck has updated Singulair's prescribing information and patient information to include the following postmarketing adverse events: tremor (March 2007), depression (April 2007), suicidality (October 2007), and anxiousness (February 2008).
In February 2008, the FDA and Merck discussed how best to communicate these labeling changes to prescribers and patients. According to the FDA, Merck plans to highlight the recent changes in the prescribing information in face-to-face interactions with prescribers and to provide prescribers patient information leaflets about Singulair.
In response to inquiries received by the FDA, the FDA has asked Merck to evaluate Singulair study data for more information about suicidality and suicide. The FDA is also reviewing its postmarketing reports of behavior/mood changes, suicidality, and suicide in patients who took Singulair.
Singulair's web site includes the most current prescribing information and patient information for Singulair, according to the FDA.
Drug Companies Respond
"The notification by FDA is not an indication that they believe that health care providers should change their prescribing practices based on this alert," George Philip, MD, Merck's senior director of clinical research and chair of the product development team for Singulair worldwide, tells WebMD. "Instead, if patients have questions, they should contact their doctor before making any changes in their use of Singulair and should not stop Singluair on the basis of this report."
Philip notes that postmarketing reports "can be quite sketchy and difficult to make solid conclusions and certainly not sufficient for us to conclude that Singulair has caused any particular effect."
In 40 clinical studies of some 11,000 patients who took Singulair as part of a placebo-controlled trial, there were no reports of suicide, according to Philip.
And in other studies comparing Singulair to other types of asthma therapies including inhaled corticosteroids and long-acting beta agonists, out of roughly 3,900 patients taking Singulair and 3,400 using other asthma treatments, one patient taking Singulair and three patients taking other asthma treatments attempted -- but did not complete -- suicide.
Accolate is made by AstraZeneca. "AstraZeneca is aware of the posting by the FDA, but to date has not been asked for any further information," Blair Hains, AstraZencea spokesman, tells WebMD.
Zyflo and Zyflo CR are made by Critical Therapeutics. "We are actively reviewing our current safety database and will take appropriate action if deemed necessary," Linda Lennox, Critical Therapeutics' vice president for investor and media relations, tells WebMD via email.
Asthma, Allergy Doctors Respond
"There are no data from well-designed studies to indicate a link between Singulair and suicide. The concern expressed by the FDA is based entirely on case reports and there is no indication that such effects apply to other leukotriene-modifying medications," the statement reads.
The statement also recommends that "based on the information currently available, patients taking Singulair should continue to take the medication as prescribed provided: 1) the patient and physician feel the medication is effective; and 2) the patient does not experience any suicidal behavior or thoughts. Patients who experience suicidal thoughts or demonstrate suicidal behavior should consult their physician immediately to discuss whether to continue with this medication. Patients should not hesitate to consult their physician if they feel uncomfortable continuing on the medication."
Report Adverse Events
The FDA urges health care 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.
MedWatch reports can be filed the following ways:
- On the FDA's web site
- By returning the postage-paid FDA form 3500 to 5600 Fishers Lane, Rockville, MD 20852-9787
- By faxing the form to 800-FDA-0178
- By phone at 800-332-1088