FDA and the manufacturers of Singulair (montelukast), Accolate (zafirlukast), Zyflo (zileuton) and Zyflo CR (zileuton extended release) are announcing an update to the Precautions section of the prescribing information to include information about neuropsychiatric events reported in patients using these products.
FDA's request for the addition of this information to the prescribing information for these products was described in the agency’s June 2009 “Update to the Follow Up to the Early Communication about an Ongoing Safety Review for Leukotriene Inhibitors."
For the latest prescribing information for these products, see Regulatory History and Labeling from Drugs@FDA.
Neuropsychiatric events have been reported in some patients taking montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). FDA has requested that manufacturers include a precaution in the drug prescribing information (drug labeling).
Montelukast 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. Zafirlukast and zileuton are used to treat asthma.
The reported neuropsychiatric events include postmarket cases of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor.
This information reflects FDA’s current analysis of available data concerning this drug.
To report any serious adverse events associated with the use of this drug, please contact the FDA MedWatch program using the contact information at the bottom of this web page.
Advice to patients and healthcare professionals
- Patients and healthcare professionals should be aware of the potential for neuropsychiatric events with these medications.
- Patients should talk with their healthcare providers if these events occur.
- Healthcare professionals should consider discontinuing these medications if patients develop neuropsychiatric symptoms.
In April 2009, FDA completed its review of neuropsychiatric events, (mood and behavioral changes) possibly related to drugs that act through the leukotriene pathway (montelukast, zafirlukast, zileuton). As part of its review, FDA reviewed post-marketing reports and also requested that manufacturers submit all available clinical trial data for these products.
The post-market reports of patients on these medications included cases of neuropsychiatric events. Some reports included clinical details consistent with a drug-induced effect. In the clinical trial data submitted by manufacturers, neuropsychiatric events were not commonly observed. However, the available data were limited because the trials were not designed to look for neuropsychiatric events. Sleep disorders (primarily insomnia) were reported more frequently with all three products compared to placebo.