Daliresp, Otezla and Belsomra Side Effects May Cause Suicidal Behaviors: ISMP Warns

A new drug safety report suggests that Daliresp, Otezla and Belsomra have each been linked to reports of problems with depression, suicidal thoughts and suicidal behaviors, according to adverse event data submitted to federal regulators over the past year. 

The Institute for Safe Medication Practices (ISMP) released its QuarterWatch report (PDF) on April 19, which outlines incidents submitted through the FDA Adverse Event Reporting System (FAERS) during the 12 months ending on September 30, 2016.

The group highlights a safety signal that suggest side effects of the three newer medications may be associated with a risk of suicidal behavior, urging the manufacturers to update the prescribing and patient information to better disclose the risk.

Daliresp (roflumilast) was approved in 2011, for the treatment of chronic obstructive pulmonary disease, and it was the first member of a new class of drugs known as phosphodiesterase-4 (PDE4) inhibitors. Otezla (apremilast) was approved in 2014 for the treatment of psoriatic arthritis, and is similar to Daliresp in that it is also a PDE4 inhibitor.

Belsomra (suvorexant), however, was approved in 2014 for the treatment of insomnia and belongs to a different class of drugs that blocks neurotransmitters called orexins.

In some cases, there were signs that these drugs may increase suicidal behavior as early as the clinical trials, particularly for PDE4 inhibitors. However, those incidents were few, and the post-approval adverse event reports now coming in suggest that the links may have been stronger than first anticipated.

Daliresp received 176 adverse reports during the time period observed by the ISMP, during which there was a mean of 62,000 patients who were prescribed the drug per month. Of those, 11 cases of suicide and self-injurious behavior were reported, including seven cases of suicidal ideation, 3 suicide attempts and one case where the patient actually died committing suicide.

“To compare roflumilast with other drugs, we focused on reports of suicidal ideation; despite the small total number of reports, we found that roflumilast accounted for 7.8 times the number of suicidal ideation reports that would have been expected based on the results for all other drugs combined,” the ISMP report noted. “In addition, we identified 5 cases of depressive disorders, but this small number could have occurred by chance.”

The findings for Otezla included even stronger indications, including 631 reports specifically for depressed mood disorders, which is 6.3 times the number one would expect out of the 13,601 adverse event reports for Otezla during that time period. In addition, there were 68 cases of suicidal and self-injurious behavior reported, 61 of which involved suicidal ideation, four involving suicidal behavior or attempts, and three completes suicides. The rate of suicidal ideation was 1.6 times higher than expected.

The 2,290 adverse event reports for Belsomra included 40 cases of suicidal or self-injurious behavior, including 19 cases of suicidal ideation, 11 cases of attempted suicide and eight instances where patients died committing suicide. There were also 38 cases of depressed mood disorders.

The ISMP report suggested that there were 3.1 times as many cases of Belsomra suicidal ideation as should be expected.

The group found that, for all three drugs, the FDA had included warnings to physicians for suicide risks and depression. However, Otezla did not contain a warning for patients and none of the three had been updated with postmarketing data since they were released.

Daliresp has the clearest warning of the three, according the group. However, Otezla only warns about an increased risk of depression, and the only warning for Belsomra was “buried” deep in the medication guide, according to the report.

The ISMP called for all three to have Medication Guide warnings for patients that were similar to Daliresp.