An FDA analysis showed an increase of 65% of testosterone product usage from 2009 through 2013.
Varenicline, used for smoking cessation, was the subject of a recent Institute for Safe Medication Practices (ISMP) Medication Safety Alert.4 The ISMP reassessed adverse drug event (ADE) data from 2007 through the third quarter of 2013. The assessed endpoints included suicidal thoughts, self-injury and homicide. Their analysis showed that varenicline use was accompanied by more cases of homicidal thoughts, self-injury or suicide than any other drug during that timeframe.
Since its approval in 2007, varenicline has been the primary suspected drug in 293 completed suicides and another 490 attempted suicides. For homicidal ideation, varenicline had a fivefold margin over quetiapine. Of 10 drugs that were ranked for these psychiatric ADEs, all but one (isotretinoin, ranked at 7) had wider patient exposure due to the number of dispensed outpatient prescriptions according to IMS Health. Other drugs in the ranking from 2 through 10 were montelukast (ranked at 2), paroxetine (ranked at 3), quetiapine (ranked at 4), venlafaxine (ranked at 5), interferon beta (ranked at 6), duloxetine (ranked at 8), pregabalin (ranked at 9) and bupropion (ranked at 10).
The FDA met to reassess the varenicline data in a meeting of two advisory boards held in mid-October. Of 18 voting members, 11 noted that the agent should continue to carry the boxed warning about the risk of severe neuropsychiatric events, of which six panel members suggested strengthening the boxed warning.5 The boxed warning should remain until the outcome of a prospective trial currently underway to assess varenicline’s psychiatric risks is known. FDA reviewers suggested that some of the studies cited by the manufacturer of the agent defending its safety profile may have deterred patients at high risk for neuropsychiatric adverse events from being enrolled. The manufacturer has cited research that suggests minimal or no psychiatric risk due to the drug. However, most of this was in the form of observational studies and meta-analyses. The manufacturer was told when the prospective postmarketing study was requested that observational studies would not be acceptable to assess these safety risks. The results are expected in 2015.
Only time will tell.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
References
- Zogenix. News release. Zogenix submits modified formulation of Zohydro® ER with potential abuse deterrent properties for FDA review. Oct. 1, 2014. http://ir.zogenix.com/phoenix.zhtml?c=220862&p=irol-newsArticle&cat=news&id=1972777.
- Novartis. Media releases. Novartis AIN457 (secukinumab) is the first ever IL-17A inhibitor to meet primary endpoint in two Phase III studies in psoriatic arthritis. Sept. 25, 2014. http://www.novartis.com/newsroom/media-releases/en/2014/1858095.shtml.
- Tucker ME. FDA panel urges restrictions on testosterone use. MedScape. Sept. 18, 2014. http://www.medscape.com/viewarticle/831897.
- Quarterwatch Report (Quarters 2 and 3, 2013): Signals for Chantix, Xyrem, Gilenya, and Tecfidera. Acute Care ISMP Medication Safety Alert. Sept. 25, 2014;19(19):1–2.
- Gever J. FDA Panel: Chantix boxed warning should stay. MedPage Today. Oct. 17, 2014. http://www.medpagetoday.com/PrimaryCare/Smoking/48119.
