FDA Removal of Black-Box Warning Sets Dangerous Precedent

In December, the Food and Drug Administration (FDA) recklessly decided to remove the important black-box warning on the smoking cessation medication varenicline (CHANTIX). The warning had previously alerted doctors and patients to the drug’s potential to cause serious psychiatric and neurologic side effects.[1]

The black-box warning was originally put in place in 2009, in response to a large number of reports to the FDA of depression, suicidal thoughts, psychosis, mania, aggression, and other severe psychiatric and neurologic side effects.[2] In 2014, Public Citizen, along with the Institute for Safe Medication Practices, the National Center for Health Research, Consumers Union, and the National Physicians Alliance petitioned the FDA for a stronger black-box warning on varenicline,[3] a request that was denied by the FDA on Dec. 16, 2016, when the agency decided to remove the black-box warning altogether.[4] The FDA took this action despite acknowledging that the risk for severe neurologic and psychiatric side effects “is still present.”[5] The FDA removed the warning based on the results of a single, poorly designed clinical trial that was supposedly designed to determine the frequency and severity with which these side effects occur. But FDA scientists identified no fewer than six major flaws in the trial, and concluded that it did not accurately capture the precise number and scope of adverse events.[6]

Public Citizen noted that the FDA’s unprecedented decision to remove a black-box warning has opened the door for other companies to do away with black-box warnings on their products by conducting similarly flawed studies.[7]

Varenicline is effective in helping people quit smoking and can be tried, only in patients without serious mental illness, if nicotine replacement therapies fail to work. But, by removing the black-box warning, the FDA has made it less likely that doctors and patients will be aware of varenicline’s dangers. Despite the FDA’s error in judgment, patients and physicians need to know that varenicline can cause violent and suicidal behavior, paranoia, and psychosis—often beginning soon after starting the treatment, and in people with no previous history of any psychiatric disorder.

References

[1] Food and Drug Administration. FDA drug safety communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. December 16, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm. Accessed December 19, 2016.

[2] Food and Drug Administration. FDA Briefing Document. Joint meeting of the Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee. Chantix and serious neuropsychiatric adverse events. October 16, 2014. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM418705.pdf. Accessed December 28, 2016.

[3] Public Citizen. Petition to the FDA requesting a stronger boxed warning and new restrictions on the use of varenicline (Chantix). October 8, 2014. http://www.citizen.org/documents/2225.pdf. Accessed December 19, 2016.

[4]Public Citizen. FDA response to Public Citizen’s petition to the FDA requesting a stronger boxed warning and new restrictions on the use of Varenicline (Chantix). December 16, 2016. http://www.citizen.org/documents/Chantix-FDA-Petition-Response.pdf. Accessed December 19, 2016.

[5] Food and Drug Administration. FDA drug safety communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. December 16, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm532221.htm. Accessed December 19, 2016.

[6] Public Citizen. Testimony before the FDA’s Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee regarding the black box warning on the smoking cessation drug varenicline (Chantix). September 14, 2016. http://www.citizen.org/documents/2340.pdf. Accessed December 19, 2016.

[7] Public Citizen. FDA wrong to remove Chantix’s black box warning based on one flawed study, sets dangerous precedent for future medication safety. December 19, 2016. http://www.citizen.org/pressroom/pressroomredirect.cfm?ID=10102. Accessed January 5, 2017.