Last September, a Food and Drug Administration (FDA) advisory committee met to discuss whether to remove the existing black-box warning — about serious psychological side effects — on the label of smoking cessation drug varenicline (CHANTIX). Ten members voted to remove the warning, four to retain it with modifications, and five to maintain the warning in its current form. This split vote narrowly favoring removal of the black-box warning was reached despite serious doubts, expressed...
Last September, a Food and Drug Administration (FDA) advisory committee met to discuss whether to remove the existing black-box warning — about serious psychological side effects — on the label of smoking cessation drug varenicline (CHANTIX). Ten members voted to remove the warning, four to retain it with modifications, and five to maintain the warning in its current form. This split vote narrowly favoring removal of the black-box warning was reached despite serious doubts, expressed by the FDA’s own staff, about the design and conduct of the clinical trial that served as the sole basis for the committee’s recommendation to remove the warning.
Importance of smoking cessation
Cigarette smoking kills almost half a million Americans every year and does enormous harm to the health of both smokers and nonsmokers exposed to secondhand smoke. Cigarette smoking is the leading cause of preventable disease and death in the U.S., which means getting Americans to stop smoking is the single most effective way to reduce the overall burden of death and disease in this country.
However, nicotine is highly addictive, and quitting smoking is notoriously difficult. In recent years, several effective drugs have been approved by the FDA to help people quit, and millions of smokers have found these drugs to be vital tools in their quitting strategies. Nicotine replacement therapies, or NRTs, were first approved about 30 years ago as a way to help smokers quit more easily. Today, various forms of NRTs, including skin patches and gum or lozenges, are available over-the-counter and by prescription (COMMIT, HABITROL, NICODERM CQ, NICORETTE, NICOTROL, THRIVE). But not all drugs are nicotine- based. Varenicline, approved in 2006, is a non-nicotine-based drug also effective in helping people quit smoking.
Varenicline’s dangers and 2014 petition
In the years following varenicline’s approval, numerous reports of psychiatric side effects, ranging from mild depression to suicidal thoughts and actual suicides, streamed into the FDA, with many occurring in patients with no history of psychiatric problems.
While it was difficult to know for sure whether these adverse events were caused by the drug, the pattern was concerning enough that, in 2009, the FDA required a black-box warning, the strongest type of warning, to be placed on varenicline’s label alerting users to these and other severe side effects.
In 2014, Public Citizen joined four other groups (the Institute for Safe Medication Practices [ISMP], the National Center for Health Research [NCHR], Consumer Reports, and the National Physicians Alliance) in a petition to the FDA asking for a stronger black-box warning on varenicline’s label. The petition requested that the FDA add psychotic symptoms; blackouts; convulsions; impaired vision; and unexplained hostility, anger and aggression toward others to the black-box warning. The petition also asked that the label warn against any use of the drug by pilots, air traffic controllers, military missile crews, police, firefighters and emergency medical workers, because the adverse events described above could cause them to harm themselves or others in the course of their work. The FDA has not yet responded to the petition.
The FDA advisory committee
The 2016 advisory committee meeting was convened primarily to discuss a new clinical trial that the FDA had asked Pfizer, the maker of CHANTIX, to conduct. The trial aimed to assess the psychiatric and neurologic side effects seen in numerous reports to the agency.
Pfizer hoped that the trial would result in the removal of varenicline’s black-box warning and limited the trial in several ways that made it difficult to rule out varenicline as a cause of these side effects. FDA experts found widespread inconsistencies in how the researchers went about detecting what they deemed “ill-defined and complex” side effects. The experts therefore concluded that the trial did not accurately capture the true number and nature of these side effects.
Public Citizen and two of the groups that signed the 2014 petition (the ISMP and NCHR) testified at the advisory committee meeting, urging the committee members to recommend retaining the black-box warning. In addition to pointing out the many limitations of the clinical trial, the groups reminded committee members of the thousands of reports to the FDA of these effects, which could potentially lead to fatal consequences for varenicline-treated patients or, in cases of drug-induced hostility or aggression, for others.
It is unclear when the FDA will make a final decision on the black-box warning. The agency usually follows the advice of its advisory committees, but, with a split vote such as this, it is impossible to know which way the agency will go.
What You Can Do
If you smoke, you should try to quit as soon as possible. Seeing your doctor or a professional smoking counselor is a good first step to devise a long-term strategy for quitting. For a comprehensive guide on how to quit smoking safely and effectively, see our article “Smoking Cessation” on WorstPills.org.
It is important to remember that NRTs work just as well as varenicline and do not come with as many risks. Before trying varenicline, you should talk to your doctor about trying one of the currently available NRTs, as well as some form of counseling with a health professional. These methods are highly effective in helping people quit smoking.
Not all smokers respond the same way to every NRT, so you should try several formulations, such as the patch and the inhaled variety, to see which one works best for you. Because of its serious risks, varenicline should be used only as a last resort. You should not take varenicline if you have a history of serious mental illness.
 Food and Drug Administration. September 14, 2016: Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm513811.htm. Accessed October 17, 2016.
 Food and Drug Administration. Summary Minutes of the September 14, 2016, Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drug s/PsychopharmacologicDrugsAdvisoryCommittee/UCM524402.pdf. Accessed October 17, 2016.
 Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults in the United States. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/i ndex.htm. Accessed October 17, 2016.
 Food and Drug Administration. Nicotine replacement therapy labels may change. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm345087.htm. Accessed October 17, 2016.
 Food and Drug Administration. Information for healthcare professionals: Varenicline (marketed as Chantix) and bupropion (marketed as Zyban, Wellbutrin, and generics). July 1, 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsa ndProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm. Accessed October 17, 2016.
 Food and Drug Administration. Public health advisory: FDA requires new boxed warnings for the smoking cessation drugs Chantix and Zyban. July 1, 2009. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsa ndProviders/ucm169988.htm. Accessed October 17, 2016.
 Public Citizen (and others). 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 October 17, 2016.
 Food and Drug Administration. Briefing Information for the September 14, 2016, Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee. PDF p. 5. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drug s/PsychopharmacologicDrugsAdvisoryCommittee/UCM520103.pdf. Accessed October 17, 2016.
 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 October 17, 2016.
 Worstpills.org. Smoking cessation. /chapters/view/16. Accessed October 17, 2016.