Public Citizen Joins Other Groups in Requesting Additional Warnings on CHANTIX Label

Cigarette smoking kills almost half a million Americans every year and causes enormous harm to the health of both smokers and nonsmokers exposed to secondhand smoke.[1] Despite the tobacco industry’s best efforts, it is now widely known that cigarettes cause various types of fatal cancers, heart disease leading to heart attacks, chronic obstructive pulmonary disease (COPD) and numerous other serious diseases. Experts agree that getting Americans to stop smoking is the single most effective way to reduce the burden of death and disease in this country.[2]

How to accomplish this is another matter. Nicotine is highly addictive, and quitting smoking is notoriously difficult. Many smokers are unsuccessful despite multiple attempts. But in recent years, several drugs have been approved by the Food and Drug Administration (FDA) to help people quit, with millions of smokers considering them vital tools in their quit strategies.

However, one such drug, varenicline (CHANTIX), while effective in helping smokers quit, carries particularly serious risks. In October 2014, Public Citizen joined four other nonprofit consumer advocacy and research groups to petition the FDA to require stronger warnings on varenicline’s label, alerting users to several severe psychiatric and neurological side effects that could potentially lead to fatal consequences for them or others.[3]

Varenicline’s dangers evident following approval

Nicotine replacement therapies, or NRTs, were first approved 30 years ago as a way to help smokers quit more easily.[4] Today, various forms of NRTs, including skin patches, gum and inhaled versions, are available over the counter and by prescription (COMMIT, HABITROL, NICODERM CQ, NICORETTE, NICOTROL, THRIVE).

Approved in 2006,[5] varenicline was a new, non-nicotine-based drug proven effective in helping people quit smoking.[6] However, in the years following its approval, numerous reports of psychiatric side effects, ranging from mild depression to suicidal thoughts and actual suicides, streamed into the FDA. Many of these effects occurred in patients with no prior psychiatric history.[7]

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.[8] The FDA also issued a notice, warning the public and physicians of these potential side effects.[9] (Two years later, the FDA issued another notice warning that varenicline also may increase the risk of heart attack and peripheral vascular disease.[10] For more information on this risk, see our article in the September 2011 issue of Worst Pills, Best Pills News.)

Likely due to the publicity surrounding these actions, prescriptions for varenicline declined precipitously over the next few years. In 2007, 3.9 million patients received a prescription for CHANTIX, but in 2013, only 1.2 million were given the drug.[11]

Public Citizen petitions for stronger warnings

The FDA’s requirement of a black-box warning was a good first step, but the agency left out of the warning several other psychiatric and neurological side effects that have been linked to varenicline.[12],[13],[14] After reviewing the evidence, Public Citizen and four other groups (the Institute for Safe Medication Practices, Consumer Reports, the National Center for Health Research and the National Physicians Alliance) asked that the following side effects be added to the black-box warning:[15]

• Psychotic symptoms
• Blackouts, convulsions and impaired vision
• Unexplained hostility, anger and aggression toward others

The petition also asked that the label warn against any use of the drug in patients working “in sensitive or hazardous occupations such as pilots, air traffic controllers, military missile crews, police, fire fighters, and emergency medical workers”[16] because the adverse events described above could cause them to harm themselves or others in the course of their work. Finally, the petition asked to remove from the warning label language touting the drug’s benefits, which the petition noted was inappropriate — and highly unusual — in a section of the label intended only to describe serious safety concerns.

FDA advisory committee

The groups’ petition was submitted to the FDA just before the agency convened a pivotal advisory committee meeting to discuss the side effects of varenicline. The meeting, held on Oct. 16, 2014, was a joint session of experts from two different FDA advisory committees responsible for evaluating psychiatric drugs and drug safety. The purpose of the meeting was to discuss recently completed studies conducted by varenicline’s manufacturer, Pfizer Inc. The studies seemed to cast doubt on the link between varenicline and various psychiatric and neurological side effects.[17]

At the meeting, Pfizer attempted to use data from these studies to persuade the committees to recommend removal of the existing black-box warning describing varenicline’s psychiatric side effects from the drug’s label and substitution with a weaker warning.[18]

However, the petition filed by Public Citizen and others documented several limitations to the studies and raised concerns about whether they were adequately designed to accurately detect the drug’s side effects.[19] For example, several of the studies did not look for some of the most serious effects, such as psychosis and hostility toward others.[20] The most comprehensive study omitted from its analysis several clinical trials investigating the psychiatric side effects of varenicline.[21]

Fortunately, a majority of committee members (11 of 18) voted to retain the current black-box warning, noting that a trial designed to further assess varenicline’s risks was currently underway and results could be expected soon. An additional six members voted to strengthen the warning to include information about additional side effects, some of which were mentioned in Public Citizen’s joint petition. Only one member agreed with Pfizer and voted to remove and downgrade the black-box warning.

The FDA is not required to follow the advice of its advisory committee members, but it usually does, especially in cases such as this, when that advice is in agreement with its own position.[22] Therefore, it is expected that the black-box warning currently in the varenicline label will remain for the foreseeable future. Public Citizen’s joint petition to strengthen the warning even further is currently awaiting an FDA response.

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 on “Smoking Cessation” on WorstPills.org.

Varenicline is undoubtedly effective in helping many people quit smoking. However, it is important to remember that NRTs work just as well 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, along with some form of counseling with a health professional. This method has proven to be highly effective in helping people quit smoking.[23]

Not all smokers respond the same 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.

References

[1] Centers for Disease Control and Prevention. Adult cigarette smoking in the United States: Current estimates. http://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm. Accessed December 16, 2014.

[2] Centers for Disease Control and Prevention. Cigarette smoking in the United States. http://www.cdc.gov/tobacco/campaign/tips/resources/data/cigarette-smoking-in-united-states.html. Accessed December 16, 2014.

[3] 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 December 15, 2014. [Hereafter referred to as “Chantix Petition”]

[4] Food and Drug Administration. Nicotine replacement therapy labels may change. http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm345087.htm. Accessed December 16, 2014.

[5] Chantix drug label. October 2014.

[6] Cahill K, Stevens S, Perera R, Lancaster T. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013 May 31;5:CD009329.

[7] 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/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm169986.htm. Accessed December 15, 2014.

[8] 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/PostmarketDrugSafetyInformationforPatientsandProviders/ucm169988.htm. Accessed December 15, 2014.

[9] Ibid.

[10] Food and Drug Administration. FDA drug safety communication: Chantix (varenicline) may increase the risk of certain cardiovascular adverse events in patients with cardiovascular disease. June 16, 2011. http://www.fda.gov/Drugs/DrugSafety/ucm259161.htm. Accessed December 16, 2014.

[11] Food and Drug Administration. Briefing materials for the October 16, 2014, joint meeting of the Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM418705.pdf. Accessed December 15, 2014.

[12] Moore TJ, Glenmullen J, Furberg CD. Prescription drugs associated with reports of violence towards others. PLoS One. 2010 Dec 15;5(12):e15337.

[13] Rouve N, Bagheri H, Telmon N, et al. Prescribed drugs and violence: a case/noncase study in the French PharmacoVigilance Database. Eur J Clin Pharmacol. 2011 Nov;67(11):1189-98.

[14] Moore TJ, Cohen MF, Furberg CD (Institute for Safe Medication Practices). QuarterWatch. Strong signal seen on new varenicline risks. Institute for Safe Medication Practices. http://www.ismp.org/QuarterWatch/chantixReport.asp. Accessed December 15, 2014.

[15] Chantix Petition.

[16] Ibid.

[17] Food and Drug Administration. Draft agenda. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM418698.pdf. Accessed December 15, 2014.

[18] Food and Drug Administration. Briefing materials for the October 16, 2014 joint meeting of the Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM418705.pdf. Accessed December 15, 2014.

[19] Chantix petition.

[20] Ibid.

[21] Chantix petition. Based on: Tonstad S, Davies S, Flammer M, et al. Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: A pooled analysis. Drug Saf. 2010;33(4):289-301.

[22] Food and Drug Administration. Briefing materials for the October 16, 2014 joint meeting of the Psychopharmacologic Drugs Advisory Committee (PDAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM). http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM418705.pdf. Accessed December 15, 2014.

[23] WorstPills.org. Smoking cessation. /chapters/view/16. Accessed December 16, 2014.