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Publication Briefs

Unintentional Consequences of FDA Warnings: Varenicline

FDA drug safety communications and public health advisories are intended to inform the public about emerging drug-related safety issues. This retrospective longitudinal study examined the association between FDA drug safety communications and the use of varenicline (Chantix) – a prescription drug used to treat addiction to smoking. In November 2007, the FDA released the first safety communication regarding suicidal thoughts and aggressive and erratic behavior associated with varenicline, followed by a public health advisory in February 2008 and a boxed warning in July 2009. The boxed warning was removed in December 2016 after published findings from a randomized clinical trial [Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES)] showed no significant increase in psychiatric/behavioral effects with varenicline compared with nicotine replacement therapy (NRT) or placebo. Using VA outpatient data from October 2001 through December 2018 – and Medicaid data from July 2006 through September 2018, investigators tracked varenicline and NRT prescribing. Investigators also evaluated the potential consequences of decreased varenicline use on lost opportunities to assist patients with quitting smoking and health outcomes, including mortality.


  • Within 12 months of FDA communications about a labeling change for varenicline, there was a 69% reduction in VA outpatient prescriptions and a 38% decrease in Medicaid prescriptions. Varenicline use reached its low point in VA in early 2014, when the number of unique quarterly users was 5,990, representing an 82% decline from the first quarter of 2008. In addition, from 2008 to 2018, NRT users in VA increased by 73% (from 55,728 to 96,103 patients).
  • One year after the publication of EAGLES, quarterly varenicline use had increased by 43% in VA patients and by 26% in Medicaid patients.
  • The number of VA patients who did not quit smoking due to decreased varenicline use was estimated to be 20,544, which likely was associated with negative health effects.


  • Early FDA communications led to additional safety measures within VA and a subsequent decrease in varenicline prescribing, which may have been associated with negative health consequences. In responding to these early communications, healthcare systems should consider the magnitude of potential harm against known benefit from use of that medication.


  • Investigators were unable to differentiate prescribing changes related to FDA warnings and labeling changes from those related to VA drug safety communications and changes in prescribing guidance and national temporal trends.

Dr. CB Good is part of HSR&D’s Center for Health Equity Research & Promotion (CHERP) located in Pittsburgh and Philadelphia, PA; Mr. Desai and Dr. M Good are with VA Pittsburgh Healthcare System; Mr. Henriksen and Drs. Cunningham and CB Good are with the VA Center for Medication Safety, Hines, IL.

PubMed Logo Desai R, Good M, San-Juan-Rodriguez A, Henriksen A, Cunningham F, Hernandez I, and Good C. Varenicline and Nicotine Replacement Use Associated with US Food and Drug Administration Drug Safety Communications. JAMA Network Open. September 4, 2019;2(9):e1910626.

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What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

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