Research Letter | Health Policy

Association of the Chantix Recall With US Prescribing of Varenicline

and Other Medications for Nicotine Dependence
Adam Edward Lang, PharmD; Urvashi Patel, PhD, MPH; Jonathan Fitzpatrick, MBA, MSF; Tiffany Lee, PhD, MPH; Margo McFarland, PharmD; Chester B. Good, MD, MPH

Introduction + Supplemental content

In July 2021, Pfizer halted the production of Chantix (varenicline tartrate) and recalled select lots due Author affiliations and article information are
1 listed at the end of this article.
to elevated nitrosamine levels. This recall created a shortage of an effective treatment for tobacco
and nicotine dependence.2,3 Later that month the US Food and Drug Administration (FDA) allowed
the US distribution of the Canadian generic Apo-varenicline (varenicline tartrate).1 In September
2021, all lots of Chantix were recalled by Pfizer.1 Shortly thereafter, the first FDA-approved generic
varenicline became available. Our objective was to evaluate the Chantix recall in terms of prescribing
of varenicline and other medications for nicotine dependence in a large US national patient cohort.

Methods
Data for this cross-sectional study were extracted from a national pharmacy benefit database (of
which 73.3% patients had commercial insurance) from January 1, 2021, to June 30, 2022. The search
was limited to patients with commercial insurance and a prescription for a medication to treat
nicotine dependence. Medications included were varenicline (generic, branded generic
Apo-varenicline, and Chantix), nicotine replacement therapy (NRT) (all forms), and sustained-release
bupropion (150-mg tablets only). Metrics of use and prevalence were created for each month for
each medication. This study was deemed exempt by the University of Pittsburgh institutional review
board because all data were deidentified administrative data. This study followed the STROBE
reporting guideline for cross-sectional studies.
An interrupted time series analysis was conducted using SAS, version 9.4 (SAS Institute Inc),
including covariates for time and a binary indicator for intervention period or not and time after
intervention. All P values were from 2-sided tests and results were deemed statistically significant at
P < .05. The prerecall period was defined as January 1 to June 30, 2021, and the postrecall period
was October 1, 2021, to June 30, 2022. A washout period was defined as July 1 to September
30, 2021.

Results
Among 21 653 835 patients in 2021 and 19 978 911 in 2022, 312 708 prescriptions (30-day
equivalent) for varenicline were filled by 238 258 patients. In August 2021, the month after the
production halt of Chantix, the prevalence of patients prescribed varenicline decreased from 536 per
1 million in June to 146 per 1 million (Figure 1). By September 2021, use of varenicline was 136 per 1
million, which represented a 74.7% absolute reduction (P < .001) compared with the prewashout
period before increasing monthly thereafter. There was a significant increase in varenicline use in the
period starting October 2021; however, by June 2022, the use of varenicline was still lower than in
June 2021. There was no significant change in the use of sustained-release bupropion or NRT
throughout the study period (Figure 2).

Open Access. This is an open access article distributed under the terms of the CC-BY-NC-ND License.

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 JAMA Network Open | Health Policy Association of the Chantix Recall With Prescribing of Therapy for Nicotine Dependence

Discussion
Tobacco cessation is associated with immediate and long-term improvement in clinical outcomes,
including morbidity and mortality.4 Prescriptions of varenicline, an effective strategy for treating
nicotine dependence, were reduced by the limitation and subsequent removal of Chantix from the
market in 2021. Furthermore, there was no concomitant increase in the prescribing of NRT or
sustained-release bupropion. Limitations to this study include that these results cannot account for
over-the-counter NRT purchases and that the population was limited to those with commercial
insurance.

Figure 1. Prevalence of Varenicline Prescribing From January 2021 to June 2022

800

Apo-varenicline 1 mg
700 Apo-varenicline 0.5 mg
Varenicline tartrate 1 mg
600 Varenicline tartrate 0.5 mg
Chantix 1 mg (including continuation pak)
Prevalence per 1 000 000

500 Chantix starter pak

Chantix 0.5 mg

400

300

a
200
b

100

0
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

2021 2022
Months

b
Prevalence = (number of members/total member months) × 1 000 000. All lots of Chantix recalled by Pfizer; FDA approves generic varenicline in the US.
a
Production of Chantix halted by Pfizer; US Food and Drug Administration (FDA) allows
use of Canadian generic Apo-varenicline in the US.

Figure 2. Use of Medications for Nicotine Dependence From January 2021 Through June 2022

0.025

Varenicline (brand and generic)

0.020
Use, d/member

0.015

Nicotine replacement therapy

0.010

0.005
Sustained-release bupropion, 150 mg

0
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun

2021 2022
Months

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 JAMA Network Open | Health Policy Association of the Chantix Recall With Prescribing of Therapy for Nicotine Dependence

In the US, the continuing dearth of varenicline claims through June 2022 was not due to a lack
of drug availability but to accessibility. The lack of clinician and patient awareness regarding the
availability of varenicline after the recall and concerns about nitrosamine were likely factors. The US
could benefit from FDA-initiated public service announcements to spread knowledge of the
availability of generic varenicline and to counter myths that nitrosamines in varenicline products
outweigh harms from cigarettes. Policy changes to improve medication recall procedures and
communication could help mitigate recurrence of an event at this magnitude. The substantial
decrease in varenicline use after the Chantix recall represented potential lost opportunities for
nicotine cessation with likely immediate and long-term adverse health outcomes.

ARTICLE INFORMATION
Accepted for Publication: December 17, 2022.
Published: February 6, 2023. doi:10.1001/jamanetworkopen.2022.54655
Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2023
Lang AE et al. JAMA Network Open.
Corresponding Author: Adam Edward Lang, PharmD, Department of Primary Care, McDonald Army Health
Center, 576 Jefferson Ave, Ft Eustis, VA 23604 (a.edward.lang@gmail.com).
Author Affiliations: Department of Primary Care, McDonald Army Health Center, Ft Eustis, Virginia (Lang);
Department of Family Medicine and Population Health, Virginia Commonwealth University School of Medicine,
Richmond (Lang); Research Institute Department, Evernorth Health Services, St Louis, Missouri (Patel, Lee);
Department of Client Solution Product Strategy, Evernorth Health Services, St Louis, Missouri (Fitzpatrick);
Pharmacy Services, Insurance Services Division, UPMC Health Plan, Pittsburgh, Pennsylvania (McFarland); Centers
for High Value Health Care and Value Based Pharmacy Initiatives, Insurance Services Division, UPMC Health Plan,
Pittsburgh, Pennsylvania (Good).
Author Contributions: Drs Lee and Good had full access to all of the data in the study and take responsibility for
the integrity of the data and the accuracy of the data analysis.
Concept and design: Lang, Patel, Fitzpatrick, McFarland, Good.
Acquisition, analysis, or interpretation of data: Lang, Patel, Fitzpatrick, Lee, Good.
Drafting of the manuscript: Lang, Fitzpatrick, Good.
Critical revision of the manuscript for important intellectual content: Patel, Fitzpatrick, Lee, McFarland, Good.
Statistical analysis: Fitzpatrick, Lee.
Administrative, technical, or material support: Lang, Patel, Good.
Supervision: Lang, Patel, Good.
Conflict of Interest Disclosures: Dr Lang reported previously owning stock in Walmart, Target, and Johnson &
Johnson outside the submitted work. No other disclosures were reported.
Disclaimer: The views expressed in this publication are those of the authors and do not necessarily reflect the
official policy of the Department of Defense, Department of the Army, US Army Medical Department, Defense
Health Agency, or the US government.
Data Sharing Statement: See the Supplement.
Additional Contributions: The authors thank Mark Eatherly, BS, Evernorth Research Institute, for his assistance
with data pulls and presentation of those data. He did not receive compensation for his assistance.

REFERENCES
1. U.S. Food and Drug Administration. FDA updates and press announcements on nitrosamine in varenicline
(Chantix). August 23, 2021. Accessed September 10, 2021. https://www.fda.gov/drugs/drug-safety-and-availability/
fda-updates-and-press-announcements-nitrosamine-varenicline-chantix
2. Leone FT, Zhang Y, Evers-Casey S, et al. Initiating pharmacologic treatment in tobacco-dependent adults. an
official American Thoracic Society clinical practice guideline. Am J Respir Crit Care Med. 2020;202(2):e5-e31. doi:
10.1164/rccm.202005-1982ST
3. Krist AH, Davidson KW, Mangione CM, et al; US Preventive Services Task Force. Interventions for tobacco
smoking cessation in adults, including pregnant persons: US Preventive Services Task Force recommendation
statement. JAMA. 2021;325(3):265-279. doi:10.1001/jama.2020.25019

JAMA Network Open. 2023;6(2):e2254655. doi:10.1001/jamanetworkopen.2022.54655 (Reprinted) February 6, 2023 3/4

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 JAMA Network Open | Health Policy Association of the Chantix Recall With Prescribing of Therapy for Nicotine Dependence

4. U.S. Department of Health and Human Services. The Health Consequences of Smoking—50 Years of Progress:
A Report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and
Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health;
2014.

SUPPLEMENT.
Data Sharing Statement

JAMA Network Open. 2023;6(2):e2254655. doi:10.1001/jamanetworkopen.2022.54655 (Reprinted) February 6, 2023 4/4

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