Varenicline and Nicotine Replacement Use Associated With US Food and Drug Administration Drug Safety Communications

Source: Desai RJ, Good MM, San-Juan-Rodriguez A, et al. Varenicline and Nicotine Replacement Use Associated With US Food and Drug Administration Drug Safety Communications. JAMA Netw Open. Published online September 04, 20192(9):e1910626. doi:10.1001/jamanetworkopen.2019.10626

Key Points

Question  Did use of varenicline change after early US Food and Drug Administration drug safety communications regarding neuropsychiatric adverse events?

Findings  This cross-sectional study observed a reduction in varenicline prescribing following the release of US Food and Drug Administration drug safety communications on the medication. Interrupted time series analysis showed a 68.7% decrease in Veterans Health Administration outpatient prescriptions and a 38.0% decrease in Medicaid prescriptions.

Meaning  In the wake of US Food and Drug Administration and Veterans Health Administration communications, prescriptions for varenicline decreased significantly, which may have been associated with negative public health consequences.

Abstract

Importance  Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may serve as a relevant case study because it was the target of several FDA communications in 2008 and 2009; ultimately, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior on December 16, 2016.

Objective  To examine the association between FDA drug safety communications and the use of varenicline.

Design, Setting, and Participants  Retrospective, longitudinal, cross-sectional study of Veterans Health Administration (VHA) outpatient data from October 1, 2001, through December 31, 2018, and Medicaid drug state use data from July 1, 2006, through September 30, 2018, on varenicline prescribing.

Main Outcomes and Measures  Prescribing records for varenicline and nicotine replacement therapy (NRT) in the VHA were extracted, and the number of unique varenicline and NRT users in the VHA per quarter was measured. An interrupted time series analysis was performed to describe the association between FDA safety warnings and the use of varenicline and NRT. To test the generalizability of the findings, similar analyses were conducted using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006-2018.

Results  After its addition to the VHA national drug formulary in January 2007, varenicline use presented a steady increase, reaching a peak of 32 581 quarterly unique users in the first quarter of 2008. Within 12 months of the February 1, 2008, public health advisory, quarterly varenicline use in VHA patients decreased by 68.7% (from 32 581 to 10 182 patients; P < .001 for slope change), and NRT use increased by 32.1% (from 55 728 to 73 629 patients; P < .001 for slope change). In Medicaid prescriptions, varenicline use decreased by 38.0% (from 109 308 to 67 761 prescriptions; P < .001 for slope change) within 12 months of the 2008 public health advisory. Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to NRT, use of varenicline increased by 42.7% in VHA patients (from 9251 to 13 199 patients; P = .01 for slope change) and by 26.0% in Medicaid prescriptions (112 063 to 141 122; P = .26 for slope change).

Conclusions and Relevance  With use of varenicline as a case study, early communications from the FDA and VHA followed by a labeling change appeared to be associated with a considerable decrease in drug use, which may have been associated with negative public health consequences.