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

Abstract

Importance Drug safety communications released by the Food and Drug Administration (FDA) are often based on limited evidence on safety signals post-approval. Varenicline constitutes an interesting case study, because it was the target of several FDA communications in 2008 and 2009; ultimately the EAGLES trial dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior in 2016. Objective To examine the association between FDA drug safety communications and the utilization of varenicline. Design/ Setting/ Participants/ Exposures Retrospective longitudinal study of 2002–2018 VHA outpatient data and 2006–2018 Medicaid drug state utilization data. Main Outcomes/Measures We extracted prescribing records for varenicline and nicotine replacement therapy (NRT) in VHA and measured the number of unique varenicline and NRT users in VHA per quarter. We implemented an interrupted time-series analysis to describe the association between FDA safety warnings and the utilization of varenicline and of NRT. To test the generalizability of our findings, we duplicated similar analyses using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006–2018. Results After its addition to VHA national drug formulary in January 2007, varenicline presented a rapid uptake growing from 70 to over 50,000 prescriptions by the end of the year. Within 12 months of the 2008 public health advisory, quarterly varenicline utilization decreased by 68.7% from 32,581 to 10,182 patients (p-value for trend change<0.001), while NRT utilization increased by 32.1%, from 55,728 to 73,629 patients (p-value for trend change<0.001). In Medicaid, varenicline utilization decreased by 38.0% from 109,308 to 67,761 prescriptions within 12 months of the 2008 public health advisory (p-value for trend change<0.001). Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to nicotine replacement therapy (NRT), utilization increased by 42.7% in VHA patients (p-value for trend change=0.01), and by 26.0% in Medicaid (p-value for trend change=0.26). Conclusions and Relevance Using varenicline as a case study, we found that early communications from the FDA and VHA followed by a labelling change was associated with a considerable decrease in drug utilization, which may have been associated with negative public health consequences.

Receipt of and Spending on Cessation Medication Among US Adults With Employer-Sponsored Health Insurance, 2010 and 2017

“…27 The substantial percentage increases in receipt of over-the-counter NRTs observed were likely due in part to the black box warning for serious adverse neuropsychiatric events that the FDA placed on varenicline in 2009, which remained in effect until December 2016. 28 These increases may also be due in part to changes in the types and characteristics of nicotine lozenges available on the market, which potentially made these products more palatable, appealing, and easier to use than traditional nicotine lozenges, including the FDA's approval of nicotine mini-lozenges for over-the-counter use for smoking cessation in 2009. 2 Despite a slight increase in the number of tobacco users receiving cessation medication during the study period, fewer than 1 in 5 tobacco users had claims for cessation medication in 2017.…”

“…The observed gap in cessation medication use is consistent with previous research. [28][29][30] This relatively low receipt of cessation medications might stem, in part, from a large proportion of smokers not receiving advice to quit when they saw their health care professional. 2 Quitting smoking at any age has substantial health benefits, 2 some of which begin to accrue quickly.…”

Suicide Attempt in a 38-Year-Old Patient on Varenicline While Intoxicated With Alcohol

“…In 2009, a black box warning was added to the medication, which was rescinded in 2016 following the EAGLES trial. Prescribing patterns were significantly altered following these decisions, with a sharp decline in prescriptions following the black box warning, which was then followed by a sharp increase in usage after the repeal of the warning [15].…”

Looking Back and Going Forward: Roles of Varenicline and Electronic Cigarettes in Smoking Cessation

“…However, based on the results of the EAGLES trial discussed above [ 25 ], the FDA lifted the black box warning in 2016. Subsequently, varenicline prescriptions have risen among Veterans Health Administration and Medicaid patients [ 51 ], and by extension, smoking prevalence should continue to fall.…”