Medicare Prescription Drug Plan Formulary Restrictions After Postmarket FDA Black Box Warnings

J Manag Care Spec Pharm. 2019 Nov;25(11):1201-1217. doi: 10.18553/jmcp.2019.25.11.1201.


Background: The boxed warning (also known as "black box warning") is one of the FDA's strongest safety actions for pharmaceuticals. After the FDA issues black box warnings for drugs, prescribing changes have been inconsistent. Formulary management may provide an opportunity to restrict access to drugs with serious safety concerns.

Objective: To examine Medicare prescription drug plan formulary changes after new FDA postmarket black box warnings and major updates to preexisting black box warnings.

Methods: In this cohort study, we identified each drug that received a new FDA postmarket black box warning or a major update to a preexisting black box warning from January 2008 through June 2015 and examined its formulary coverage. The main outcome measure was the proportion of Medicare prescription drug plan formularies providing unrestrictive coverage immediately before the black box warning, at least 1 year after the warning and at least 2 years after the warning. Unrestrictive formulary coverage was defined as coverage of a drug without prior authorization or step-therapy requirements.

Results: Of 101 new black box warnings and major updates to preexisting warnings affecting 68 unique drug formulations, the mean percentage of formularies providing unrestrictive coverage changed from 65.4% (95% CI = 59.6%-71.2%) prewarning; 62.6% (95% CI = 56.3%-68.9%, P = 0.04) at least 1 year postwarning; and 61.9% (95% CI = 55.4%-68.5%, P = 0.10) at least 2 years postwarning.

Conclusions: The mean percentage of Medicare prescription drug plan formularies providing unrestrictive coverage decreased modestly by approximately 3 percentage points after drugs received postmarket FDA black box warnings. Formulary restrictions may present an underused mechanism to reduce use of potentially unsafe medications.

Disclosures: This study was supported by a student research grant received by Solotke and provided by the Yale School of Medicine Office of Student Research under National Institutes of Health training grant award T35DK104689. Karaca-Mandic, Shah, and Ross acknowledge support from Agency for Healthcare Research and Quality (AHRQ) grant R01 HS025164, which studies factors associated with de-adoption of drug therapies shown to be ineffective or unsafe. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors assume full responsibility for the accuracy and completeness of the ideas presented. Ross has received support from the following: the U.S. Food and Drug Administration (FDA) as part of the Centers for Excellence in Regulatory Science and Innovation (CERSI) program; Johnson and Johnson through Yale University to develop methods of clinical trial data sharing; Medtronic and the FDA to develop methods for postmarket surveillance of medical devices; the Blue Cross Blue Shield Association to better understand medical technology evaluation; the Centers for Medicare & Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting; the AHRQ to examine community predictors of health care quality; and the Laura and John Arnold Foundation, which established the Collaboration for Research Integrity and Transparency at Yale University. Shah has received support from the FDA as part of the CERSI program. In addition, he has received support through the Mayo Clinic from CMS, AHRQ, National Science Foundation, and Patient-centered Outcomes Research Institute. Karaca-Mandic has provided consulting services to Precision Health Economics and Tactile Medical for work unrelated to this manuscript. Dhruva and Solotke have no conflicts of interest to report.

MeSH terms

  • Drug Labeling / legislation & jurisprudence*
  • Drug Prescriptions / statistics & numerical data
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / prevention & control*
  • Formularies as Topic
  • Humans
  • Male
  • Medicare / economics
  • Medicare / legislation & jurisprudence*
  • Prescription Drugs / adverse effects*
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence*


  • Prescription Drugs