Prioritizing drug label warnings called for by UCSF School of Pharmacy authors

In the current issue of The Archives of Internal Medicine, two faculty members of the UCSF School of Pharmacy, Department of Clinical Pharmacy issue a call for prioritization in prescription labels’ increasingly long lists of adverse drug events (ADEs).

In their invited Archives commentary, Christine Cheng, PharmD, and department chairman Joseph Guglielmo, PharmD, respond to “A Quantitative Analysis of Adverse Events and ‘Overwarning’ in Drug Labeling” Research Letter by investigators at the Regenstrief Institute and Indiana University School of Medicine, Indianapolis and the UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill.

The investigators found nearly 600 drug labels listing more than 150 adverse drug events (ADEs) and 84 with more than 300 ADEs.

The new analysis, which looked at more than 530,000 adverse events from 5,602 labels, found a 2006 FDA revision of prescription drug labeling guidelines—the Physicians Labeling Rule (PLR)—aimed at “reducing the burden of overwarning” and discouraging “exhaustive lists of every reported adverse event, no matter how infrequent or minor,” is failing to stem the tide.

Indeed, the study found so-called Structured Product Labels formatted to comply with the 2006 regulations actually listed more adverse events, which “may induce information overload and reduce physician comprehension of important safety warnings.”

The investigators found nearly 600 drug labels listing more than 150 ADEs and 84 with more than 300 ADEs. Median ADEs per prescription drug label have increased from 43 for drugs approved in the 1960s, to 63 within the past decade.

Cheng and Guglielmo’s commentary noted that FDA guidance on “Adverse Reactions” has provided a framework and starting point for addressing the problem:

  • ADEs that occur at the same rate as placebo should generally not be included.
  • Vague terms like “common,” “rare,” “infrequent,” or “frequent” should be avoided unless linked to specific frequencies. For example, a “common” ADE would be one that occurred in at least 10% of treated patients at a rate at least twice that of placebo.
  • ADEs should be reported hierarchically—with those occurring with higher frequency first, followed by those that caused therapy discontinuation and those that occurred with lower frequency but were serious (e.g. fatal, life-threatening, causing/prolonging hospitalization).
  • Only ADEs for which there is plausible causality should be included.

The catch, say the UCSF authors, is that “since these guidances are not legally binding, it is not known to what extent drugs labels follow these recommendations.”

Given this new documentation of the proliferation of drug label ADEs, Cheng and Guglielmo assert that: “A consistent approach to the selection and risk characterization of ADEs in the drug label is needed…

“At the minimum, drug labels should present ADE information in a standardized format using common terminology and definitions, so that health care providers can systematically process and manage the deluge of clinical data.”



School of Pharmacy, Department of Clinical Pharmacy, PharmD Degree Program

About the School: The UCSF School of Pharmacy aims to solve the most pressing health care problems and strives to ensure that each patient receives the safest, most effective treatments. Our discoveries seed the development of novel therapies, and our researchers consistently lead the nation in NIH funding. The School’s doctor of pharmacy (PharmD) degree program, with its unique emphasis on scientific thinking, prepares students to be critical thinkers and leaders in their field.