Ethical and Practical Considerations in Removing Black Box Warnings from Drug Labels

Drug Saf. 2016 Aug;39(8):709-14. doi: 10.1007/s40264-016-0419-8.


Boxed warnings-also known as "black box" warnings-can be a powerful tool in communicating drug risks to physicians and patients. The overall number of boxed warnings has grown in recent years as the US Food and Drug Administration (FDA) has approved more drugs on the basis of limited pre-marketing information and as new safety issues for marketed drugs have been identified. Two recent manufacturers' petitions to remove boxed warnings on the drugs rosiglitazone (Avandia) and varenicline (Chantix) have led to divergent FDA decisions and revealed different considerations involved in boxed warning imposition and removal. For ethical and practical reasons, the FDA is justified in applying a higher standard for boxed warning removal than for imposition, as removal of a boxed warning may have unintended effects on physician and patient behavior. However, no guidelines on boxed warning removal currently exist. To promote safe use of approved prescription drugs, the FDA should adopt a uniform and transparent process governing decisions to impose or remove boxed warnings.

MeSH terms

  • Drug Approval
  • Drug Industry*
  • Drug Labeling / ethics
  • Drug Labeling / legislation & jurisprudence*
  • Drug-Related Side Effects and Adverse Reactions / prevention & control
  • Humans
  • Legislation, Drug*
  • Prescription Drugs / administration & dosage
  • Prescription Drugs / adverse effects*
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / adverse effects
  • United States
  • United States Food and Drug Administration
  • Varenicline / administration & dosage
  • Varenicline / adverse effects


  • Prescription Drugs
  • Thiazolidinediones
  • Rosiglitazone
  • Varenicline