New and incremental FDA black box warnings from 2008 to 2015

Background: The boxed warning (also known as ‘black box warning [BBW]’) is one of the strongest drug safety actions that the U.S. Food & Drug Administration (FDA) can implement, and often warns of serious risks. The objective of this study was to comprehensively characterize BBWs issued for drugs after FDA approval.

Methods: We identified all post-marketing BBWs from January 2008 through June 2015 listed on FDA’s MedWatch and Drug Safety Communications websites. We used each drug’s prescribing information to classify its BBW as new, major update to a preexisting BBW, or minor update. We then characterized these BBWs with respect to pre-specified BBW-specific and drug-specific features.

Results: There were 111 BBWs issued to drugs on the US market, of which 29% (n = 32) were new BBWs, 32% (n = 35) were major updates, and 40% (n = 44) were minor updates. New BBWs and major updates were most commonly issued for death (51%) and cardiovascular risk (27%). The new BBWs and major updates impacted 200 drug formulations over the study period, of which 64% were expected to be used chronically and 58% had available alternatives without a BBW.

Conclusions: New BBWs and incremental updates to existing BBWs are frequently added to drug labels after regulatory approval.