Black Box Warnings—Implications in Practice

Abstract

Medication safety concerns continue to escalate and have led to revitalization of the Food and Drug Administration’s (FDA’s) efforts around boxed warnings and utilization of large relational databases for early identification of drug safety concerns. Box warnings, commonly referred to as Black Boxed Warnings, are developed by the FDA to communicate critical information to providers (physicians, nurse practitioners, and other prescribers). The warnings are separated and thus highlighted from other text in the product information (package insert) by a prominent black box border. A boxed warning on the label of a prescription drug is the strongest warning that the FDA requires. Boxed warnings signify that the medication carries a significant risk of serious or even life-threatening adverse effects. A boxed warning provides a brief, concise summary of the information that is critical for a prescriber to be aware of, including any restriction on distribution or use of the medication. Boxed warnings can focus on adverse effects, monitoring requirements, drug-drug interactions, drug-disease interactions, and drug-laboratory interactions. In a clinical effectiveness research trial sponsored by the Agency for Health Research and Quality (AHRQ), Harvard investigators analyzed the health records of approximately 930,000 patients in 10 health care plans (integrated delivery systems) and found that approximately 40% of these patients took medications with boxed warnings. Prescriber compliance to black box warnings varied, ranging from 0.3 to 49.6%, depending on the medication. The study revealed that prescribers were most lax about monitoring, failing to order laboratory tests in nearly 50% of patients receiving a boxed warning medication that recommends baseline laboratory evaluation before the medication should be started. The conclusions of the authors were that current use (2004–2005) of black box warnings was not