Timing of New Black Box Warnings and Withdrawals for Prescription Medications

Abstract

Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.

Different Black Box Warning Labeling for Same-Class Drugs

“…Withdrawal information for the US market was retrieved from the "MedWatch"-based Safety Alerts for Human Medical Products database, 26 the Reports to the Nation from the Center for Drug Evaluation and Research, [27][28][29][30][31][32][33][34] and a published list of withdrawn drugs for pre-2000 withdrawals. 13 For each of these drugs, we confirmed its current marketing status in the US using information available on Drugs@FDA. We recorded whether a withdrawn drug had a BBW at the time of its withdrawal and, if so, whether that BBW was the same as the BBW of the index top-selling drug or the other same-class drugs that were still marketed.…”

“…12 About 20% of approved chemical entities acquire a BBW label or are withdrawn from the market because of causing serious harms within 25 years from their approval. 13 Currently, over 400 drugs have BBWs, 10,14 an almost two-fold increase within the past 15 years. 15 Because serious drug-related adverse events (e.g., teratogenicity during pregnancy due to angiotensin-receptor blockers) are more often a function of the pharmacologic class of a drug rather than specific medication features, most BBWs are typically applied to all members of a given class ("class-wise fashion"), 13,14,16 which is defined on the basis of the mechanism of action, e.g., fluoroquinolone antibiotics.…”

“…13 Currently, over 400 drugs have BBWs, 10,14 an almost two-fold increase within the past 15 years. 15 Because serious drug-related adverse events (e.g., teratogenicity during pregnancy due to angiotensin-receptor blockers) are more often a function of the pharmacologic class of a drug rather than specific medication features, most BBWs are typically applied to all members of a given class ("class-wise fashion"), 13,14,16 which is defined on the basis of the mechanism of action, e.g., fluoroquinolone antibiotics. 17 Nevertheless, differences in the BBW acquisition have been reported, 13 where addition of a BBW is not universal for all drugs in the category.…”

“…15 Because serious drug-related adverse events (e.g., teratogenicity during pregnancy due to angiotensin-receptor blockers) are more often a function of the pharmacologic class of a drug rather than specific medication features, most BBWs are typically applied to all members of a given class ("class-wise fashion"), 13,14,16 which is defined on the basis of the mechanism of action, e.g., fluoroquinolone antibiotics. 17 Nevertheless, differences in the BBW acquisition have been reported, 13 where addition of a BBW is not universal for all drugs in the category. 17 Such differences in the acquisition of a BBW or timing thereof may sometimes be justified and may reflect differences in the available accumulated evidence for different agents.…”

Linking Drugs to Obscure Illnesses: Lessons from Pure Red Cell Aplasia, Nephrogenic Systemic Fibrosis, and Reye’s Syndrome. A Report From the Southern Network on Adverse Reactions (SONAR)

“…1 Post-marketing changes in practice, target populations, formulation, and dosing can lead to sADRs. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) are three sADRs that were clinical mysteries when first identified in 1951, 2000, and 1998.…”