Adverse Reactions Identified after Approval of Novel Medicines: Analysis of 339 New Molecular Entities and Therapeutic Biologics

Postmarketing safety surveillance data identify safety issues not identified in preapproval clinical trials. We describe the frequency of new safety issues overall and by labeling section and the relationship of the most commonly added safety issues with the cumulative number of prescriptions dispensed via retail pharmacies. Using publicly available sources, we determined the frequency of the most common safety issues added after approval overall and by labeling section (Boxed Warning, Warnings and Precautions, and Adverse Reactions) for new molecular entities (NMEs) and new therapeutic biologics (NTBs) approved between 10/1/2002 and 12/31/2014. There were 339 products in the cohort (278 NMEs and 61 NTBs) with a median follow up of 13.1 years. There were 5,161 new safety issues overall. The most frequently added to the product labeling were anaphylactic reaction, angioedema, Stevens–Johnson syndrome (SJS), hypersensitivity, and toxic epidermal necrolysis (TEN), which were added to the labeling of at least 12% of the 339 products. This was similar between NMEs and NTBs, except for cardiac failure, which was among the five most frequent adverse reactions (AR) added to NTBs, while TEN was less frequently added. Most other ARs were added to 10% or fewer products. Among drugs used primarily in the outpatient setting, the mean number of cumulative dispensed prescriptions exceeded 1 million at the time a safety issue was added to the labeling. Many of the most frequently added ARs are drug hypersensitivities. These findings are relevant to practitioners and patients, who should be alerted to the possibility of such reactions.