Beyond the black box: drug- and device-associated hypersensitivity events

BACKGROUND: Drug- and device-associated hypersensitivity reactions are serious toxicities that can result in respiratory failure or acute cardiac ischemic events, or even severe hypersensitivity syndromes such as Stevens–Johnson syndrome. These toxicities are usually poorly described in the “black box” warnings section of the product labels. METHODS: Adverse event reports contained in databases maintained by the Project on Medical Research on Adverse Drug Events and Reports (Med-RADAR), product labels, safety advisories disseminated by pharmaceutical manufacturers, the Food and Drug Administration (FDA), and the Centers for Disease Control and Prevention (CDC) were reviewed. RESULTS: Adverse event reports identified three health care workers who developed nevirapine-associated Stevens–Johnson syndrome following occupational exposure to HIV-infected blood or blood products; four persons with localized hypersensitivity and fatal cardiac events associated with rapamycin- or paclitaxel-coated coronary artery stent placements; and six persons with breast cancer who developed severe or fatal anaphylaxis after receiving adjuvant chemotherapy with Cremophor-EL containing paclitaxel. Safety advisories from the FDA, CDC, and the relevant pharmaceutical manufacturers were ambiguous in their description in “black box” warning sections of package inserts describing these serious and potentially fatal toxicities. CONCLUSION: Improvements are needed in pharmacovigilance and subsequent dissemination of safety advisories for drug/device-associated hypersensitivity reactions.