Session number: 1078
Abstract title: Improving patient safety: Physician recognition of 9 rare & potentially fatal drug adverse reactions
Author(s):
CL Bennett - The Chicago VA Healthcare System/Lakeside Division and the Mid-West Center for Health Services and Policy Research
GT Shumock - The University of Illinois at Chicago College of Pharmacy
R Newlin - The Chicago VA Healthcare System/Lakeside Division and the Mid-West Center for Health Services and Policy Research
DW Raisch - VA Cooperative Studies Program Clinical Research Pharmacy Coordination Center, University of New Mexico, Albuquerque, New Mexico
DP Nathan - The Chicago VA Healthcare System/Lakeside Division and the Mid-West Center for Health Services and Policy Research
Objectives: Adverse drug events account for 2 million hospitalizations and 100,000 deaths annually. While physicians frequently identify drug-associated adverse events, only 1% of these occurrences is reported to the FDA. We report on our efforts to identify rare, but serious drug-associated complications.
Methods: Drugs were selected for evaluation based on: 1) occurrence of rare drug-associated adverse events that resulted in hospitalization, death, or severe medical illness and 2) absence of a prominent description of the identified toxicity in the drug’s FDA approved package insert. Evaluations included identification of clinical descriptions for at least 10 cases of the same toxicity, detection of class effects, and estimation of toxicity prevalence. Reviewing from FDA approval until initial recognition of the adverse event, adverse event reports were obtained from the FDA, published literature, physicians, and national conferences. Prevalence estimation was based on studies of well-characterized populations or review of clinical trial toxicity reports.
Results: Twelve patients developed life threatening, and 22 patients developed fatal, but previously rarely or unreported drug-associated adverse events, including: ticlopidine-associated thrombotic thrombocytopenic purpura (1 case, 0 deaths), clopidogrel-associated aplastic anemia (1 case, 0 deaths), nevirapine-associated hepatotoxicity (1 case, 0 deaths), thalidomide-associated deep vein thrombosis (9 cases, 1 deaths), bicalutamide-associated pneumonitis (1 case, 0 deaths), and irinotecan-associated severe vascular or gastrointestinal toxicity (21 cases, 21 deaths). Data review identified 197 additional instances of related serious drug-associated adverse events, of which 37 were fatal. Class effects were identified for clopidogrel-associated thrombotic thrombocytopenic purpura (11 cases, 2 deaths), ticlopidine-associated aplastic anemia (12 cases, 2 deaths), and flutamide-associated pneumonitis (16 cases, 7 deaths). Prevalence estimates were reported for ticlopidine-associated thrombotic thrombocytopenic purpura (1 in 1,600), thalidomide and chemotherapy-associated (1 in 4), and irinotecan-associated fatalities (1 in 30). Six revised package labels, three “Dear Doctor” letters, and 24 publications described these adverse events.
Conclusions: Our identification of 6 serious, but previously rarely or underreported drug-associated adverse events and 3 class effects indicates a need for physician intervention to protect patients.
Impact statement: Physician recognition can facilitate understanding of clinical characteristics, incidence, and mechanisms of serious, unrecognized drug-associated toxicities. The methodology described can assist with post-marketing safety assessments for pharmaceutical agents.