Antidote Shortages in the USA: Impact and Response

We developed recommendations for antidote stocking at hospitals that provide emergency care. An expert panel representing diverse perspectives (clinical pharmacology, clinical toxicology, critical care medicine, clinical pharmacy, emergency medicine, internal medicine, pediatrics, poison centers, pulmonary medicine, and hospital accreditation) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for the quantity of an antidote that should be stocked and the acceptable period for delivery of each antidote. The panel recommended consideration of 24 antidotes for stocking. The panel recommended that 12 of the antidotes be available for immediate administration on patient arrival. In most hospitals, this period requires that the antidote be stocked in the emergency department. Another 9 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel identified additional antidotes that should be stocked by the hospital but are not usually needed within the first hour of treatment. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine the need for antidote stocking in that hospital. The antidote expert recommendations provide a tool to be used in creating practices for appropriate and adequate antidote stocking in hospitals that provide emergency care.

The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3,005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot.

Appropriate therapies for commonly encountered poisonings, medication overdoses, and other toxicological emergencies are reviewed, with discussion of pharmacists' role in ensuring their ready availability and proper use. Poisoning is the second leading cause of injury-related morbidity and mortality in the United States, with more than 2.4 million toxic exposures reported each year. Recently published national consensus guidelines recommend that hospitals providing emergency care routinely stock 24 antidotes for a wide range of toxicities, including toxic-alcohol poisoning, exposure to cyanide and other industrial agents, and intentional or unintentional overdoses of prescription medications (e.g., calcium-channel blockers, β-blockers, digoxin, isoniazid). Pharmacists can help reduce morbidity and mortality due to poisonings and overdoses by (1) recognizing the signs and symptoms of various types of toxic exposure, (2) guiding emergency room staff on the appropriate use of antidotes and supportive therapies, (3) helping to ensure appropriate monitoring of patients for antidote response and adverse effects, and (4) managing the procurement and stocking of antidotes to ensure their timely availability. Pharmacists can play a key role in reducing poisoning and overdose injuries and deaths by assisting in the early recognition of toxic exposures and guiding emergency personnel on the proper storage, selection, and use of antidotal therapies.