Atropine availability as an antidote for nerve agent casualties: Validated rapid reformulation of high-concentration atropine from bulk powder

Study objective: Atropine is the preferred antidote for immediate management of toxicity associated with nerve agents or other cholinergic syndromes. A large-scale exposure to a nerve agent or organophosphate insecticide might result in many victims presenting for care within a short period of time. This situation would require the prompt availability of a large amount of atropine to provide treatment. Antidote stocks at many hospitals are inadequate to meet this demand. Atropine that is commercially available comes supplied at concentrations of either 0.4 mg/mL or 1 mg/mL, thereby requiring intravenous administration because of the volume necessary to administer the commonly recommended initial dose of 2 to 6 mg. Moderately ill victims may not require an intravenous line for other care, and in the setting of overwhelmed resources, intramuscular administration is faster and easier to perform. Methods: To facilitate the delivery of larger atropine doses, we developed a method of fortifying existing injectable atropine with bulk pharmaceutical-grade atropine powder to a concentration of 2 mg/mL, thereby increasing the amount available and facilitating its intramuscular administration. An independent analysis of the resulting formulation was undertaken to assess its potency, absence of pyrogens, and stability. Results: The amount of atropine initially present varied by less than 5%, within the range allowed by the US Pharmacopeia for the original product. The product was pyrogen free and maintained its potency at refrigeration temperature for at least 8 weeks after preparation and at room temperature for 4 weeks. Once all materials were available, the compounding of this preparation required about 1 hour to complete. Conclusion: Existing atropine stocks can be readily augmented by fortification with powdered atropine accurately and inexpensively. Common pharmaceutical guidelines recommend refrigeration for compounded products such as this if not completely used within 28 days.