Concentrated Atropine Sulfate Formulations

Organophosphorus nerve agents are extremely toxic, and even small amounts can be rapidly fatal. Due to the manner in which nerve agents are used, the DOD must be prepared to respond to poisonings of multiple individuals at once. The current standard of care is to first deliver a drug cocktail of three compounds: atropine sulfate, 2-pyridine aldoxime chloride (2-PAM), and an anticonvulsant (typically diazepam). These are available in a prefilled autoinjector called the Antidote Treatment Nerve Agent Autoinjector (ATNAA), which delivers the three medications simultaneously. In severe poisonings, the initial ATNAA treatment alone isn’t enough to stop the muscarinic effects, and continued treatment with atropine sulfate injections is required (totaling as much as 50-100 mg/day). Unfortunately, the maximum commercially available multi-dose atropine sulfate formulation is 0.4 mg/mL in a 20 mL vial. This means a single patient could require 13 vials in a day. Given the nature of nerve agent attacks, they are rarely single casualty events. Therefore, maintaining the required supply of atropine sulfate, and the burden of care of administering many vials of the current low-concentration formulations, could quickly become unmanageable. It would be far better to supply atropine in a concentrated formulation so that only a single vial would be needed to treat a severely poisoned soldier. In this project, TDA is developing a concentrated atropine sulfate formulation that improves logistics to expand access to atropine sulfate in the field.