Several investigational drugs currently under study for snakebite treatment have received significant public and media attention in recent years.^263,264 The most promising are small-molecule therapeutics (SMTs), notably the phospholipase A₂ (PLA₂) inhibitor varespladib and the snake-venom metalloprotease (SVMP) inhibitor marimastat. However, they have been frequently mischaracterized in press reports as “universal antivenoms” when they are neither universal nor antivenoms, leading to significant confusion among medical providers and policymakers. In some cases, this confusion has complicated the efforts of medical providers seeking to obtain CPG recommended antivenoms for deployments OCONUS, negatively impacting Force Health Protection. It is therefore critical to clarify the position of the Joint Trauma System on investigational drugs for snakebite treatment.

1. The only definitive treatment for a snake envenomation is the timely administration of appropriate antivenom at the appropriate dose required to neutralize circulating venom compounds. SMTs may eventually prove useful as adjunct therapies to be given in addition to recommended antivenoms, but not as replacements. Due to the complexity of snake venoms and envenomations, this is unlikely to change in the next 20+ years.
2. The utility of SMTs lies not in replacing antivenoms, but in supporting them as adjunct therapies much like TXA, either in prehospital settings when ALS-capable providers are not available to administer IV/IO antivenoms or, in some cases, potentially as co-administered medications given with antivenom to improve outcomes where coverage may be lacking. In all cases, the best outcome depends on timely administration of the appropriate antivenom to the patient. Definitive treatment with antivenoms given at the earliest opportunity will remain the single most important factor in determining patient outcomes in these cases.
3. While some SMTs have shown early promise, their safety, tolerability, and efficacy must be demonstrated in rigorous, peer‑reviewed clinical trials before any consideration for inclusion in the Clinical Practice Guidelines can be made. This process will likely take years and the outcome is uncertain. The JTS Snakebite Envenomation Working Group will continue to monitor advances in snakebite therapies and will incorporate new treatments into the guidelines when it is appropriate to do so based on rigorous scientific evidence and clinical best practices.