UMEM Educational Pearls

Title: Cyanide antidote in the pipeline (submitted by James Leonard, PharmD)

Category: Toxicology

Keywords: cyanide toxicity, sodium tetrathionate, (PubMed Search)

Posted: 6/27/2019 by Hong Kim, MD
Click here to contact Hong Kim, MD

 

Cyanide poisoning, while uncommon, is frequently fatal. Current antidotes include methemoglobinemia inducers (nitrites), sulfur donators (thiosulfate), and hydroxocobalamin. Each has risks and benefits that must be considered. Three new potential antidotes, including sodium tetrathionate, have recently been evaluated in swine models.

 
Intramuscular sodium tetrathionate1

  • Sodium tetrathionate can bind and eliminate two cyanide molecules compared to one cyanide molecule by thiosulfate.
  • Studied in a large (50 kg) female swine model of cyanide poisoning.
  • All pigs were given cyanide via IV until 6 minutes post-onset of apnea, then given an approximately 1.5 mL IM injection of sodium tetrathionate (18 mg/kg).
  • Survival at 90 minutes was 100% (6/6) in the treated group and 16% in the control arm (1/6). 

Advantages:

  • Small volume injection (~1.5-2 mL in humans)
  • No interference with routine laboratory tests.
  • Ease of administration in pre-hospital or potential mass casulty setting.

Bottom line:

  • New cyanide antidotes are being developed.
  • The FDA does NOT require human trials of efficacy for cyanide antidotes.
  • It is unclear where these drugs are in the approval process at this time, but look for them in the future.

References

Hendry-Hofer TB, Witeof AE, Ng PC, et al. Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity. Clin Toxicol (Phila). 2019;105:1-7. doi:10.1080/15563650.2019.1602272.