CroFab® reconstitution in various media: an in vitro solubility study

Abstract

Background. We investigated the solubility of Crotalidae Polyvalent Ovine Immune Fab antivenom (CroFab®, Savage Labs and Protherics Inc., Brentwood, TN, USA) in solutions not listed in the Food and Drug Administration (FDA)-approved product package insert. We also assessed whether adsorption to plastic tubing occurs with CroFab® preparations. Methods. Nine vials of expired CroFab® were divided into three groups according to the solution used for reconstitution. Assignment to the solution groups of normal saline, lactated Ringer's solution, or half-normal saline (NS, LR, 1/2NS) was blinded. The antivenom was diluted to a final volume of 75 mL of test solution. Protein concentration was measured after reconstitution, after storage at 4–6°C for 4 h, and after passage through plastic intravenous (IV) tubing. Results. Higher measured protein yields were noted when half-normal saline was used in comparison with normal saline at each step of the study. Lactated Ringer's solution yielded higher protein concentrations than normal saline only at one out of the three measurement steps. There was no adsorption effect when CroFab® was infused through plastic IV tubing. Discussion. These data suggest that CroFab® is slightly more soluble in the hypotonic solution we tested, and the amounts of measured antivenom did not diminish after 4 h of refrigeration or passage through plastic tubing. Conclusion. Our study may be of relevance when clinicians or pharmacists mix CroFab® into non-standard solutions.

Keywords:

• Antivenom
• CroFab
• Crotaline envenomation
• Pharmacy