Vipera ammodytes bites treated with antivenoms Viperfav® and ViperaTAb®

Objective: Clinically Vipera berus and Vipera ammodytes envenomation are difficult to differentiate. In the past this was not a concern, but due to the current shortage in European viper venom antiserum availability, V. ammodytes venomous bites have recently been treated with ViperfavTM and ViperaTAb®. Viperfav contains polyvalent equine F(ab')2 fragments as an active principle against V. aspis, V. berus and V. ammodytes, while ViperaTAb contains monospecific ovine Fab fragments against V. berus. ViperaTAb’s and Viperfav’s therapeutic convenience for use against V. ammodytes venom- induced toxicity in humans has not been described, although protective efficacy has been proved preclinically. The aim of this study was to evaluate Viperfav and ViperaTAb in V. ammodytes envenomations. Methods: A prospective case series of consecutive patients envenomed by V. ammodytes treated with Viperfav and/or ViperaTAb in the University Medical Centre Ljubljana in 2015 and 2016. V. ammodytes venom, neurotoxic ammodytoxins, and F(ab')2 and/or Fab fragments concentrations were determined in serum samples with a pharmacokinetic analysis of the antivenoms. Results: Ten patients bitten by V. ammodytes were treated using Viperfav and/or ViperaTAb ; 5 received Viperfav, 4 ViperaTAb, and 1 patient received both. V. ammodytes venom and antivenom concentrations were measured in 5 patients. V. ammodytes venom was detected in serum of all 5 patients, but ammodytoxins were detected in only the most severely envenomed patient who developed neurological symptoms. Viperfav (4 mL) promptly reduced local swelling and improved systemic pathological signs, except recurrent thrombocytopenia. ViperaTAb (8 mL) reduced moderate swelling and temporarily improved systemic effects as well. However, this dose of ViperaTAb had no effect on neurological signs. ViperaTAb and Viperfav administration induced a decrease in V. ammodytes venom serum concentrations, but only Viperfav affected the serum ammodytoxins concentration. Viperfav’s systemic clearance and elimination half-life were 1.64 (mL/h)/kg and 97 hours, while ViperaTAb’s were 4.3–13.4 (mL/h)/kg and 14.1– 55.4 hours, respectively. Conclusion: In patients bitten by V. ammodytes, both Viperfav and ViperaTAb reduce local swelling and temporarily improve systemic effects. ViperaTAb did not affect neurological symptoms or the serum concentration of neurotoxic ammodytoxins. The recommended dose of Viperfav and ViperaTAb may be inadequate in serious cases of V. ammodytes bites, therefore duplication and repetition of the treatment, with an adjustment of administration timing, should be considered. However, it should be pointed out that this study was the result of V. ammodytes antivenom shortage and it emphasises the importance of the specific antivenom availability.