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INTRODUCTION

  1. Pharmacology. The older equine-based product, Antivenom Crotalinae Polyvalent (Wyeth-Ayerst), is no longer produced in the United States and it has been replaced by the ovine-based Crotalinae polyvalent immune Fab (CroFab, Protherics).

    To produce this antivenom, sheep are hyperimmunized with pooled venom from four North American snakes: Crotalus adamanteus, Crotalus atrox, Crotalus scutulatus, and Agkistrodon piscivorus. Papain is added to the pooled serum product collected from the donor animals to cleave the immunogenic Fc fragment from the IgG antibody. The result is an affinity-purified Fab fragment antivenom. After administration, the antivenom is distributed widely throughout the body, binding to venom.

  2. Indications. Antivenom is used for the treatment of signs and symptoms of envenomation by Crotalinae species (Table III–4 and Snakebite).

  3. Contraindications. Known hypersensitivity to sheep or sheep serum, or to papain or papayas.

  4. Adverse effects

    1. Immediate hypersensitivity reactions (including life-threatening anaphylaxis) are rare but may occur, even in patients with no history of animal serum sensitivity. Skin testing is not indicated with CroFab.

    2. Mild flushing and wheezing is rare but can occur within the first 30 minutes of intravenous administration and often will decrease after the rate of infusion has been slowed.

    3. Delayed hypersensitivity (serum sickness) used to occur in many patients who received the whole-IgG equine antivenom. CroFab administration can also lead to delayed hypersensitivity reactions, but these are rare.

    4. Use in pregnancy. FDA Category C (indeterminate; see Table III–1). There are no data on teratogenicity. Anaphylactic reaction resulting in shock or hypoxemia in the mother could conceivably adversely affect the fetus. However, severe snake envenomation of the mother should be treated aggressively to limit venom effects that could affect the fetus or placenta.

  5. Drug or laboratory interactions. There are no known interactions.

  6. Dosage and method of administration. The initial dose is based on the severity of symptoms, not on body weight (see Table III–4). Children may require doses as large as or larger than those for adults. The end point of antivenom therapy is the reversal of systemic manifestations (eg, shock, coagulopathy, and paresthesias) and the halting of progressive edema and improvement in pain. In some severe cases, large quantities of antivenom may be required (eg, 4–6 vials every hour), and laboratory blood clotting parameters may be refractory to even large doses. However, most cases can at least be stabilized with aggressive antivenom therapy. Antivenom may be effective even if given up to several days after envenomation.

    1. Treat all patients in an intensive care or monitored setting.

    2. Before antivenom administration, insert at least one and preferably two secure intravenous lines.

    3. Reconstitute each lyophilized vial of CroFab antivenom with the 10 mL of diluent provided or sterile saline and gently swirl to solubilize the material. Avoid shaking, which may destroy the immunoglobulins (as indicated by foam formation). Further dilution with normal saline may facilitate solubilization. Reconstituted product should be used within 4 hours.

    4. Administer antivenom by the intravenous route only. Start slowly, increasing the rate as tolerated. The ...

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