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Achieving Control

3 Areas of Pathologic Impact

Initial Control Requires Addressing All 3 Areas of Pathologic Impact 


A single venom contains a wide array of toxins—necrotoxins, pre- and postsynaptic neurotoxins, and nephrotoxins, among others. This complexity, along with other biological factors, makes it difficult in clinical practice to predict specific effects of an individual envenomation. 

However, all envenomations can exhibit some or all of the following effects :

Arresting local effects of envenomation icon

Arrest

    Pain and local soft tissue damage are the first symptoms of envenomation. Necrotoxins may produce clinical effects almost immediately postbite, resulting in tissue digestion and vascular permeability.
    Edema
    • Is produced by permeable vessels, caused by venom, allowing fluid and blood to extravasate
    • Is the first objective sign of envenomation and should prompt immediate attention
    • Can progress to hypovolemic shock
    • Decreases slowly with treatment and is therefore a poor indicator of clinical improvement
    • Creates skin issues relative to the extent of the edema
      • Loss of skin elasticity
      • Skin stretches and fissures
      • Fissures, while generally superficial, should be monitored as sources of secondary infection
    Ecchymosis
    • May occur with edema
    • May indicate severity of envenomation by speed of progression
    • Caused by bleeding into skin due to venom-induced coagulopathy
    Vesiculations and Bullae
    • May be filled with clear serous fluid (vesicles) or with blood (bullae)
    • Develops most frequently in the bite area, but may be visible over the entire extremity
    Skin Necrosis
    • Can result from tissue destruction by venom proteins (snake venom metalloproteinases)
    • May occur distal to bite site
    Potential Consequences
    • Partial or complete loss of affected limbs
    • Loss of joint functionality
    • Loss or impairment of tactile sensation
    • Infection
    • Cosmetic issues

    Local Effects2,3

    Resolving systemic effects of envenomation icon

    Resolve

      General systemic effects include:
      • Headache
      • Diarrhea
      • Nausea
      • Syncope
      • Vomiting
      • Convulsions
      • Abdominal Pain
      • Metallic taste (likely due to metalloproteinases in the venom)
      Specific systemic effects include, but are not limited to:
      Neurotoxic Paralysis
      • Caused by pre- and/or postsynaptic neurotoxins
        • Presynaptic paralysis usually involves terminal axon damage. Reversal requires regeneration of axons, which takes days, weeks, or even months
      • May take 1 to 12 hours to become evident
      • Is progressive, often first seen in cranial nerves
        • Is easily missed if not specifically sought in exam
      • Is also evidenced early by ptosis, ophthalmoplegia, dysarthria, and/or dysphagia
      • Can lead to respiratory failure
        • Paralysis of the diaphragm may be delayed up to 24 hours post-bite
      Cardiac Effects
      • Hypo- or hypertension
      • Bradycardia
      • Tachycardia
      Potential Consequences
      • Death is a possibility
      • Irreversible damage
      • Respiratory compromise/failure
      • Neurologic deficits
      • Cardiovascular/pulmonary collapse due to shock
      • End organ damage

      Systemic Effects2,3

      Reducing hematologic effects of envenomation icon

      Reduce

        The 3 hematologic effects of envenomation are:
        Coagulopathy
        • Decreased fibrinogen levels
        • Elevated International Normalized Ratio (INR) and Prothrombin Time (PT)
        Thrombocytopenia
        • Defined as less than 150,000 platelets/microliter (platelets <50,000 are considered clinically important)
        • In severe pit viper envenomations, platelet counts may be undetectable
        • Transfusion alone can produce transient improvement in coagulation parameters and platelet counts, but rarely has a sustained effect in the absence of adequate dosing of antivenom
        Bleeding
        • Oozing of blood from the bite site and ecchymosis of the surrounding tissue
        • Nuisance bleeding, such as gingival bleeding or haemolacria, or more serious bleeding, such as significant epistaxis, gastrointestinal bleeding, intracranial hemorrhage
        • Medically significant and spontaneous bleeding is rare
        Potential Consequences
        • Coagulation abnormalities
        • Increased risk of bleeding complications (0.5% incidence of medically significant late bleeding)
        • Significant ecchymosis
        • Anemia

        Hematologic Effects2,3,4

        Watch Dr. Arnold discuss his experience with CroFab and why initial control is extremely important.

        Algorithm Icon

        Recommendations for the management of North American pit viper envenomation

        Launch Treatment Algorithm
        Vial Icon

        Appropriate dosing achieves initial and sustained control of envenomation 

        Learn How to Dose CroFab
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        Real-world use supports improved outcomes with CroFab 

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        References

        1. CroFab®. Prescribing information. BTG International Inc.; August 2018.

        2. Lavonas EJ, Ruha A-M, Banner W, et al. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med. 2011;11:2.

        3. Smith J, Bush S. Envenomations by reptiles in the United States. In: Mackessy SP, ed. Handbook of Venoms and Toxins of Reptiles. CRC Press; 2010:475-488.

        4. Lavonas EJ, Khatri V, Daugherty C, Bucher-Bartelson B, King T, Dart RC. Medically significant late bleeding after treated crotaline envenomation: a systematic review. Ann Emerg Med. 2014;63(1):71-78

        Indication and Important Safety Information
        Indication

        CroFab® Crotalidae Polyvalent Immune Fab (Ovine) is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation. The term crotalid is used to describe the Crotalinae subfamily (formerly known as Crotalidae) of venomous snakes which includes rattlesnakes, copperheads and cottonmouths/water moccasins.

        Important Safety Information
        Contraindications

        Do not administer CroFab® to patients with a known history of hypersensitivity to any of its components, or to papaya or papain unless the benefits outweigh the risks and appropriate management for anaphylactic reactions is readily available.

        Warnings and Precautions

        Coagulopathy: In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterized by decreased fibrinogen, decreased platelets, and elevated prothrombin time, occurred in approximately half of the patients studied; one patient required re-hospitalization and additional antivenin administration. Recurrent coagulopathy may persist for 1 to 2 weeks or more. Patients who experience coagulopathy due to snakebite should be monitored for recurrent coagulopathy for up to 1 week or longer. During this period, the physician should carefully assess the need for re-treatment with CroFab® and use of any type of anticoagulant or anti-platelet drug.

        Hypersensitivity Reactions: Severe hypersensitivity reactions may occur with CroFab®. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to CroFab®. Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia).

        Adverse Reactions

        The most common adverse reactions (incidence ≥ 5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus and back pain. Adverse reactions involving the skin and appendages (primarily rash, urticaria, and pruritus) were reported in 12 of the 42 patients. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment and one patient discontinued CroFab® due to an allergic reaction. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur.

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