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Frequently Asked Questions

    • CroFab is a sheep-derived antivenom 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. 

    What is CroFab (crotalidae polyvalent immune fab [ovine])?

      How do I order CroFab?

        • The Unified Treatment Algorithm for the Management of North American Pit Viper Envenomation recommends administering
        • CroFab when any of the following signs are present :
          • Swelling that is more than minimal and that is progressing.
          • Hematologic venom effects, including elevated prothrombin time; decreased fibrinogen or platelets.
          • Any systemic signs attributable to venom (eg, hypotension, bleeding beyond the puncture site, refractory vomiting, diarrhea, angioedema, neurotoxicity).
        • Learn more about the Unified Treatment Algorithm.

        When should I use CroFab?

          • Administer CroFab as soon as possible in patients who develop any signs of envenomation to prevent clinical deterioration.  In a clinical study, early administration of CroFab resulted in significantly shorter time to full recovery compared with later treatment.  
            Learn more about the efficacy of CroFab.

          How quickly should CroFab be administered for pit viper envenomation?

            Yes! CroFab is the only antivenom derived from geographically and clinically relevant US snakes (ie, Western Diamondback rattlesnake, Eastern Diamondback rattlesnake, Mojave rattlesnake, and cottonmouth or water moccasin), allowing for coverage of all North American pit viper envenomations. 

            Does CroFab work for rattlesnake envenomation?

              • The venom of North American pit vipers is complex and contains at least 50 different components, including clinically important cytotoxins, hemotoxins, and neurotoxins.  Each snake has a unique venomic fingerprint that is also influenced by environmental and individual factors.  According to the World Health Organization (WHO), an effective antivenom is one derived from clinically relevant snakes native to the geographic region in which the antivenom is used and collectively encompass the wide diversity of clinically relevant toxins in the same geographic region.  CroFab is derived from 4 US snake species strategically chosen based on their unique venom fingerprints, which together provide comprehensive coverage across the diverse venom compositions of North American pit vipers. 

              Why is it important that CroFab is derived from native US pit vipers?

                • CroFab dosage requirements are contingent upon an individual patient’s response. Based on clinical experience with CroFab, the recommended initial dose is 4 to 6 vials; however, the starting dose may vary from a minimum of 4 vials to a maximum of 12 vials based on clinical judgment and severity of envenomation.  An additional 4-6 vials should be administered if initial control is not achieved within 1 hour after the first dose.
                  • Once initial control has been achieved, additional 2-vial doses of CroFab every 6 hours for up to 18 hours (3 doses) are recommended. 

                How many vials of CroFab are needed to treat an envenomation?

                  • Published clinical experience has not shown that a dosage adjustment for age should be made.  Antivenom dosing is based on neutralizing the dose of injected venom, and is titrated to clinical response, therefore CroFab dosing is the same for both pediatric and adult patients. 

                  Is dosing for CroFab different between children and adults?

                    • Each batch of CroFab is tested for reconstitution time and must reconstitute in <7 minutes. 
                      • Based on data from 72 batches of CroFab, the median time to reconstitute CroFab is 3 minutes.
                    • Learn more about the reconstitution of CroFab.

                    How long does it take to reconstitute CroFab?

                      • Medically significant late bleeding is uncommon after treatment with CroFab.
                        • In a systematic review of published postmarketing cohort studies, late bleeding was reported in 0.9% of patients (n=9/1017), and medically significant late bleeding was reported in 0.5% of patients (n=5/1017).10
                        • In a report from the ACMT’s ToxIC NASBR from 2013-2015, major late bleeding complication occurred in 0.2% of patients (n=1/450).11
                      • Learn more about the established safety profile of CroFab.
                         

                      ACMT, American College of Medical Toxicology; ToxIC, Toxicology Investigators Consortium; NASBR, North American Snakebite Registry. 

                      How common is late bleeding after treatment with CroFab?

                        • CroFab is the only antivenom derived from geographically and clinically relevant US snakes for comprehensive coverage of all North American pit viper envenomations, including rattlesnakes, copperheads, and cottonmouths/water moccasins. 

                        What types of snakebites are covered by CroFab?

                          • Expert consensus guidelines recommend stocking CroFab at any facility that provide emergency care. 
                            • The amount recommended to treat 1 patient for a period of 24 hours (hospitals admitting snakebite patients): 18 vials*
                            • The amount recommended to treat 1 patient for a period of 8 hours (hospitals that stabilize and transfer snakebite patients): 12 vials


                          *Physical stocking location may vary by institution and by drug preparation requirements.

                          How many vials of CroFab should my institution stock?

                            • The most common adverse reactions (incidence ≥ 5% of subjects) reported in the clinical studies were urticaria, rash, nausea, pruritus, and back pain. 

                            What are the most common adverse events/side effects of CroFab?

                            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. Anderson VE, Gerardo CJ, Rapp-Olsson M, et al. Early administration of Fab antivenom resulted in faster limb recovery in copperhead snake envenomation patients. Clin Toxicol. 2019;57(1):25-30.

                            4. WHO Expert Committee on Biological Standardization. WHO Technical Report Series, No. 1004, Annex 5; 2017. Accessed September 13, 2023. https://cdn.who.int/media/docs/default-source/biologicals/blood-products/document-migration/antivenomglrevwho_trs_1004_web_annex_5.pdf?sfvrsn=ef4b2aa5_3&download=true.

                            5. Gutiérrez JM et al. [Erratum in: Nat Rev Dis Primers. 2017;3:17079]. Nat Rev Dis Primers. 2017;3:17063.

                            6. Ferraz CR, Arrahman A, Xie C, Casewell NR, Lewis RJ, Kool J, Cardoso FC. Multifunctional toxins in snake venoms and therapeutic implications: from pain to hemorrhage and necrosis. Frontiers Ecol Evolution. 2019;7:218. 

                            7. Riley BD et al. In: Nelson LS et al, eds. Goldfrank’s Toxicologic Emergencies. 9th ed. McGraw-Hill Professional; 2010.

                            8. Tasoulis T, Isbister GK. Toxins (Basel). 2017;9(9):290

                            9. Data on file. BTG International Inc.

                            10. 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.

                            11. Ruha AM, Kleinschmidt KC, Greene S, et al. The epidemiology, clinical course, and management of snakebites in the North American Snakebite Registry. J Med Toxicol. 2017;13(4):309-320.

                            12. Dart RC, Goldfrank LR, Erstad BL, et al. Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care. Ann Emerg Med. 2018;71(3):314-325.

                            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.

                            Please see full Prescribing Information.