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About Pit Viper Envenomation

Pit Viper Envenomation in the United States

In the United States, 98% of venomous snakebites―also known as envenomations―are from the North American pit vipers and have been reported in all states, with the exception of Hawaii :

  • According to the Department of Wildlife Ecology & Conservation, approximately 8000 venomous snakebites occur each year in the United States. 
  • The number of envenomations reported to poison centers has increased in recent years, and research suggests that many states across the United States will be at even higher risk for snakebites in the future. 

Since the consequences of pit viper envenomation may be severe, it’s important to understand the impact of venom on the patient and follow an established treatment protocol.

North American pit viper envenomations progress over time. Outcomes vary from patient to patient, depending on many variables, including timeliness of treatment. 

Envenomation can affect 3 critical and potentially life- or limb-threatening areas :

  • Local
  • Systemic
  • Hematologic

Learn more about the effects of envenomation.

Watch Dr. Rutherfoord Rose discuss why it is important to always start treatment with CroFab early.

Pit Viper Venom Effects

North American pit viper venom contains a complex mixture of toxins that often includes *:

  • Procoagulants
  • Anticoagulants
  • Hemotoxins
  • Neurotoxins
  • Cytotoxins

Each toxin may have distinct actions on diverse body systems, and different toxins may work synergistically to increase toxicity. 

  • Effects can range from no apparent clinical effects or local effects at the bite site to life-threatening effects that can affect every major organ in the body
  • Effects may begin within minutes or be delayed for hours, with the more severe effects not becoming evident for many hours
  • Locally active toxins may show clinical effects almost immediately
  • Systemically active toxins must first reach the bloodstream, where they will rapidly exert their effect
  • Toxins with extravascular targets, such as neurotoxins and myotoxins, generally have a more delayed onset
  • Rapidity of effect can also be influenced by any latency period between time of binding to the target tissue and onset of detectable activity

After envenomation, a depot of venom often remains at the site of the bite, which may prolong the clinical effects of the venom. 

  • Following intramuscular injection of venom in animal models, absorption of venom has been shown to last for 72 hours 

*Venom toxins vary from species to species.

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Recommendations for the management of North American pit viper envenomation

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Appropriate dosing achieves initial and sustained control of envenomation 

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Real-world use supports improved outcomes with CroFab 

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References

  1. Gummin DD, Mowry JB, Spyker DA, Brooks DE, Fraser MO, Banner W. 2016 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 34th Annual Report. Clin Toxicol. 2017;55(10):1072-1252.

  2. Gold BS, Barish RA, Dart RC. North American snake envenomation: diagnosis, treatment, and management. Emerg Med Clin N Am. 2004;22(2):423-443

  3. Seifert SA, Boyer LV, Benson BE, Rogers JJ. AAPCC database characterization of native U.S. venomous snake exposures, 2001-2005. Clin Toxicol. 2009;47(4):327-335.

  4. Frequently Asked Questions. Department of Wildlife Ecology and Conservation website. Accessed September 13, 2023. Ufwildlife.ifas.ufl.edu/venomous_snake_faqs.shtml

  5. Spiller HA, Bosse GM, Ryan ML. Use of antivenom for snakebites reported to United States poison centers. Am J Emerg Med. 2010;28(7):780-785.

  6. Yanez-Arenas C, Peterson AT, Rodriguez-Medina K, Barve N. Mapping current and future potential snakebite risk in the new world. Clim Change. 2016;134:697-711.

  7. 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.

  8. Rattlesnake Envenomation. Emed website. Accessed September 13, 2023. www.emed.ie/Trauma/Environmental/Snakebite.php

  9. 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.

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

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.