For the first time, healthcare providers were given a choice in 2019 between two antivenins to treat pit viper envenomations in the United States — CroFab®, a product that has been used for over 20 years, and a newer equine-derived antivenin, Anavip®. There are several known differences between the two products, but rightly or wrongly, the difference that may have generated the most discussion was cost per vial.

Now that the dust has settled, and toxicologists have collected data across multiple snakebite seasons, it’s increasingly clear that how these two antivenoms are used is not the same. Because the dosing of the two treatments is so vastly different, the perceived cost difference is called into question.

What The Latest Data Suggests

The North American Snakebite Registry (NASBR), overseen and managed by the American College of Medical Toxicology (ACMT), has tracked data on treating snakebite patients since 2013. It is a nationwide surveillance tool that prospectively gathers de-identified information from medical toxicologists providing bedside care for patients with snakebite envenomations. While BTG Pharmaceuticals, a SERB company, licenses data from ACMT annually, it does not influence the collection of data, selection of study sites, or its protocols.

With key measurements on over 291 patients treated for rattlesnake bites in the NASBR from 2019 to 2021, this real-world data is revealing. Findings include:

• The average number of Anavip® vials per patient is 1.8 times the number of CroFab® vials when treating rattlesnakes.
  
  When Anavip® first became available in the US, healthcare professionals were unsure how many vials of this new antivenin would be needed to treat patients. According to an analysis of the data published this month in the Journal of Medical Toxicology [LINK], medical staff need to administer 1.8 times as many vials of Anavip® on average to treat patients who have suffered a rattlesnake envenomation. Note that this analysis excluded envenomation from copperhead (Agkistrodon) species as so few of these patients in the NASBR database received Anavip®.
  
  NASBR data collected between 2019 and 2021 shows that, on average, doctors administer a median of 10 vials of CroFab per patient, while they use a median of 18 vials of Anavip.
• More patients need additional doses of Anavip for initial control.
  
  Upon its launch, many providers were assured that Anavip would be dosed as only one round of 10 vials. The recent NASBR analysis shows that 69% of Anavip-treated patients required additional doses to achieve initial control, or late dosing for re-emerging symptoms of swelling, pain, thrombocytopenia and/or coagulopathy. As a comparison, 39% of CroFab-treated patients required additional doses to achieve initial control (dosing unrelated to scheduled maintenance). Analysis shows this finding is statistically significant.
• Anavip-treated patients are more likely to need pain medication.
  
  According to an abstract shared at the North American Congress of Clinical Toxicology in September 2020, 96.4% of patients treated with Anavip were treated with opioid analgesics during their initial hospitalization compared to 74.1% of CroFab users. Opioid administration and the additional risk and expense associated with it, is another factor that should be considered.

How Do You Measure Cost?

Healthcare professionals may be tempted to stock Anavip® because it costs less per vial and promises savings for hospitals and health systems. The NASBR data suggests that the difference in total treatment cost between products is probably much less than healthcare providers think. Instead of looking only at per vial costs, the focus should be on the total cost of treatment required to deliver the best care for their patients overall.

In addition to considering total treatment costs, healthcare providers should be aware that BTG, now a SERB company, has been working with hospitals, health systems, and purchasing organizations to adjust contracts and make price less of an issue. Physicians can speak with their hospital pharmacy to understand the cost of CroFab® at their specific institution. Ultimately, we believe antivenom decisions should be based on data and what’s best for patients.

Brandehoff, N., Dalton, A., Daugherty, C. et al. Total CroFab and Anavip Antivenom Vial Administration in US Rattlesnake Envenomations: 2019–2021. J. Med. Toxicol. (2023). https://doi.org/10.1007/s13181-023-00941-7

Anavip® is a registered trademark of Laboratorios Silanes S.A. De C.V. Corporation Mexico Av. Paseo De Las Palmas 340 Lomas De Chapultepec, Miguel Hidalgo Mexico City Mexico 11000.

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.