General Snakebite FAQS
CroFab has an excellent safety profile.
Per Dr. Greene:
Although every medication has the potential to cause an adverse reaction, CroFab has an excellent safety profile. In a large meta-analysis, the incidence of acute adverse reactions to CroFab was estimated at 8% (Schaeffer et al.). A study using data from the North American Snakebite Registry found the incidence of acute adverse reactions to be ~ 2.3% (Kleinschmidt et al.). Authors from the Arizona Poison and Drug Information Center calculated the incidence of acute adverse reactions to be approximately 1.4%, and nobody in this relatively large study required antivenom discontinuation (Khobrani et al.).
There are certain conditions (e.g. latex allergy) that may predispose to an adverse reaction, but there’s no absolute contraindication to antivenom. If somebody’s envenomation warrants treatment, you treat with antivenom. You can always run an epinephrine infusion simultaneously, or at least have it readily available.
The cited articles can be found in our files section, and you can see the abstracts here:
Khobrani: Incidence of allergic reactions to Crotalidae polyvalent immune Fab
You can receive antivenom more than once.
Per Dr. Greene:
It’s a misconception that, once you receive antivenom, you can never be treated with it again. That was kinda, sorta true with the antivenom used before 2000, because the incidence of side effects was so high. CroFab has a much better safety profile, and our experts have treated dozens of patients multiple times with CroFab.
There’s a great case report by Dr. Eric Lavonas (author of the unified treatment algorithm) of someone who was treated with CroFab at least 19 times: https://pubmed.ncbi.nlm.nih.gov/23433022/
Comparing Anavip and CroFab
Per Dr. Greene:
Preparation
Anavip Is easier to mix, but most hospitals pharmacies exaggerate how difficult it is to prepare CroFab. A study by Quan, et al conducted in Phoenix, where I trained, found that a vial could be reconstituted in a little over one minute. It does not take nearly as long as many pharmacists will tell you.
Cost
There are many things that determine the overall price of a vial, and even more that determine the overall cost of treatment. The last I heard, the wholesale price for a vial of Anavip was approximately $1440. The wholesale cost per vial of CroFab is about $3200. But if you look at some of the post marketing data, the median dose used was 6 vials of CroFab versus 17 vials of Anavip, which would suggest that Crofab is cheaper. That said, my colleagues out west tell me that they have found it’s cheaper overall to use Anavip.
Efficacy
There are some data that suggest Anavip provides better control of late hematologic recurrence. There are others that show no statistically significant difference. On the other hand, there are great data, including a randomized clinical trial, showing that Crofab stops the progression of local findings, which is what we see much more commonly than other manifestations of snake envenomation. There are no clinical data showing that Anavip stops the progression of local findings.
Safety
Most of the data - including the package inserts from both products - suggest that the incidence of adverse reactions is higher in Anavip. Anavip is derived from horses whereas CroFab is derived from sheep, and there’s evidence that horse serum is more immunogenic.
Overall, they’re both good products. Crofab has been used in the US for 21 years and has been used in over 50,000 patients. Anavip was first approved for use in the United States form rattlesnake envenomations in 2018 and got approval copperhead and cottonmouth envenomations in April. I’ve only used Crofab in my clinical practice (and Wyeth ACP, before that).
Per Dr. Brandehoff:
Preparation
The Fab2 products seem to mix much more easily than Fab or IgG products. Anavip reconstitutes in 15 seconds or so. Crofab can reconstitute in a few minutes if done right. I have yet to get down to a minute. The biggest delay is usually pharmacy takes 30 minutes or so to get it all mixed so I typically ask for it to be tubed to me so I can mix it.
Cost
Less costly - remains to be seen. As stated above, Anavip is cheaper wholesale but requires 10 vials vs 4-6 for Crofab at initial dose. The real total cost will be total vials given which still needs to be sorted out via larger studies. I rarely get away with only 6 vials with Crofab in California and Colorado. I’ve had mixed results with Anavip and only giving 10 vials. We just need more data.
Efficacy
Anavip does have a longer half live compared to Crofab (~150 vs ~40). What this means clinically is unclear other than maybe decreasing delayed coagulopathy. Proper dosing needs to be used with both antivenoms. So often I hear about improper dosing. We can’t compare efficacy if dosing strategies aren’t followed appropriately.
Safety
Many hospitals are switching to Anavip. I’m sure there will be a back and forth as different hospitals change their formulations based on what they end up liking. Adverse reactions are probably about the same, maybe a percentage point difference in the long run.
I’ve used both and think both are solid products. Clinically, I think they’re similar so far. Again, need more head to head data with both on the market. I think we’ll find one is better in some areas while the other is better in other areas.