Crotalidae polyvalent immune Fab: Difference between revisions

{{Short description|Antivenom drug}}

{{Infobox drug

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| tradename = CroFab

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| CAS_number = 339086-32-7

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'''Crotalidae polyvalent immune Fab (ovine)''', sold under the brandname '''CroFab''', is a snake [[antivenin]], indicated for North American crotalid ([[rattlesnake]], [[Agkistrodon contortrix|copperhead]] and [[Agkistrodon piscivorus|cottonmouth/water moccasin]]) snake envenomation.<ref>{{Cite web |title=CroFab {{!}} Copperhead, Cottonmouth, and Rattlesnake Antivenom {{!}} CroFab.com |url=https://crofab.com/ |access-date=2023-05-23 |website=crofab.com}}</ref>

CroFab is composed of several monovalent Fab ([[fragment antigen-binding]]) proteins derived from the blood of sheep immunized with one of four snake [[Venom|venoms]]: ''Crotalus atrox'' ([[western diamondback rattlesnake]]), ''Crotalus adamanteus'' ([[Eastern diamondback rattlesnake]]), ''[[Crotalus scutulatus]]'' (Mojave rattlesnake), or ''[[Agkistrodon piscivorus]]'' (cottonmouth or water moccasin). Each monospecific antivenin is purified from [[sheep]] serum, digested with the enzyme [[papain]], and purified further, resulting in specific Fab fragments. The resulting four different Fab preparations are mixed to formulate the final product.<ref>{{cite web |title=Notice Regarding Change in Version of CROFAB (Crotalidae Polyvalent FAB (Ovine)) Prescribing Information |url=https://crofab.com/CroFab/media/CroFab/PDF%20Files/CroFab-Prescribing-Information.pdf |website=CroFab-Prescribing-Information |publisher=BTG International Inc. |access-date=17 August 2020}}</ref>

== Background ==

The production technology was invented by Drs. John Sullivan and [[Findlay E. Russell|Findlay Russell]],<ref>{{Cite patent|number=US8048414B1|title=Antivenom composition containing Fab fragments|gdate=2011-11-01|invent1=Sullivan|invent2=Russell|inventor1-first=John B.|inventor2-first=Findlay E.|url=https://patents.google.com/patent/US8048414B1/en}}</ref> developed clinically via multicenter clinical trials in the United States<ref>{{cite journal | vauthors = Dart RC, Seifert SA, Boyer LV, Clark RF, Hall E, McKinney P, McNally J, Kitchens CS, Curry SC, Bogdan GM, Ward SB, Porter RS | display-authors = 6 | title = A randomized multicenter trial of crotalinae polyvalent immune Fab (ovine) antivenom for the treatment for crotaline snakebite in the United States | journal = Archives of Internal Medicine | volume = 161 | issue = 16 | pages = 2030–2036 | date = September 2001 | pmid = 11525706 | doi = 10.1001/archinte.161.16.2030 }}</ref> and commercialized by [[BTG (company)|BTG Limited]] (formerly Protherics PLC). As reported in the Washington Post in July 2015, this was the only commercially available antivenin in the United States for the treatment of venomous snakebites until the release of a competing product, [[Anavip]].<ref name="Ingraham" />

== Treatment ==

Crotalid snakebites can range from mild to life-threatening, depending on the size and type of snake, the amount of venom injected and the location of the bite. This in turn determines the number of vials of CroFab that are required by the patient. Untreated, the snake venom can cause severe pain and tissue damage that can result in the loss of a limb or even death. Prompt (within six hours of snake bite) treatment with CroFab is recommended.

The most common adverse events reported in clinical studies were mild or moderate reactions involving the skin and appendages (primarily [[urticaria]], [[rash]], or [[pruritus]]), which occurred in 14 out of 42 patients. Three patients experienced a serious adverse event. Two patients had a severe allergic reaction (severe hives and a severe rash and pruritus) following treatment. One patient had a recurrent [[coagulopathy]] due to envenomation, which required re-hospitalisation and additional antivenin administration. In clinical trials, recurrent coagulopathy (the return of a coagulation abnormality after it has been successfully treated with antivenin), characterised by decreased [[fibrinogen]], decreased platelets and elevated [[prothrombin]] time, occurred in approximately half of the patients studied. Recurrent coagulopathy may persist for one to two weeks or more. One patient discontinued CroFab therapy due to an allergic reaction. Patients with allergies to [[papain]], [[chymopapain]], other [[papaya]] extracts or the pineapple [[enzyme]] [[bromelain]] may also be at risk for an allergic reaction to CroFab.<ref name="Treatment with CroFab">{{cite web|title=Treatment with CroFab|url = https://crofab.com/Treating-With-CroFab/Dosing-and-administration |access-date=18 June 2015 | work = BTG Specialty Pharmaceuticals }}</ref>

==Cost==

The industry website Fierce Pharma called the product a “drug launch disaster” and “one of the most bizarre marketing tales in the industry.”

Leslie Boyer, director of the VIPER Institute and a member of the team that developed CroFab, said that CroFab, a US drug whose sister product retailed in Mexico at $100, was resulting in bills to Arizona patients of between $7,900 and $39,652 per vial. One person rejected treatment and died because he could not afford to pay for it.{{fact|date=April 2024}}

Boyer collected data on the cost of production and marketing, and found that the largest true cost to payers, $4,100/vial, was that of the legal, regulatory and hospital activities involved in selling the drug. Clinical trials contributed $300/vial, and 25% of that had been paid for by government grants. Other costs were the same as in Mexico.<ref name="Boyer">{{cite journal | vauthors = Boyer LV | title = On 1000-Fold Pharmaceutical Price Markups and Why Drugs Cost More in the United States than in Mexico | journal = The American Journal of Medicine | volume = 128 | issue = 12 | pages = 1265–1267 | date = December 2015 | pmid = 26302139 | doi = 10.1016/j.amjmed.2015.08.007 | s2cid = 45007792 | doi-access = free }}</ref><ref name=Ingraham>{{cite news | url = https://www.washingtonpost.com/news/wonkblog/wp/2015/07/20/this-153000-rattlesnake-bite-is-everything-wrong-with-american-health-care/ | title = This $153,000 rattlesnake bite is everything wrong with American health care. | vauthors = Ingraham C | newspaper = The Washington Post | date = 20 July 2015 }}</ref>

{{Reflist}}

== External links==

* [https://web.archive.org/web/20060424075834/http://www.rxlist.com/cgi/generic/crofab.htm RxList: Crotalidae Polyvalent Immune Fab (Ovine)]

[[Category:Antitoxins]]

[[Category:Medical treatments]]