Crotalidae polyvalent immune Fab (ovine), sold under the brandname CroFab, is a snake antivenin, indicated for North American crotalid (

rattlesnake Rattlesnakes are venomous snakes that form the genus, genera ''Crotalus'' and ''Sistrurus'' of the subfamily Crotalinae (the pit vipers). All rattlesnakes are vipers. Rattlesnakes are predators that live in a wide array of habitats, hunting sm ...

, copperhead and cottonmouth/water moccasin) snake envenomation. CroFab is composed of several monovalent Fab (

fragment antigen-binding The fragment antigen-binding region (Fab region) is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope (the ...

) proteins derived from the blood of sheep immunized with one of four snake

venoms Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...

: ''Crotalus atrox'' (

western diamondback rattlesnake The western diamondback rattlesnake or Texas diamond-backWright AH, Wright AA. (1957). ''Handbook of Snakes''. Comstock Publishing Associates. (7th printing, 1985). . (''Crotalus atrox'') is a rattlesnake species and member of the viper family, ...

), ''Crotalus adamanteus'' (

Eastern diamondback rattlesnake The eastern diamondback rattlesnake (''Crotalus adamanteus'') is a species of pit viper in the family Viperidae. The species is endemic to the Southeastern United States. It is the largest rattlesnake species and one of the heaviest venomous sna ...

), ''

Crotalus scutulatus ''Crotalus scutulatus'' is known commonly as the Mohave Rattlesnake. Other common English names include Mojave Rattlesnake Stebbins, R.C. (2003). ''A Field Guide to Western Reptiles and Amphibians''. Boston: Houghton Mifflin & Co. pp. 416–417 ...

'' (Mojave rattlesnake), or ''

Agkistrodon piscivorus ''Agkistrodon piscivorus'' is a species of venomous snake, a pit viper in the subfamily Crotalinae of the family Viperidae. It is one of the world's few semiaquatic vipers (along with the Florida cottonmouth), and is native to the Southeaster ...

'' (cottonmouth or water moccasin). Each monospecific antivenin is purified from

sheep Sheep (: sheep) or domestic sheep (''Ovis aries'') are a domesticated, ruminant mammal typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus '' Ovis'', in everyday usage it almost always refers to d ...

serum, digested with the enzyme

papain Papain, also known as papaya proteinase I, is a cysteine protease () enzyme present in papaya (''Carica papaya'') and mountain papaya (''Vasconcellea cundinamarcensis''). It is the namesake member of the papain-like protease family. It has wi ...

, and purified further, resulting in specific Fab fragments. The resulting four different Fab preparations are mixed to formulate the final product.

Background

The production technology was invented by Drs. John Sullivan and Findlay Russell, developed clinically via multicenter clinical trials in the United States and commercialized by 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.

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.

Adverse events

The most common adverse events reported in clinical studies were mild or moderate reactions involving the skin and appendages (primarily

urticaria Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...

, or

pruritus An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

), 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 Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding ( bleeding diathesis), which may occur s ...

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 Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...

, decreased platelets and elevated

prothrombin Prothrombin (coagulation factor II) is encoded in the human by the F2-gene. It is proteolytically cleaved during the clotting process by the prothrombinase enzyme complex to form thrombin. Thrombin (Factor IIa) (, fibrose, thrombase, throm ...

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

, chymopapain, other

papaya The papaya (, ), papaw, () or pawpaw () is the plant species ''Carica papaya'', one of the 21 accepted species in the genus '' Carica'' of the family Caricaceae, and also the name of its fruit. It was first domesticated in Mesoamerica, within ...

extracts or the pineapple

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

bromelain Bromelain is an enzyme extract derived from the plant stem, stems of pineapples, although it exists in all parts of the fresh plant and fruit. The extract has a history of folk medicine use. As a culinary ingredient, it may be used as a Meat tender ...

may also be at risk for an allergic reaction to CroFab.

Cost

Leslie Boyer, director of the VIPER Institute and a member of the team that developed CroFab, collected data on the cost of production and marketing, and found that the largest true cost to payers in the United States was that of the legal, regulatory and hospital activities involved in selling the drug, nearly 75% of the total. Clinical trials contributed less than 10% of the cost, and 25% of that had been paid for by government grants. Other costs were the same as in Mexico.

References

External links

RxList: Crotalidae Polyvalent Immune Fab (Ovine)
{{DEFAULTSORT:Crofab Antitoxins Medical treatments