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| Primary information |
|---|
| ID | 15301 |
| Therapeutic ID | Th1584 |
| Protein Name | Agkistrodon piscivorus antivenin |
| Sequence | NA
|
| Molecular Weight | NA |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 12 to 23 hours [FDA label]. |
| Description | Agkistrodon piscivorus antivenin is derived and purified immunoglobulin fragments obtained from other domestic animals such as sheep previously immunized with Agkistrodon piscivorus (_Cottonmouth_ or _Water Moccasin snake_). The final purified antivenin product is obtained by mixing other different monospecific snake antivenins and isolating the antivenin of interest through fractionation and chromatography techniques. It is intravenously (IV) administered to limit/prevent systemic toxicity [FDA label]. Approximately 99% of all venomous snake bites in the United States are caused by Crotalidae, also known as _pit vipers_. In North America, members of the family Crotalidae belong to three genera: the rattlesnakes (Crotalus and Sistrurus spp.) and the copperheads and cottonmouth water moccasins (Agkistrodon spp.) [L2891]. The cottonmouth, Agkistrodon piscivorus, is a large, venomous snake in the pit viper subfamily (Crotalinae). As the only semi-aquatic viper species, cottonmouth snakes are strong swimmers and are frequently found in or near water [L2888]. This species of snake is endemic to the United States. The cottonmouth habitat range extends from southeastern Virginia (near the junction of the Appomattox and James rivers) to southern Florida, west to central Texas, Oklahoma, Arkansas, Missouri, and southeastern Kansas, and north in the middle Mississippi River drainage to southern Illinois [L2893]. |
| Indication/Disease | CROFAB is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation [FDA label]. |
| Pharmacodynamics | The Crotalidae family produces venoms which are generally necrolytic and hemolyzing to tissues. _Hemorrhagins_ in crotalid venom is toxic to the blood vessels and therefore cause hemorrhage and edema at the wound site, in addition to systemic hemorrhage and shock. Significant anemia is observed due to hemolysis and extravasation of blood due to damaged vessels. Disseminated intravascular coagulation (DIC) has been observed in some cases. The most frequent initial clinical pathological changes include echinocytosis, thrombocytopenia, leukocytosis and prolonged activated clotting time. In general, edema and erythema along with fang marks (_Crotalidae _family) may be seen at the site of bite although it is tough to identify due to thick hair coat in animals [L2889]. The Crofab antivenin antagonizes the venom of this the Cottonmouth snake, preventing or antagonizes the above effects [L2889]. |
| Mechanism of Action | CROFAB is a mixture of 4 different monospecific antivenoms derived from serum of healthy sheep immunized with one of the following North American snake venoms: C. atrox (Western diamondback rattlesnake), C. adamanteus (Eastern diamondback rattlesnake), C. scutulatus (Mojave rattlesnake), or A. piscivorus (cottonmouth or water moccasin) [FDA label]. CROFAB consists of venom-specific Fab fragments of immunoglobulin G (IgG) that work by binding to and neutralizing venom toxins, facilitating their redistribution away from target tissues and their elimination from the body [FDA label]. CROFAB contains only the Fab fragments from ovine-derived immunoglobulins. The enzyme papain is used to cleave the IgG antibody, creating 2 separate Fab fragments and 1 Fc fragment. After the cleavage step, another protein binds to the Fc fragments, which are not essential for binding snake venom, allowing the pure Fab fragments to be recovered. The Fab fragments of an immunoglobulin contain the variable regions that recognize and bind to specific antigens [FDA label]. |
| Toxicity | ED50: 4 (mg antivenin/mg venom)[FDA label] Most common adverse reactions (incidence =5% of subjects) are urticaria, rash nausea, pruritus, and back pain [FDA Label]. Severe hypersensitivity reactions may occur with the use of CROFAB. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment [FDA Label]. CROFAB contains purified immunoglobulin fragments from the blood of sheep that have been immunized with snake venoms. Injection of heterologous animal proteins can lead to severe acute and delayed hypersensitivity reactions (late serum reaction or serum sickness) and a possible febrile (fever) response to immune complexes formed by animal antibodies and neutralized venom components [FDA label]. The _papain_ enzyme is used to cleave antibodies into fragments during the processing of CROFAB, and negligible amounts of papain or inactivated papain residues may be present. Patients allergic to papain, _chymopapain_, other papaya extracts, or the pineapple enzyme, _bromelain_, may also have an allergic reaction to CROFAB. Certain dust mite allergens and some latex allergens share antigenic structures with papain and patients with these allergies may be allergic to papain [FDA Label]. |
| Metabolism | NA |
| Absorption | NA |
| NA |
| Clearance | Systemic clearance of 32 mL/min (approximately 0.4 mL/min/kg [FDA label] |
| Categories | Venom Neutralization |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Group 10 secretory phospholipase A2 |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |