Identification
- Summary
Agkistrodon piscivorus antivenin is a mixture of antibodies used to treat venomous snake bites from the Crotalinae family (pit vipers).
- Brand Names
- Crofab
- Generic Name
- Agkistrodon piscivorus antivenin
- DrugBank Accession Number
- DB13894
- Background
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 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.) 5.
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 2.
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 6.
- Type
- Biotech
- Groups
- Approved, Experimental
- Biologic Classification
- Protein Based Therapies
Other protein based therapies - Protein Chemical Formula
- Not Available
- Protein Average Weight
- Not Available
- Sequences
- Not Available
- Synonyms
- Agkistrodon piscivorus immune fab antivenin (ovine)
Pharmacology
- Indication
CROFAB is a sheep-derived antivenin indicated for the management of adult and pediatric patients with North American crotalid envenomation Label.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Reversal of Venom poisoning caused by agkistrodon piscivorus •••••••••••• - Contraindications & Blackbox Warnings
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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 3.
The Crofab antivenin antagonizes the venom of this the Cottonmouth snake, preventing or antagonizes the above effects 3.
- 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) 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 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 Label.
Target Actions Organism AGroup 10 secretory phospholipase A2 antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Renal excretion, which can lead to renal failure 3.
- Half-life
12 to 23 hours Label.
- Clearance
Systemic clearance of 32 mL/min (approximately 0.4 mL/min/kg Label
- Adverse Effects
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ED50: 4 (mg antivenin/mg venom)Label
Most common adverse reactions (incidence ≥5% of subjects) are urticaria, rash nausea, pruritus, and back pain 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 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 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 Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
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Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image CroFab Agkistrodon piscivorus antivenin (1 g/1) + Crotalus adamanteus antivenin (1 g/1) + Crotalus atrox antivenin (1 g/1) + Crotalus scutulatus antivenin (1 g/1) Injection, powder, lyophilized, for solution Intravenous BTG International Inc. 2000-02-10 Not applicable US 
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- IA6O0K772M
- CAS number
- Not Available
References
- General References
- Jia Y, Ermolinsky B, Garza A, Provenzano D: Phospholipase A2 in the venom of three cottonmouth snakes. Toxicon. 2017 Sep 1;135:84-92. doi: 10.1016/j.toxicon.2017.06.010. Epub 2017 Jun 17. [Article]
- Agkistrodon piscivorus — Details Cottonmouth [Link]
- Review of Agkistrodon-Piscivorus [Link]
- Crofab website [Link]
- Agkistrodon [Link]
- Agkistrodon piscivorus [Link]
- THE PHOSPHOLIPASE OF THE VENOM OF THE COTTONMOUTH SNAKE [File]
- U Tox update, UTAH document [File]
- External Links
- FDA label
- Download (407 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Snake Bite 1 4 Terminated Treatment Snake Envenomation 1 3 Completed Treatment Snake Bite 1 2 Completed Treatment Coagulation Disorder / Snake Bite 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Not Available
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Phospholipase activity
- Specific Function
- PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a powerful potency for releasing arachidonic acid from cell membrane phospholipids. Prefers phosph...
- Gene Name
- PLA2G10
- Uniprot ID
- O15496
- Uniprot Name
- Group 10 secretory phospholipase A2
- Molecular Weight
- 18153.04 Da
References
Drug created at September 08, 2017 20:22 / Updated at June 19, 2021 00:27