Agkistrodon piscivorus antivenin

Identification

Name
Agkistrodon piscivorus antivenin
Accession Number
DB13894
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 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.

Associated Conditions
Contraindications & Blackbox Warnings
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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 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.

TargetActionsOrganism
AGroup 10 secretory phospholipase A2
antagonist
Humans
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
Learn about our commercial Adverse Effects data.
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Toxicity

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.

Affected organisms
  • Humans
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
Not Available

Products

Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
CroFabAgkistrodon 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 solutionIntravenousBTG International Inc.2000-02-10Not applicableUS flag

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

Chemical Identifiers

UNII
IA6O0K772M
CAS number
Not Available

References

General References
  1. 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. [PubMed:28633930]
  2. Agkistrodon piscivorus — Details Cottonmouth [Link]
  3. Review of Agkistrodon-Piscivorus [Link]
  4. Crofab website [Link]
  5. Agkistrodon [Link]
  6. Agkistrodon piscivorus [Link]
  7. THE PHOSPHOLIPASE OF THE VENOM OF THE COTTONMOUTH SNAKE [File]
  8. U Tox update, UTAH document [File]
PubChem Substance
347911463
RxNav
885183
FDA label
Download (407 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentSnake Bites1
4TerminatedTreatmentSnake Envenomation1
3CompletedTreatmentSnake Bite1
2CompletedTreatmentDisorders, Blood Coagulation / Snake Bite1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous
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
  1. 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. [PubMed:28633930]
  2. THE PHOSPHOLIPASE OF THE VENOM OF THE COTTONMOUTH SNAKE [File]

Drug created on September 08, 2017 14:22 / Updated on June 12, 2020 10:53

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