Crotalus adamanteus antivenin

Identification

Name
Crotalus adamanteus antivenin
Accession Number
DB13893
Description

Each year it is estimated there are 45,000 snakebites in the US and 300,000 to 400,000 bites worldwide. About 8000 of these snakebites involve venomous snake species. The majority of people bitten are males and about 50% occur in the age group of 18 to 28 9.

The eastern diamondback rattlesnake is the largest of the 32 species of rattlesnake currently recognized. They are large, heavy-bodied snakes with large, broad heads with two light lines on the face 3.

Crotalus adamanteus antivenin is derived and purified immunoglobulin fragments obtained from other domestic animals such as sheep previously immunized with Crotalus adamanteus (Eastern Diamondback rattlesnake). 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 administered to limit systemic toxicity Label.

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
  • Crotalus adamanteus immune fab antivenin (ovine)

Pharmacology

Indication

Indicated for North American crotalid envenomation by Crotalinae rattlesnakes (eg, cottonmouths/water moccasins, copperheads, rattlesnakes) Label, 2.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Reverses the effects of envenomation with Crotalus adamanteus Label.

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 may be seen at the site of bite although it is tough to identify due to thick hair coat in animals 8.

Mechanism of action

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
Not Available
Half-life

12 to 23 hours Label

Clearance

This product was shown to have a systemic clearance of 32 mL/minute (approximately 0.4 mL/minute/kg) 4.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

Most common adverse reactions (incidence ≥5% of subjects): urticaria, rash, nausea, pruritus and back pain. Allergic reaction (severe hives and a severe rash and pruritus) has been observed following treatment. Recurrent coagulopathy due to envenomation and requiring additional treatment may occur 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 response to immune complexes formed by animal antibodies and neutralized venom components Label.

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 and other mammals
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
CroFabCrotalus adamanteus antivenin (1 g/1) + Agkistrodon piscivorus 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
A4229A7019
CAS number
Not Available

References

General References
  1. Crotalidae Antivenin, Drugs.com [Link]
  2. Drugs.com, Crofab [Link]
  3. Eastern Diamondback Rattlesnake (Crotalus adamanteus) - Venomous [Link]
  4. PDR, Crofab [Link]
  5. Crotalus adamanteus [Link]
  6. Uniprot PDE3 [Link]
  7. Amino Acid Sequence of Phospholipase AZ-a! from the Venom of Crotalus adamanteus [Link]
  8. Review of Agkistrodon-Piscivorus [Link]
  9. Crotalidae Polyvalent, Ovine [File]
  10. Amino Acid Sequence of Phospholipase AZ-a! from the Venom of Crotalus adamanteus [File]
PubChem Substance
347911462
RxNav
885185
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. Amino Acid Sequence of Phospholipase AZ-a! from the Venom of Crotalus adamanteus [File]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Ligand
General Function
Zinc ion binding
Specific Function
By generating PPi, plays a role in regulating pyrophosphate levels, and functions in bone mineralization and soft tissue calcification. PPi inhibits mineralization by binding to nascent hydroxyapat...
Gene Name
ENPP1
Uniprot ID
P22413
Uniprot Name
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1
Molecular Weight
104923.58 Da
References
  1. Uniprot PDE3 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Perumal Samy R, Gopalakrishnakone P, Chow VT: Therapeutic application of natural inhibitors against snake venom phospholipase A(2). Bioinformation. 2012;8(1):48-57. doi: 10.6026/97320630008048. Epub 2012 Jan 6. [PubMed:22359435]
  2. Panfoli I, Calzia D, Ravera S, Morelli A: Inhibition of hemorragic snake venom components: old and new approaches. Toxins (Basel). 2010 Apr;2(4):417-27. doi: 10.3390/toxins2040417. Epub 2010 Mar 25. [PubMed:22069593]
  3. Sartim MA, Menaldo DL, Sampaio SV: Immunotherapeutic potential of Crotoxin: anti-inflammatory and immunosuppressive properties. J Venom Anim Toxins Incl Trop Dis. 2018 Dec 17;24:39. doi: 10.1186/s40409-018-0178-3. eCollection 2018. [PubMed:30564276]
  4. Amino Acid Sequence of Phospholipase AZ-a! from the Venom of Crotalus adamanteus [File]

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

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