Antivenin (Crotalidae) Polyvalent (equine origin) - North American pit viper (snake) equine antivenin
Status: approved, but being discontinued
Organizations involved:
Wyeth – Manuf.; R&D; Tech.; World mark.
Cross ref.: See the Antivenin Products entry above. See also Crotalidae Polyvalent Immune Fab (Ovine) or CroFab (used for neutralization of many of the same snake venoms).
Description: Antivenin (Crotalidae) Polyvalent, Wyeth (referred to as Antivenin) is a refined and concentrated lyophilized (freeze-dried) mixture of immune globulins fractionated from pooled plasma of healthy horses (equine) immunized with the following snake venoms: Crotalus adamanteus (Eastern diamond rattlesnake); Crotalus atrox (Western diamond rattlesnake); Crotalus durissus (tropical rattlesnake, Cascabel); and Bothrops atrox (Fer-de-lance), along with 0.25% phenol and 0.005% thimerosal (mercury derivative; see entry #939) added as preservatives. The content of each antivenin is standardized by its ability to neutralize the lethal action of standard venoms injected into mice (Gingrich, W., et. al., Standardization of Polyvalent Antivenin, in Venoms, edited by E. Buckely and N. Porges, Amer. Assoc. for the Adv. of Sci., pub. no. 44, p. 337-80, 1956).
Antivenin (Crotalidae) Polyvalent, Wyeth contains equine immune globulin (antibodies) capable of neutralizing in humans the toxic effects of venoms of various crotalids (pit vipers) native to North, Central and South America, including rattlesnakes (Crotalus, Sistrurus); copperhead and cottonmouth moccasins (Agkri-stro-don), including Agkri-stro-don helys of Korea and Japan; the Fer-de-lance and other species of Both-rops; the tropical rattler (Crotalus durissus and similar species); the Cantil (A. bilineatus); and bushmaster (Lachesis mutus) of South and Central America.
The product is supplied in single use vials along with 10 mL water for reconstitution (Bacteriostatic Water for Injection, USP, with 0.01% phenylmercuric nitrate as preservative).
Nomenclature: Antivenin (Crotalidae) [BIO]; Antivenin (Crotalidae) Polyvalent (equine origin) [FDA]; rattlesnake antivenin [SY]; pit viper antivenin [SY]; North American crotalid antivenom [SY]; Crotalus adamanteus antivenin [SY]; Eastern diamond rattlesnake antivenin [SY]; Crotalus atrox antivenin [SY]; Western diamond rattlesnake antivenin [SY]; Crotalus durissus antivenin [SY]; tropical rattlesnake antivenin [SY]; Cascabel antivenin [SY]; Bothrops atrox antivenin [SY]; Fer-de-lance antivenin [SY]; NDC 0008-0332-04 [NDC]
Companies.: Antivenin (Crotalidae) Polyvalent was manufactured by Wyeth Pharmaceuticals, Marietta, PA; CBER/FDA est. no. 0003. It was marketed in the U.S. and internationally by Wyeth and affiliates. Wyeth is closing down its Marietta, PA, facilities. Marketing will halt once current supplies are exhausted.
FDA class: Biologic PLA
CBER class: Antitoxins, Antivenins, Enzymes and Venoms
Approvals: Date = 19540208; first approval
Status: Wyeth is discontinuing this product. Manufacturing has been halted. This product is considered as no longer needed (see the entry below for CroFab, a more modern product).
As of mid-2012, the BLA was still approved (not withdrawn) with the product considered "discontinued," meaning it is exempt from annual CBER user fees. It was converted to discontinued on Oct. 1, 2007.
Indications: [full text of “Indication” section of product insert/labeling]:
Antivenin is indicated only for the treatment of envenomization caused by bites of those crotalid (pit vipers) specified in the immediately preceding paragraph [Crotalus adamanteus (Eastern diamond rattlesnake); Crotalus atrox (Western diamond rattlesnake); Crotalus durissus (tropical rattlesnake, Cascabel); and Bothrops atrox (Fer-de-lance)]
Trials: This product has been criticized because no controlled study of its safety and efficacy was ever reported.
Medical: The product is administered by intravenous infusion. It is most effective when administered within four hours of the snakebite. Dosage depends on the physician’s estimate of the amount of venom injected into the victim. “The following initial doses are recommended: no envenomization – none; minimal envenomization – 20-40 mL (contents of 2 to 4 vials); moderate envenomization – 50-90 mL (contents of 5 to 9 vials); severe envenomization – 100-150 mL or more (contents of 10 to 15 or more vials).”
As an equine immune globulin product, this product has significant potential adverse effects, including anaphylaxis and serum sickness. Other acute reactions, including rash, hypertension, wheezing and phlebitis, occur in about 20% or more of treated patients. About 70%-80% of patients experience serum sickness, a type III hypersensitivity reaction causing malaise, fever, chills, arthralgia and diffuse rash. This aller-genicity is primarily attributed to immunoglobulin G(T) [IgG(T)], a highly glycosylated form of IgG produced by horses immunized with snake venom.
Market: The 2007 Average Wholesale Price (AWP) is $1,125.00/kit, and the Direct Price (Manufacturer’s discount price) is $937.60/kit (Red Book, 2007).
Companies involvement:
Full monograph
907 Antivenin (Crotalidae)
Nomenclature:
Antivenin (Crotalidae) antivenin [BIO]
Antivenin (Crotalidae) Polyvalent (equine origin) antivenin [FDA]
Bothrops atrox antivenin [SY]
Cascabel antivenin [SY]
Crotalus adamanteus antivenin [SY]
Crotalus atrox antivenin [SY]
Crotalus durissus antivenin [SY]
Eastern diamond rattlesnake antivenin [SY]
Fer-de-lance antivenin [SY]
North American crotalid antivenom [SY]
pit viper antivenin [SY]
rattlesnake antivenin [SY]
tropical rattlesnake antivenin [SY]
Western diamond rattlesnake antivenin [SY]
NDC 0008-0332-04 [NDC]
FDA Class: Biologic PLA
Year of approval (FDA) = 1954
Date of 1st FDA approval = 19540208
(in format YYYYMMDD)
Index Terms:
antibodies (see also immune globulins; monoclonal antibodies)
antivenins
biopharmaceutical products
blood products
equine immune globulins <!-- immunoglobulins -->
equine materials used
immune globulins, equine <!-- immunoglobulins -->
Bothrops atrox
Crotalus adeamanteus venom
Crotalus atrox venom
Crotalus durissus venom
equine plasma/serum
Fer-de-lance
pit vipers
plasma proteins, immunoglobulin-depleted
rattlesnakes
snake venoms
water moccasin venom
amino acid oxidases
Bacteriostatic Water for Injection
collagenases
deoxyribonuclease (DNase)
hyaluronidase
lactate dehydrogenases
nucleotidases
phenol
phosphatases
phospholipases
proteolytic enzymes
rattlesnake venom
ribonucleases
snake venoms
thimerosal (mercury derivative)
approval dates uncertain (FDA reports erroneous, conflicting, or simply has lost the original approval dates) (FDAapproved)
EU200 Currently Approved in EU
UM999 Not Available/Not Marketed in US
US200 Currently Approved in US
EM001 Marketed Product in EU
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