Details About Overdose or Poisoning Generic Salt ::  Antivenom, Crotalinae, Rattlesnake

Antivenom, Crotalinae (Rattlesnake)

    

Drug Pharmacology ::

I. Pharmacology. Althoughtwo antivenoms are still available for the treatment of crotalineenvenomation in some parts of the United States, the older product,Crotalinae polyvalent antivenom (equine) (Antivenom CrotalinaePolyvalent, Wyeth-Ayerst), largely has been replaced by the newerCrotalinae polyvalent immune Fab (ovine) (CroFab®, Protherics). Toproduce the polyvalent Fab antivenom, sheep are hyperimmunized withpooled venom from four North American snakes: Crotalus adamanteus, C atrox, C scutulatus, and A piscivorus.Papain then is added to the pooled serum product collected from thedonor animals to cleave the immunogenic Fc fragment from the IgGantibody. The result is an affinity-purified Fab fragment antivenom.After administration, the antivenom is distributed widely throughoutthe body, where it binds to venom.

Drug Indications ::

Indications. Antivenom is used for treatment of significant envenomation by Crotalinae species (see Table III–4 and Snakebite).

Drug Contra-Indications ::

III. Contraindications. Knownhypersensitivity to the antivenom or to horse serum is a relativecontraindication for the Wyeth product; antivenom may still beindicated for severe envenomation despite a patient history of allergicreaction. Known hypersensitivity to sheep or sheep serum, or to papainor papayas, is a contraindication for the Protherics product (CroFab).

Drug Adverse Effects ::

IV. Adverse effects

   

Immediatehypersensitivity reactions (including life-threatening anaphylaxis) mayoccur from both products, even in patients with no history of animalserum sensitivity and negative skin test results. Skin testing is not indicated with CroFab, and immediate hypersensitivity reactions appear to be less common.

Mildflushing and wheezing can occur within the first 30 minutes ofintravenous administration and often will improve after slowing of therate of infusion.

Delayedhypersensitivity (serum sickness) occurs in over 75% of patients whoreceive more than four vials of Wyeth antivenom and virtually allpatients who receive more than 12 vials. Onset occurs in 5–14 days.CroFab administration can also lead to delayed hypersensitivityreactions, but this may be much less common than with the Wyeth product.

Use in pregnancy. FDAcategory C (indeterminate). (See Table III–1.) There are no data onteratogenicity. Anaphylactic reaction resulting in shock or hypoxemiain the mother could conceivably adversely affect the fetus. However,severe envenomation of the mother should be treated aggressively tolimit venom effects that could affect the fetus or placenta.

Drug Lab Interactions ::

Drug or laboratory interactions. There are no known interactions.

Drug Dose Management ::

Dosage and method of administration. Theinitial dose is based on the severity of symptoms, not on body weight(Table III–4). Children may require doses as large as or larger thanthose for adults. The endpoint of antivenom therapy is the reversal ofsystemic manifestations (eg, shock, coagulopathy, and paresthesias) andthe halting of progressive edema and pain. Repeat 4–6 vial incrementsof Fab antivenom (or 5–10 vial increments of Wyeth antivenom) per houruntil progression of symptoms is halted. In some severe cases, largequantities of antivenom may be required, and in some cases, laboratoryblood-clotting parameters may be refractory to even large doses.However, most cases can at least be stabilized with aggressiveantivenom therapy. Antivenom may be effective up to 3 days or moreafter envenomation. If you suspect envenomation by the Mojaverattlesnake (Crotalus scutulatus) and symptoms are present,especially increased serum creatine phosphokinase (CPK) level,administer 10 vials of Wyeth antivenom or 4 vials of CroFab even whenthere is minimal swelling or local pain.

   

Treat all patients in an intensive care or monitored setting.

Before skin tests or antivenom administration, insert at least one and preferably two secure intravenous lines.

Perform the skin test for horse serum sensitivity for the Wyeth product (not indicated with CroFab),using a 1:10 dilution of antivenom (some experts prefer this method) orthe sample of horse serum provided in the antivenom kit (follow packageinstructions). Do not perform the skin test unless signsof envenomation are present and imminent antivenom therapy isanticipated. If the skin test is positive, reconsider the need forantivenom as opposed to supportive care but do not abandon antivenomtherapy if it is needed. Even if the skin test is negative, anaphylaxismay still occur unpredictably.

Ifantivenom is used in a patient with a positive skin test, pretreat withintravenous diphenhydramine (see Diphenhydramine) and cimetidine (oranother H2 blocker; see Cimetidine and Other H2 Blockers)and have ready at the bedside a preloaded syringe containingepinephrine (1:10,000 for intravenous use) in case of anaphylaxis.Dilute the antivenom 1:10 to 1:1000 before administration and give eachvial very slowly at first (ie, over 30–45 minutes), increasing the rateof infusion as tolerated.

E. Reconstitutethe lyophilized vial of either product with the 10 mL of diluentprovided or sterile saline and gently swirl for 10–30 minutes tosolubilize the material. Avoid shaking, which may destroy theimmunoglobulins (as indicated by foam formation). Further dilution with50–200 mL of saline may facilitate solubilization.

F. Administerantivenom by the intravenous route only. Start slowly, increasing therate as tolerated. In nonallergic individuals, 5–10 vials of Wyethantivenom or 4–6 vials of CroFab can be diluted in 250–500 mL salineand given over 60–90 minutes.

G. Ifthere is an inadequate response to the initial dose, give an additional4 vials of CroFab (5–10 vials of Wyeth) over 60 minutes, or give anadditional 6 vials of CroFab if signs of severe envenomation are stillpresent. Repeat in 4- to 6-vial increments (5–10 vials of Wyeth) perhour until the progression of symptoms is halted.

H. Recurrenceof symptoms of envenomation may occur with use of either antivenom butmay be more common with CroFab owing to its shorter half-life withinthe body of the Fab molecule. Recurrence after CroFab usually ismanifested 12–36 hours after stabilization is achieved with the initialdosing of CroFab. Repeating laboratory tests and observing forprogression of swelling therefore are recommended for 24 hours or morewhen CroFab antivenom is used. The repeat administration of CroFab in2-vial (or more if needed) increments is recommended if recurrenceoccurs. As an alternative, the package insert suggests consideration ofrepeat 2-vial dosing every 6 hours for 3 additional doses in severeenvenomations.

Drug Chemical Formulations ::

Formulations

   

Antivenom Crotalinae (formerly Crotalidae) polyvalent or Crotalinae polyvalent immune Fab. Supplies can be located by a regional poison center ([800] 222-1222).

The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is 20 vials of Wyeth antivenom or 12 vials of CroFab.

Table III–4. Initial Dose of Crotalinae Antivenom


Severity of Envenomation Initial Dose (vials)Antivenom Crotalinae Polyvalent (Wyeth) CroFab (Protherics) None or minimalNoneNoneMild (local pain and swelling)54Moderate (proximal progression of swelling, ecchymosis, mild systemic symptoms)104–6Severe (hypotension, rapidly progressive swelling and ecchymosis, coagulopathy)158

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