Antivenin (Crotalidae) Polyvalent

Pronunciation (an tee VEN in (kroe TAL ih die) pol i VAY lent)

Related Information

U.S. Brand Names Antivenin Polyvalent [Equine]; CroFabTM [Ovine]

Synonyms Crotaline Antivenin, Polyvalent; North and South American Antisnake-bite Serum; Pit Viper Antivenin; Snake (Pit Vipers) Antivenin

Generic Available No

Pharmacologic Category Antivenin

Use Neutralization of venoms of North and South American crotalids: Rattlesnake, copperhead, cottonmouth, tropical moccasins, fer-de-lance, bushmaster

Pregnancy Risk Factor C

Pregnancy Implications Reproduction studies have not been conducted. Products contain thimerosal, which may be associated with neurological and renal toxicities in the fetus and very young children.

Lactation Excretion in breast milk unknown

Contraindications Hypersensitivity to any component of the formulation, unless the benefits outweigh the risks and appropriate management for anaphylaxis is available

Warnings/Precautions Should be used within 4-6 hours of snakebite to prevent clinical deterioration and development of coagulation abnormalities. Coagulation abnormalities are due directly to snake venom interference with the coagulation cascade. Recurrent coagulopathy occurs in approximately 50% of patients and may persist for 1-2 weeks or more. Patients should be monitored for at least one week and evaluated for other, pre-existing conditions, associated with bleeding disorders. In severe rattlesnake bites, a decrease in platelets may occur, lasting hours to several days, and whole blood transfusions may not be effective treatment. Anaphylaxis and anaphylactoid reactions are possible due to animal proteins in the antivenin. Patients should also be monitored for delayed allergic reactions or serum sickness. Antivenin polyvalent (equine) contains phenol, thimerosal, and is made from horse serum. A skin test for horse-serum sensitivity should be done prior to treatment. Antivenin polyvalent (ovine) is processed with papain and may cause hypersensitivity reactions in patients allergic to papaya, other papaya extracts, papain, chymopapain, or the pineapple enzyme bromelain. There may also be cross allergy with dust mite and latex allergens. Antivenin polyvalent (ovine) also contains thimerosal and is made from sheep plasma.

Adverse Reactions Frequency not defined.

Cardiovascular: Chest pain, hypotension

Central nervous system: Chills, nervousness

Dermatologic: Cellulitis, bruising, pruritus, rash, urticaria

Gastrointestinal: Anorexia, nausea

Hematologic: Coagulation disorder

Neuromuscular & skeletal: Back pain, circumoral paresthesia, general paresthesia, myalgia

Respiratory: Asthma, cough, dyspnea, sputum increased, wheezing

Miscellaneous: Allergic reaction, serum sickness, subcutaneous nodule, wound infection

Overdosage/Toxicology The maximum safe amount has not been determined. Up to 18 vials of antivenin polyvalent (ovine) have been safely administered. Treatment of overdose should be symptom-directed and supportive.

Drug Interactions No drug interaction studies have been conducted

Stability

Antivenin polyvalent (equine): Store in refrigerator, avoid temperatures >37°C. For I.V. infusion; reconstitute each vial with 10 mL of bacteriostatic water for injection, provided with the antivenin; mix by gentle swirling; use within 48 hours. To prepare for I.V. use, further prepare a 1:1-1:10 dilution of reconstituted antivenin in normal saline or D5W; use within 24 hours

Antivenin polyvalent (ovine): Store between 2°C to 8°C (36°F to 46°F); do not freeze. Reconstitute each vial with 10 mL sterile water and mix by gentle swirling. Further dilute total dose in 250 mL NS; use within 4 hours of reconstitution

Pharmacodynamics/Kinetics

Half-life elimination: Antivenin polyvalent (ovine): 12-23 hours (based on limited data)

Time to peak: Antivenin polyvalent (equine): I.M.: 8 hours

Dosage Children and Adults: Crotalid envenomation:

Antivenin polyvalent (equine): I.M., I.V.: Initial sensitivity test: 0.02 mL-0.03 mL of a 1:10 dilution of normal horse serum or antivenin given intracutaneously; also give a control test using normal saline in the opposite extremity. A positive reaction occurs within 5-30 minutes. A negative reaction does not rule out the possibility of an immediate or delayed reaction with treatment.

Minimal envenomation: 20-40 mL (2-4 vials)

Moderate envenomation: 50-90 mL (5-9 vials)

Severe envenomation: 100-150 mL (10-15 vials) or more

Note: The entire initial dose of antivenin should be administered as soon as possible to be most effective (within 4 hours after the bite). I.V. is the preferred route of administration. When administered I.V., infuse the initial 5-10 mL dilution over 3-5 minutes while carefully observing the patient for signs and symptoms of sensitivity reactions. If no reaction occurs, continue infusion at a safe I.V. fluid delivery rate. Additional doses of antivenin are based on clinical response to the initial dose. If swelling continues to progress, symptoms increase in severity, hypotension occurs, or decrease in hematocrit appears, an additional 10-50 mL (1-5 vials) should be administered.

Antivenin polyvalent (ovine): I.V.: Minimal or moderate envenomation:

Initial dose: 4-6 vials, dependent upon patient response. Treatment should begin within 6 hours of snakebite; monitor for 1 hour following infusion. Repeat with an additional 4-6 vials if control is not achieved with initial dose. Continue to treat with 4- to 6-vial doses until complete arrest of local manifestations, coagulation tests, and systemic signs are normal. Administer I.V. over 60 minutes at a rate of 25-50 mL/hour for the first 10 minutes. If no allergic reaction is observed, increase rate to 250 mL/hour. Monitor closely

Maintenance dose: Once control is achieved, administer 2 vials every 6 hours for up to 18 hours; optimal dosing past 18 hours has not been established; however, treatment may be continued if deemed necessary based on the patients condition

Administration

I.M.: Antivenin polyvalent (equine): May be used in cases of minimal envenomation; I.V. route is preferred. Administer into a large muscle mass, preferably the gluteal area. Avoid nerve trunks. Do not inject into finger or toe.

I.V.:

Antivenin polyvalent (equine): Infuse the initial 5-10 mL dilution over 3-5 minutes while carefully observing the patient for signs and symptoms of sensitivity reactions. If no reaction occurs, continue infusion at a safe I.V. fluid delivery rate. Total dose should be administered as soon as possible.

Antivenin polyvalent (ovine): Administer I.V. over 60 minutes at a rate of 25-50 mL/hour for the first 10 minutes. If no allergic reaction is observed, increase rate to 250 mL/hour. Monitor closely Epinephrine and diphenhydramine should be available during the infusion. Decreasing the rate of infusion may help control some adverse effects.

Monitoring Parameters Vital signs; hematocrit, hemoglobin, platelet count (multiple times daily); prothrombin time, clot retraction, bleeding and coagulation times, BUN, electrolytes, bilirubin, size of bitten area (repeat every 15-30 minutes); intake and output, signs and symptoms of anaphylaxis/allergy

Patient Information Immediate sensitivity reactions occur within 30 minutes after administration; serum-sickness reaction may occur 5-24 days after a dose. Contact prescriber immediately for rash, itching, unusual bleeding (nosebleeds, bleeding after teeth brushing, blood in stool or urine, excessive menstrual bleeding), or bruising that occur after discharge. Do not take any aspirin or blood thinners during recovery without first talking to your prescriber. Pregnancy/breast-feeding precautions: Inform prescriber you are pregnant or breast-feeding.

Nursing Implications Administer at a slower rate initially; monitor for signs and symptoms of sensitivity reactions. Reactions to antivenin may occur anytime during treatment and for weeks after administration.

Antivenin polyvalent (equine): Antivenin may be administered I.M. for minimal envenomation. I.V. administration of antivenin is preferred for moderate to severe envenomation or in the presence of shock; do not inject into a finger or toe

Additional Information

Minimal envenomation: Swelling, pain, and bruising are limited to immediate bite site; no systemic signs and symptoms; normal coagulation parameters; no clinical evidence of bleeding

Moderate envenomation: Swelling, pain, and bruising are limited to less than a full extremity (or <50 cm if bite was on head or trunk); systemic signs and symptoms are not life-threatening (nausea, vomiting, oral paresthesia, unusual taste, mild hypotension, mild tachycardia, tachypnea); coagulation parameters may be abnormal; no bleeding other than minor hematuria, gum bleeding, or nosebleeds, if not severe

Severe envenomation: Swelling, pain, and bruising involve more than the entire extremity or threaten the airway; systemic signs and symptoms are markedly abnormal (severe alteration of mental status, severe hypotension, severe tachycardia, tachypnea, respiratory insufficiency); coagulation parameters are abnormal; serious bleeding or severe threat of bleeding

Dosage Forms Injection, powder for reconstitution:

Equine origin [contains phenol and thimerosal] [with 10 mL diluent]

Ovine origin (CroFab®) [contains thimerosal] (2 vials/box)