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Crotalidae Polyvalent Immune FAB (Ovine)

Generic name: antivenin (crotalidae) polyvalent systemic

Brand names: Antivenin Polyvalent, CroFab, Anavip

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

CroFab: (1 ea) [contains thimerosal]


Mechanism of Action

A venom-specific fragment of IgG, which binds and neutralizes venom toxin, helping to remove the toxin from the target tissue and eliminate it from the body.



Vd: Unbound Fab: 110 mL/kg (Seifert 2001)


Excretion of the venom:antibody complex is speculated to occur via the reticuloendothelial system (Dart 1997); Clearance: Unbound Fab: 5.9 mL/h/kg (Seifert 2001)

Onset of Action

Stability of patient or reduction in symptoms may be seen within 1 hour of administration

Half-Life Elimination

12-23 hours (based on limited data)

Use: Labeled Indications

Crotalid envenomation: Management of adult and pediatric patients with North American crotalid envenomations (eg, rattlesnakes [Crotalus, Sistrurus], copperheads, and cottonmouth/water moccasins [Agkistrodon])


Hypersensitivity to any component of the formulation (including papaya or papain), unless the benefits outweigh the risks and appropriate management for anaphylaxis is readily available

Dosage and Administration

Dosing: Adult

Crotalid envenomation: IV:

Initial dose: 4 to 6 vials; treatment should begin as soon as possible and preferably within 6 hours of envenomation. Monitor for up to 1 hour following the infusion to determine if initial control has been achieved as evidenced by the arrest of local signs of envenomation (eg, leading edge of local injury is not progressing). Some clinicians recommend an initial dose of 8 to 12 vials for patients who present with immediately life-threatening effects (eg, shock, serious active bleeding) (Lavonas 2011). Repeat with an additional 4 to 6 vials if control is not achieved with the initial dose. Continue to treat with 4- to 6-vial doses until local manifestations, coagulation tests, and systemic signs are normal. Maximum initial dose: 12 vials.

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Crotalid envenomation: Children and Adolescents: Clinical trials included patients as young as 11 years of age. Use has been reported to be both safe and effective in children as young as 1 year of age (Johnson 2008; Schmidt 2005; Seifert 2009). Note: Antivenom dosage is based on venom load and severity of symptoms and not on patient size; therefore, a reduced, weight-based antivenom dose in pediatric patients is not recommended (Behm 2003; Lavonas 2011a; Offerman 2002). Clinicians are encouraged to contact their local poison control center or clinical toxicologist for consultation when treating any envenomed patient, but especially pediatric patients.

Initial dose: IV: 4 to 6 vials as soon as possible and preferably within 6 hours of snakebite; monitor for 1 hour following infusion to determine if initial control has been achieved as evidenced by arrest of local signs of envenomation (eg, leading edge of local injury is not progressing). Some clinicians recommend an initial dose of 8 to 12 vials in patients presenting with immediately life-threatening effects (eg, shock, respiratory distress, cardiovascular collapse, significant hemorrhage, or severe neurologic toxicity) (Goto 2009; Lavonas 2011a). If control is not achieved, repeat with additional dose of 4 to 6 vials until initial control is achieved and local manifestations, coagulation tests and systemic signs are normal. Maximum initial dose: 12 vials.

Maintenance dose (begin once control of envenomation achieved): IV: 2 vials every 6 hours for up to 18 hours. Optimal dosing beyond 18 hours has not been established; however, treatment may be continued if deemed necessary based on patient condition.


Reconstitute each vial with 18 mL NS and mix by continuous manual inversion at the rate of 1 to 2 inversions per second until no solid material is visible. Do not shake. The contents of all of the reconstituted vials should be further diluted to a total volume of 250 mL NS; swirl gently to mix.

Note: Reconstitution with 25 mL SWFI and hand rolling/inverting may result in shorter dissolution times and allow for more rapid administration (Quan 2010).


IV: Administer IV over 60 minutes at a rate of 25 to 50 mL/hour for the first 10 minutes. If no allergic reaction is observed, increase rate to 250 mL/hour. Monitor closely. Immediate treatment for anaphylactoid and/or hypersensitivity reactions should be available during the infusion. Decreasing the rate of infusion may help control some infusion-related adverse effects (eg, fever, low back pain, wheezing and nausea).


Store at 2°C to 8°C (36°F to 46°F); excursions are permitted between -20°C and 25°C (-4°F and 77°F) for no longer than 7 days. Do not freeze. Use within 4 hours after reconstitution and dilution.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not always defined.

Cardiovascular: Hypotension

Central nervous system: Chills

Dermatologic: Pruritus, skin rash, urticaria

Gastrointestinal: Anorexia, nausea

Hypersensitivity: Hypersensitivity reaction (5% to 19%), serum sickness (5%), anaphylactoid reaction, anaphylaxis

Respiratory: Asthma, cough, dyspnea, wheezing

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Angioedema, blood coagulation disorder (delayed, recurrent), chest discomfort, delayed hypersensitivity, dizziness, erythema, headache, hemorrhage, hyperhidrosis, laryngeal edema, musculoskeletal chest pain, swelling of lips, swelling (recurrent and refractory to treatment), swollen tongue, tachycardia, tachypnea, thrombocytopenia (refractory to treatment), tremor


Concern related to adverse effects:

  • Hypersensitivity reactions: Derived from sheep plasma; anaphylaxis and anaphylactoid reactions are possible, especially in patients with known allergies to sheep protein. Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available prior to administration. In case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment. Incidence of acute hypersensitivity reactions may be lower than previously thought (Buchanan 2009; Cannon 2008; Lavonas 2011). This product lacks the immunogenic Fc fragments and proteins found in the older equine-derived product. Sensitization may occur with repeated doses.

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 allergenicity with dust mite and latex allergens.

Disease-related concerns:

  • Crotalid envenomation: Should be used within 4 to 6 hours of the envenomation to prevent clinical deterioration and the development of coagulation abnormalities; however, the administration of antivenom may be beneficial even if treatment has been delayed (Bush 2013). 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 to 2 weeks or more; patients who have evidence of coagulopathy during the first 12 hours postantivenom treatment have an ~66% chance of recurrence, which typically occurs 2 to 14 days after completion of antivenom administration (Boyer 2001). Repeat dosing may be indicated (Miller 2010; Ruha 2011). Patients should be monitored for at least 1 week and evaluated for other preexisting conditions associated with bleeding disorders. In severe envenomations, a decrease in platelets may occur, lasting hours to several days. Blood products are generally ineffective as they are rapidly consumed by circulating venom.

Monitoring Parameters

Vital signs; CBC, platelet count, prothrombin time, aPTT, fibrinogen levels, fibrin split products, clot retraction, bleeding and coagulation times, BUN, electrolytes, bilirubin; size of bite area (repeat every 15 to 30 minutes); intake and output; signs and symptoms of anaphylaxis/allergy; signs and symptoms of delayed allergic reaction or serum sickness (rash, fever, myalgia, arthralgia). CBC, platelet counts, and clotting studies are evaluated at 6-hour intervals until patient is stable.


Pregnancy Considerations

Information related to the use of crotalidae polyvalent immune FAB (ovine) in pregnancy is limited (Brown 2013; Ghosh 2018; LaMonica 2010; Langley 2010).

In general, the health and prognosis of the mother should be taken into consideration when using medications as antidotes; they should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey 2003). Treatment with antivenom should be considered in snake envenomations in which it is usually required as definitive management or in envenomations refractory to supportive care (Brown 2013). Extended monitoring of the mother and fetus is recommended (Brown 2013; Ghosh 2018).

Patient Education

What is this drug used for?

  • It is used to treat some snake bites.

Frequently reported side effects of this drug

  • Itching
  • Nausea
  • Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Wheezing
  • Cough
  • Severe dizziness
  • Passing out
  • Fast heartbeat
  • Muscle pain
  • Joint pain
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated February 3, 2020.