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Crotalidae Polyvalent Immune FAB (Ovine)

Pronunciation

(kroe TAL ih die pol i VAY lent i MYUN fab (oh vine))

Index Terms

  • Antivenin
  • Antivenin (Crotalidae) Polyvalent, FAB (Ovine)
  • Antivenom
  • Antivenom (Crotalidae) Polyvalent, FAB (Ovine)
  • Crotaline Antivenin, Polyvalent, FAB (Ovine)
  • Crotaline Antivenom, Polyvalent, FAB (Ovine)
  • FabAV, FAB (Ovine)
  • North American Antisnake-Bite Serum, FAB (Ovine)
  • Snake Antivenin, FAB (Ovine)
  • Snake Antivenom, FAB (Ovine)

Dosage Forms

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

Solution Reconstituted, Intravenous:

CroFab: (1 ea) [contains thimerosal]

Brand Names: U.S.

  • CroFab

Pharmacologic Category

  • Antivenin

Pharmacology

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.

Distribution

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

Excretion

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])

Contraindications

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

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 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

Refer to adult dosing. Note: 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). 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; 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.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

Reconstitute each vial with 18 mL NS and mix by continuous manual inversion until no solid material is visible. Do not shake. Further dilute total dose in 250 mL NS. Swirl gently to mix. Due to fluid overload concerns in children who weigh <10 kg, it has been proposed that approximately half of the normal fluid volume for dilution (ie, 125 mL NS) should be used in this patient population (Johnson 2008).

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

Administration

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).

Storage

Store at 2°C to 8°C (36°F to 46°F). Do not freeze. Use within 4 hours after reconstitution and dilution.

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% (Limited to important or life-threatening): Angioedema, chest discomfort, dizziness, erythema, headache, hyperhidrosis, laryngotracheal edema, musculoskeletal chest pain, swelling of lips, swollen tongue, tachycardia, tachypnea

Warnings/Precautions

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.

Special populations:

• Pediatric: Product contains thimerosal with 0.03 mg of mercury per vial. Developing fetuses and young children may be at higher risk for mercury-related toxicities.

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

Animal reproduction studies have not been conducted. Products contain thimerosal which may be associated with mercury-related toxicities, including neurological and renal toxicities in the fetus and very young children. 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). Experience with the use of antivenom in pregnancy is limited; however, 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), wheezing, cough, severe dizziness, passing out, tachycardia, muscle pain, or joint pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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