(kroe TAL ih die pol i VAY lent i MYUN fab (oh vine))
Envenomation: For the management of 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
Crotalid envenomation: IV:
Initial dose: 4-6 vials; treatment should begin as soon as possible and preferably within 6 hours of envenomation; monitor for 1 hour following the infusion. Some clinicians recommend an initial dose of 8-12 vials for patients who present with immediately life-threatening effects (eg, shock, serious active bleeding) (Lavonas, 2011). Repeat with an additional 4-6 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.
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 patients condition.
Refer to adult dosing.
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.
No dosage adjustment provided in manufacturer 's labeling.
No dosage adjustment provided in manufacturer 's labeling.
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. 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).
Administer IV 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.
Store at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Do not freeze. Use within 4 hours after reconstitution and dilution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
CroFab: (1 ea) [contains thimerosal]
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 15-30 minutes); intake and output; signs and symptoms of anaphylaxis/allergy. CBC, platelet counts, and clotting studies are evaluated at 6-hour intervals until patient is stable.
Frequency not always defined.
Cardiovascular: Hypotension
Central nervous system: Chills, fever
Dermatologic: Pruritus, rash, urticaria
Gastrointestinal: Anorexia, nausea
Respiratory: Asthma, cough, dyspnea, wheezing
Miscellaneous: Hypersensitivity reactions (5% to 19%), serum sickness (5%), anaphylaxis, anaphylactoid reaction
<1% (Limited to important or life-threatening): Angioedema, chest discomfort, dizziness, erythema, headache, hyperhidrosis, lip swelling, musculoskeletal chest pain, tachycardia, tachypnea, tongue swelling, tracheal edema
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. 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 4-6 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.
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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).
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)
Stability of patient or reduction in symptoms may be seen within 1 hour of administration
12-23 hours (based on limited data)
- 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; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any bleeding that is very bad or that will not stop), 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.