Crotalidae polyvalent immune Fab (Crofab)

Background

  • The original Antivenin Crotalidae Polyvalent (ACP)[1] was manufactured by Wyeth Pharmaceutical for use in the US but due to severe delayed allergic reactions was discontinued.
  • The FDA approved Crofab, an antivenom derived from sheep serum[2] in 2000. The antibodies bind and neutralize venom components.

Synthesis and Production

  • Produced from sheep serum after inoculation with venom from:
    • Eastern diamondback rattlesnake (Crotalus adamants)
    • Western diamondback rattlesnake (Crotalus atria)
    • Mojave rattlesnake (Crotalus scutulatus).
    • Cottonmouth (Agkistrodon piscivorus)
  • The Fc portion of the antibody is eliminated after mixture with papain and subsequent purification.

Indications for Administration of CroFab[3]

  • Progression of swelling
  • Abnormal results on lab tests (platelets < 100,000 or fibrinogen < 100)
  • Systemic manifestations (unstable vitals or altered mental status)

Dosing and Administration

Initial Administration

  • Initial dose: 6 vials[4]
  • Typically diluted into 250 cc or 1 L of normal saline and infused over an hour
  • Same dose for both adults and pediatrics (may have to adjust the dilution of CroFab for small children so that they are not volume overloaded)

Maintenance therapy

  • May repeat dose (2 vials) at 6, 12, and 18 hours later if symptoms not controlled[5]
    • Maintance therapy may be indicated after initial dosing based on local protocols even if control is achieved.[6]

Envenomation control measurement

  • Observe for progression of envenomation during and after antivenom infusion
  • Measure limb circumference at several sites above and below bite
  • Mark advancing border of edema q30min
  • Repeat labs q4hr or after each course of antivenom (whichever is more frequent)

Side Effects

  • Acute allergic reactions occur in <10% pts
    • If occurs stop infusion and give epinephrine/antihistamines if needed
  • Recurrent thrombocytopenia has been described up to 2 weeks after transfusion with FabAV and is likely a result of isolated renal clearance of FabAV and persistent presence of actual venom in serum.[7]
    • Warrants close monitoring of platelets by primary physician or return visit after discharge
  • Serum sickness is unlikely but precautions should be given to patents upon discharge

Pregnancy category C

See Also

References

  1. Howland MA, Smilkstein MJ. Primer on immunology with applications to toxicology. Contemp Manage Crit Care. 1991;1:109–145.
  2. Ruha AM et al: Initial postmarketing experience with crotalidae polyvalent immune Fab for treatment of rattlesnake envenomation. Ann Emerg Med. 2002;39:609–615.
  3. Dart RC et al. Efficacy of post envenomation administration of antivenin. Toxicon. 1988;26:1218–1221.
  4. Gerardo CJ. The efficacy of crotalidea polyvalent immune fab (ovine) antivenom versus placebo plus optional rescue therapy on recovery from copperhead snake envenomation: A randomized, double-blind, placebo-controlled, clinical trial. Annals of EM. August 2017. 70(2):233-244.
  5. Gerardo CJ. The efficacy of crotalidea polyvalent immune fab (ovine) antivenom versus placebo plus optional rescue therapy on recovery from copperhead snake envenomation: A randomized, double-blind, placebo-controlled, clinical trial. Annals of EM. August 2017. 70(2):233-244.
  6. Crofab treatment agorithmn http://www.crofab.com/documents/CroFab-Treatment_Algorithm.pdf
  7. Ruha AM et al. Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom. Toxicon. 2011;57:53–59.