Crotalidae polyvalent immune Fab (Crofab)

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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

Crotalidae polyvalent immune Fab (Crofab) is 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

The following are criteria for administration after Crotalidae bite[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

  • Administer antivenom as soon as possible if the indications are met and antivenom is available.[4]
  • Administration should slow swelling and decrease pain

Initial Administration

CroFab is reconstituted in normal saline and typically diluted into 250 cc or 1 L of normal saline and infused over an hour.

  • The dosing of CroFab is the same for adults and children (may have to adjust the dilution of CroFab for small children so that they are not volume overloaded)
  • Establish initial control of envenomation by giving 4-6 vials
  • Control achieved? (Cessation of progression of all components of envenomation, including labs checked 2 hours after infusion started)
    • If yes: then perform serial exams and consider maintenance therapy
    • If no: repeat infusion of 4-6 vials and then re-evaluate for control

Maintenance therapy

  • Maintance therapy may be indicated after initial dosing based on local protocols even if control is achieved.[5]
    • Infuse 2-vial doses at 6, 12, and 18hr after initial control achieved

Envenomation control measurement

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

Antivenom 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.[6]
    • 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

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. Dart RC et al. Efficacy of post envenomation administration of antivenin. Toxicon. 1988;26:1218–1221.
  5. Crofab treatment agorithmn ../docss/CroFab-Treatment_Algorithm.pdf
  6. Ruha AM et al. Late hematologic toxicity following treatment of rattlesnake envenomation with crotalidae polyvalent immune Fab antivenom. Toxicon. 2011;57:53–59.