CroFab is an Ovine polyvalent crotalidae North and South American snake antivenom derived from serum sheep.

CroFab (Ovine polyvalent crotalidae) Uses:

• Crotalid envenomation:

  •  Adult and pediatric patients management with North American crotalid envenomations (eg, rattlesnakes [Crotalus, Sistrurus], copperheads, and cottonmouth/water moccasins [Agkistrodon])

See Coral Snake Antivenom.

CroFab (Ovine polyvalent crotalidae) Dose in Adults

CroFab Antivenom Dose in the treatment of Crotalid envenomation:

IV:

Initial dose:

• 4 to 6 vials.
• Treatment should start as early as possible and preferably within 6 hours of envenomation.
• To determine if initial control has been achieved as evidenced by the arrest of local signs of envenomation, monitor for up to 1 hour following the infusion  (eg, leading edge of local injury is not progressing).
• For patients who are present with immediately life-threatening effects, some clinicians recommend an initial dose of 8-12 vials  (eg, shock, serious active bleeding).
• If control is not achieved with the initial dose, repeat with an additional 4-6 vials.
•  doses until local manifestations, coagulation tests, and systemic signs are normal.

Maximum initial dose:

• 12 vials, continue to treat with 4-6-vial.

• Maintenance dose:

  • Administer 2 vials every 6 hours for up to 18 hours, once control is achieved.
  • Beyond 18 hours, Optimal dosing has not been established.
  • however, based on the patient's condition, treatment may be continued if deemed necessary.

CroFab (Ovine polyvalent crotalidae) Dose in Childrens

CroFab Antivenom Dose in the treatment of Crotalid envenomation:

• Children and Adolescents:

  • patients as young as 11 years of age are included in Clinical trials.
  • In children as young as 1 year of age, use has been reported to be both safe and effective  (Johnson 2008; Schmidt 2005; Seifert 2009).

Note:

• Antivenom dosage is based on venom load & severity of symptoms & not on patient size.
• So, in pediatric patients, a reduced, weight-based antivenom dose is not recommended.
• When treating any envenomed patient, but especially pediatric patients, Clinicians are encouraged to contact their local poison control center or clinical toxicologist for consultation.

Initial dose:

• IV:
  • 4-6 vials as soon as possible & preferably within six hours of snakebite.
  • Following infusion, examine for 1 hour 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).
  • In patients presenting with immediately life-threatening effects (eg, shock, respiratory distress, cardiovascular collapse, significant hemorrhage, or severe neurologic toxicity), some clinicians recommend an initial dose of 8 to 12 vials  (Goto 2009; Lavonas 2011a).
  • Repeat with additional dose of 4-6 vials if control is not achieved, until initial control is achieved and local manifestations, coagulation tests and systemic signs are normal.

Maximum initial dose:

• 12 vials.

The maintenance dose (begin once control of envenomation achieved):

• IV:
  • 2 vials every 6 hours for up to 18 hours.
  • Beyond 18 hours, optimal dosing has not been established.
  • However, based on patient condition, treatment may be continued if deemed necessary .

CroFab Pregnancy Risk Category: C

• Limited information is available on the pregnancy effects of crotalidae polyvalent immuno FAB (ovine).
• When taking antidotes or medications, it is important to consider the mother's health and prognosis.
• They should be given to pregnant women if there is a clear indication of their use.
• Antivenom is a treatment option for snake envenomations. It can be used in cases where it is required as a final management or when the condition is refractory.
• It is recommended to keep the mother and the fetus under constant surveillance.

Use of polyvalent crotalidae from Ovines during breastfeeding

• It is unknown if the product is found in breast milk.
• The manufacturer suggests that it be administered to breastfeeding women with caution.

CroFab Dose in Kidney Disease:

• In the manufacturer’s labeling, there are no dosage adjustments provided.

CroFab Dose in Liver Disease:

• In the manufacturer’s labeling, there are no dosage adjustments provided.

CroFab antivenom Side effects:

• Cardiovascular:

  • Hypotension

• Central Nervous System:

  • Chills

• Dermatologic:

  • Pruritus
  • Skin Rash
  • Urticaria

• Gastrointestinal:

  • Anorexia
  • Nausea

• Hypersensitivity:

  • Hypersensitivity Reaction
  • Serum Sickness
  • Anaphylactoid Reaction
  • Anaphylaxis

• Respiratory:

  • Asthma
  • Cough
  • Dyspnea
  • Wheezing

• Miscellaneous:

  • Fever

Contraindications to CroFab (Ovine polyvalent crotalidae):

• Hypersensitivity to any ingredient of the formulation (including papaya and papain) is possible if the benefits are not outweighed by the risks.
• Appropriate management for anaphylaxis can be found readily.

Warnings and precautions

• Hypersensitivity reactions

  • This is a product made from sheep plasma.
  • Anaphylaxis or anaphylactoid reactions can be dangerous for patients who have known allergies to sheep protein.
  • Hypersensitivity reactions should be reported immediately and epinephrine 1mg/mL for immediate treatment of anaphylactoid.
  • In case of severe hypersensitivity reactions (anaphylaxis or anaphylactoid reactions), discontinue infusion and seek emergency treatment.
  • It is possible that acute hypersensitivity reactions are less common than previously believed.
  • This product does not contain the immunogenic Fc fragments 7, proteins that were found in older equine products.
  • Sensitization can occur when repeated doses are taken.
  • This product is processed with papain and may cause hypersensitivity reactions in people allergic to papaya, other extracts from papaya, papain, chymopapain or the pineapple enzyme bromelain.
  • Cross allergenicity can also occur with latex and dust mite allergens.

• Crotalid Envenomation

  • It should be administered within 4 to 6 hours after the envenomation. This will prevent any clinical deterioration or coagulation abnormalities.
  • However, antivenom can be helpful if the treatment is delayed.
  • The coagulation cascade is a direct result of snake venom interference.
  • Recurrent coagulopathy can occur in approximately 50% of patients and may last for up to 2 weeks.
  • Patients with coagulopathy have a 66% chance for recurrence within the first 12 hours of postantivenom treatment (Boyer 2001).
  • Repeat dosing is possible (Miller 2010, Ruha 2011,).
  • Patients with bleeding disorders should be seen for at least one week and evaluated for any other conditions.
  • A decrease in platelets can occur during severe envenomations that last from hours to days.
  • Because blood products are quickly consumed, they can be ineffective because of the circulating venom.

Monitoring Parameters:

• Vital signs.
• CBC
• Platelet count
• Prothrombin time, aPTT, fibrinogen levels, fibrin split products, clot retraction, bleeding & coagulation times
• BUN
• Electrolytes
• Bilirubin
• Size of bite area (repeat every 15-30 minutes)
• Intake and output
• Signs and symptoms of anaphylaxis/allergy
• Signs & symptoms of a delayed allergic reaction or serum sickness (rash, fever, myalgia, arthralgia)
• Until the patient is stable, CBC, platelet counts & clotting studies are evaluated at 6-hour intervals.

How to administer CroFab (Ovine polyvalent crotalidae)?

IV:

• Administer IV over 60 mins at a rate of 25-50 mL/hour for the first 10 mins.
• Increase rate to 250 mL/hour, if no allergic reaction is observed.
• Examine closely.
• During the infusion, immediate treatment for anaphylactoid & hypersensitivity reactions should be available.
• Decreasing the rate of infusion may help control some infusion-related adverse effects (eg, fever, low back pain, wheezing, and nausea).

Mechanism of action of CroFab (Ovine polyvalent crotalidae):

• A fragment of IgG that binds and neutralizes the venom toxin. It also helps to remove the toxin form the target tissue.

The beginning of action:

• The stability or reduction of symptoms can be seen within 60 minutes of administration.

Distribution:

• Unbound Fab:
  • 110 mL/kg
• Half-life elimination:
• 12-23 hours (based on limited data)

Excretion:

• Excretion of the venom:
• Via the reticuloendothelial system, the antibody complex is speculated to occur.

Clearance:

• Unbound Fab:
• 5.9 mL/h/kg

International Brands of Ovine polyvalent crotalidae:

• CroFab

Ovine polyvalent crotalidae Brand Names in Pakistan:

No Brands Available in Pakistan.