Crotalidae polyvalent immune FAB (ovine) (Rx)

Frequency Not Defined

Pruritus

Rash

Urticaria

Hypotension

Chills

Fever

Anorexia

Nausea

Asthma

Cough

Dyspnea

Wheezing

Anaphylaxis

Anaphylactoid reaction

>10%

Hypersensitivity reactions (5-19%)

1-10%

Serum sickness (5%)

<1%

Angioedema

Chest discomfort

Dizziness

Erythema

Headache

Hyperhydrosis

Lip swelling

Musculoskeletal chest pain

Tachycardia

Tachypnea

Tongue swelling

Tracheal edema

Postmarketing reports

Delayed allergic reaction manifested by fever, pruritus and/or rash

Delayed or recurrent coagulopathy or thrombocytopenia

Failure to achieve intial control

Recurrent swelling refractory to treatment

Thrombocytopenia refractory to treatment

Prolonged hospitalization

Bleeding

Nausea

Tremor

Worsening eye sight

Treatment failure resulting in death

Contraindications

(Relative) History of hypersensitivity to papaya or papain unless benefits outweigh risks and appropriate anaphylaxis treatment is readily available

Cautions

Contains up to 30 mcg of ethyl mercury from thimerosal or approximately 0.03 mg of mercury per vial or no more than 0.6 mg of mercury per dose

Coagulopathy

• Use treatment within 4-6 hr of envenomation to prevent clinical deterioration and development of coagulation abnormalities
• Coagulopathy is a complication noted in many victims of crotalid envenomation that arises due to ability of snake venom to interfere with blood coagulation cascade and is seen more frequently in severely envenomated patients
• Optimal dosing to completely prevent recurrent coagulopathy has not been determined; because this product has a shorter persistence in the blood than the snake venoms that can leak from depot sites over a prolonged period of time, repeat dosing to prevent or treat such recurrence may be necessary
• Recurrent coagulopathy may persist for 1 to 2 weeks or more; patients who experience coagulopathy due to snakebite during hospitalization for initial treatment should be monitored for signs and symptoms of recurrent coagulopathy for up to 1 week or longer at physician’s discretion; during this period, the physician should carefully assess the need for re-treatment with this product and use of any type of anticoagulant or anti-platelet drug
• Because snake envenomation can cause coagulation abnormalities, the following conditions, which are also associated with coagulation defects, should be considered: cancer, collagen disease, congestive heart failure, diarrhea, elevated temperature, hepatic disorders, hyperthyroidism, poor nutritional state, steatorrhea, vitamin K deficiency

Hypersensitivity reactions

• Severe hypersensitivity reactions may occur with this medication; in case of acute hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, discontinue infusion and institute appropriate emergency treatment
• This product contains purified immunoglobulin fragments from blood of sheep immunized with snake venoms; injection of heterologous animal proteins can cause severe acute and delayed hypersensitivity reactions (late serum reaction or serum sickness) and a possible febrile response to immune complexes formed by animal antibodies and neutralized venom components
• Papain is used to cleave antibodies into fragments during the processing of this product, and trace amounts of papain or inactivated papain residues may be present; patients allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may also have an allergic reaction to this product
• Some dust mite allergens and some latex allergens share antigenic structures with papain and patients with these allergies may be allergic to papain
• Patients who receive a course of treatment with a foreign protein such as this product may become sensitized to it; therefore, use caution when administering a repeat course of treatment with this product for a subsequent envenomation episode
• Skin testing has not been used in clinical trials of this product and is not required
• Use the following precautions to manage hypersensitivity reactions:
• Emergency medical care (eg, epinephrine, intravenous antihistamines and/or albuterol) should be readily available
• Carefully monitor patients for signs and symptoms of an acute allergic reaction (eg, urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia)
• Follow-up all patients for signs and symptoms of delayed allergic reactions or serum sickness (eg, rash, fever, myalgia, arthralgia)

Pregnancy

Animal reproduction studies have not been conducted with this medication It is also not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity; administer to a pregnant woman only if clearly needed

Lactation

It is not known whether CROFAB is excreted in human breast milk; because many drugs are excreted in human milk, caution should be exercised when CROFAB is administered to a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Venom-specific Fab fragment of immunoglobulin G (IgG) that works by binding and neutralizing the venom toxins and facilitate their redistribution away from the target tissue and their elimination from the body

Absorption

Onset: Within 1 hr of administration

Distribution

Vd (total Fab): 300 mL/kg

Elimination

Systemic clearance: 32 mL/min (approximately 0.4 mL/min/kg)

Half-life: 12-23 hr

IV Preparation

Inspect visually for particulate matter and discoloration prior to administration

Reconstitute each vial in 18 mL of 0.9% saline and mix; do not shake

Further dilute content of reconstituted vials in 250 mL of 0.9% NaCl; mix gently

Use within 4 hr of reconstitution

IV Administration

IV infusion over 60 min

Infuse slowly over first 10 min at 25-50 mL/hr rate with careful observation for allergic reaction

If no allergic reaction, increase infusion rate to 250 mL/hr

Administer within 6 hr of snakebite advised

Storage

Refrigerate virgin vials, don't freeze