Centruroides Immune F(ab′)2 (Monograph)

Brand name: Anascorp
Drug class: Antitoxins and Immune Globulins
VA class: IM300

Introduction

Antivenom; equine IgG F(ab′)₂ fragments capable of binding and neutralizing venom toxins of Centruroides scorpions.

Uses for Centruroides Immune F(ab′)2

Scorpion Envenomation

Treatment of clinical signs of scorpion envenomation; designated an orphan drug by FDA for this use.

May shorten time to resolution of envenomation symptoms, possibly eliminating need for treatment in an intensive care unit.

In the US, Centruroides sculpturatus (commonly known as the bark scorpion) is the only scorpion considered potentially dangerous to humans; found mainly in Arizona, but may be found in parts of California, New Mexico, Texas, Nevada, and northern Mexico.

Consider consultation with experts experienced in treating Centruroides envenomation (e.g., Arizona Poison and Drug Information Center in Tucson, Banner Good Samaritan Poison and Drug Information Center in Phoenix).

Centruroides Immune F(ab′)2 Dosage and Administration

General

Initiate treatment as soon as possible after a scorpion sting in patients who develop clinically important signs of scorpion envenomation (e.g., loss of muscle control, roving or abnormal eye movements, slurred speech, respiratory distress, excessive salivation, frothing at the mouth, vomiting).
Monitor closely during and for up to 1 hour after completion of IV infusion to confirm resolution of clinically important signs of envenomation.

Administration

IV Administration

Administer by IV infusion.

Reconstitution and Dilution

Reconstitute each vial of lyophilized Centruroides (scorpion) immune F(ab′)₂ (equine) with 5 mL of 0.9% sodium chloride; mix using continuous gentle swirling. When multiple vials are indicated (e.g., for initial dose), combine required number of reconstituted vials immediately following reconstitution.

Prior to infusion, dilute total dose (total combined reconstituted vials) to a total volume of 50 mL using 0.9% sodium chloride.

Rate of Administration

Administer by IV infusion over 10 minutes.

Dosage

Dosage expressed in terms of number of vials.

Pediatric Patients

Scorpion Envenomation

IV

Initially, 3 vials.

Give additional 1-vial doses every 30–60 minutes as needed.

Adults

Scorpion Envenomation

IV

Initially, 3 vials.

Give additional 1-vial doses every 30–60 minutes as needed.

Special Populations

No special population dosage recommendations.

Cautions for Centruroides Immune F(ab′)2

Contraindications

Manufacturer states none.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions.

Severe hypersensitivity reactions, including anaphylaxis, may occur.

Patients with known allergies to equine protein are at increased risk for anaphylactic reactions. Patients who previously received Centruroides (scorpion) immune F(ab′)₂ (equine) or another equine antivenom or antitoxin may be at increased risk for severe hypersensitivity reactions.

Monitor closely for hypersensitivity during antivenom infusion; IV epinephrine, corticosteroids, and diphenhydramine should be readily available.

If anaphylactic reaction occurs, immediately discontinue antivenom infusion and initiate appropriate emergency medical care.

Delayed Hypersensitivity or Serum Sickness Reactions.

Delayed hypersensitivity or serum sickness reactions may occur. Mild symptoms may include pruritus, nausea, urticaria, low-grade fever, and malaise; severe manifestations include persistent urticaria, vomiting, arthralgia, myalgia, syncope, and angioedema.

Monitor for manifestations of delayed allergic reactions or serum sickness (e.g., rash, fever, myalgia, arthralgia) at follow-up visits. Treat such reactions as necessary; treatment is generally symptomatic (e.g., antihistamines, analgesics, antipyretics, corticosteroids).

Risk of Transmissible Infectious Agents

Prepared from equine plasma; potentially may transmit infectious agents, including viruses. Several steps in manufacturing process (e.g., pepsin digestion, ammonium sulfate precipitation/heat treatment, nanofiltration) reduce risk of transmission of viruses.

Cresol Content

Contains trace amounts of cresol (<0.41 mg per vial) from manufacturing process. Cresol used as an injectable excipient has resulted in localized reactions and generalized myalgia.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether distributed into milk. Use with caution in nursing women.

Pediatric Use

Efficacy and safety in pediatric patients comparable to that in adults. Has been used in children ranging from younger than 1 month to 18 years of age.

Geriatric Use

Efficacy and safety in geriatric patients not studied specifically; considered comparable to that in overall patient population.

Common Adverse Effects

Vomiting, pyrexia, rash, nausea, pruritus.

Drug Interactions

No formal drug interaction studies to date.

Centruroides Immune F(ab′)2 Pharmacokinetics

Absorption

Onset

Following IV infusion, clinically important manifestations of scorpion envenomation generally resolve within 4 hours.

Elimination

Half-life

Approximately 6.6 days in healthy (nonenvenomed) adults. Additional study needed to determine pharmacokinetics in patients with scorpion envenomation.

Stability

Storage

Parenteral

For Injection, for IV Use

Room temperature (up to 25°C); may be exposed to temperatures up to 40°C. Do not freeze. Discard partially used vials.

Actions

Centruroides (scorpion) immune F(ab′)₂ (equine) is a polyvalent preparation of venom-specific F(ab′)₂ fragments of equine IgG that bind and neutralize Centruroides venom toxins, facilitating redistribution of the venom away from target tissues and elimination from the body.
Manufactured from plasma of horses immunized with venom of C. noxius, C. limpidus limpidus, C. limpidus tecomanus, and C. suffusus suffusus. Although C. sculpturatus venom not used in manufacturing process, in vitro studies demonstrate similar binding affinities and high degree of cross-reactivity among venoms of the various Centruroides species, including C. sculpturatus.
Standardized by ability to neutralize Centruroides scorpion venom in mice (mouse LD₅₀ neutralizing units). Each commercially available vial will neutralize ≥150 mouse LD₅₀ units of Centruroides venom.

Advice to Patients

Importance of immediately contacting clinician or seeking emergency treatment if manifestations of delayed allergic reactions or serum sickness (e.g., rash, pruritus, joint pain, arthralgia, fever, lymphadenopathy, malaise) develop within 14 days following hospital discharge. (See Delayed Hypersensitivity or Serum Sickness Reactions under Cautions.)
Importance of women informing clinicians if they are pregnant or breast-feeding.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.