Introduction

Antivenin; equine immunoglobulins capable of neutralizing venom toxins of black widow spiders (Latrodectus mactans).

Uses for Antivenin (Latrodectus mactans) (Equine)

Latrodectus mactans Envenomation

Treatment of symptoms resulting from black widow spider (Latrodectus mactans) bite.

May shorten duration of symptoms and reduce need for hospitalization.

Consultation with experts experienced in treating black widow spider envenomation recommended to guide treatment decisions regarding individual patients.

Antivenin (Latrodectus mactans) (Equine) Dosage and Administration

General

• Perform sensitivity testing (skin or conjunctival test) in all patients prior to administration. Desensitization can be attempted in individuals with history of allergy or with mildly or questionably positive sensitivity tests, but only if antivenin is considered necessary to save patient’s life and epinephrine is readily available. (See Sensitivity Testing and Desensitization under Dosage and Administration.)

• Negative sensitivity test does not preclude possibility of sensitivity reaction. Monitor closely for immediate sensitivity reactions during administration; monitor for serum sickness for average of 8–12 days after administration. (See Sensitivity Reactions under Cautions.)

• Early use advised for prompt relief, but delayed administration (up to 90 hours after envenomation) has accelerated recovery and alleviated manifestations.

Sensitivity Testing and Desensitization

• Skin sensitivity test (intradermal): Inject no more than 0.02 mL of the 1:10 dilution of normal equine serum provided by manufacturer; inject equal volume of 0.9% sodium chloride injection on contralateral extremity to serve as control. Observe results after 10 minutes. Positive skin test reaction consists of urticarial wheal surrounded by zone of erythema.

• Conjunctival sensitivity test (topical): Place 1 drop of normal equine serum provided by manufacturer (1:10 dilution in adults or 1:100 dilution in children) into conjunctival sac and observe for 10 minutes. Positive conjunctival test usually occurs within 10 minutes and consists of itching of eye and reddening of conjunctiva.

• Desensitization procedure (sub-Q): Prepare 1:10 and 1:100 dilutions of the antivenin in separate vials or syringes using 0.9% sodium chloride injection. Inject 0.1, 0.2, and then 0.5 mL of the 1:100 dilution at 15- or, preferably, 30-minute intervals; if there has been no reaction to previous doses, repeat using 1:10 dilution and then with undiluted antivenin. If immediate sensitivity reaction occurs at any time, apply tourniquet proximal to injection sites and administer epinephrine proximal to tourniquet or into another extremity. After at least 30 minutes, may continue desensitization procedure using last dose that did not produce reaction. If no reaction occurs after administration of 0.5 mL of undiluted antivenin, give additional 0.5-mL doses of undiluted antivenin at 15-minute intervals until entire 1-vial dose has been injected.

Administration

Administer by IM injection or slow IV infusion. IV infusion preferred for severe black widow spider envenomation or when patient is <12 years of age or in shock.

IM Administration

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer or 2.5 mL of sterile water for injection; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.

Make IM injections preferably into anterolateral thigh; this allows tourniquet to be applied if adverse systemic reactions occur.

IV Administration

Do not administer IV undiluted; do not administer by rapid IV injection or infusion. (See Immediate Sensitivity or Anaphylaxis under Cautions.)

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer or 2.5 mL of sterile water for injection; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.

Dilute reconstituted antivenin in 10–50 mL of 0.9% sodium chloride injection. Alternatively, reconstituted antivenin has been diluted in 50–100 mL of 0.9% sodium chloride injection.

Rate of Administration

Infuse dose over 15 minutes. Alternatively, dose has been infused over 20–60 minutes.

Dosage

Dosage usually expressed in terms of number of vials.

Pediatric Patients

Latrodectus mactans Envenomation

IM or IV

Single 1-vial dose. Symptoms usually subside in 1–3 hours.

Second 1-vial dose may be necessary in some patients.

Adults

Latrodectus mactans Envenomation

IM or IV

Single 1-vial dose. Symptoms usually subside in 1–3 hours.

Second 1-vial dose may be necessary in some patients.

Special Populations

No special population dosage recommendations.

Contraindications

• Manufacturer states none.

Warnings/Precautions

Sensitivity Reactions

Contains immunoglobulins from serum of horses immunized with black widow spider (L. mactans) venom. (See Actions.)

Prior to administration, make careful inquiry regarding prior exposure to preparations containing equine serum or history of any allergies.

Regardless of patient's clinical history, perform sensitivity testing (skin or conjunctival test). (See Sensitivity Testing and Desensitization under Dosage and Administration.) Anaphylactic reaction to the antivenin may still occur in patients with negative skin or conjunctival sensitivity tests.

Immediate Sensitivity or Anaphylaxis

Immediate sensitivity reactions (e.g., shock, anaphylaxis, anaphylactoid reactions, urticaria) reported rarely. May develop within minutes after beginning or during administration; may include apprehension; flushing; pruritus; urticaria; edema of face, tongue, and throat; cough; dyspnea; bronchospasm; cyanosis; vomiting; hypotension; cardiovascular collapse.

Risk may be increased in individuals with atopic sensitivity to horses.

Fatalities related to severe hypersensitivity reactions (severe bronchospasm, severe anaphylaxis resulting in cardiac arrest) reported; at least 1 case occurred after rapid IV administration of undiluted antivenin (see IV Administration under Dosage and Administration). Anaphylactic reactions and death reported in patients with history of asthma.

Continuously monitor for immediate sensitivity reactions; have appropriate equipment for maintenance of an adequate airway and other supportive measures and epinephrine or other agents for treatment of anaphylaxis or other severe systemic reactions readily available.

If severe immediate sensitivity reaction occurs, immediately discontinue antivenin administration, at least temporarily, and initiate appropriate therapy (e.g., epinephrine, antihistamines, IV fluids, IV vasopressor agents, maintenance of an adequate airway, oxygen) as indicated.

Immediate sensitivity reactions usually may be managed by temporarily interrupting antivenin administration (or decreasing rate of administration) and administering antihistamines and/or epinephrine. If administration is temporarily interrupted and then reinitiated after reaction is controlled, reinitiate at slower rate.

Delayed Hypersensitivity or Serum Reactions

Serum sickness reported rarely.

Malaise, fever, urticaria, lymphadenopathy, edema, arthralgia, nausea, and vomiting are usual manifestations of serum sickness; usually evident within 2–14 days after antivenin dose.

Monitor for signs and symptoms of serum sickness for an average of 8–12 days after dose.

Although efficacy not clearly established for treatment of envenomation or venom shock, corticosteroids and antihistamines are usual treatment of choice for serious serum sickness reactions.

Thimerosal Allergy

Contains thimerosal, a mercury-containing preservative. The 1:10 dilution of normal equine serum provided by manufacturer for sensitivity testing also contains thimerosal. (See Thimerosal Precautions under Cautions.)

Hypersensitivity reactions to thimerosal contained in vaccines reported rarely. These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling), but generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely. Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals receiving thimerosal-containing vaccines do not develop such hypersensitivity reactions.

Thimerosal Precautions

Antivenin (Latrodectus mactans) (equine) and normal equine serum provided by manufacturer for sensitivity testing contain mercury in the form of ethyl mercury from thimerosal, a mercury-containing preservative.

Each vial of lyophilized antivenin (Latrodectus mactans) (equine) and each vial of 1:10 normal equine serum contain 0.01% thimerosal (1:10,000) as preservative (50 mcg of mercury/mL).

Only limited toxicology data available regarding ethyl mercury; neurologic and renal toxicities associated with high dose and acute exposures to methyl mercury. Developing fetuses and young children, especially neonates and infants <6 months of age, are at greatest risk of mercury toxicity.

Although it has been suggested that thimerosal added as a preservative or used during the manufacturing process of vaccines or plasma-derived products theoretically could have adverse effects in recipients, there is no conclusive evidence that low concentrations of thimerosal contained in vaccines cause harm in vaccine recipients. Efforts to eliminate or reduce the thimerosal content in such products are recommended as a prudent measure to reduce mercury exposure in infants and children and part of an overall strategy to reduce mercury exposures from all sources, including food and drugs.

Specific Populations

Pregnancy

Category C.

Has been used in pregnant women without unusual adverse effects.

Lactation

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

Pediatric Use

Safety and efficacy not specifically studied. Has been used in children without unusual adverse effects.

Geriatric Use

No evidence of different responses between geriatric adults and younger patients. Because of increased risk of envenomation complications in geriatric adults, use antivenin in patients >60 years of age whenever indicated.

Common Adverse Effects

Sensitivity reactions, muscle cramps.

General

• Perform sensitivity testing (skin or conjunctival test) in all patients prior to administration. Desensitization can be attempted in individuals with history of allergy or with mildly or questionably positive sensitivity tests, but only if antivenin is considered necessary to save patient’s life and epinephrine is readily available. (See Sensitivity Testing and Desensitization under Dosage and Administration.)

• Negative sensitivity test does not preclude possibility of sensitivity reaction. Monitor closely for immediate sensitivity reactions during administration; monitor for serum sickness for average of 8–12 days after administration. (See Sensitivity Reactions under Cautions.)

• Early use advised for prompt relief, but delayed administration (up to 90 hours after envenomation) has accelerated recovery and alleviated manifestations.

Sensitivity Testing and Desensitization

• Skin sensitivity test (intradermal): Inject no more than 0.02 mL of the 1:10 dilution of normal equine serum provided by manufacturer; inject equal volume of 0.9% sodium chloride injection on contralateral extremity to serve as control. Observe results after 10 minutes. Positive skin test reaction consists of urticarial wheal surrounded by zone of erythema.

• Conjunctival sensitivity test (topical): Place 1 drop of normal equine serum provided by manufacturer (1:10 dilution in adults or 1:100 dilution in children) into conjunctival sac and observe for 10 minutes. Positive conjunctival test usually occurs within 10 minutes and consists of itching of eye and reddening of conjunctiva.

• Desensitization procedure (sub-Q): Prepare 1:10 and 1:100 dilutions of the antivenin in separate vials or syringes using 0.9% sodium chloride injection. Inject 0.1, 0.2, and then 0.5 mL of the 1:100 dilution at 15- or, preferably, 30-minute intervals; if there has been no reaction to previous doses, repeat using 1:10 dilution and then with undiluted antivenin. If immediate sensitivity reaction occurs at any time, apply tourniquet proximal to injection sites and administer epinephrine proximal to tourniquet or into another extremity. After at least 30 minutes, may continue desensitization procedure using last dose that did not produce reaction. If no reaction occurs after administration of 0.5 mL of undiluted antivenin, give additional 0.5-mL doses of undiluted antivenin at 15-minute intervals until entire 1-vial dose has been injected.

Administration

Administer by IM injection or slow IV infusion. IV infusion preferred for severe black widow spider envenomation or when patient is <12 years of age or in shock.

IM Administration

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer or 2.5 mL of sterile water for injection; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.

Make IM injections preferably into anterolateral thigh; this allows tourniquet to be applied if adverse systemic reactions occur.

IV Administration

Do not administer IV undiluted; do not administer by rapid IV injection or infusion. (See Immediate Sensitivity or Anaphylaxis under Cautions.)

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer or 2.5 mL of sterile water for injection; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.

Dilute reconstituted antivenin in 10–50 mL of 0.9% sodium chloride injection. Alternatively, reconstituted antivenin has been diluted in 50–100 mL of 0.9% sodium chloride injection.

Rate of Administration

Infuse dose over 15 minutes. Alternatively, dose has been infused over 20–60 minutes.

Dosage

Dosage usually expressed in terms of number of vials.

Pediatric Patients

Latrodectus mactans Envenomation

IM or IV

Single 1-vial dose. Symptoms usually subside in 1–3 hours.

Second 1-vial dose may be necessary in some patients.

Adults

Latrodectus mactans Envenomation

IM or IV

Single 1-vial dose. Symptoms usually subside in 1–3 hours.

Second 1-vial dose may be necessary in some patients.

Special Populations

No special population dosage recommendations.

Data not available regarding drug interactions.