Antivenin (Latrodectus mactans) (Equine)

Class: Serums
ATC Class: J06AA
VA Class: IM300

Introduction

Antivenin; equine immunoglobulins capable of neutralizing venom toxins of black widow spiders (Latrodectus mactans).1 4

Uses for Antivenin (Latrodectus mactans) (Equine)

Latrodectus mactans Envenomation

Treatment of symptoms resulting from black widow spider (Latrodectus mactans) bite.1 4

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May shorten duration of symptoms and reduce need for hospitalization.2 4 5 7 11

Consultation with experts experienced in treating black widow spider envenomation recommended to guide treatment decisions regarding individual patients.1 4

Antivenin (Latrodectus mactans) (Equine) Dosage and Administration

General

  • Perform sensitivity testing (skin or conjunctival test) in all patients prior to administration.1 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.1 (See Sensitivity Testing and Desensitization under Dosage and Administration.)

  • Negative sensitivity test does not preclude possibility of sensitivity reaction.7 Monitor closely for immediate sensitivity reactions during administration;4 7 monitor for serum sickness for average of 8–12 days after administration.1 (See Sensitivity Reactions under Cautions.)

  • Early use advised for prompt relief,1 but delayed administration (up to 90 hours after envenomation) has accelerated recovery and alleviated manifestations.2

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.1 Observe results after 10 minutes.1 Positive skin test reaction consists of urticarial wheal surrounded by zone of erythema.1

  • 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.1 Positive conjunctival test usually occurs within 10 minutes and consists of itching of eye and reddening of conjunctiva.1

  • 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.1 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.1 If immediate sensitivity reaction occurs at any time, apply tourniquet proximal to injection sites and administer epinephrine proximal to tourniquet or into another extremity.1 After at least 30 minutes, may continue desensitization procedure using last dose that did not produce reaction.1 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.1

Administration

Administer by IM injection or slow IV infusion.1 IV infusion preferred for severe black widow spider envenomation or when patient is <12 years of age or in shock.1

IM Administration

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.1

Make IM injections preferably into anterolateral thigh; this allows tourniquet to be applied if adverse systemic reactions occur.1

IV Administration

Do not administer IV undiluted;5 7 do not administer by rapid IV injection or infusion.5 7 (See Immediate Sensitivity or Anaphylaxis under Cautions.)

Reconstitute vial of lyophilized powder with 2.5 mL of sterile diluent provided by manufacturer; shake vial (with diluent needle still in rubber stopper) until contents completely dissolved.1

Dilute reconstituted antivenin in 10–50 mL of 0.9% sodium chloride injection.1 Alternatively, reconstituted antivenin has been diluted in 50–100 mL of 0.9% sodium chloride injection.2 7

Rate of Administration

Infuse dose over 15 minutes.1 Alternatively, dose has been infused over 20–60 minutes.2 5 7 11

Dosage

Dosage usually expressed in terms of number of vials.1

Pediatric Patients

Latrodectus mactans Envenomation
IM or IV

Single 1-vial dose.1 2 7 11 12 Symptoms usually subside in 1–3 hours.1

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

Adults

Latrodectus mactans Envenomation
IM or IV

Single 1-vial dose.1 2 7 11 12 Symptoms usually subside in 1–3 hours.1

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

Special Populations

No special population dosage recommendations.1

Cautions for Antivenin (Latrodectus mactans) (Equine)

Contraindications

  • Manufacturer states none.1

Warnings/Precautions

Sensitivity Reactions

Contains immunoglobulins from serum of horses immunized with black widow spider (L. mactans) venom.1 (See Actions.)

Prior to administration, make careful inquiry regarding prior exposure to preparations containing equine serum or history of any allergies.1

Regardless of patient's clinical history, perform sensitivity testing (skin or conjunctival test).1 (See Sensitivity Testing and Desensitization under Dosage and Administration.)

Immediate Sensitivity or Anaphylaxis

Immediate sensitivity reactions (e.g., shock, anaphylaxis, anaphylactoid reactions, urticaria) reported rarely.1 4 5 12 14 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.a

Risk may be increased in individuals with atopic sensitivity to horses.1

Fatalities related to severe hypersensitivity reactions (severe bronchospasm, severe anaphylaxis resulting in cardiac arrest) reported;4 5 11 14 at least 1 case occurred after rapid IV administration of undiluted antivenin (see IV Administration under Dosage and Administration).5 11

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.4 7

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.5

Immediate sensitivity reactions usually may be managed by temporarily interrupting antivenin administration (or decreasing rate of administration) and administering antihistamines and/or epinephrine.5 If administration is temporarily interrupted and then reinitiated after reaction is controlled, reinitiate at slower rate.5

Delayed Hypersensitivity or Serum Reactions

Serum sickness reported rarely.1 7

Malaise, fever, urticaria, lymphadenopathy, edema, arthralgia, nausea, and vomiting are usual manifestations of serum sickness;a usually evident within 2–14 days after antivenin dose.7 6

Monitor for signs and symptoms of serum sickness for an average of 8–12 days after dose.1 6

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.6

Thimerosal Allergy

Contains thimerosal, a mercury-containing preservative.1 22 The 1:10 dilution of normal equine serum provided by manufacturer for sensitivity testing also contains thimerosal.1 (See Thimerosal Precautions under Cautions.)

Hypersensitivity reactions to thimerosal contained in vaccines reported rarely.21 31 33 These reactions usually manifest as local, delayed-type hypersensitivity reactions (e.g., erythema, swelling),21 23 25 but generalized reaction manifested as pruritus and an erythematous, maculopapular rash on all 4 extremities has been reported rarely.33 Even when patch or intradermal tests for thimerosal sensitivity are positive, most individuals receiving thimerosal-containing vaccines do not develop such hypersensitivity reactions.21 23

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.1 22

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).1

Only limited toxicology data available regarding ethyl mercury; neurologic and renal toxicities associated with high dose and acute exposures to methyl mercury.20 Developing fetuses and young children, especially neonates and infants <6 months of age, are at greatest risk of mercury toxicity.18 19 20

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.27 28 29 32 34 35 36 37 38 39 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.18 19 20 23 27

Specific Populations

Pregnancy

Category C.1

Has been used in pregnant women without unusual adverse effects.9 15 16

Lactation

Not known whether distributed into milk.1 Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not specifically studied.1 Has been used in children without unusual adverse effects.1 2 11

Geriatric Use

No evidence of different responses between geriatric adults and younger patients.1 Because of increased risk of envenomation complications in geriatric adults, use antivenin in patients >60 years of age whenever indicated.1

Common Adverse Effects

Sensitivity reactions, muscle cramps.1

Interactions for Antivenin (Latrodectus mactans) (Equine)

Data not available regarding drug interactions.1

Antivenin (Latrodectus mactans) (Equine) Pharmacokinetics

Absorption

Data not available regarding pharmacokinetics after IM or IV administration.1

Onset

Symptomatic relief of envenomation may occur within 30 minutes following dose;4 11 manifestations usually subside within 1–3 hours.1

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze or expose to excessive heat.1 3

Actions

  • Antivenin (Latrodectus mactans) (equine) is a preparation of equine venom-neutralizing immunoglobulins capable of neutralizing venom toxins of black widow spiders (L. mactans).1 Exact pharmacologic mechanism of action unknown.1

  • Manufactured from serum of healthy horses immunized against venom of black widow spiders (Latrodectus mactans).1

  • Standardized by ability to neutralize action of L. mactans venom given IV to mice (mouse LD50 neutralizing units).1 3 Each vial contains at least 6000 mouse LD50 of antivenin.1 3

Advice to Patients

  • Importance of informing clinicians of prior exposure to preparations containing equine serum or history of any allergies.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

Antivenin (Latrodectus mactans) (Equine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

Containing at least 6000 antivenin units

Antivenin (Latrodectus mactans) Black Widow Spider Antivenin Equine (with thimerosal [50 mcg of mercury per mL] and with 2.5 mL of sterile diluent and a 1-mL vial of normal equine serum [1:10 dilution with thimerosal (50 mcg of mercury per mL)] for sensitivity testing)

Merck

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 16, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Merck & Co, Inc. Antivenin (Latrodectus mactans) (Black Widow Spider Antivenin) Equine Origin prescribing information. Whitehouse Station, NJ; 2010 Dec.

2. O'Malley GF, Dart RC, Kuffner EF. Successful treatment of latrodectism with antivenin after 90 hours. N Engl J Med. 1999; 340:657. [PubMed 10049091]

3. The United States pharmacopeia, 25th rev, and The national formulary, 20th ed. Rockville, MD: The United States Pharmacopeial Convention, Inc; 2002:158.

4. Clark RF, Wethern-Kestner S, Vance MV et al. Clinical presentation and treatment of black widow spider envenomation: a review of 163 cases. Ann Emerg Med. 1992;21:782-7

5. Clark RF. The safety and efficacy of antivenin Latrodectus mactans. Clin Toxicol. 2001;39:125-7.

6. Erffmeyer JE. Serum sickness. Ann Allergy. 1986;56:105-9.

7. Utah Poison Control Center for Health Professionals. Black widow spider envenomation. 2002 Dec. From website.

9. Monte AA, Bucher-Bartelson B, Heard KJ. A US perspective of symptomatic Latrodectus spp. envenomation and treatment: a National Poison Data System review. Ann Pharmacother. 2011; 45:1491-8. [PubMed 22116992]

10. Isbister GK, Fan HW. Spider bite. Lancet. 2011; 378:2039-47. [PubMed 21762981]

11. Offerman SR, Daubert GP, Clark RF. The treatment of black widow spider envenomation with antivenin latrodectus mactans: a case series. Perm J. 2011; 15:76-81. [PubMed 22058673]

12. Nordt SP, Clark RF, Lee A et al. Examination of adverse events following black widow antivenom use in California. Clin Toxicol (Phila). 2012; 50:70-3. [PubMed 22175789]

14. Murphy CM, Hong JJ, Beuhler MC. Anaphylaxis with Latrodectus antivenin resulting in cardiac arrest. J Med Toxicol. 2011; 7:317-21. [PubMed 22052335]

15. Handel CC, Izquierdo LA, Curet LB. Black widow spider (Latrodectus mactans) bite during pregnancy. West J Med. 1994; 160:261-2. [PubMed 8191768]

16. Sherman RP, Groll JM, Gonzalez DI et al. Black widow spider (Latrodectus mactans) envenomation in a term pregnancy. Curr Surg. 2000; 57:346-348. [PubMed 11024247]

18. Centers for Disease Control and Prevention. Recommendations regarding the use of vaccines that contain thimerosal as a preservative. MMWR Morb Mortal Wkly Rep. 1999; 48:996-8. [IDIS 435348] [PubMed 10577494]

19. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Environmental Health. Thimerosal in vaccines: an interim report to clinicians (RE9935). Pediatrics. 1999; 104:570-4. [PubMed 10469789]

20. Centers for Disease Control and Prevention. Thimerosal in vaccines: a joint statement of the American Academy of Pediatrics and the Public Health Service. MMWR. 1999; 48:563-5. [IDIS 429225] [PubMed 10418806]

21. Aberer W. Vaccination despite thimerosal sensitivity. Contact Dermatitis. 1991; 24:6-10. [PubMed 2044374]

22. Food and Drug Administration (FDA). Mercury in plasma-derived products. From FDA website. Accessed 2012 Mar 12.

23. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64.

25. Food and Drug Administration. Thimerosal in vaccines. From FDA website. Accessed 2008 Oct 27.

27. Food and Drug Administration. Thimerosal in vaccines. Frequently asked questions (FAQ). From FDA website. Accessed 2008 Oct 27.

28. Institute of Medicine. Immunization safety review: thimerosal-containing vaccines and neurodevelopmental disorder. Washington DC; National Academy Press; 2001. From IOM website. Accessed 2003 Jul 24.

29. Thompson WW, Price C, Goodson B et al. Early thimerosal exposure and neuropsychological outcomes at 7 to 10 years. N Engl J Med. 2007; 357:1281-92. [PubMed 17898097]

30. Pichichero ME, Gentile A, Giglio N et al. Mercury levels in newborns and infants after receipt of thimerosal-containing vaccines. Pediatrics. 2008; 121:e208-14. [PubMed 18245396]

31. Zheng W, Dreskin SC. Thimerosal in influenza vaccine: an immediate hypersensitivity reaction. Ann Allergy Asthma Immunol. 2007; 99:574-5. [PubMed 18219843]

32. Madsen KM, Lauritsen MB, Pedersen CB et al. Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Pediatrics. 2003; 112:604-6. [PubMed 12949291]

33. Lee-Wong M, Resnick D, Chong K. A generalized reaction to thimerosal from an influenza vaccine. Ann Allergy Asthma Immunol. 2005; 94:90-4. [PubMed 15702823]

34. Parker S, Todd J, Schwartz B et al. Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published original data. Pediatrics. 2005; 115:200. [PubMed 15630018]

35. Schechter R, Grether JK. Continuing increases in autism reported to California's developmental services system: mercury in retrograde. Arch Gen Psychiatry. 2008; 65:19-24. [PubMed 18180424]

36. Andrews N, Miller E, Grant A et al. Thimerosal exposure in infants and developmental disorders: a retrospective cohort study in the United kingdom does not support a causal association. Pediatrics. 2004; 114:584-91. [PubMed 15342825]

37. Verstraeten T, Davis RL, DeStefano F et al. Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. Pediatrics. 2003; 112:1039-48. [PubMed 14595043]

38. Hviid A, Stellfeld M, Wohlfahrt J et al. Association between thimerosal-containing vaccine and autism. JAMA. 2003; 290:1763-6. [PubMed 14519711]

39. Institute of Medicine. Immunization safety review: vaccines and autism. Washington DC; National Academy Press; 2004. From IOM website. Accessed 2008 Oct 28.

a. AHFS Drug Information 2012. McEvoy GK, ed. Antivenin (Latrodactus mactans) (Equine). Bethesda, MD: American Society of Health-System Pharmacists; 2012.

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