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Antivenin (Latrodectus mactans)

Pronunciation

(an tee VEN in lak tro DUK tus MAK tans)

Index Terms

  • Latrodectus mactans Antivenin
  • Latrodectus mactans Antivenom
  • Latrodectus Antivenin
  • Latrodectus Antivenom
  • Antivenin
  • Antivenin Black Widow Spider
  • Antivenom
  • Antivenom Black Widow Spider
  • Black Widow Spider Species Antivenin
  • Black Widow Spider Species Antivenom

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Injection:

Generic: 6000 Antivenin units

Pharmacologic Category

  • Antivenin

Pharmacology

Neutralizes the venom of Latrodectus mactans (black widow spiders), but may also be effective following envenomation by other Latrodectus species (including L. bishopi, L. geometricus, L. hesperus, and L. variolus) (Clark, 2001; Isbister, 2003).

Onset of Action

Within 30 minutes; symptoms of envenomation usually subside after 1-3 hours

Use: Labeled Indications

Envenomation: Treatment of patients with symptoms (eg, cramping, intractable pain, hypertension that are unresponsive to other therapies [eg, benzodiazepines, opioids]) due to Latrodectus mactans (black widow spider) envenomation. The morbidity associated with Latrodectus envenomation is high, but mortality is low; therefore, the antivenin should not be used unless necessary. Clinical trials are being conducted on a purified F(ab)2 antivenom that may be as effective and with a reduced likelihood of adverse effects.

Off Label Uses

Envenomation: Treatment of symptoms (eg, cramping, intractable pain, hypertension) due to Latrodectus spp

Based on experimental studies and clinical observation, latrodectism due to other Latrodectus species found in North America (eg, L. bishopi, L. geometricus, L. hesperus, L. variolus) may be treated with antivenin intended for use in patients envenomed by Latrodectus mactans [Clark 2001], [Isbister 2003]. Additional data may be necessary to further define the role of antivenin ( Latrodectus mactans ) in the treatment of symptoms due to other Latrodectus spp.

Dosing: Adult

The initial dose of antivenin should be administered as soon as possible for prompt relief of symptoms. Delayed antivenin administration may still be effective in treating patients with prolonged or refractory symptoms resulting from black widow spider bites (case report of antivenin administration up to 90 hours after bite; O’Malley, 1999). However, delayed administration may decrease effectiveness (Edberg, 2009).

Sensitivity testing: Skin testing may identify allergic individuals, but the lack of an initial reaction does not eliminate the possibility of a hypersensitivity reaction; therefore, always be prepared to treat an unanticipated hypersensitivity reaction. Intradermal skin test or conjunctival test may be performed prior to antivenin administration:

Skin test: Intradermal: Up to 0.02 mL of a 1:10 dilution of normal horse serum in NS; evaluate after 10 minutes against a control test (intradermal injection of NS). Note: A positive reaction is an urticarial wheal surrounded by a zone of erythema.

Conjunctival test: Ophthalmic: Instill 1 drop of a 1:10 dilution of normal horse serum into the conjunctival sac

Note: Itching of the eye and/or reddening of conjunctiva indicates a positive reaction, usually occurring within 10 minutes.

Desensitization: Note: In separate vials or syringes, prepare 1:10 and 1:100 dilutions of antivenin in NS.

SubQ: Inject 0.1 mL, 0.2 mL, and 0.5 mL of the 1:100 dilution at 15- to 30- minute intervals. During this procedure, proceed with the next dose only if a reaction has NOT occurred following the previous dose. Repeat procedure using the 1:10 dilution and then undiluted antivenin. If no reaction has occurred following administration of 0.5 mL of undiluted antivenin, continue the dose at 15-minute intervals until the entire dose has been administered.

If a reaction occurs, apply a tourniquet proximal to the injection site and administer epinephrine (1 mg/mL) SubQ or IV proximal to the tourniquet or into another extremity. Wait at least 30 minutes; then administer another antivenin injection at the previous dilution which did not evoke a reaction.

Envenomation due to Latrodectus mactans (black widow spider); envenomation due to other Latrodectus spp (off-label use) (Clark 2001; Isbister 2003): If a positive reaction to a skin or conjunctival test occurs and antivenin therapy is necessary, pretreat the patient with intravenous diphenhydramine and an H2-blocker while having a syringe of epinephrine (1 mg/mL) at the bedside: IM, IV: One vial (2.5 mL); a second dose may be needed in some cases; more than 1-2 vials are rarely required

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

The initial dose of antivenin should be administered as soon as possible for prompt relief of symptoms. Delayed antivenin administration may still be effective in treating patients with prolonged or refractory symptoms resulting from black widow spider bites (case report of antivenin administration up to 90 hours after bite; O’Malley 1999). However, delayed administration may decrease effectiveness (Edberg 2009).

Sensitivity testing: Intradermal skin test or conjunctival test may be performed prior to antivenin administration:

Skin test: Intradermal: Refer to adult dosing.

Conjunctival test: Ophthalmic: Instill 1 drop of a 1:100 dilution of normal horse serum into the conjunctival sac

Note: Itching of the eye and/or reddening of conjunctiva indicates a positive reaction, usually occurring within 10 minutes.

Desensitization: Refer to adult dosing.

Envenomation due to Latrodectus mactans (black widow spider); envenomation due to other Latrodectus spp (off-label use) (Clark 2001; Isbister 2003): If a positive reaction to a skin or conjunctival test occurs and antivenin therapy is necessary, pretreat the patient with intravenous diphenhydramine and an H2-blocker while having a syringe of epinephrine (1 mg/mL) at the bedside:

Children <12 years: IV: One vial (2.5 mL); a second dose may be needed in some cases; more than 1-2 vials are rarely required

Children ≥12 years: IM, IV: One vial (2.5 mL); a second dose may be needed in some cases; more than 1-2 vials are rarely required

Dosing: Renal Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling.

Reconstitution

Reconstitute antivenin powder with 2.5 mL of SWFI; do not mix antivenin powder with the vial of horse serum which is supplied for sensitivity testing. With needle still in rubber stopper, shake vial to dissolve. Prior to IV infusion, dilute further in 10 to 50 mL NS. When reconstituted, solution can range from a light straw to a dark tea color.

Administration

Antivenin:

IM: Administer antivenin in the anterolateral thigh; apply a tourniquet proximal to the injection site if an adverse systemic reaction occurs.

IV: Administer antivenin over 15 to 30 minutes (Clark, 2001); IV administration is preferred in severe cases, with shock, or in children <12 years of age. There appears to be no clinical difference in efficacy between the IM and IV route of administration (Isbister 2008).

Horse serum for sensitivity testing:

Intradermal: Inject the horse serum test solution into (not under) the skin; evaluate after 10 minutes against a control test (intradermal injection of NS).

Ophthalmic: Instill the horse serum test solution into the conjunctival sac; a positive reaction, if present, will generally occur within 10 minutes

Antivenin for desensitization: SubQ: Administer the antivenin via SubQ injection. Allow 15 to 30 minutes between injections; proceed with the next dose only if a reaction has NOT occurred following the previous dose. If a reaction occurs, apply a tourniquet proximal to the injection site and administer epinephrine (1 mg/mL) SubQ or IV proximal to the tourniquet or into another extremity. Wait at least 30 minutes prior to continuing the desensitization procedure. If no reaction occurs after administration of 0.5 mL of antivenin (undiluted), then may consider administering dose at 15 minute intervals.

Storage

Refrigerate at 2°C to 8°C (36°F to 46°F). Do not freeze.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Frequency not defined.

Dermatologic: Skin rash (rare; associated with hypersensitivity reaction)

Hypersensitivity: Anaphylaxis, hypersensitivity reaction, serum sickness

Neuromuscular & skeletal: Muscle cramps

Warnings/Precautions

Concerns related to adverse effects:

• Allergic reactions: May be less frequent than described in initial studies (Clark, 2001; Offerman, 2011). One retrospective study reviewed 163 cases of black widow spider envenomation; 58 patients received antivenin therapy and only 1 case of anaphylaxis occurred (Clark, 1992). The risk of reaction appears to be greatest with bolus administration of undiluted antivenin (Clark, 2001).

• Delayed serum sickness: Delayed serum sickness, albeit uncommon, may occur 1 to 2 weeks following administration, especially when large doses are used (Clark, 2001).

• Horse serum hypersensitivity: Carefully review allergies and history of exposure to products containing horse serum. History of atopic sensitivity to horses may increase the risk of immediate sensitivity reactions. Use with caution in patients with asthma, hay fever, or urticaria; fatal anaphylaxis has been reported in patients with a history of asthma. All patients require close monitoring in a setting where resuscitation can be performed.

Special populations:

• Elderly patients: Due to an increased risk for complications of envenomation, the administration of antivenin may be the preferred initial therapy in patients >60 years of age.

Dosage form specific issues:

• Thimerosal: Some products may contain thimerosal.

Other warnings/precautions:

• Desensitization: A desensitization protocol is available if sensitivity tests are mildly or questionably positive to reduce risk of immediate severe hypersensitivity reaction. According to the manufacturer, desensitization should be performed when antivenin administration would be lifesaving; however, the risk of anaphylaxis should be weighed against the risks associated with delayed antivenin administration (Rojnuckarin, 2009).

• Skin/conjunctival test: A skin or conjunctival test may be performed prior to use; however, the utility of skin and conjunctival tests to accurately identify patients at risk of early (anaphylactic) or late (serum sickness) hypersensitivity reactions to horse-derived antivenins has been questioned (WHO, 2005). Normal horse serum (1:10 dilution) is included for sensitivity testing. The absence of a skin or conjunctival hypersensitivity reaction does not exclude the possibility of anaphylaxis or hypersensitivity following antivenin administration. The false-negative rate for skin testing is 10% with similar agents. Conversely, hypersensitivity is not an absolute contraindication in a significantly envenomated patient.

Monitoring Parameters

Vital signs; hypersensitivity reactions; serum sickness reaction (for 2 to 3 weeks following administration); worsening of symptoms due to envenomation

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Use during pregnancy (second and third trimester) has been described in case reports; all patients delivered healthy infants (Handel, 1994; Russell, 1979; Sherman, 2000). In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003). Treatment of a pregnant patient with antivenom should be considered early in the course of an envenomation and in patients experiencing local, regional, or systemic effects refractory to opioids and/or benzodiazepines (Brown, 2013).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience muscle cramps (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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