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 SubQ, IV, or IM (AAAAI [Lieberman 2015]) proximal to the tourniquet or into another extremity. Wait at least 30 minutes; then administer another antivenin injection at the previous dilution that 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 at the bedside: IM, IV: One vial (2.5 mL); a second dose may be needed in some cases; more than 1 to 2 vials are rarely required
There are no dosage adjustments provided in manufacturer’s labeling.
There are no dosage adjustments provided in manufacturer’s labeling.
(For additional information see "Black widow spider (Latrodectus mactans) antivenom: Pediatric drug information")
Note: 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; a case report describes use of antivenin administration up to 90 hours after bite (O'Malley 1999); however, delayed administration may decrease effectiveness (Edberg 2009).
Sensitivity testing: Infants, Children, and Adolescents: 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 (provided in kit) in NS; evaluate after 10 minutes against a control test (intradermal injection of 0.02 mL NS). Note: Positive reaction consists of an urticarial wheal surrounded by a zone of erythema.
Conjunctival test: Instill 1 drop of 1:100 dilution of normal horse serum into conjunctival sac; a positive reaction is indicated by itching of the eye and/or reddening of conjunctiva, usually occurring within 10 minutes.
Desensitization: Infants, Children, and Adolescents: In separate vials or syringes, prepare 1:10 and 1:100 dilutions of antivenin in NS:
SUBQ: Inject 0.1 mL, followed by 0.2 mL and 0.5 mL of a 1:100 dilution at 15- to 30-minute intervals. During desensitization procedure, proceed with the next dose only if a reaction has not occurred following the previous dose. Repeat procedure with a 1:10 dilution of antivenin; and then with 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 IM, SubQ, or IV proximal to the tourniquet or into another extremity (AAAAI [Lieberman 2015]). Wait at least 30 minutes, then administer another antivenin injection at the previous dilution which did not evoke a reaction.
Latrodectus mactans (black widow spider) envenomation; other Latrodectus spp envenomation: Limited data in infants (Monte 2011; Nordt 2012; Goel 2014): Limited data available for some types of envenomations:
Note: Controlled clinical studies for effectiveness and safety in pediatric patients have not been conducted. Antivenin has reportedly been used successfully in a 2-year-old pediatric patient who experienced black widow spider envenomation (Goel 2014).
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 at the bedside:
Infants and Children <12 years: IM; IV (preferred): One vial (2.5 mL); a second dose may be needed in some cases; more than 1 to 2 vials are rarely required.
Children ≥12 years and Adolescents: IM, IV: One vial (2.5 mL); a second dose may be needed in some cases; more than 1 to 2 vials are rarely required.
There are no dosage adjustments provided in manufacturer’s labeling.
There are no dosage adjustments provided in manufacturer’s labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Injection:
Generic: 6000 Antivenin units
Yes
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. 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 SubQ, IV, or IM (AAAAI [Lieberman 2015]) 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.
Antivenin for treatment:
IM: Administer antivenin into the anterolateral thigh. Apply tourniquet proximal to the injection site if an adverse reaction occurs.
IV: Infuse antivenin over 15 to 30 minutes (Clark 2001). IV administration 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). If an immediate hypersensitivity reaction occurs, immediately interrupt antivenin infusion and provide appropriate supportive therapy. If administration of antivenin can be resumed after control of the reaction, reinitiate at a slower infusion rate.
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 (appropriate dilution: Pediatric: 1:100; Adult: 1:10) into the conjunctival sac; a positive reaction, if present, will generally occur within 10 minutes.
Antivenin for desensitization: SubQ: Administer the antivenin solution (See Dosing: Pediatric for appropriate concentration) 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 IM, SubQ, or IV proximal to the tourniquet or into another extremity (AAAAI [Lieberman 2015]). Wait at least 30 minutes prior to continuing the desensitization procedure. If no reaction occurred after administration of 0.5 mL of antivenin (undiluted), then may consider administering dose at 15 minute intervals.
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.
Envenomation: Treatment of symptoms (eg, cramping, intractable pain, hypertension) due to Latrodectus spp
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Dermatologic: Skin rash (rare; associated with hypersensitivity reaction)
Hypersensitivity: Anaphylaxis, hypersensitivity reaction, serum sickness
Neuromuscular & skeletal: Muscle cramps
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. Sensitivity testing for antivenom reactions is frequently unreliable with false-positive and false-negative results (Klaewsongkram 2009).
None known.
There are no known significant interactions.
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).
It is not known if antivenin (Latrodectus mactans) is excreted in breast milk. The manufacturer recommends that caution be exercised when administering antivenin (Latrodectus mactans) to nursing women.
Vital signs; hypersensitivity reactions; serum sickness reaction (for 2 to 3 weeks following administration); worsening of symptoms due to envenomation
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 to 3 hours.
