Dosage / administration:

• Antivenom starting dose is 1 vial reconstituted in 2.5 mL of sterile water and then diluted in 50 mL of 0.9% normal saline infused intravenously (IV) over 15 minutes to 1 hour.
• Intramuscular (IM) administration is not recommended due to decreased efficacy and inability to stop infusion if adverse effects occur.
• Dosage is the same for adults and children.
• Rarely more than 1 vial is necessary.
• Treatment is usually given within the first 48 hours; however, 1 case report showed effectiveness when given 90 hours after envenomation.

Black widow antivenom is a crude horse serum immunoglobulin G (IgG) antibody that carries a risk of hypersensitivity reactions.

• It is reasonable to pretreat with antihistamines and corticosteroids and have epinephrine available.
• Skin testing before administration is not currently recommended because absence of a reaction does not exclude the occurrence of hypersensitivity reactions.

Consultation with medical toxicologists or regional poison control centers (800-222-1222) is highly recommended.

Indications:

• Black widow spider venom contains α-latrotoxin that causes exocytosis of neurotransmitters including norepinephrine and acetylcholine.
• The large release of neurotransmitters is responsible for symptoms that may include pain at bite site, severe muscle pain and spasms, abdominal pain or rigidity, diaphoresis, hypertension, and tachycardia.
• Latrodectism is the clinical syndrome that results from a black widow spider envenomation.
• First-line treatment includes analgesics, opioids, and benzodiazepines. Resources for opioid prescribing guidelines, as well as nonopioid alternatives, can be found here.
• An IgG crude hyperimmune horse serum antibody is available in the United States and can be given to patients who have intractable pain, older adults, and children, and to those who develop rare complications of envenomation including:
  • Compartment syndrome
  • Myocarditis
  • Priapism
  • Pregnancy with symptoms mimicking spontaneous abortion or preeclampsia
• The IgG antivenom carries a risk of anaphylaxis and serum sickness.
  • Pretreatment with antihistamines and corticosteroids is recommended.
  • Have epinephrine and airway supplies available at bedside.
• Controversy exists on whether to administer antivenom given the hypersensitivity risks and extremely low mortality risk due to envenomation.
• Symptom resolution after antivenom administration ranges from 1-3 hours.
• A new FAB2 fragment is in phase 3 clinical trials but is not currently commercially available in the United States.

Contraindications: Relative contraindications to the antivenom include:

• History of anaphylaxis to horse serum
• Multiple allergies
• History of asthma

The total volume of protein is extremely small; however, faster rates of infusion increase the likelihood of histamine or IgE-mediated reactions.

There are a few case reports of death after antivenom administration:

• A patient with a history of asthma and multiple allergies to medication was administered an undiluted bolus of antivenom in a short period of time. Resuscitation efforts were also complicated by pneumothorax.
• Another patient with a history of asthma developed anaphylaxis after antivenom administration. The patient was stabilized with standard treatment and intubation. The patient went into cardiac arrest on hospital day 2 after developing a fever and low oxygen saturations.

Pregnancy:

• Studies have found that pregnant women are more likely than nonpregnant women to receive antivenom.
• No maternal or fetal deaths have been reported in reviews of the National Poison Control Center data from 2001-2018.

Monitoring:

• Laboratory studies are not helpful in clinical management or predicting outcomes.
• Patients can be discharged from the emergency department after antivenom treatment with symptom resolution and after an observation period monitoring for signs of adverse reactions.
• Symptoms are unlikely to recur after treatment with antivenom.
• Educate the patient on adverse effects of antivenom including allergic reaction, anaphylaxis, and serum sickness.
• Patients can self-monitor for symptoms of serum sickness (eg, fever, rash, joint pain) at home and follow-up with a primary care doctor if symptoms arise.

Adverse effects: Allergic reactions, ranging from mild to anaphylaxis:

• Mechanism:
  • Type 1 hypersensitivity reaction
  • Immediate IgE-mediated reaction
  • Anaphylaxis is defined as more than one system involvement
• Symptoms:
  • Cutaneous – hives, pruritus, angioedema
  • Respiratory – wheezes, throat tightness, stridor
  • Gastrointestinal – nausea, vomiting
  • Cardiovascular – chest pain, hypotension, palpitations
• Treatment:
  • Epinephrine (1 mg/mL) concentration – 0.3-0.5 mg IM repeat every 5-10 minutes
  • Methylprednisolone 125 mg IV
  • Diphenhydramine 25-50 mg IV
  • Bronchodilators
    • Albuterol 2.5-5 mg nebulized
    • Ipratropium 500 µg nebulized
  • IV fluids 500 ml-1L normal saline bolus
  • H2 antagonist famotidine 20 mg IV

Serum sickness:

• Mechanism
  • Type III hypersensitivity reaction
  • Delayed immune-mediated reaction
  • Seen 7-21 days after administration of antivenom
• Symptoms
  • Characterized by skin rashes, joint stiffness, and fever
  • Thought to be low incidence because of the small volume of antivenom given in comparison to pit viper envenomation
• Treatment
  • Antihistamines and NSAIDs for mild symptoms
  • In patients with high fevers or extensive skin lesions, prednisone 1 mg/kg/day for 1-2 weeks

Toxicity: A retrospective review of 163 patients presenting to an urban toxicology referral center between 1982-1990 found that:

• 58 patients received antivenom with resolution of symptoms 31 +/- 26.7 minutes (range from immediate to 120 minutes).
• No relapse in symptoms.
• 50 patients received 1 vial with resolution of symptoms and 7 patients required an additional vial.
• Duration of symptoms was 9 hours in patients receiving antivenom and 22 hours in patients not receiving antivenom.
• 4 patients developed urticarial reactions during infusion that warranted overnight observation.
• 1 patient died from fatal respiratory arrest after antivenom (refractory to epinephrine and resuscitative measures).
• Only 9 of 58 patients were able to be contacted for follow-up questioning regarding serum sickness; none reported symptoms.

An observational case series from the California Poison Control System database between 1999-2009 found that:

• 96 patients received antivenom.
• No patient required more than 1 vial of antivenom.
• 4% developed adverse effects due to the antivenom.
• 1 patient developed urticaria mid-infusion, and infusion was stopped without further complications.
• 3 patients developed mild symptoms (myalgias / fatigue, flushing, paresthesias) after the infusion.
• No deaths, respiratory compromise, or severe allergic reactions were seen.
• No follow-up was undertaken to assess for serum sickness.

Mechanism of action:

• Antivenom works by blocking the ability of venom to bind to presynaptic membranes.
• The Fc portion of the IgG antibody is thought to be responsible for immune-mediated reactions.
• Antivenom is filtered and excreted by the glomerulus.
• No published pharmacokinetic or pharmacodynamic information is available.