botulism antitoxin, heptavalent

General

Pronunciation:
bot–yoo-lizm an-ti-toks-in hep-ta-vay-lent


Ther. Class.

antidotes

Pharm. Class.

immune globulins

Indications

Symptomatic botulism after documented/suspected exposure to botulism neurotoxins A, B, C, D, E, F or G.

Action

Contains antibody fragments prepared from immunized horses. Provides passive immunization by binding the neurotoxins, bound complex is then cleared from circulation.

Therapeutic Effect(s):

Decreased duration/sequelae of neurotoxin poisoning (muscle paralysis) in botulism.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Neurotoxin/antitoxin complex cleared by organs involved in immune processing.

Half-life: Serotype A antitoxin: 8.6 hr,  serotype B antitoxin: 34.3 hr,  serotype C antitoxin: 29.6 hr,  serotype D antitoxin: 7.5 hr,  serotype E antitoxin: 7.7 hr,  serotype F antitoxin: 14.1 hr,  serotype G antitoxin: 11.7 hr.

TIME/ACTION PROFILE (preservation of muscle function)

ROUTEONSETPEAKDURATION
IVunknownunknownup to 28 days

Contraindication/Precautions

Contraindicated in:

  • None.

Use Cautiously in:

  • Patients at risk of acute hypersensitivity reactions, including history of hypersensitivity to horses, equine products, asthma or hay fever (consider skin sensitivity testing)
  • OB:  Use during pregnancy only if potential maternal benefits justify potential fetal risks;
  • Lactation: Use while breastfeeding only if potential maternal benefits justify potential risks to infant.

Adverse Reactions/Side Effects

CV: edema, vasovagal reaction

Derm: pruritus, urticaria, rash

GI: nausea

MS: arthralgia, myalgia

Neuro: headache, fatigue

Misc: chills, delayed allergic reactions (including serum sickness), fever, HYPERSENSITIVITY REACTIONS (including anaphylaxis), infusion reactions, transmission of infectious agents (equine plasma source)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IV (Adults): One vial.

IV (Children  ≥1 and >55 kg): 100% of adult dose

IV (Children  ≥1 and 50–54 kg): 80% of adult dose

IV (Children  ≥1 and 45–49 kg): 75% of adult dose

IV (Children  ≥1 and 40–44 kg): 70% of adult dose

IV (Children  ≥1 and 35–39 kg): 65% of adult dose

IV (Children  ≥1 and 30–34 kg): 60% of adult dose

IV (Children  ≥1 and 25–29 kg): 50% of adult dose

IV (Children  ≥1 and 20–24 kg): 40% of adult dose

IV (Children  ≥1 and 15–19 kg): 30% of adult dose

IV (Children  ≥1 and 10–14 kg): 20% of adult dose

IV (Infants <1 yr): 10% of adult dose.

Availability

Solution for injection (contains maltose): serotype A antitoxin 4,500 units, serotype B antitoxin 3,300 units, serotype C antitoxin 3,000 units, serotype D antitoxin 600 units, serotype E antitoxin 5,100 units, serotype F antitoxin 3,000 units, and serotype G antitoxin 600 units/vial

Assessment

  • Assess severity of signs/symptoms of botulism (double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, muscle weakness that spreads through body, difficulty breathing) during therapy. May occur as early as 3 hr or as late as a few days. May take weeks or months to resolve.
  • Monitor vital signs during infusion. If tolerated, infusion rate can be ↑ incrementally up to max infusion rate, and continued for remainder of administration. ↓ infusion rate if discomfort or infusion-related adverse reactions occur.
  • Assess for infusion reactions (chills, fever, headaches, nausea, vomiting, arthralgia, myalgia, fatigue, vasovagal reactions).  If infusion reaction occurs, ↓ rate of infusion; if continues or worsens, discontinue infusion.
  • Monitor for signs/symptoms of allergic reaction (urticaria, pruritus, erythema, angioedema, bronchospasm, wheezing, cough, stridor, laryngeal edema, hypotension, tachycardia) during and following infusion.  If reaction occurs,  immediately discontinue infusion and administer emergency care (epinephrine) as indicated.

Lab Test Considerations:

Maltose in infusion may interfere with glucose monitoring based on glucose dehydrogenase pyrroloquinoline-quinone method leading to falsely ↑ blood glucose and excess insulin administered. Use only test systems that are glucose specific.

Implementation

  • Administer in a facility with medication, personnel, and equipment to manage anaphylaxis.
  • Skin Test: For patients at risk of acute hypersensitivity reactions, consider skin sensitivity testing. Administer 0.02 mL of 1:1,000 saline-diluted botulism antitoxin heptavalent intradermally on palmar surface of forearm. If test is negative, repeat test using 1:100 dilution. Perform concurrent positive (histamine) and negative (saline) control tests. A positive test is a wheal with surrounding erythema >3 mL larger than negative control test; read at 15–20 min. Histamine control must be positive for valid interpretation.

IV Administration

  • Intermittent Infusion:  Bring vial to room temperature; thaw by placing in warm water bath for 1 hr. Dilution:  Dilute 1:10 in 0.9% NaCl by adding solution from vial to appropriate amount of saline in an IV bag. Do not use any other diluents. As fill volume per vial varies by lot number (10–26 mL per vial), 90–235 mL of 0.9% NaCl will be needed. Withdraw entire contents of vial to obtain total volume in vial. If a partial vial is required (for pediatric dosing), withdraw entire contents of vial to ensure accurate dose calculation. Do not shake. Do not use solutions that are turbid, cloudy, or contain particles. Discard unused portion. Rate: Infuse slowly. Use an IV line with constant infusion pump. Use of an in-line filter is optional. Infuse at lowest rate possible for patients with risk for hypersensitivity.  For adults,  begin infusion at 0.5 mL/min; may double rate every 30 min as tolerated to a max of 2 mL/min.  For children 1–17 yr,  begin infusion at 0.01 mL/kg/min; do not exceed adult rate. May ↑ by 0.01 mL/kg/min every 30 min, if tolerated, to a max of 0.03 mL/kg/min. Do not exceed adult rate.  For infants <1 yr,  begin infusion at 0.01 mL/kg/min; may ↑ by 0.01 mL/kg/min every 30 min if tolerated up to a max of 0.03 mL/kg/min.

Patient/Family Teaching

  • Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy.
  • Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
  • Advise patient to report signs/symptoms of delayed allergic reactions (serum sickness, fever, urticarial or maculopapular rash, myalgia, arthralgia, lymphadenopathy) to health care provider promptly. Usually occurs 10–21 days after infusion, but may occur sooner.
  • Advise patient that despite screening of horses, botulism antitoxin heptavalent is prepared from equine plasma and may contain infectious agents such as viruses that can cause disease.
  • Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Decreased duration/sequelae of neurotoxin poisoning (muscle paralysis) in botulism.