AHFS Class:

• Antitoxins and Immune Globulins 80:04

Generic Name(s):

• Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) - (Equine)

Botulism antitoxin (equine) is a sterile solution of equine immunoglobulin F(ab')₂ and F(ab')₂-related fragments capable of neutralizing botulinum neurotoxins.1 Botulism antitoxin is available in the US as botulism antitoxin heptavalent (A, B, C, D, E, F, G) (equine), which contains antibody to 7 botulinum toxin types (A-G).1,13 Other botulism antitoxin (equine) preparations containing antibody to fewer botulinum neurotoxins (e.g., bivalent botulinum antitoxin AB, monovalent botulinum antitoxin E) were previously available in the US and may be available elsewhere.13

Treatment of Botulism

Botulism antitoxin (equine) heptavalent is used for the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A, B, C, D, E, F, or G.1,9,12,70,105 Botulism antitoxin (equine) is designated an orphan drug by the US Food and Drug Administration (FDA) for treatment of botulism.2

Botulism is a potentially fatal neuroparalytic illness caused by neurotoxin produced by Clostridium botulinum , a gram-positive, spore-forming, obligate anaerobe that is found naturally in soil.5,8,9,10,12,70,105 Certain strains of C. argentinense , C. baratii , and C. butyricum also can produce neurotoxin and cause botulism.9,10,12,70,105 C. botulinum spores are ubiquitous in the environment in soil and water sediments and can germinate into the vegetative bacteria that produce toxin.9,12,70,105 Botulism occurs when botulinum toxin is absorbed into the circulation from a mucosal surface (intestines, lung) or wound;9,12,70,105 botulism is not transmitted person to person.5,8,70,105

There are 7 known serotypes of botulinum toxin (A, B, C, D, E, F, G) and all cause similar disease;5,8,9,10,12,70,105 naturally occurring human botulism usually involves serotypes A, B, E, and F.5,8,9,10,12,70,105 Foodborne botulism occurs following ingestion of food contaminated with botulinum toxin (e.g., improperly canned food);5,8,9,10,105 symptoms usually begin 12-48 hours (range: 2 hours to 10 days) after ingestion.5,10,70,105 Wound botulism occurs when wounds are contaminated with C. botulinum spores from the environment and these spores then germinate and produce botulinum toxin;5,8,9,10,105 the time between wound contamination and onset of symptoms usually is 4-14 days.105 Infant botulism occurs when infants younger than 1 year of age ingest C. botulinum spores that then germinate, colonize the GI tract, and produce botulinum toxin;5,8,9,10,105 the time between exposure to spores and onset of symptoms is estimated to be 3-30 days.105 Intestinal botulism (child or adult) occurs following intestinal colonization with C. botulinum and subsequent production of botulinum toxin.5,8,10 Botulism also could potentially occur from iatrogenic overdose or misinjection of commercially available botulinum toxin used therapeutically (e.g., abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, rimabotulinumtoxinB) or from inhalation of aerosolized botulinum toxin (e.g., in the context of biologic warfare or bioterrorism).8,9,10,12,70,105 Following an inhalation exposure, symptoms of botulism may be evident within 12-72 hours.12,70

Botulism is a neuroparalytic syndrome characterized by an acute afebrile, symmetric, descending, flaccid paralysis.5,8,9,12,70,105 Initial signs and symptoms of botulism include blurred vision, diplopia, ptosis, dysarthria, dysphagia, dysphonia, and dry mouth;5,9,10,12,70,105 symptoms may progress to paralysis of respiratory and peripheral muscles, which requires ventilator support.5,9,12,70,105 Paralysis is caused by blockade of neurotransmitter release at the voluntary motor and autonomic neuromuscular junctions.9,12,70,105

Efficacy of botulism antitoxin (equine) heptavalent for the treatment of symptomatic botulism is based on data from 2 adequate and well-controlled efficacy studies in animals that demonstrated a survival benefit.1,3 Since lethal challenges with botulinum toxin are unethical in humans, it is not possible to conduct controlled human clinical trials of botulism antitoxin (equine) heptavalent.1,3 In a randomized, blinded, placebo-controlled study in guinea pigs that received IM injections of 1 of 7 botulinum toxin serotypes (A, B, C, D, E, F, or G) and then developed clinical signs of botulism (right hind limb weakness, salivation, lacrimation, weak limbs, noticeable changes in breathing rate or pattern), the survival rate was 0-50% in those treated with placebo versus 97-100% in those treated with a single dose of botulism antitoxin (equine) heptavalent.1,3 In a placebo-controlled study in Rhesus macaques that received IV injections of botulinum toxin serotype A and then developed clinical signs of botulism (ptosis, muscular weakness, respiratory distress), the survival rate was 0% in those treated with placebo versus 47% in those treated with a single dose of botulism antitoxin (equine) heptavalent.1,3

Information regarding safety and efficacy of botulism antitoxin (equine) heptavalent in humans is available from a US Centers for Disease Control and Prevention (CDC) expanded access, open-label, observational study in patients who received botulism antitoxin (equine) heptavalent for treatment of suspected or confirmed botulism.1,3,11 Data from 148 patients indicate that the median time from onset of symptoms to treatment with botulism antitoxin (equine) heptavalent was 3.6 days (range 0.25-38 days) and most patients (93%) received a single dose of the antitoxin.1,11 Botulism antitoxin (equine) heptavalent treatment given within 2 days after onset of symptoms was associated with shorter length of hospitalization (12 versus 26 days), shorter duration of intensive care stay (9 versus 16 days), and shorter duration of mechanical ventilation (12 versus 23 days) compared to antitoxin treatment given more than 2 days after onset of symptoms.1,3

General

Botulism antitoxin (equine) heptavalent should be administered as soon as possible after a clinical diagnosis of botulism (ideally within 24 hours after onset of symptoms),5,8,9,12,105 and is used in conjunction with intensive supportive care (e.g., respiratory, fluid, and nutritional support).5,8,9,12,70,105 Treatment of botulism should not be delayed while waiting for confirmatory diagnostic testing (e.g., mouse bioassay, toxin assay and/or culture of wound, tissue, feces, or suspect food).5,8,9,12,70,105 Although prompt administration of botulism antitoxin (equine) heptavalent can neutralize circulating botulinum toxin thereby preventing additional nerve damage and disease progression,9,8,12,70,105 the antitoxin cannot reverse existing paralysis.1,8,9,12,70,105

Intradermal Sensitivity Testing

Because of the possibility of acute hypersensitivity reactions (e.g., anaphylaxis), skin sensitivity testing should be considered prior to administration of botulism antitoxin (equine) heptavalent in patients at risk for severe hypersensitivity reactions, including individuals with a history of hypersensitivity to horses or equine blood products, other allergies (e.g., hay fever), or asthma.1 (See Sensitivity Reactions under Cautions: Warnings/Precautions.)

The skin sensitivity test consists of intradermal injection of 0.02 mL of a 1:1000 dilution of botulism antitoxin (equine) heptavalent (prepared by diluting the antitoxin in 0.9% sodium chloride injection) into the volar surface of the patient's forearm; this quantity should raise a small intradermal wheal.1 To facilitate interpretation of results, intradermal controls should be administered concurrently at different sites using 0.02 mL of histamine (positive control) and 0.02 mL of 0.9% sodium chloride injection (negative control).1 The test should be read 15-20 minutes after injection.1 A positive intradermal skin test reaction consists of an urticarial wheal surrounded by a zone of erythema at least 3 mm larger than the negative control test.1 If the initial intradermal skin test is negative, it should be repeated using 0.02 mL of a 1:100 dilution of the antitoxin.1 The histamine (positive) control must produce a positive skin test reaction for valid interpretation of the antitoxin intradermal sensitivity test.1

Restricted Distribution

Although botulism antitoxin (equine) heptavalent is approved by FDA for treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A, B, C, D, E, F, or G,1 the antitoxin is available in the US only from the US Centers for Disease Control and Prevention (CDC).13 The antitoxin is stored at CDC quarantine stations located in major airports throughout the US and can be delivered to any US location within hours.13 Botulism antitoxin (equine) heptavalent also is stored in the US Strategic National Stockpile for emergency preparedness and response.14

To obtain botulism antitoxin (equine) heptavalent, clinicians should contact their state health department's 24-hour telephone number.13 State health departments should contact the CDC Emergency Operation Center at 770-488-7100 to arrange a telephone consultation and, if indicated, release of the antitoxin.13 If a response cannot be obtained through the state health department, clinicians should contact the CDC Emergency Operation Center directly.105

Administration

Botulism antitoxin (equine) heptavalent is administered only by slow IV infusion.1

Botulism antitoxin (equine) heptavalent must be diluted in 0.9% sodium chloride prior to administration.1 (See Dilution under Dosage and Administration: Administration.) The diluted solution of antitoxin should be administered using a constant infusion pump;1 use of an inline filter is optional.1

Patients should be monitored closely for signs and symptoms of acute sensitivity or infusion reactions during and immediately after completion of the IV infusion.1 (See Sensitivity Reactions and see Infusion Reactions under Cautions: Warnings/Precautions.)

Botulism antitoxin (equine) heptavalent is provided in single-use vials and may arrive from CDC either frozen or thawed.13 If frozen, the antitoxin should be thawed by placing the vials in a refrigerator at 2-8°C for approximately 14 hours until the contents are thawed.1 More rapid thawing can be accomplished by placing the vials at room temperature for 1 hour, followed by immersion in a water bath at 37°C until thawed.1 The antitoxin should not be thawed in a microwave oven and should not be refrozen.1

Dilution

Prior to dilution, botulism antitoxin (equine) heptavalent should be thawed, if necessary, and brought to room temperature.1

Vials of botulism antitoxin (equine) heptavalent should not be shaken at any time since this may cause foaming.1

Botulism antitoxin (equine) heptavalent must be diluted 1:10 in 0.9% sodium chloride injection by withdrawing the entire contents of the vial and adding it to the appropriate amount of 0.9% sodium chloride in an IV bag.1 The appropriate amount of 0.9% sodium chloride injection varies from 90-200 mL since the antitoxin has a fill volume per vial that varies from approximately 10-22 mL depending on the lot number of the antitoxin.1 To ensure accurate calculation of pediatric dosage when a partial vial of the antitoxin is required, the entire contents of the vial should be withdrawn.1

The diluted antitoxin solution should be inspected visually for particulate matter and discoloration, and should not be used if it is turbid, cloudy, or contains particulates.1

Rate of Administration

The rate of IV infusion of botulism antitoxin (equine) heptavalent should be individualized based on patient age and tolerance.1

Patients should be monitored throughout the IV infusion.1 If tolerated, the infusion rate can be increased incrementally up to the maximum infusion rate and continued until the dose is completely administered.1 If the infusion is not tolerated and adverse reactions occur, the infusion rate should be decreased or the infusion discontinued if necessary.1

In infants younger than 1 year of age, the IV infusion should be initiated at a rate of 0.01 mL/kg per minute for the first 30 minutes;1 if tolerated, the infusion rate can then be increased by 0.01 mL/kg per minute every 30 minutes up to a maximum infusion rate of 0.03 mL/kg per minute.1

In children 1 through 16 years of age, the IV infusion should be initiated at a rate of 0.01 mL/kg per minute for the first 30 minutes;1 if tolerated, the infusion rate can then be increased by 0.01 mL/kg per minute every 30 minutes up to a maximum infusion rate of 0.03 mL/kg per minute.1 Infusion rates in these children should not exceed those recommended for adults.1

In adults, the IV infusion should be initiated at a rate of 0.5 mL per minute for the first 30 minutes; if tolerated, the infusion rate can then be doubled every 30 minutes up to a maximum infusion rate of 2 mL per minute.1

If botulism antitoxin (equine) heptavalent is used in patients at risk for hypersensitivity reactions (see Sensitivity Reactions under Cautions: Warnings/Precautions), the IV infusion should be initiated using the lowest rate achievable (i.e., less than 0.01 mL per minute) and the patient monitored closely.1

Dosage

For the treatment of symptomatic botulism following documented or suspected exposure to botulinum neurotoxin serotypes A, B, C, D, E, F, or G, botulism antitoxin (equine) heptavalent is given as a single dose.1

Each single-use vial of botulism antitoxin (equine) heptavalent (regardless of vial size or fill volume) contains at least 4500, 3300, 3000, 600, 5100, 3000, and 600 units of serotype A, B, C, D, E, F, and G antitoxin, respectively.1

Adult Dosage

The recommended dosage of botulism antitoxin (equine) heptavalent for treatment of botulism in adults 17 years of age or older is one single-use vial.1 The dose should be diluted as recommended and given as a single IV infusion using the age-appropriate infusion rate.1 (See Dosage and Administration: Administration.)

Pediatric Dosage

The recommended dosage of botulism antitoxin (equine) heptavalent for treatment of botulism in infants younger than 1 year of age is 10% of the recommended adult dosage, regardless of body weight.1 Therefore, children younger than 1 year of age should receive one-tenth of a vial of botulism antitoxin (equine) heptavalent diluted as recommended and administered as a single IV infusion using the age-appropriate infusion rate.1 (See Dosage and Administration: Administration.)

The recommended dosage of botulism antitoxin (equine) heptavalent for the treatment of botulism in children 1 through 16 years of age is 20-100% of the recommended adult dosage based on the Salisbury Rule, which takes into consideration weight differences between pediatric patients and adults.1 (See Table 1.) The dose should be diluted as recommended and given as a single IV infusion using the age-appropriate infusion rate.1 (See Dosage and Administration: Administration.)

Special Populations

There are no special population recommendations.1

Contraindications

The manufacturer states there are no contraindications.1

Warnings/Precautions

Sensitivity Reactions

Immediate Hypersensitivity or Anaphylaxis

Severe hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, may occur with botulism antitoxin (equine) heptavalent.1

Patients with a history of sensitivity to horses or equine blood products, other allergies (e.g., hay fever), or asthma are at increased risk for severe hypersensitivity reactions if they receive botulism antitoxin (equine) heptavalent.1 Skin sensitivity testing to ascertain the risk of allergic reactions should be considered prior to administration of the antitoxin in such individuals.1 (See Intradermal Sensitivity Testing under Dosage and Administration: General.)

Botulism antitoxin (equine) heptavalent should be administered in a setting with appropriate equipment, medication (e.g., epinephrine), and personnel trained in the management of hypersensitivity, anaphylaxis, and shock.1

Patients should be monitored closely for signs and symptoms of acute allergic reactions (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia) during and after IV infusion of botulism antitoxin (equine) heptavalent.1

If a hypersensitivity reaction occurs, the IV infusion should be immediately discontinued and appropriate emergency medical care initiated.1

If botulism antitoxin (equine) heptavalent is used in patients at risk for hypersensitivity reactions, the IV infusion should be initiated using the lowest infusion rate achievable (i.e., less than 0.01 mL per minute) and the patient closely monitored.1

Delayed Hypersensitivity or Serum Sickness Reactions

Delayed hypersensitivity or serum sickness reactions may occur with botulism antitoxin (equine) heptavalent.1 These reactions usually manifest as fever, urticarial or maculopapular rash, myalgia, arthralgia, and lymphadenopathy, and typically occur 10-21 days after IV infusion of the antitoxin.1

Patients should be monitored for signs and symptoms of delayed allergic reactions or serum sickness.1 If such reactions are suspected, appropriate medical care should be administered.1

Infusion Reactions

Infusion-related reactions, including chills, fever, difficulty breathing, headache, nausea, and vomiting, have been reported during or within 20-60 minutes after IV infusion of botulism antitoxin (equine) heptavalent.1 Arthralgia, myalgia, fatigue, and vasovagal reactions have also been reported.1

Patients should be monitored during and immediately after IV infusion of the antitoxin.1 If infusion-related reactions occur, the infusion rate should be reduced and symptomatic care administered.1 If infusion-related reactions worsen, the IV infusion should be discontinued and appropriate medical care administered.1

Interference with Blood Glucose Testing

Parenteral preparations containing maltose, including botulism antitoxin (equine) heptavalent, may cause falsely elevated results in blood glucose determinations that use glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ).1 Falsely elevated glucose determinations in patients receiving parenteral preparations containing maltose may lead to inappropriate administration of insulin resulting in life-threatening hypoglycemia or may mask true hypoglycemic states.1

Only glucose-specific test methods that are not affected by maltose should be used to measure blood glucose concentrations in patients receiving botulism antitoxin (equine) heptavalent.1 The product information for the blood glucose testing system (including glucose test strips) should be carefully reviewed to determine if the testing system is appropriate.1 If any uncertainty exists, the manufacturer of the glucose testing system should be contacted to determine if the system will provide accurate blood glucose determinations in a patient receiving a parenteral preparation that contains maltose.1

Risk of Transmissible Infectious Agents in Plasma-derived Preparations

Because botulism antitoxin (equine) heptavalent is prepared from pooled equine plasma, it may carry a risk of transmitting infectious agents, including viruses.1

Equine plasma pools used for preparation of botulism antitoxin (equine) heptavalent are screened for the presence of certain infectious agents and the manufacturing process includes procedures to inactivate and remove viruses.1 (See Description.) Although transmission of viruses has not been reported with use of botulism antitoxin (equine) heptavalent, the possibility still exists that transmission of viruses and other infectious agents could occur.1

Any suspected infections associated with administration of botulism antitoxin (equine) heptavalent should be reported to the manufacturer at 800-768-2304.1

Antibody Formation

As with all therapeutic proteins, there is potential for immunogenicity.1 In healthy individuals who were negative for anti-equine antibodies before receiving botulism antitoxin (equine) heptavalent, 11 of 39 (28%) developed antibodies against botulism antitoxin (equine).1,7 These were mainly IgG antibodies; IgE antibodies were not detected in these individuals.7

Specific Populations

Pregnancy

Category C.1 (See Users Guide.)

Lactation

It is not known whether botulism antitoxin (equine) heptavalent is distributed into milk.1 The antitoxin should be used with caution in nursing women.1

Pediatric Use

Botulism antitoxin (equine) heptavalent is labeled by FDA for use in pediatric patients.1 However, efficacy of botulism antitoxin (equine) heptavalent has not been established in pediatric patients, and only limited safety data are available regarding use of the antitoxin in pediatric patients.1

Although only limited data are available, the US Centers for Disease Control and Prevention (CDC) and other experts state that treatment of botulism in pediatric patients should be the same as that in adults.8,70 For treatment of infant botulism caused by botulinum toxin serotypes A or B, botulism immune globulin IV (BIG-IV) is available for use in those younger than 1 year of age.105 (See Botulism Immune Globulin IV 80:04.)

In the CDC expanded access observational study of botulism antitoxin (equine) heptavalent, 15 children ranging from 10 days to 17 years of age received the antitoxin.1 Pyrexia occurred in one child following IV infusion of the antitoxin; a serious adverse reaction consisting of hemodynamic instability, characterized by tachycardia, bradycardia, and asystole, occurred in another child during IV infusion of the antitoxin.1

Geriatric Use

Efficacy and safety of botulism antitoxin (equine) heptavalent have not been established in geriatric patients.1 In the CDC expanded access observational study of botulism antitoxin (equine) heptavalent, 36 patients were 65 years of age or older.1

Common Adverse Effects

Adverse effects reported in 5% or more of healthy individuals who received botulism antitoxin (equine) heptavalent include headache, nausea, pruritus, and urticaria.1 Adverse effects reported in 1% or more of patients who received the antitoxin in the CDC expanded access observational study were pyrexia, rash, chills, nausea, and edema.1

Formal drug interaction studies have not been performed with botulism antitoxin (equine) heptavalent.1

Description

Botulism antitoxin (equine) heptavalent contains purified F(ab')₂ and F(ab')₂-related immune globulin fragments prepared from equine plasma and has antitoxin activity against botulinum neurotoxins A, B, C, D, E, F, and G.1

Botulism antitoxin (equine) heptavalent is used to provide passive immunity to botulinum neurotoxins A, B, C, D, E, F, and G.1 Following IV administration, polyclonal antibodies, primarily F(ab')₂ and Fab, contained in botulism antitoxin (equine) heptavalent combine with and neutralize circulating (unbound) neurotoxins produced by Clostridium botulinum .1 This prevents the neurotoxins from interacting with ganglioside anchorage sites and protein receptors on cholinergic nerve endings and also prevents the neurotoxins from internalizing in cells.1 Botulism antitoxin (equine) heptavalent does not neutralize neurotoxin that is already fixed to tissues.1 After antibodies contained in botulism antitoxin (equine) heptavalent neutralize circulating botulinum neurotoxins, the botulinum antibody/antigen complexes are cleared from the circulation by organs involved in processing immune complexes.1 The exact amount of antitoxin needed to treat botulism intoxication is unknown.1

Following IV administration of a dose of botulism antitoxin (equine) heptavalent in healthy individuals 19-52 years of age, the half-life of each specific antitoxin differs.1,3 Antitoxin serotypes A, D, and E have the shortest half-lives (approximately 9, 8, and 8 hours, respectively).1 Antitoxin serotypes B, C, F, and G have half-lives of approximately 34, 30, 14, and 12 hours, respectively.1

Each antitoxin serotype contained in botulism antitoxin (equine) heptavalent is prepared individually from pooled plasma of horses immunized with a specific C. botulinum neurotoxin or toxoid (serotype A, B, C, D, E, F, or G), and the antitoxins are then blended to provide the final preparation.1 The manufacturing process for each antitoxin serotype includes cation-exchange chromatography to purify the immune globulin fraction, digestion with pepsin to produce F(ab')₂ and F(ab')₂-related immune globulin fragments, anion exchange chromatography to remove the pepsin as well as other impurities, and filtration.1 The manufacturing process also includes viral inactivation/removal steps (solvent/detergent treatment, virus filtration) to reduce the risk of transmission of known lipid-enveloped viruses (e.g., equine encephalitis, equine arteritis, West Nile virus, equine infectious anemia, equine herpes virus, rabies, equine influenza) and nonenveloped viruses (e.g., equine rhinovirus, equine adeno- and adeno-associated viruses, equine parvovirus).1 (See Risk of Transmissible Infectious Agents in Plasma-derived Preparations under Cautions: Warnings/Precautions.) Botulism antitoxin (equine) solution contains 10% maltose and 0.03% polysorbate.1 The antitoxin does not contain any preservative.1

Botulism antitoxin (equine) heptavalent is standardized by its ability to neutralize C. botulinum neurotoxin given intraperitoneally to mice (mouse IPLD₅₀ neutralizing units).1 Each single-use vial of botulism antitoxin (equine) heptavalent (regardless of vial size or fill volume) contains at least 4500, 3300, 3000, 600, 5100, 3000, and 600 units of serotype A, B, C, D, E, F, and G antitoxin, respectively.1 Each unit of the respective antitoxin will neutralize at least 10,000 mouse IPLD₅₀ units of botulinum neurotoxin serotypes A, B, C, D, F, and G and 1,000 mouse IPLD₅₀ of botulinum neurotoxin serotype E.1

Advice to Patients

Advise patients that botulism antitoxin (equine) heptavalent is prepared from horse plasma and that individuals with allergy to horses or equine blood products, other allergies (e.g., hay fever), or asthma may be at increased risk of hypersensitivity reactions and should receive the antitoxin only if benefits outweigh risks.1 Importance of informing clinician of such allergies.1

Advise patients that botulism antitoxin (equine) heptavalent may cause immediate sensitivity reactions.1 Importance of immediately contacting clinician or seeking emergency treatment if manifestations of serious allergic reactions (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm, stridor, laryngeal edema, hypotension, tachycardia) develop.1 (See Immediate Hypersensitivity or Anaphylaxis under Warnings/Precautions: Sensitivity Reactions, in Cautions.)

Advise patients that botulism antitoxin (equine) heptavalent may cause delayed allergic reactions.1 Importance of immediately contacting clinician if manifestations of delayed allergic reactions or serum sickness (e.g., rash, fever, pruritus, myalgia, arthralgia, fever, lymphadenopathy) develop within 10-21 days after administration of the antitoxin.1 (See Delayed Hypersensitivity or Serum Sickness Reactions under Warnings/Precautions: Sensitivity Reactions, in Cautions.)

Advise patients that botulism antitoxin (equine) heptavalent is a potential vehicle for transmission of infectious agents, including viruses, since it is prepared using horse serum.1 Although screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, the possibility still exists that transmission of viruses and other infectious agents could occur.1

Advise patients that the antitoxin contains maltose and may cause falsely elevated glucose readings when blood glucose monitoring systems based on glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) are used.1 Falsely elevated glucose determinations may lead to inappropriate insulin administration resulting in life-threatening hypoglycemia or may mask true hypoglycemic states.1 Importance of using glucose-specific test methods not affected by maltose.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 women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

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

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Cangene Corporation. BAT (botulism antitoxin heptavalent [A, B, C, D, E, F, G] - [equine] ) sterile solution for injection prescribing information. Winnipeg, Canada. 2013 Mar.

2. US Food and Drug Administration. List of orphan designations and approvals. From FDA web site. [Web]

3. US Food and Drug Administration. Botulism antitoxin heptavalent (A, B, C, D, E, F, G) - (Equine) summary basis for regulatory action. March 21, 2013. From FDA website. [Web]

5. Centers for Disease Control and Prevention. Botulism in the United States, 1899-1996. Handbook for epidemiologists, clinicians, and laboratory workers. Atlanta, GA: Centers for Disease Control and Prevention; 1998.

7. US Food and Drug Administration. Clinical review memo: Botulism antitoxin heptavalent (A, B, C, D, E, F, G) - (Equine) March 18, 2013. From FDA website. [Web]

8. Centers for Disease Control and Prevention. Botulism: Information and guidance for clinicians. From CDC website. Accessed 2015 Feb 3. [Web]

9. Sobel J. Botulism. Clin Infect Dis . 2005; 41:1167-73. [PubMed 16163636]

10. Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases. Botulism. From CDC website. Accessed 2015 Feb 3. [Web]

11. US Food and Drug Administration. OBE/DE review memo: review of the pharmacovigilance plan (PVP) for botulism antitoxin heptavalent (A, B, C, D, E, F, G) (equine) indicated for the treatment of symptomatic botulism following documented or suspected exposure to botulism neurotoxin (BoTN) serotypes A, B, C, D, E, F or G. February 28, 2013. From FDA website. [Web]

12. US Army Medical Research Institute of Infectious Disease. USAMRIID's medical management of biologic casualties handbook. 7th ed. USAMRIID: Fort Detrick, MD; 2011 Sept:121-8.

13. Centers for Disease Control and Prevention. CDC Drug Service. Our formulary. From CDC website. Accessed 2015 Feb 3. [Web]

14. US Food and Drug Administration. FDA approves first botulism antitoxin for use in neutralizing all seven known botulinum nerve toxin serotypes. From FDA website. Accessed 2015 Feb 3. [Web]

70. Arnon SS, Schechter R, Inglesby TV et al for the Working Group on Civilian Biodefense. Botulinum toxin as a biologic weapon: medical and public health management. JAMA . 2001; 285:1059-70. [PubMed 11209178]

105. American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.