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BOTULINUM ANTITOXIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Botulinum antitoxins are used in the treatment of botulism. They consist of immunoglobulins, derived from either human or horse serum, most commonly directed against inactivated type A, B, C, D and E strains of Clostridium botulinum. A newer heptavalent antitoxin is used to treat neurotoxin serotypes A, B, C, D, E, F or G strains.

Specific Substances

    1) Botulism Immune Globulin Intravenous (Human) (BIG-IV)
    2) Botulism Antitoxin
    3) Botulism Antitoxin Bivalent (Equine) Types A and B
    4) Botulism Antitoxin Heptavalent (ABCDEFG) Equine
    5) Botulism Antitoxin (Equine) Type E
    6) Botulinum Toxoid pentavalent (ABCDE)
    7) Immunoserum Botulinicum

Available Forms Sources

    A) SOURCES
    1) Botulism antitoxin bivalent (Equine) Types A and B is a refined, concentrated liquid preparation of horse (equine) globulins and is produced by Aventis Pasteur for emergency use (Centers for Disease Control and Prevention, 2008). A trivalent botulinum equine antitoxin is also available and distributed to laboratory workers as necessary. Each preparation contains 7,400 International Units of type A, 5,500 International Units type B, and 8,500 International Units of type E given intravenously (Patocka et al, 2005).
    2) Botulism antitoxin (Equine) Type E (usually associated with eating contaminated fish products) is also prepared by equine globulins modified by enzymatic digestion. It is also produced by Aventis Pasteur for emergency use (Centers for Disease Control and Prevention, 2008).
    3) Botulism antitoxin (Equine) Type A, B, C, D, E, F, G is a mixture of immune globulin fragments used to treat symptomatic botulism following documented or suspected exposure to botulinum neurotoxic serotypes A, B, C, D, E, F or G in both adults and children (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013).
    B) USES
    1) GENERAL: Administration of botulinum antitoxin is the only specific treatment for botulism, which can stop the progression of symptoms including paralysis and decrease the duration of intensive care (ie, mechanical ventilation). Ideally, antitoxin should be given as soon as possible following diagnosis, less than 24 hours after onset of symptoms if possible, because antitoxin is only able to neutralize the toxin molecules that are unbound to nerve endings (Sobel, 2005).
    2) INFANT BOTULISM: Botulism Immune Globulin Intravenous (Human) (BabyBIG(R): is a slovent-detergent-treated lyophilized powder of immunoglobulin G (IgG). This purified immunoglobulin is derived from pooled adult plasma from persons immunized with pentavalent botulinum toxoid with high titers of neutralizing antibody against botulinum toxins type A and B. It is indicated for use in infants less than one year of age with infant botulism produced by toxin type A and B (Prod Info BabyBIG(R), 2003a).
    3) FOODBORNE, WOUND or BOTULISM of unknown source: For suspected cases a State or local health department should be notified. If there is no response, the Centers for Disease Control (CDC) should be contacted on a 24 hour basis at 770-488-7100 (Sobel, 2005).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Based on limited experience, minor adverse events have been reported with human botulinum antitoxin. Mild, transient rash may develop. Other symptoms associated with botulism immune globulin therapy include: chills, muscle cramps, back pain, fever, nausea, vomiting, and wheezing. Patients receiving immune globulin intravenous products may be at risk for developing renal dysfunction, acute renal failure, and osmotic nephrosis, especially in patients with pre-existing renal insufficiency. Hypersensitivity reactions (mild or severe) are possible with the use of EQUINE antitoxins. Precautions may include adjusting or stopping the infusion, and epinephrine as indicated.
    B) WITH POISONING/EXPOSURE
    1) Limited data. Clinical experience with other immunoglobulins suggests that symptoms related to volume overload might occur in overdose with botulism immune globulin.
    0.2.3) VITAL SIGNS
    A) Fever and chills have been associated with botulism immune globulin therapy.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no reproductive studies have been conducted with botulism immune globulin, botulism antitoxin or botulism antitoxin heptavalent.

Laboratory Monitoring

    A) During infusion monitor for evidence of an acute allergic reaction (rash, angioedema, or bronchospasm), monitor vital signs, pulse oximetry, respiratory status, ECG and cardiac rhythm.
    B) Assess renal function including BUN and creatinine after a significant botulism immune globulin exposure. Monitor fluid balance.

Treatment Overview

    0.4.6) PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive. Minor reactions (chills, fever, pain, nausea and vomiting and wheezing) have been associated with botulism immune globulin therapy. During infusion monitor for evidence of an acute allergic reaction (rash, angioedema, or bronchospasm), monitor vital signs, pulse oximetry, respiratory status, ECG and cardiac rhythm. Monitor vital signs and fluid status.
    B) Severe anaphylaxis has not been reported with botulism immune globulin, but may develop with equine-derived products.
    1) ALLERGIC REACTION: MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.

Range Of Toxicity

    A) A toxic dose has not been established.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Based on limited experience, minor adverse events have been reported with human botulinum antitoxin. Mild, transient rash may develop. Other symptoms associated with botulism immune globulin therapy include: chills, muscle cramps, back pain, fever, nausea, vomiting, and wheezing. Patients receiving immune globulin intravenous products may be at risk for developing renal dysfunction, acute renal failure, and osmotic nephrosis, especially in patients with pre-existing renal insufficiency. Hypersensitivity reactions (mild or severe) are possible with the use of EQUINE antitoxins. Precautions may include adjusting or stopping the infusion, and epinephrine as indicated.
    B) WITH POISONING/EXPOSURE
    1) Limited data. Clinical experience with other immunoglobulins suggests that symptoms related to volume overload might occur in overdose with botulism immune globulin.

Vital Signs

    3.3.1) SUMMARY
    A) Fever and chills have been associated with botulism immune globulin therapy.
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) Fever and chills have been associated with botulism immune globulin therapy (Prod Info BabyBIG(R), 2003).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) CARDIOVASCULAR FINDING
    1) WITH THERAPEUTIC USE
    a) Transient changes in blood pressure (both increased and decreased) were reported with therapeutic use of botulism immune globulin (Prod Info BabyBIG(R), 2003).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) ASEPTIC MENINGITIS
    1) WITH THERAPEUTIC USE
    a) Aseptic meningitis syndrome has been reported infrequently with the administration of immune globulin intravenous products. The syndrome can include: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Symptoms usually begin within several hours to 2 days following therapy, and generally resolve with the discontinuation of therapy (Prod Info BabyBIG(R), 2003).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH THERAPEUTIC USE
    a) Infusion-related nausea and vomiting have been associated with botulism immune globulin (Prod Info BabyBIG(R), 2003).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) Patients receiving immune globulin intravenous products may be at risk for developing renal dysfunction, acute renal failure, and osmotic nephrosis, especially in patients with pre-existing renal insufficiency. Increases in serum BUN and creatinine levels have been reported in patients several days after receiving immune globulin therapy (Prod Info BabyBIG(R), 2003).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) In controlled studies, mild, transient erythematous rash of the face or trunk was reported in 14% of patients (n=65) treated with botulism immune globulin, as compared to 8% of placebo-treated patients (n=64) (Prod Info BabyBIG(R), 2003). However, causality of the rash could not be determined.

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) PAIN
    1) WITH THERAPEUTIC USE
    a) Infusion-related back pain and muscle cramps have been associated with botulism immune globulin (Prod Info BabyBIG(R), 2003).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Anaphylaxis was not observed during clinical trials of botulism immune globulin, but is theoretically possible (Prod Info BabyBIG(R), 2003).
    b) There are very few published reports regarding the safety of botulinum antitoxins. In general, acute hypersensitivity reactions to horse serum may include urticaria, angioneurotic edema, bronchospasm, and anaphylactic shock (Greenfield & Bronze, 2003; Arnon et al, 2001). Serum sickness may develop as a delayed reaction (Greenfield & Bronze, 2003; Arnon et al, 2001).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no reproductive studies have been conducted with botulism immune globulin, botulism antitoxin or botulism antitoxin heptavalent.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) There is no data on the use of botulism immune globulin, botulism antitoxin or botulism antitoxin heptavalent in pregnant women. The effects, if any, on the developing fetus are unknown (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013; Prod Info BabyBIG(R), 2003a). Currently, botulism immune globulin is only approved for use in patients less than one year of age, so information regarding its use in human pregnancy is not expected.
    B) PREGNANCY CATEGORY
    1) Botulism Antitoxin Heptavalent (A - G): The manufacturer has classified this antitoxin as FDA pregnancy category C (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013)
    C) ANIMAL STUDIES
    1) At the time of this review, no animal reproductive studies have been conducted with botulism immune globulin, botulism antitoxin or botulism antitoxin heptavalent (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013; Prod Info BabyBIG(R), 2003).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) LACK OF INFORMATION
    1) No reports describing the use of botulism immune globulin, botulism antitoxin or botulism antitoxin heptavalent during human lactation are available and the effects on the nursing infant from exposure to the drug in milk are unknown (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013; Prod Info BabyBIG(R), 2003). It is not known if botulism immune globulin affects the quantity and composition of breast milk. Currently, botulism immune globulin is only approved for use in patients less than one year of age, so information regarding use in lactating women is not expected (Prod Info BabyBIG(R), 2003).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) During infusion monitor for evidence of an acute allergic reaction (rash, angioedema, or bronchospasm), monitor vital signs, pulse oximetry, respiratory status, ECG and cardiac rhythm.
    B) Assess renal function including BUN and creatinine after a significant botulism immune globulin exposure. Monitor fluid balance.
    4.1.2) SERUM/BLOOD
    A) Assess renal function including BUN and creatinine after a significant botulism immune globulin exposure. Monitor fluid balance.
    B) During infusion monitor for evidence of an acute allergic reaction (rash, angioedema, or bronchospasm), monitor vital signs, pulse oximetry, respiratory status, ECG and cardiac rhythm.
    4.1.4) OTHER
    A) OTHER
    1) CARDIAC MONITORING
    a) Perform continuous cardiac monitoring during the infusion. Equine-derived products may produce anaphylaxis.

Methods

    A) ASSAYS
    1) BIOASSAYS - The neutralizing potency of therapeutic botulinum antitoxins has been performed by using in vivo bioassay (Sesardic, 2002). Immunoassay, however, is limited in distinguishing between neutralizing and non-neutralizing antibodies.
    2) More recently in vivo and in vitro assays have been used to analyze the neutralizing potency of botulinum antitoxin (ie, monovalent, trivalent and botulinum F(ab')2 heptavalent) and human botulism immune globulin, and in vitro assays were found to be similar to bioassay for quantification of toxin neutralizing antibodies. Sensitivity was in the range of 10 mU/mL (Sesardic, 2002).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) During infusion monitor for evidence of an acute allergic reaction (rash, angioedema, or bronchospasm), monitor vital signs, pulse oximetry, respiratory status, ECG and cardiac rhythm.
    B) Assess renal function including BUN and creatinine after a significant botulism immune globulin exposure. Monitor fluid balance.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not indicated; antitoxins given parenterally.

Range Of Toxicity

Summary

    A) A toxic dose has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) BIVALENT (A and B) EQUINE ANTITOXIN
    1) In the US, a licensed bivalent (A and B) equine antitoxin is available from the Centers for Disease Control (CDC) for emergent use. It is a licensed product supplied in single dose vials and only released for suspected cases of botulinum poisoning. To obtain the antitoxin, physicians should first contact their State or local health department, and then contact the CDC at 770-488-7100 (Centers for Disease Control and Prevention, 2008).
    B) TRIVALENT (A, B, E) EQUINE ANTITOXIN
    1) In the US, trivalent botulinum antitoxin is available from the CDC via State and local health departments for emergent use. A single 10 mL vial of antitoxin is recommended per patient. The antitoxin should be diluted 1:10 in 0.9% saline solution and administered by slow intravenous infusion. Each vial contains between 5500 and 8500 International Units of each type of specific antitoxin (Arnon et al, 2001). Skin testing prior to infusion is preferred to determine potential sensitivity to the serum or antitoxin (Centers for Disease Control and Prevention, 2006).
    a) Administration of antitoxin early in the course of illness is needed to slow the progression of illness and shorten the clinical course. The antitoxin can be obtained by contacting a State or local health department. If not available contact the CDC 24-hour telephone number at 770-488-7100. The call is taken by the CDC Emergency Operations Center which will contact the Foodborne and Diarrheal Diseases Branch MD on call (Centers for Disease Control and Prevention, 2008; Centers for Disease Control and Prevention, 2006; Sobel, 2005).
    C) HEPTAVALENT (A, B, C, D, E, F, G) EQUINE ANTITOXIN
    1) ADULT (greater than or equal to 17 years): DOSE: For treatment of suspected or documented exposure to botulinum neurotoxin, the recommended dose is 1 vial IV beginning at an infusion rate of 0.5 mL/min for the first 30 minutes. Monitor vital signs, and if tolerated, infusion rate may be doubled every 30 minutes to a maximum rate of 2 mL/min (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013)
    a) Prior to infusion, consider skin sensitivity testing for patients at risk (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013):
    1) Administer 0.02 mL of 1:1000 saline-diluted botulism antitoxin heptavalent intradermally on the volar surface of forearm (a small wheal should be raised)
    2) If test is negative, repeat with a 1:100 dilution
    3) Perform concurrent positive (histamine) and negative (saline) control tests
    4) A positive test is a wheal with erythema that is 3 mm or more larger than the negative control test at 15 to 20 minutes past administration of test
    7.2.2) PEDIATRIC
    A) BOTULISM IMMUNE GLOBULIN
    1) BabyBIG(R), Botulism Immune Globulin Intravenous (Human) is an orphan drug indicated for the treatment of infant botulism types A and B. Recommended total dosage is 1 mL/kg (50 mg/kg) given as a single intravenous infusion. Start the infusion as soon as the clinical diagnosis is made. Administer at 0.5 cc per kg body weight per hour (25mg/kg/hr) for 15 minutes, then increase rate to 1.0 cc/kg/hr (50 mg/kg/hr) if no reactions. A separate intravenous line is recommended, along with an infusion pump. The infusion should begin within 2 hours of reconstitution (Prod Info BabyBIG(R), 2003a).
    a) To obtain BabyBIG(R) for a patient with suspected infant botulism, a physician must contact the California Department of Health (Prod Info BabyBIG(R), 2003a): 
    Infant Botulism Treatment and Prevention Program
California Department of Health Services
850 Marina Bay Parkway, Room E-361
Richmond, CA 94804
Telephone: (510) 231-7600

    B) HEPTAVALENT (A, B, C, D, E, F, G) EQUINE ANTITOXIN
    1) INFANTS (Less Than 1 Year of Age)
    a) DOSE: The recommended dose in infants is 10% of the adult dose (ie, 1 single-use vial), regardless of body weight. The fill volume of the single-use vials varies by lot number (approximately 10 to 22 mL/vial). Use entire contents of a vial to prepare a 1:10 dilution in NS in an IV bag and then administer 10% of the prepared product by slow IV infusion beginning at a rate of 0.01 mL/kg/min. Monitor vital signs, and if tolerated, infusion rate may be increased by 0.01 mL/kg/min every 30 minutes to a maximum rate of 0.03 mL/kg/min (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013).
    2) CHILDREN (1 to Less Than 17 Years of Age)
    a) DOSE: The recommended dose in children is a percentage of the adult dose (ie, 1 single-use vial) based on the child's body weight (see table below). The fill volume of the single-use vials varies by lot number (approximately 10 to 22 mL/vial). Use entire contents of a vial to prepare a 1:10 dilution in NS in an IV bag and then administer the recommended percentage of the prepared product by slow IV infusion beginning at a rate of 0.01 mL/kg/min, not to exceed a total rate of 0.5 mL/min. Monitor vital signs, and if tolerated, the infusion rate may be increased by 0.01 mL/kg/min every 30 minutes to a maximum rate of 0.03 mL/kg/min (but not to exceed a rate of 2 mL/min) (Prod Info BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, 2013).
    Body Weight (kg)Percentage of Adult Dose*
    10 to 1420
    15 to 1930
    20 to 2440
    25 to 2950
    30 to 3460
    35 to 3965
    40 to 4470
    45 to 4975
    50 to 5480
    55 or greater100
    * Adult dose is 1 single-use vial. Do not exceed 1 vial, regardless of body weight; minimum dose is 20% of adult dose

Minimum Lethal Exposure

    A) At the time of this review, a toxic dose has not been established. Based on other immune globulin products renal dysfunction, acute renal failure, osmotic nephrosis and death have developed with therapy (Prod Info BabyBIG(R), 2003). Anaphylaxis has been reported with equine-derived products (Arnon et al, 2001).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) BOTULISM IMMUNE GLOBULIN (BIG-IV)
    1) Human botulism immune globulin (antitoxin) intravenous (BIG-IV) is indicated for the treatment of infant botulism caused by toxin type A or B (Prod Info BabyBIG(R), 2003b; Anon, 2003; Arnon, 1993; Frankovich & Arnon, 1991). One unit of botulinum antitoxin (type A or B) neutralizes 10,000 intraperitoneal mouse LD50 of botulinum toxin. For toxin types C, D, and E the titers of antibody against botulinum neurotoxins have not been determined (Prod Info BabyBIG(R), 2003b).
    2) It contains neutralizing antibodies to botulinum toxin types A-E, and has been produced by plasmapheresis of subjects immunized with botulinum toxoid, then fractionation of pooled plasma (Prod Info BabyBIG(R), 2003b; Arnon, 1993). The rationale for BIG-IV therapy in infant botulism is to neutralize both the toxin in circulation and extracellular fluid prior to binding at the neuromuscular junction; inactivation of the toxin subsequently absorbed from the large intestine (site of production) is also expected (Arnon, 1993).
    B) EQUINE-DERIVED BOTULISM ANTITOXIN
    1) Equine-derived botulism antitoxin preparations are also available, and contain antibodies against toxins produced by C. botulinum (A, B, and/or E) (CPS, 2001; Reynolds, 1993; Hibbs et al, 1996). These are indicated for treatment of foodborne and wound botulism, and the relatively rare cases of adult intestinal colonization botulism (Pers Comm, 2003; May et al, 2002; Anon, 2003). Equine-source anti-A and B antitoxin (licensed) and equine-source anti-E antitoxin (IND status) are available from the CDC (Centers for Disease Control and Prevention, 2008). A trivalent antitoxin (types A, B, and E) is manufactured by Aventis Pasteur (Canada) (CPS, 2001).
    2) The equine-derived antitoxin is not indicated for the treatment of infant botulism, due to evidence of inefficacy and the risk of adverse effects (eg, anaphylaxis, serum sickness) and induction of lifelong hypersensitivity to equine antigens (May et al, 2002; Arnon, 1993). Antitoxin contents per dose are lower with BIG-IV as compared to the equine antitoxin; the plasma half-life of antitoxins are longer with BIG-IV (Pers Comm, 2003; Arnon, 1993).
    3) It has been suggested that BIG-IV may also have a role in treating foodborne and wound botulism, and as an adjunct to botulinum toxin therapy (ie, to neutralize toxin escaping from injected muscle tissue, thus minimizing refractoriness of future therapy due to antibody production) (Arnon, 1993).

Toxicologic Mechanism

    A) Botulism Immune Globulin (BIG-IV) is a purified immune globulin derived from pooled adult plasma from persons immunized with pentavalent botulinum toxoid. Immune globulin intravenous (human) IGIV products have been associated with renal dysfunction, acute renal failure, osmotic nephrosis and death. Patients with pre-existing renal insufficiency may be at risk for volume overload following excessive or inadvertent fluids during antitoxin administration (Prod Info BabyBIG(R), 2003b).

References

General Bibliography

    1) Anon: Infant botulism - New York City, 2001-2002. MMWR 2003; 52:21-26.
    2) Arnon SS, Schechter R, Inglesby TV, et al: Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001; 285(8):1059-1070.
    3) Arnon SS: Clinical trial of human botulism immune globulin. Botulinum Tetanus Neurotox-Neurotrans 1993:477-482, 1993.
    4) CPSCPS: Compendium of Pharmaceuticals Specialties: The Canadian Reference for Health Professionals, 36th. Webcom Limited, Toronto, Canada, 2001.
    5) Centers for Disease Control and Prevention: Botulism: information and guidance for clinicians. Centers for Disease Control and Prevention. Atlanta, GA. 2006. Available from URL: http://www.bt.cdc.gov/agent/botulism/clinicians/index.asp. As accessed Jan 3, 2008.
    6) Centers for Disease Control and Prevention: National Center for Infectious Diseases - Scientific Resources Program (SRP). Centers for Disease Control and Prevention. Atlanta, GA. 2008. Available from URL: http://www.cdc.gov/ncidod/srp/drugs/formulary.html. As accessed Jan 3, 2008.
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    9) Hibbs RG, Weber JT, Corwin A, et al: Experience with the use of an investigational F(ab')2 heptavalent botulism immune globulin of equine origin during an outbreak of type E botulism in Egypt. Clin Infect Dis 1996; 23:337-340.
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    13) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
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    16) Personal Communication: Botulism immune globulin. United States Centers for Disease Control and Prevention, Foodborne and Diarrheal Diseases Branch (cited 05/2003). Available at: dbmdnet@cdc.gov, April 22, 2003.
    17) Product Information: BAT Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) Equine intravenous injection solution, botulism antitoxin heptavalent (A, B, C, D, E, F, G) equine intravenous injection solution. Cangene Corporation (per manufacturer), Winnipeg, Manitoba, Canada, 2013.
    18) Product Information: BabyBIG(R), Botulism Immune Globulin Intravenous (Human) (BIG-IV). California Department of Health Services, Richond, CA, 2003b.
    19) Product Information: BabyBIG(R), botulism immune globulin intravenous (human). Massachusetts Public Health Biologic Laboratories, Boston, MA, 2003a.
    20) Product Information: BabyBIG(R), botulism immune globulin intravenous (human). Massachusetts Public Health Biologic Laboratories. Boston, MA, 2003.
    21) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    22) Reynolds JEFReynolds JEF (Ed): Martindale: The Extra Pharmacopoeia, 30th. The Pharmaceutical Press, London, England, 1993.
    23) Sesardic D: Alternatives in testing of bacterial toxins and antitoxins. Dev Biol (Basel) 2002; 111:101-108.
    24) Sobel J: Botulism. Clin Infect Dis 2005; 41(8):1167-1173.
    25) Vanden Hoek,TL; Morrison LJ; Shuster M et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.