Professional Information
Tetanus Antitoxin (Systemic)
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VA CLASSIFICATION
Primary: IM300
Note: This monograph is specific to the sterile solution of tetanus antitoxin prepared from the plasma of healthy horses immunized against tetanus toxin.
Another commonly used name is
TAT .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
*Not commercially available in the U.S.
†Not commercially available in Canada.
Category:
Immunizing agent (passive)—
Indications
General considerations
Tetanus (lockjaw) is a neurologic disease characterized by severe muscular spasms {01}. It is caused by the neurotoxin produced by the anaerobic bacterium Clostridium tetani in a contaminated wound {01}. Onset is gradual, occurring over 1 to 7 days, and progresses to severe generalized muscle spasms (severe enough to cause spinal fractures), which frequently are aggravated by any external stimulus {01}. Severe spasms persist for 1 week or more and subside over a period of weeks in those who recover {01}. Neonatal tetanus, a common cause of neonatal mortality in developing countries but a rare condition in the U.S., is caused by contamination of the umbilical stump {01}. Local tetanus is manifested by local muscle spasms in areas contiguous to a wound infected with C. tetani {01}.
Wound cleaning, debridement when indicated, and proper immunization are important in the prevention and management of tetanus {02}. The need for active immunization with tetanus toxoid, with or without tetanus antitoxin, depends on both the condition of the wound and the patient's vaccination history {02}.
Determining whether the wound is clean or dirty is extremely important in categorizing patients {03}. A wound is considered to be dirty if it is more than 6 hours old, if the wound is penetrating or deep, if the instrument that caused the wound is contaminated, if the wound is infected, if the wound is caused by a deep partial- or full-thickness burn, or if it is a crush injury {03}.
A thorough attempt must be made to determine whether a patient has completed primary vaccination {02}. Patients with unknown or uncertain previous vaccination histories should be considered to have had no previous tetanus toxoid doses {02}. Patients who have not completed a primary series may require tetanus toxoid and passive immunization with either tetanus antitoxin or tetanus immune globulin at the time of wound cleaning and debridement {02}.
Tetanus immune globulin provides protection for a longer time than does tetanus antitoxin, and causes fewer adverse reactions {02} {04}. Therefore, if passive immunization is needed, tetanus immune globulin is the agent of choice {02} {04}.
A U.S. serologic survey of tetanus immunity indicated that in the majority of the population, tetanus immunity decreases with time after the recipient's most recent vaccination {05}. If a contraindication to using tetanus toxoid–containing preparations exists for a person who has not completed a primary series of tetanus toxoid immunizations and that person has a wound that is neither clean nor minor, only passive immunization should be given, preferably with tetanus immune globulin {06} {07}.
In the U.S., tetanus is primarily a disease of older adults {02}. Of the 99 tetanus patients for whom complete information was reported to the Centers for Disease Control and Prevention (CDC) during 1987 and 1988, 68% were 50 years of age or older {02}. The age distribution of recent cases and the results of serologic surveys indicate that many U.S. adults are not protected against tetanus {02} {08}.
Accepted
Note: Because tetanus antitoxin is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this medication in these countries.
[Clostridium tetaniinfection (prophylaxis)]1—Tetanus antitoxin is indicated for prophylaxis against C. tetani infection, and the severe complications that arise from the toxins produced by C. tetani , following injury in patients whose immune status against tetanus is uncertain or incomplete {09}.
Note: Tetanus antitoxin should be used for passive immunization only when tetanus immune globulin is not available {09}.
[C. tetani infection (treatment)]1—Tetanus antitoxin is indicated for the treatment of C. tetani infection {09}.
1 Not included in Canadian product labeling.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Tetanus antitoxin is a sterile, nonpyrogenic solution of the refined and concentrated proteins, chiefly globulins, containing antitoxic antibodies obtained from the blood serum or plasma of healthy horses that have been immunized against tetanus toxin or toxoid {09} {11}. It has a potency of not less than 400 antitoxin units per mL based on the U.S. Standard Tetanus Antitoxin and the U.S. Control Tetanus Test Toxin, tested in guinea pigs {11}.
Mechanism of action/Effect:
Tetanus antitoxin neutralizes the toxin produced by Clostridium tetani {09}.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients allergic to any product prepared from horse serum may also be allergic to tetanus antitoxin {09}.
Pregnancy/Reproduction
Pregnancy—
Studies have not been done in humans.
Studies have not been done in animals.
Breast-feeding
It is not known whether tetanus antitoxin is distributed into breast milk. However, problems in humans have not been documented.
Pediatrics
Appropriate studies on the relationship of age to the effects of tetanus antitoxin have not been performed in the pediatric population. However, pediatrics-specific problems that would limit the usefulness of this medication in children are not expected.
Geriatrics
No information is available on the relationship of age to the effects of tetanus antitoxin in geriatric patients.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problem exists
» Hypersensitivity to tetanus antitoxin or horse serum
Side/Adverse Effects
Note: Anaphylaxis may occur following tetanus antitoxin administration, even in individuals with no prior history of hypersensitivity to tetanus antitoxin or horse serum {09}. Epinephrine hydrochloride injection (1:1000) should be readily available for use in case of anaphylactic or acute hypersensitivity reaction {09}. All patients should be observed or followed for serum sickness {09}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Anaphylactic reaction {09}(difficulty in breathing and swallowing; hives; itching; reddening of skin, especially around ears; swelling of eyes, face, or inside of nose; unusual tiredness or weakness, sudden and severe)
serum sickness {09}(feeling of discomfort; fever; inflammation of joints; itching; muscle aches; rash; swollen lymph glands)
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Tetanus Antitoxin (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Hypersensitivity to tetanus antitoxin or horse serum
Proper use of this medication
» Proper dosing
Side/adverse effects
Signs of potential side effects, especially anaphylactic reaction and serum sickness
General Dosing Information
Anaphylaxis may occur following tetanus antitoxin administration, even in individuals with no prior history of hypersensitivity to tetanus antitoxin or horse serum {09}. Prior to use of tetanus antitoxin, appropriate measures should be taken to detect the presence of dangerous sensitivity {09}. The patient's history should be reviewed carefully, including any report of asthma, hay fever, urticaria, or other allergic manifestations; allergic reactions upon exposure to horses; and prior injections of horse serum {09}. An intradermal skin test or conjunctival test for serum sensitivity using normal horse serum or the antitoxin and 0.9% sodium chloride injection should be performed under close medical supervision in every patient prior to administration of tetanus antitoxin, regardless of clinical history {09}. Epinephrine hydrochloride injection (1:1000) should be on hand to treat an anaphylactic or other allergic reactions {08} {09}.
The skin test consists of an intracutaneous injection of 0.1 mL of a 1:100 dilution of 0.05 mL or a 1:1000 dilution (for persons with a history of allergy) of normal horse serum in 0.9% sodium chloride injection, and an equal volume of 0.9% sodium chloride injection at a separate site to serve as a control {09}. A positive skin test result consists of an urticarial wheal surrounded by an erythematous zone {09}.
The conjunctival test consists of instillation of one drop of a 1:10 dilution (for adults) or a 1:100 dilution (for children) of normal horse serum into the conjunctival sac {09}. One drop of 0.9% sodium chloride injection is instilled into the other conjunctival sac to serve as a control {09}. A positive conjunctival test result consists of itching of the eye and reddening of the conjunctiva {09}.
Whenever there is a history of allergy, sensitivity to horse serum, or manifestations of sensitivity when in proximity to horses, or if the reaction to the skin or eye test is positive, great care must be exercised in the administration of tetanus antitoxin {09}.
No single method can be advised for the administration of tetanus antitoxin for sensitive persons, as each presents an individual problem {09}. Desensitization of the patient should be carried out by serial injections of diluted tetanus antitoxin as indicated below at intervals of 20 minutes, provided no reaction occurs {09}.
Schedules for desensitization: • 0.05 mL of 1:20 dilution subcutaneously {09}.
• 0.1 mL of 1:10 dilution subcutaneously {09}.
• 0.3 mL of 1:10 dilution subcutaneously {09}.
• 0.1 mL of undiluted tetanus antitoxin subcutaneously {09}.
• 0.2 mL of undiluted tetanus antitoxin subcutaneously {09}.
• 0.5 mL of undiluted tetanus antitoxin subcutaneously {09}.
• The remaining therapeutic dose of tetanus antitoxin should be injected intramuscularly {09}.
After a patient can properly withstand these doses of tetanus antitoxin, it is usually safe to inject larger doses of tetanus antitoxin intramuscularly at intervals of 20 minutes {09}. If a reaction occurs after a desensitizing dose, injections should be stopped for 1 hour and the schedule recommenced at intervals of 20 minutes, with the last dose that failed to cause a reaction repeated {09}.
For treatment of adverse effects
Recommended treatment consists of the following: • For a mild hypersensitivity reaction—Administering antihistamines and, if necessary, corticosteroids {10}. In mild anaphylaxis, antihistamines or subcutaneous epinephrine may be all that is necessary if the condition is progressing slowly and is not life-threatening, regardless of the organ or system affected {10}. Under these circumstances the risks associated with intravenous epinephrine administration outweigh the benefits {10}.
• For a severe hypersensitivity or anaphylactic reaction—Administering epinephrine {10}. Antihistamines or corticosteroids may also be administered as required {10}. Epinephrine is the treatment of choice for a severe hypersensitivity or anaphylactic reaction {10}. If the patient's condition is not stable, epinephrine should be infused {10}. Norepinephrine may be preferable if there is no bronchospasm {10}. For bronchospasm, epinephrine should be given with corticosteroids {10}. Other bronchodilators, such as intravenous aminophylline or albuterol by nebulization, also should be considered {10}.
Parenteral Dosage Forms
Note: Because tetanus antitoxin is not commercially available in the U.S. or Canada, the bracketed uses and the use of superscript 1 in the Dosage Forms section reflect the lack of labeled (approved) indications for this product in these countries.
TETANUS ANTITOXIN USP
Usual adult and adolescent dose
[Clostridium tetani infection (prophylaxis)]1
Patients weighing up to 65 pounds (29.5 kgs): Intramuscular, 1500 Units as a single dose {09}.
Patients weighing 65 pounds (29.5 kgs) or more: Intramuscular, 3000 to 5000 Units as a single dose {09}.
[C. tetani infection (treatment)]1
Intramuscular, 50,000 to 100,000 Units as a single dose {09}.
Note: For the treatment of C. tetani infection, it is recommended that at least part of the dose be given intravenously {09}. Tetanus antitoxin treatment should be instituted as soon as possible following injury {09}.
Usual pediatric dose
[C. tetani infection (prophylaxis)]1
Intramuscular, 1500 Units as a single dose {09}.
[C. tetani infection (treatment)]1
See Usual adult and adolescent dose {09}.
Strength(s) usually available
U.S.—
Not commercially available.
Canada—
Not commercially available.
Africa, Asia, and Latin America—
1500 Units per vial (Rx)[Generic]{09}
3000 Units per vial (Rx)[Generic]{09}
5000 Units per vial (Rx)[Generic]{09}
20,000 Units per vial (Rx)[Generic]{09}
Packaging and storage:
Store between 2 and 8 ºC (36 and 46 ºF), unless otherwise specified by the manufacturer {09} {11}.
Stability:
Tetanus antitoxin should not be used if exposed to freezing temperatures {09}.
Auxiliary labeling:
• Do not freeze {09}.
Developed: 07/31/1998
References
- American Academy of Pediatrics (AAP). Tetanus. In: Peter G, editor. 1997 Red Book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997. p. 518-23.
- Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): diphtheria, tetanus, and pertussis—recommendations for vaccine use and other preventive measures. MMWR Morb Mortal Wkly Rep 1991; 40(RR-10): 1-25.
- Giangrasso J, Smith RK. Misuse of tetanus immunoprophylaxis in wound care. Ann Emerg Med 1985; 14: 573-9.
- Passen EL, Andersen BR. Clinical tetanus despite a “protective” level of toxin-neutralizing antibody. JAMA 1986; 225(9): 1171-3.
- Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): recommended childhood immunization schedule—United States, 1995. MMWR Morb Mortal Wkly Rep 1995; 44(RR-5): 1-9.
- Centers for Disease Control and Prevention. Recommendations of the Advisory Committee on Immunization Practices (ACIP): update—vaccine side effects, adverse reactions, contraindications, and precautions. MMWR Morb Mortal Wkly Rep 1996; 40(RR-12): 1-35.
- American College of Emergency Physicians. Tetanus immunization recommendations for persons seven years of age and older. Ann Emerg Med 1986; 15: 1111-2.
- Dal-Ré, Gil A, González A, et al. Does tetanus immune globulin interfere with the immune response to simultaneous administration of tetanus-diphtheria vaccine? A comparative clinical trial in adults. J Clin Pharmacol 1995; 35: 420-5.
- Tetanus antitoxin package insert (Sclavo—Italy), Rev 5/76, Rec 3/85.
- Fisher M. Treatment of acute anaphylaxis. BMJ 1995; 311: 731-3.
- The United States Pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed. (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention Inc; 1994. p. 1502.
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