Tetanus Toxoid Adsorbed, aluminum phosphate-adsorbed, PUROGENATED® is a sterile preparation of refined tetanus toxoid for intramuscular use only. After shaking, the product is a homogenous white suspension.

The tetanus toxin is produced according to the method of Mueller and Miller 1 and is detoxified by use of formaldehyde. The toxoid is refined by the Pillemer alcohol fractionation method 2 and is diluted with a solution containing sodium phosphate dibasic, sodium phosphate monobasic, glycine, sodium chloride and thimerosal (mercury derivative) in a final concentration of 1:10,000 as a preservative and aluminum phosphate as adjuvant. The aluminum content does not exceed 0.80 mg per 0.5 mL dose.

Each 0.5 mL dose is formulated to contain 5 Lf units of tetanus toxoid.

Tetanus is an intoxication manifested primarily by neuromuscular dysfunction caused by a potent exotoxin elaborated by Clostridium tetani. The incidence of tetanus in the U.S. has dropped dramatically with the routine use of tetanus toxoid, remaining relatively constant over the last decade at about 90 cases reported annually. 3 Spores of C tetani are ubiquitous and there is essentially no natural immunity to tetanus toxin. Thus, universal primary immunization with tetanus toxoid, and subsequent maintenance of adequate antitoxin levels by means of timed boosters, is necessary to protect all age groups. 3 Tetanus toxoid is a highly effective antigen, and a completed primary series generally induces protective levels of serum antitoxin that persist for at least 10 years. 3

Tetanus Toxoid Adsorbed is indicated for active immunization against tetanus in adults and children 2 months of age or older.

Immunization of persons 7 years of age or older may be accomplished by the use of Tetanus and Diphtheria Toxoids Adsorbed, for Adult Use (Td), Tetanus Toxoid Adsorbed, or Tetanus Toxoid Fluid. The Immunization Practices Advisory Committee (ACIP) of the U.S. Public Health Service recommends the use of the combined toxoids vaccine rather than single component vaccines for both primary and booster injections, including active tetanus immunization in wound management. 3 Individuals for whom the use of a vaccine containing diphtheria toxoid is contraindicated should receive a single-component tetanus toxoid-containing vaccine.

Immunization of infants and children 2 months of age up to the seventh birthday is usually accomplished by the use of Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTP) or Diphtheria and Tetanus Toxoids Adsorbed, for pediatric use (DT). Tetanus Toxoid Adsorbed may be used for immunizing infants and children for whom the use of a vaccine containing diphtheria toxoid and pertussis antigen is contraindicated.

Comparative tests have shown that the adsorbed toxoids are superior to the fluid toxoids in antibody titers produced and in the durability of protection achieved. The promptness of antibody response to booster doses of either fluid or adsorbed toxoid is not sufficiently different to be of clinical importance. When Tetanus Immune Globulin (TIG) is to be administered at the same visit as tetanus toxoid, the adsorbed toxoid should be used. 3,4

Persons recovering from tetanus. Tetanus infection may not confer immunity; therefore, initiation or completion of active immunization is indicated at the time of recovery from this infection. 3

Neonatal tetanus prevention.   There is no evidence that tetanus toxoid is teratogenic. A previously unimmunized pregnant woman who may deliver her child under nonhygienic circumstances and/or surroundings should receive two properly spaced doses of a tetanus toxoid-containing preparation before delivery, preferably during the last two trimesters. Incompletely immunized pregnant women should complete the three-dose series. Those immunized more than 10 years previously should have a booster dose. 3 (See also pregnancy information under PRECAUTIONS .)

CONTRAINDICATIONS

HYPERSENSITIVITY TO ANY COMPONENT OF THE VACCINE, INCLUDING THIMEROSAL, A MERCURY DERIVATIVE, IS A CONTRAINDICATION.

THE OCCURRENCE OF ANY TYPE OF NEUROLOGICAL SYMPTOMS OR SIGNS FOLLOWING ADMINISTRATION OF THIS PRODUCT IS A CONTRAINDICATION TO FURTHER USE.

IMMUNIZATION SHOULD BE DEFERRED DURING THE COURSE OF ANY FEBRILE ILLNESS OR ACUTE INFECTION. A MINOR AFEBRILE ILLNESS SUCH AS A MILD UPPER RESPIRATORY INFECTION IS NOT USUALLY REASON TO DEFER IMMUNIZATION. 3

The clinical judgment of the attending physician should prevail at all times.

Routine immunization should be deferred during an outbreak of poliomyelitis providing the patient has not sustained an injury that increases the risk of tetanus.

THE OCCURRENCE OF A NEUROLOGIC OR SEVERE HYPERSENSITIVITY REACTION FOLLOWING A PREVIOUS DOSE IS A CONTRAINDICATION TO FURTHER USE OF THIS PRODUCT. 3

THE ADMINISTRATION OF BOOSTER DOSES MORE FREQUENTLY THAN RECOMMENDED (See DOSAGE AND ADMINISTRATION ) MAY BE ASSOCIATED WITH INCREASED INCIDENCE AND SEVERITY OF REACTIONS. 3

Persons who experience Arthus-type hypersensitivity reactions or temperature greater than 39.4°C (103°F) after a previous dose of tetanus toxoid usually have very high serum tetanus antitoxin levels and should not be given even emergency doses of tetanus toxoid more frequently than every 10 years, even if they have a wound that is neither clean nor minor. 3

If a contraindication to using tetanus toxoid exists in a person who has not completed a primary immunizing course of tetanus toxoid, and other than a clean, minor wound is sustained, only passive immunization should be given using human Tetanus Immune Globulin (TIG). 3

Tetanus Toxoid Adsorbed should not be given to individuals with thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injection, unless the potential benefit clearly outweighs the risk of administration.

Patients with impaired immune responsiveness, whether due to the use of immunosuppressive therapy (including irradiation, corticosteroids, antimetabolites, alkylating agents, and cytotoxic agents), a genetic defect, human immunodeficiency virus (HIV) infection, or other causes, may have a reduced antibody response to active immunization procedures. 3 - 5 Deferral of administration of vaccine may be considered in individuals receiving immunosuppressive therapy. 3,4

Special care should be taken to prevent injection into a blood vessel.

PRECAUTIONS

General

  1. PRIOR TO ADMINISTRATION OF ANY DOSE OF VACCINE THE PARENT, GUARDIAN, OR ADULT PATIENT SHOULD BE ASKED ABOUT THE RECENT HEALTH STATUS AND IMMUNIZATION HISTORY OF THE PATIENT TO BE IMMUNIZED IN ORDER TO DETERMINE THE EXISTENCE OF ANY CONTRAINDICATIONS TO IMMUNIZATION (SEE CONTRAINDICATIONS , ).
  2. WHEN THE PATIENT RETURNS FOR THE NEXT DOSE IN A SERIES, THE PARENT, GUARDIAN, OR ADULT PATIENT SHOULD BE QUESTIONED CONCERNING OCCURRENCE OF ANY SYMPTOM AND/OR SIGN OF AN ADVERSE REACTION AFTER THE PREVIOUS DOSE (SEE CONTRAINDICATIONS , ADVERSE REACTIONS ).
  3. BEFORE THE INJECTION OF ANY BIOLOGICAL, THE PHYSICIAN SHOULD TAKE ALL PRECAUTIONS KNOWN FOR PREVENTION OF ALLERGIC OR ANY OTHER SIDE REACTIONS. This should include: a review of the patient' history regarding possible sensitivity; the ready availability of epinephrine 1:1,000 and other appropriate agents used for control of immediate allergic reactions; and a knowledge of the recent literature pertaining to use of the biological concerned, including the nature of side effects and adverse reactions that may follow its use.
  4. A separate sterile syringe and needle or a sterile disposable unit should be used for each individual patient to prevent transmission of hepatitis or other infectious agents from one person to another.
  5. Shake vigorously before withdrawing each dose to resuspend the contents of the vial.
  6. NATIONAL CHILDHOOD VACCINE INJURY ACT OF 1986 (AS AMENDED IN 1987)
    This Act requires that the manufacturer and lot number of the vaccine administered be recorded by the health care provider in the vaccine recipient' permanent record, along with the date of administration of the vaccine and the name, address and title of the person administering the vaccine.
    The Act further requires the health care provider to report to a health department or to the FDA the occurrence following immunization of any event set forth in the Vaccine Injury Table including: anaphylaxis or anaphylactic shock within 24 hours, encephalopathy or encephalitis within 7 days, residual seizure disorder, any acute complication or sequelae (including death) of above events, or any event that would contraindicate further doses of vaccine, according to this package insert. 6

Information for the Patient

PRIOR TO ADMINISTRATION OF THIS VACCINE, HEALTH CARE PERSONNEL SHOULD INFORM THE PARENT, GUARDIAN, OR ADULT PATIENT OF THE BENEFITS AND RISKS OF VACCINATION AGAINST TETANUS.

Use in Pregnancy

Pregnancy Category C.

Animal reproductive studies have not been conducted with this product. There is no evidence that tetanus toxoid is teratogenic. An appropriate tetanus toxoid-containing preparation (usually Td) should be given to inadequately immunized women because it affords protection against neonatal tetanus. 7 Waiting until the second trimester is a reasonable precaution to minimize any theoretical concern. 4 Maintenance of adequate immunization by routine boosters in non-pregnant women of child-bearing age (see DOSAGE AND ADMINISTRATION ) can obviate the need to vaccinate women during pregnancy.

ADVERSE REACTIONS

Local reactions, such as erythema, induration and tenderness, are common after the administration of tetanus toxoid. 8,9,10 Such local reactions are usually self-limiting and require no therapy. Nodule, 11 sterile abscess formation, or subcutaneous atrophy may occur at the site of injection. Systemic reactions such as fever, chills, myalgia, and headaches also may occur. 8,9,10

Arthus-type hypersensitivity reactions, or high fever, may occur in persons who have very high serum antitoxin antibodies due to overly frequent injections of toxoid. 3 (See .)

NEUROLOGICAL COMPLICATIONS 12 SUCH AS CONVULSIONS, 13 ENCEPHALOPATHY, 13,14 AND VARIOUS MONO- AND POLYNEUROPATHIES, 14 - 20 INCLUDING GUILLAIN-BARR[Eacute] SYNDROME, 21,22 HAVE BEEN REPORTED FOLLOWING ADMINISTRATION OF PREPARATIONS CONTAINING TETANUS ANTIGEN.

URTICARIA, ERYTHEMA MULTIFORME OR OTHER RASH, ARTHRALGIAS 13 AND, MORE RARELY, A SEVERE ANAPHYLACTIC REACTION (I.E., URTICARIA WITH SWELLING OF THE MOUTH, DIFFICULTY BREATHING, HYPOTENSION OR SHOCK) HAVE BEEN REPORTED FOLLOWING ADMINISTRATION OF PREPARATIONS CONTAINING TETANUS ANTIGEN.

DOSAGE AND ADMINISTRATION

For Intramuscular Use Only

Shake vigorously before withdrawing each dose to resuspend the contents of the vial or syringe.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. (See . )

Preferred injection sites for intramuscular injection include the anterolateral aspect of the upper thigh and the deltoid area of the upper arm. Care should be taken to avoid major peripheral nerve trunks.

Before injection, the skin at the injection site should be cleansed and prepared with a suitable germicide.

After insertion of the needle, aspirate to help avoid inadvertent injection into a blood vessel.

The primary immunizing course for unimmunized individuals one year of age or older consists of two doses of 0.5 mL each, 4 to 8 weeks apart, followed by a third (reinforcing) dose of 0.5 mL, 6 to 12 months after the second dose. The reinforcing dose is an integral part of the primary immunizing course.

If, after beginning combined immunization against diphtheria, tetanus, and pertussis, further doses of vaccine containing pertussis and diphtheria antigens become contraindicated, Tetanus Toxoid Adsorbed may be substituted for each of the remaining doses.

When immunization with Tetanus Toxoid Adsorbed is begun in the first year of life, the primary series consists of three doses of 0.5 mL each, 4 to 8 weeks apart, followed by a fourth (reinforcing) dose of 0.5 mL, 6 to 12 months after the third dose.

Interruption of the recommended schedule with a delay between doses does not interfere with the final immunity achieved with Tetanus Toxoid Adsorbed. There is no need to start the series over again, regardless of the length of time elapsed between doses. 3

Booster Doses

A single injection of 0.5 mL of Tetanus Toxoid Adsorbed is given 10 years after completion of primary immunization and every 10 years thereafter. If a dose is given sooner as part of wound management, the next booster is not needed for 10 years thereafter. MORE FREQUENT BOOSTER DOSES ARE NOT INDICATED AND MAY BE ASSOCIATED WITH INCREASED INCIDENCE AND SEVERITY OF REACTIONS. 3

Tetanus Prophylaxis in Wound Management

The need for active immunization with a tetanus toxoid-containing preparation, with or without passive immunization with human Tetanus Immune Globulin (TIG) depends on both the condition of the wound and the patient' immunization history. Tetanus has rarely occurred among persons with a documented primary series of toxoid injections. A thorough attempt must be made to determine whether a patient has completed primary immunization. 3

Individuals who have completed primary immunization against tetanus, and who sustain wounds which are minor and uncontaminated, should receive a booster dose of the appropriate tetanus toxoid-containing preparation (see ) only if they have not received tetanus toxoid within the preceding 10 years. For other wounds, a booster is appropriate if the patient has not received tetanus toxoid within the preceding 5 years. Antitoxin antibodies develop rapidly in persons who have previously received at least two doses of tetanus toxoid. 3

Individuals who have not completed primary immunization against tetanus, or whose immunization history is unknown or uncertain, should be immunized with the appropriate tetanus toxoid-containing product (see ). Completion of primary immunization thereafter should be ensured. In addition, if these individuals have sustained a tetanus-prone wound, the use of human Tetanus Immune Globulin (TIG) is recommended. A separate syringe and site of administration should be used. When TIG is to be administered at the same visit as tetanus toxoid, an adsorbed tetanus toxoid-containing preparation should be used. 3

SUMMARY GUIDE TO TETANUS PROPHYLAXIS IN ROUTINE WOUND MANAGEMENT 3 *
History of
tetanus
toxoid (doses)
Clean, minor
    wounds     		All other
  wounds #
Td § TIG Td § TIG
Unknown or<three
Yes No Yes Yes
>/=three
 No ** No  No ## No
* Important details are in the text.
# Such as, but not limited to, wounds contaminated with dirt, feces, soil, saliva, etc.; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns and frostbite.
§ For children under 7 years old DTP (DT, if pertussis vaccine is contraindicated) is preferred to tetanus toxoid alone. For persons 7 years and older, Td is preferred to tetanus toxoid alone.
¶If only three doses of fluid toxoid have been received, a fourth dose of toxoid, preferably an adsorbed toxoid, should be given.
** Yes, if more than 10 years since last dose.
## Yes, if more than 5 years since last dose. (More frequent boosters are not needed and can accentuate side effects.)

In order to enhance diphtheria protection in the population, the ACIP recommends Tetanus and Diphtheria Toxoids For Adult Use as the preferred preparation for active tetanus immunization in wound management of patients 7 years of age or older. 3

HOW SUPPLIED

NDC 0005-1938-31  5.0 mL vial

NDC 0005-1938-47  10 × 0.5 mL LEDERJECT® disposable syringe. For directions on use of LEDERJECT® disposable syringe, please see package insert accompanying product.

STORAGE

DO NOT FREEZE. STORE REFRIGERATED, AWAY FROM FREEZER COMPARTMENT, AT 2°C to 8°C (36°F to 46°F).

REFERENCES

  1. Mueller JH, Miller PA: Factors influencing the production of tetanal toxin. J Immunol 1947;56:143-147.
  2. Pillemer L, Grossberg DB, Wittler RG: The immunochemistry of toxins and toxoids. II. The preparation and immunological evaluation of purified tetanal toxoid. J Immunol 1946;54:213-224.
  3. Recommendation of the Immunization Practices Advisory Committee (ACIP): Diphtheria, tetanus and pertussis: Guidelines for vaccine prophylaxis and other preventive measures. MMWR 1985;34:405-426.
  4. Committee on Immunization, Council of Medical Societies, American College of Physicians: Guide for Adult Immunization, 1st Edition 1985; Philadelphia, PA.
  5. Recommendation of the ACIP: Immunization of children infected with Human T-Lymphotrophic Virus Type III/Lymphadenopathy associated virus. MMWR 1986;35(38):595-606.
  6. National Childhood Vaccine Injury Act: Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 1988;37(13):197-200.
  7. Recommendations of the ACIP: General recommendations on immunization. MMWR 1983;32(1):1-17.
  8. Macko MB, Powell CE: Comparison of the morbidity of tetanus toxoid boosters with tetanus-diphtheria toxoid boosters. Ann Emerg Med 1985;14:(1)33-35.
  9. Deacon SP, et al: A comparative clinical study of adsorbed tetanus vaccine and adult-type tetanus-diphtheria vaccine. J Hyg (Cambridge) 1982;89:513-519.
  10. Jacobs RL, et al: Adverse reactions to tetanus toxoid. JAMA 1982:247(1):40-42.
  11. Fawcett HA, Smith N: Injection-site granuloma due to aluminum. Arch Dermatol 1984;120:1318-1322.
  12. Rutledge SL, Snead OC: Neurologic complications of immunizations. J Pediatr 1986;109:917-924.
  13. Adverse Events Following Immunization. MMWR 1985;34(3):43-47.
  14. Schlenska GK: Unusual neurological complications following tetanus toxoid administration. J Neurol 1977;215:299-302.
  15. Blumstein GI, Kreithen H: Peripheral neuropathy following tetanus toxoid administration. JAMA 1966;198:1030-1031.
  16. Reinstein L, Pargament JM, Goodman JS: Peripheral neuropathy after multiple tetanus toxoid injections. Arch Phys Med Rehabil 1982;63:332-334.
  17. Tsairis P, Duck PJ, Mulder DW: Natural history of brachial plexus neuropathy. Arch Neurol 1972;27:109-117.
  18. Quast U, Hennessen W, Widmark RM: Mono- and polyneuritis after tetanus vaccination. Devel Bio Stand 1979;43:25-32.
  19. Holliday PL, Bauer RB: Polyradiculoneuritis secondary to immunization with tetanus and diphtheria toxoids. Arch Neurol 1983;40:56-57.
  20. Fenichel GM: Neurological complications of tetanus toxoid. Arch Neurol 1983;40:390.
  21. Pollard JD, Selby G: Relapsing neuropathy due to tetanus toxoid. J Neurol Sci 1978;37:113-125.
  22. Newton N, Janati A: Guillain-Barré syndrome after vaccination with purified tetanus toxoid. S Med J 1987;80:1053-1054.

Manufactured by:

LEDERLE LABORATORIES

Division American Cyanamid Company

Pearl River, NY 10965

US Gov't. License No. 17

Marketed by:

WYETH-LEDERLE VACCINES AND PEDIATRICS

Wyeth-Ayerst Laboratories

Philadelphia, PA 19101

CI 4417-1 Issued October 23, 1995