TETANUS PROTEIN
DESCRIPTION:
Tetanus protein(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 homogeneous white suspension.
The tetanus toxin is produced according to the method of Mueller and Miller
(REF. 1) and is detoxified by use of formaldehyde. The toxoid is refined by the
Pillemer alcohol fractionation method (REF. 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.
ACTIONS/CLINICAL PHARMACOLOGY:
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. (REF. 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. (REF. 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. (REF. 3)
INDICATIONS AND USAGE:
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.
(REF. 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. (REF. 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. (REF. 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. (REF. 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. (REF. 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.
WARNINGS:
THE OCCURRENCE OF A NEUROLOGIC OR SEVERE HYPERSENSITIVITY REACTION FOLLOWING A
PREVIOUS DOSE IS A CONTRAINDICATION TO FURTHER USE OF THIS PRODUCT. (REF. 3)
THE ADMINISTRATION OF BOOSTER DOSES MORE FREQUENTLY THAN RECOMMENDED (See DOSAGE
AND ADMINISTRATION) MAY BE ASSOCIATED WITH INCREASED INCIDENCE AND SEVERITY OF
REACTIONS. (REF. 3)
Persons who experience Arthus-type hypersensitivity reactions or temperature
greater than 39.4 deg C (103 deg 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. (REF. 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). (REF. 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. (REF. 3-5) Deferral
of administration of vaccine may be considered in individuals receiving
immunosuppressive therapy. (REF. 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, WARNINGS).
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's 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's 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. (REF. 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. (REF. 7) Waiting
until the second trimester is a reasonable precaution to minimize any
theoretical concern. (REF. 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.
DRUG INTERACTIONS:
SEE WARNINGS
ADVERSE REACTIONS:
Local reactions, such as erythema, induration, and tenderness, are common after
the administration of tetanus toxoid. (REF. 8,9,10) Such local reactions are
usually self-limiting and require no therapy. Nodule, (REF. 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. (REF.
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. (REF. 3) (See WARNINGS.)
NEUROLOGICAL COMPLICATIONS, (REF. 12) SUCH AS CONVULSIONS, (REF. 13)
ENCEPHALOPATHY, (REF. 13,14) AND VARIOUS MONO- AND POLYNEUROPATHIES, (REF. 14-
20) INCLUDING GUILLAIN-BARRE SYNDROME, (REF. 21,22) HAVE BEEN REPORTED FOLLOWING
ADMINISTRATION OF PREPARATIONS CONTAINING TETANUS ANTIGEN.
URTICARIA, ERYTHEMA MULTIFORME OR OTHER RASH, ARTHRALGIAS, (REF. 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 DESCRIPTION.)
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. (REF. 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. (REF. 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's 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. (REF. 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 INDICATIONS AND
USAGE) 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. (REF. 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 INDICATIONS AND USAGE).
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. (REF. 3)
SUMMARY GUIDE TO TETANUS PROPHYLAXIS IN ROUTINE WOUND MANAGEMENT (REF. 3)*
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CLEAN, MINOR WOUNDS ALL OTHER WOUNDS**
HISTORY OF TETANUS ----------------------- -----------------------------------------------------
TOXOID (DOSES) TD*/* TIG TD*/* TIG
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Unknown or /= three*/** No**/* No No*//* No
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* 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 Toxoid For Adult Use as the preferred preparation for
active tetanus immunization in wound management of patients 7 years of age or
older. (REF. 3)
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