DIPHTHERIA ANTITOXIN
DESCRIPTION:
Diphtheria and Tetanus Toxoids Adsorbed, aluminum phosphate-adsorbed PUROGENATED
is a sterile combination of refined diphtheria and tetanus toxoids for
intramuscular use only. After shaking, the vaccine is a homogeneous white
suspension.
The diphtheria and tetanus toxins are produced according to the method of
Mueller and Miller (REF. 1,2) and are detoxified by use of formaldehyde. The
toxoids are refined by the Pillemer alcohol fractionation method (REF. 3) and
are diluted with a solution containing sodium phosphate monobasic, sodium
phosphate dibasic, aluminum phosphate, glycine and thimerosal (mercury
derivative) as a preservative. The final concentration of thimerosal in the
combined vaccine is 1:10,000. The aluminum content of the final product does not
exceed 0.80 mg per 0.5 mL dose.
Each 0.5 mL dose is formulated to contain 12.5 Lf units of diphtheria toxoid,
and 5 Lf units of tetanus toxoid.
ACTIONS/CLINICAL PHARMACOLOGY:
Diphtheria is primarily a localized and generalized intoxication caused by
diphtheria toxin, an extracellular protein metabolite of toxinogenic strains of
Corynebacterium Diphtheriae. While the incidence of diphtheria in the U.S. has
decreased from over 200,000 cases reported in 1921 before the general use of
diphtheria toxoid, to only 15 cases reported from 1980 through 1983, the ratio
of fatalities to attack rate has remained constant at about 5% to 10%. (REF. 4)
The highest case fatality rates are in the very young and the elderly.
Following adequate immunization with diphtheria toxoid, which induces antitoxin,
it is thought that protection lasts for at least 10 years. (REF. 4) This
significantly reduces both the risk of developing diphtheria and the severity of
clinical illness. It does not, however, eliminate carriage of C Diphtheriae in
the pharynx or on the skin. (REF. 4)
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. 4) 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. 4,6) 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. 4)
INDICATIONS AND USAGE:
Diphtheria and Tetanus Toxoids Adsorbed is indicated for active immunization of
infants and children from 2 months of age up to their seventh birthday both for
routine protection and as a preventive measure against diphtheria and tetanus,
in circumstances in which the use of a combined triple vaccine containing
pertussis antigen is contraindicated. (REF. 4,5)
Tetanus or diphtheria infection may not confer immunity; therefore, initiation
or completion of active immunization is indicated at the time of recovery from
these infections. (REF. 4)
CONTRAINDICATIONS:
HYPERSENSITIVITY TO ANY COMPONENT OF THE VACCINE, INCLUDING THIMEROSAL, A
MERCURY DERIVATIVE, IS A CONTRAINDICATION.
THE OCCURRENCE OF ANY 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. 4,5)
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 and providing an outbreak of diphtheria does not occur simultaneously.
WARNINGS:
THIS PRODUCT IS NOT RECOMMENDED FOR IMMUNIZING PERSONS ON OR AFTER THEIR SEVENTH
BIRTHDAY.
For individuals 7 years of age or older, Tetanus and Diphtheria Toxoids Adsorbed
For Adult Use (Td) should be used instead of Diphtheria and Tetanus Toxoids
Adsorbed For Pediatric Use (DT). The concentration of diphtheria toxoid in
preparations intended for use in persons 7 years of age or older is lower than
that of the pediatric formulation; a lower dosage of diphtheria toxoid is
recommended for persons 7 years of age or older because adverse reactions to the
diphtheria component are thought to be related to both dose and age. (REF. 4)
THE OCCURRENCE OF A NEUROLOGICAL OR SEVERE HYPERSENSITIVITY REACTION FOLLOWING A
PREVIOUS DOSE IS A CONTRAINDICATION TO FURTHER USE OF THIS PRODUCT. (REF. 4)
DT should not be given to infants or children with thrombocytopenia or any
coagulation disorder that would contraindicate intramuscular injection unless
the potential benefits clearly outweigh 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. 4,5,6)
Deferral of administration of DT may be considered in individuals receiving
immunosuppressive therapy. (REF. 4,5) Other groups should generally receive this
vaccine according to the usual recommended schedule. (REF. 4-7)
Special care should be taken to prevent injection into a blood vessel.
PRECAUTIONS:
GENERAL:
1. THIS PRODUCT SHOULD BE USED FOR THE AGE GROUP BETWEEN 2 MONTHS AND THE
SEVENTH BIRTHDAY.
2. PRIOR TO ADMINISTRATION OF ANY DOSE OF DT, THE PARENT OR GUARDIAN SHOULD BE
ASKED ABOUT THE RECENT HEALTH STATUS OF THE INFANT OR CHILD TO BE IMMUNIZED IN
ORDER TO DETERMINE THE EXISTENCE OF ANY CONTRAINDICATION TO IMMUNIZATION WITH DT
(SEE CONTRAINDICATIONS, WARNINGS).
3. WHEN AN INFANT OR CHILD RETURNS FOR THE NEXT DOSE IN A SERIES, THE PARENT OR
GUARDIAN SHOULD BE QUESTIONED CONCERNING OCCURRENCE OF ANY SYMPTOM AND/OR SIGN
OF AN ADVERSE REACTION AFTER THE PREVIOUS DOSE (SEE CONTRAINDICATIONS, ADVERSE
REACTIONS).
4. 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.
5. 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.
6. Shake vigorously before withdrawing each dose to resuspend the contents of
the vial.
7. 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 medical 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. 8)
INFORMATION FOR THE PATIENT
PRIOR TO THE ADMINISTRATION OF THIS VACCINE, HEALTH CARE PERSONNEL SHOULD INFORM
THE PARENT, GUARDIAN, OR OTHER RESPONSIBLE ADULT OF THE BENEFITS AND RISKS TO
THE CHILD OF VACCINATION AGAINST DIPHTHERIA AND TETANUS.
USE IN PREGNANCY
This product is not recommended for administration to females of child-bearing
age.
DRUG INTERACTIONS:
SEE WARNINGS
ADVERSE REACTIONS:
Local reactions, manifested by varying degrees of erythema, induration, and
tenderness, may occur after administration of DT. (REF. 9,10) Such local
reactions are usually self-limited and require no therapy. Nodule, (REF. 11)
sterile abscess formation, or subcutaneous atrophy may occur at the site of
injection.
Systemic symptoms, including drowsiness, fretfulness, vomiting, anorexia, and
persistent crying have been described following DT immunization. (REF. 9,10)
In one study, fever >/= 38 deg C (100.4 deg F) was reported in 9.3% of DT
recipients, and fever >/= 39 deg C (102.2 deg F) was reported in 0.7% of
recipients. (REF. 9)
Pallor, coldness, and hyporesponsiveness have been reported in a child receiving
a DT vaccine. (REF. 10)
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 DIPHTHERIA AND/OR TETANUS ANTIGENS.
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 DIPHTHERIA, AND/OR TETANUS ANTIGENS.
DOSAGE AND ADMINISTRATION:
FOR INTRAMUSCULAR USE ONLY: SHAKE VIGOROUSLY BEFORE WITHDRAWING EACH DOSE TO
RESUSPEND THE CONTENTS OF THE VIAL.
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration. (See DESCRIPTION.)
The vaccine should be injected intramuscularly, preferably into the midlateral
muscles of the thigh or deltoid, with care 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.
This combined preparation against both diphtheria and tetanus is designed
particularly to meet the need of children less than 7 years of age for whom the
use of a combined triple vaccine containing pertussis antigen is
contraindicated.
It is recommended that active immunization against diphtheria and tetanus be
started at 2 months of age.
UNIMMUNIZED INFANTS AND CHILDREN LESS THAN 1 YEAR OF AGE for whom vaccine
containing pertussis antigen is contraindicated should receive three doses of
0.5 mL each of DT at 4 to 8 week intervals, followed by a fourth (reinforcing)
dose of 0.5 mL, 6 to 12 months after the third dose, for the primary series.
UNIMMUNIZED CHILDREN 1 YEAR OF AGE OR OLDER for whom vaccine containing
pertussis antigen is contraindicated should receive two doses of 0.5 mL each of
DT, 4 to 8 weeks apart, followed by a third (reinforcing) dose 6 to 12 months
later, for the primary series.
IF AFTER BEGINNING A DTP SERIES, FURTHER DOSES OF VACCINE CONTAINING PERTUSSIS
ANTIGEN BECOME CONTRAINDICATED, DT SHOULD BE SUBSTITUTED FOR EACH OF THE
REMAINING DOSES. (REF. 4,5)
The reinforcing dose is an integral part of the primary immunizing series.
Interruption of the recommended schedule with a delay between doses does not
interfere with the final immunity achieved, nor does it necessitate starting the
series over again, regardless of the length of time elapsed between doses. (REF.
4,5)
A booster dose of 0.5 mL is indicated at age 4 to 6 years, preferably prior to
entrance into kindergarten or elementary school. However, if the last dose of
the primary immunizing series was administered after the fourth birthday, a
booster prior to school entry is not considered necessary. (REF. 4,5)
For either primary or booster immunization against tetanus and diphtheria of
individuals 7 years of age and older, the use of Tetanus and Diphtheria Toxoids
Adsorbed For Adult Use is recommended. (REF. 4,5)
DIPHTHERIA PROPHYLAXIS FOR CASE CONTACTS
All case contacts, household and others, who have previously received fewer than
three doses of diphtheria toxoid should receive an immediate dose of an
appropriate diphtheria toxoid- containing preparation and should complete the
series according to schedule. Case contacts who previously received three or
more doses, but who have not received a dose of a preparation containing
diphtheria toxoid within the previous 5 years, should receive a dose of a
diphtheria toxoid-containing preparation appropriate for their age. This
combined preparation against both diphtheria and tetanus is designed
particularly to meet the need of children less than 7 years of age for whom the
use of a combined triple vaccine containing pertussis antigen is
contraindicated.
TETANUS PROPHYLAXIS IN WOUND MANAGEMENT
For routine wound management of children under 7 years of age who are not
completely immunized, DT should be used instead of single-antigen tetanus toxoid
(if pertussis antigen is contraindicated or individual circumstances are such
that potential febrile reactions following DTP might confound the management of
the patient). (REF. 4) Completion of primary vaccination thereafter should be
ensured.
For tetanus-prone wounds in children who have had fewer than three, or an
unknown number of immunizations with a tetanus-toxoid containing product,
passive immunization with human Tetanus- Immune Globulin (TIG) is also
recommended. (REF. 4) A separate syringe and site of injection should be used.
REFERENCES:
1. Mueller JH, Miller PA: Production of diphtheria toxin of high potency (100Lf)
on a reproducible medium. J Immunol 1941;40:21-32.
2. Mueller JH, Miller PA: Factors influencing the production of tetanal toxin. J
Immunol 1947;56:143-147.
3. 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.
4. 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.
5. American Academy of Pediatrics: Report of the Committee on Infectious
Diseases, ed 20. Elk Grove Village, IL, American Academy of Pediatrics, 1986.
6. Recommendation of the ACIP: Immunization of children infected with Human T-
Lymphotrophic Virus Type III/Lymphadenopathy associated virus. MMWR
1986;35(38):595-606.
7. Immunization of children infected with Human Immunodeficiency Virus--
Supplementary ACIP statement. MMWR 1988;37(12):181-183.
8. National Childhood Vaccine Injury Act: Requirements for permanent vaccination
records and for reporting of selected events after vaccination. MMWR
1988;37(13):197-200.
9. Cody C, et al: Nature and rates of adverse reactions associated with DTP and
DT immunizations in infants and children. Pediatrics 1981;68:650-660.
10. Feery BJ: Incidence and type of reactions to triple antigen (DTP) and DT
(CDT) vaccines. Med Jour Of Australia 1982;2:511-515.
11. Fawcett HA, Smith NP: Injection-site granuloma due to aluminum. Arch
Dermatol 1984;120:1318-1322.
12. Rutledge SL, Snead OC: Neurological 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-Barre syndrome after vaccination with purified
tetanus toxoid. S Med J 1987;80:1053-1054.
************************************************************************