Tetanus and Diphtheria Toxoids Adsorbed for Adult Use Preservative-Free Rx Only

TETANUS AND DIPHTHERIA TOXOIDS ADSORBED FOR ADULT USE  - clostridium tetani antigen and corynebacterium diphtheriae antigen injection 
MassBiologics

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Tetanus and Diphtheria Toxoids Adsorbed for Adult Use Preservative-Free Rx Only

DESCRIPTION

Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) is a sterile combination of Tetanus Toxoid and Diphtheria Toxoid adsorbed on aluminum phosphate, which provides simultaneous immunization against Tetanus and Diphtheria.  It is for intramuscular (IM) use only and is supplied in single dose vials.  After shaking, the vaccine appears as a homogeneous milky white suspension.

The Corynebacterium diphtheriae and Clostridium tetani organisms are grown on modified Mueller's media (1,2) which contains bovine extracts.  The bovine material used in these extracts is sourced from countries which the United States Department of Agriculture has determined neither have nor are at risk for bovine spongiform encephalopathy.  The tetanus and diphtheria toxoids are obtained from formalin treated supernatants of the cultures of the tetanus and diphtheria organisms.  The specific antigens are then partially purified by ammonium sulfate fractionation.  The diphtheria toxoid is further purified by column chromatography to a specific activity of not less than 1500 Lf per mg total protein nitrogen.  Tetanus and Diphtheria Toxoids Adsorbed for Adult Use is supplied in single (0.5 ml) dose preservative-free vials which contain a trace amount of thimerosal [mercury derivative, (≤ 0.3 µg mercury/dose)] from the manufacturing process.

In order to minimize reactions in persons age 7 or older, each 0.5 ml dose is fomulated to contain 2.0 Lf of each toxoid (3-5).  When tested per U.S. Food and Drug Administration approved procedures, the tetanus and diphtheria components induce at least 2 neutralizing units/ml of serum in guinea pigs.  Each 0.5 ml dose contains by calculation not more than 0.45 mg aluminum and less than 100 µg (0.02%) of residual formaldehyde.  The aluminum phosphate functions as an adjuvant to increase the immunogenicity of the toxoids in primary immunization.


CLINICAL PHARMACOLOGY

Immunization of infants and children against diphtheria and tetanus has been performed routinely in the U.S. since the late 1940's.  As a consequence the incidence of these diseases and their associated mortality has decreased dramatically (6).

Diphtheria - Diphtheria is a disease caused by infection of the respiratory tract with a toxigenic strain of Corynebacterium diphtheriae which typically produces membranous nasopharyngitis and/or obstructive laryngotracheitis. Intoxication by the diphtheria protein exotoxin results in systemic manifestations that may include myocarditis and neuritis.  The frequency of diphtheria in the U.S. has decreased from about 200,000 cases per year before the general use of diphtheria toxoid immunization to less than five cases per year in recent years (6).  Immunization with diphtheria toxoid induces neutralizing antibodies (antitoxin).  Antitoxin levels of at least 0.01 unit/ml are generally regarded as protective (7).  The efficacy of MassBioLogics' Tetanus and Diphtheria Toxoids Adsorbed For Adult Use is supported by the following:

  1. Response to booster doses. In clinical trials, booster doses of Td formulated to contain 1 Lf and 5 Lf of diphtheria toxoid, both induced antitoxin levels greater than 0.01 unit/ml when administered to adults with prior diphtheria immunity (3,4,8).  In 140 adolescent males given a single booster dose of the 1 Lf formulation, all achieved an antitoxin titer of 0.01 units/ml or higher (8).  It is expected that vaccine containing 2 Lf of diphtheria toxoid per dose will also induce an antitoxin level of 0.01 units/ml.
  2. Response to primary series of inoculations. Data on the anti-diphtheria toxin response of adults to primary immunization with Td is limited: Of 10 adults with less than 0.001 units/ml of diphtheria antitoxin in pre-immunization serum, 50% had antitoxin concentrations of 0.01 or greater after 2 doses of Td (2 Lf diphtheria toxoid dose). After 3 doses of Td, 6 of 6 adults achieved 0.01 antitoxin units/ml (9). Immunization reduces the risk of developing diphtheria and the severity of illness but does not eliminate carriage of the organism from the respiratory tract or skin (6).

Tetanus - Tetanus (lockjaw) is a neurologic disease with severe muscular spasms caused by a protein exotoxin produced by Clostridium tetani usually in a contaminated wound. Routine immunization with tetanus toxoid has reduced the rate of tetanus to less than 100 cases per year in the entire United States (6). Because immunity to tetanus is not induced by exposure to this organism, or even by the natural disease, immunity must be induced by primary immunization and maintained by subsequent booster immunizations with the tetanus toxoid (6). Immunization with Td vaccine induces neutralizing antibodies to tetanus toxin. Tetanus toxoid is a highly effective antigen, and a completed primary series generally induces serum antitoxin levels of at least 0.01 tetanus antitoxin units, a level which has been reported to be protective and persists for at least 10 years in most individuals after full immunization (7). The efficacy of MassBioLogics' Tetanus and Diphtheria Toxoids Adsorbed for Adult Use is supported by the following:

  1. Response to booster doses. Booster doses of Td at doses of 1 Lf and 5 Lf of tetanus toxoid, induced tetanus antitoxin levels greater than 0.01 unit/ml when administered to all 36 adults who had received prior tetanus immunizations (3). It is expected that vaccine containing 2 Lf of tetanus toxoid per dose will also induce an antitoxin level of 0.01 units/ml.
  2. Response to primary series of inoculations. Data on the anti-tetanus toxin response of adults to primary immunization with Td is limited: Of 20 adults with less than 0.0025 units/ml of tetanus antitoxin in pre-immunization serum, 14 (70%) had anitoxin concentrations of 0.01 or greater after 2 doses of Td (2 Lf tetanus toxoid). After 3 doses of Td, 16 of 16 adults achieved 0.01 antitoxin units/ml (9).

INDICATIONS AND USAGE

Tetanus and Diphtheria Toxoids Adsorbed For Adult Use is indicated for the active immunization against tetanus and diphtheria. It is not to be used for treatment of actual infection. Td should be used for immunization of all patients 7 years of age and older. Td rather than Diphtheria and Tetanus Toxoids Adsorbed (DT) is the agent of choice for patients 7 years old and older because side effects from higher doses of diphtheria toxoid are more common in older children and adults (6). For children under the age of 7, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) is the primary immunization of choice unless they have an adverse reaction to the pertussis component then DT should be given. Td can be administered in conjunction with either Tetanus Immune Globulin (Human) or Diphtheria Antitoxin (see DOSAGE AND ADMINISTRATION). It should be noted that all individuals immunized with Td vaccine may not be protected against disease. Td vaccine is also indicated for the prevention of neonatal tetanus (see PREGNANCY section).

CONTRAINDICATIONS

Hypersensitivity to any component of the vaccine is a contraindication. The occurrence of a severe adverse event following a previous dose of Td vaccine is a definitive contraindication to the receipt of further doses of Td vaccine (6). Severe adverse events include:

  1. Anaphylactic reaction (hives, swelling of the mouth, difficulty breathing, hypotension, or shock).
  2. Neurologic reaction, including encephalopathy (10).

WARNINGS

This product is not recommended for immunizing persons less than 7 years of age.

If any of the following events occur in temporal relation to receipt of Td, the decision to give subsequent doses of vaccine should be carefully considered. There may be circumstances in which the potential benefits outweigh possible risks, particularly because these events are not associated with permanent sequelae (6).

  1. Arthus-type hypersensitivity reactions, characterized by severe local reactions (general starting 2 to 8 hours after an injection).
  2. Temperature of >39.4°C (103°F) within 48 hours not due to another identifiable cause.

Individuals who experienced Arthus-type hypersensitivity reactions or fever greater than 39.4°C (103°F) following a prior dose of tetanus toxoid usually have very high serum tetanus antitoxin levels. These individuals should not be given emergency doses of Td vaccine more frequently than every 10 years, even if they have a wound that is neither clean nor minor. Safety hazards which limit but do not preclude the use of the product include:

  1. Thrombocytopenia or other coagulation disorders which contraindicate intramuscular injection. Td should not be given unless the potential benefit clearly outweighs the risk.
  2. A routine booster dose should not be given more frequently than every ten years. (This would not preclude wound management considerations.)
The Advisory Committee on Immunization Practices (ACIP) has published guidelines for vaccination of persons with recent or acute illness (11).

PRECAUTIONS

General:

  1. Care should be taken by the health care provider for the safe and effective use of this product. The health care provider should be familiar with recent medical literature and with our package literature before administration of Td.
  2. The parenteral administration of any biologic should be surrounded by every precaution for the prevention and arrest of allergic and other untoward reactions. This should include the availability of epinephrine (1:1000) for treatment of an anaphylactic reaction.
  3. The health care provider should obtain the immunization history of the vaccinee. The patient, parent or guardian should be questioned about previous reactions to a dose of this product or similar products. It is strongly recommended to document the presence or absence of prior adverse events in the patient's permanent medical record.
  4. The health care provider should inquire about the current health status of the vaccinee before administration of Td.
  5. Td vaccine should not be injected into a blood vessel.
  6. Patients who are on immunosuppressive therapy may not respond to Td vaccine. If immunosuppressive therapy is to be discontinued shortly, it is reasonable to defer vaccination until the patient has been off therapy for 1 month; otherwise, the patient should be vaccinated while still on therapy.
  7. The administration of Td vaccine is not contraindicated based on the presence of human immunodeficiency virus infection (12, 13).
  8. A separate sterile needle and syringe should be used for each administration to prevent transfer of infectious disease. Needles should be disposed of properly and should not be recapped.
  9. Health care professionals should administer this product with caution to patients with a prior history of Guillain Barre Syndrome (see ADVERSE REACTIONS).
  10. Product should be shaken vigorously to obtain a uniform suspension before administration.

Information for patients:

  1. Parents should be fully informed of the benefits and risks of immunization with Td. According to the National Childhood Vaccine Injury Act (NCVIA) of 1986, Vaccine Information Materials (VIMs) must be provided for each dose of vaccine that is administered. Copies may be obtained through the American Academy of Pediatrics.
  2. Patient, parents or guardians should be informed of the importance of completing the immunization series for Td vaccine.
  3. Patients, parents or guardians should be instructed to report any serious adverse reactions to their health care providers. These adverse events should then be reported by the health care provider to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS) utilizing the VAERS form. A 24 hours toll free information line may be contacted for information on the VAERS system, 1-800-822-7967 (14).

Drug Interactions:
As with other IM injections, caution should be exercised with patients on anticoagulant therapy. Patients that are on immunosuppressive therapy may not respond to Td vaccine (6) (see GENERAL PRECAUTIONS). The Advisory Committee on Immunization Practices (ACIP) recommends that many of the commonly used vaccines can safely and effectively be administered simultaneously (i.e., on the same day, not at the same anatomic site) (11). In addition, in general, inactivated vaccines can be administered simultaneously at separate sites (11). Tetanus Immune Globulin (Human) or Diphtheria Antitoxin, if used, should be administered in a separate site, with a separate needle and syringe.

Tetanus prophylaxis in wound management:
Available evidence shows that complete primary immunization with tetanus toxoid provides long lasting protective antitoxin levels. Additionally, protective antitoxin develops rapidly in response to a booster dose in persons who have previously received 2 or more injections of tetanus toxoid. Therefore, passive protection with Tetanus Immune Globulin (Human) need be considered only when the wound is not classified as a clean, minor wound, and the patient has less than three previous injections of tetanus toxoid (6). Documented cases of tetanus are rare in individuals with adequate primary immunization. Antitoxin persists at protective levels for at least 5 years after 4 doses of tetanus toxoid (15). Ability to react promptly to booster injections persists for a longer time. In wound management it is  therefore unnecessary to use booster injections more often than every 5 years. For persons whose immunizations remain incomplete following wound management, the remainder of the recommended series should be given. If passive immunization is needed, Tetanus Immune Globulin (Human) is the product of choice. It offers the advantages of longer protection and freedom from undesirable reactions. The recommended prophylactic dose is 250 units of Tetanus immune Globulin (Human) IM for wounds of average severity (6). When tetanus toxoid and Tetanus Immune Globulin (Human) are given concurrently, separate syringes and separate sites should be used (6).

Administration with Diphtheria Antitoxin:
Persons 7 years of age and older who have close contact with a case of diphtheria should be immunized with Td if they have not received a booster dose of diphtheria within the last 5 years (6). If diphtheria antitoxin is also administered, it should be administered in a separate syringe and at a separate body site from Td.

Carcinogenesis, Mutagenesis, Impairment of Fertility:
No long-term studies have been performed to evaluate the carcinogenic potential or effects on fertility of Td vaccine.

Pregnancy: Pregnancy Category C:
As a means of preventing neonatal tetanus, Td vaccine is recommended for use for unimmunized pregnant women. If possible, waiting until the second trimester of pregnancy to administer Td vaccine would be a reasonable precaution (3). Adequate immunization by routine booster doses in non-pregnant women of childbearing age can obviate the need to vaccinate women during pregnancy (see DOSAGE AND ADMINISTRATION). Animal reproductive studies have not been conducted with Tetanus and Diphtheria Toxoids Adsorbed For Adult Use. It is not known whether Td can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Td should be given to a pregnant woman only if clearly needed.

Nursing mothers:
There is no evidence that breast milk from women who have received Td is harmful to infants (16).

Pediatric Use:
The safety and effectiveness in children below the age of 7 years has not been established. It should be noted that the primary immunization of choice in children less than 7 years of age is Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) unless they have an adverse reaction to the pertussis component then DT should be given.

ADVERSE REACTIONS

The frequency of local reactions at the site of injection and systemic symptoms following administration of Td varies with factors such as the exposure to previous doses of diphtheria and tetanus toxoids, the dose of each toxoid, the method of administration, and the recipient's level of serum tetanus antitoxin (17). Persons with high levels of antitoxin from previous doses of tetanus toxoid are more likely to experience adverse reactions (5,8,18). For these reasons, the frequency of local and systemic reactions associated with Td have varied from 0% to 95% (17). Citation of specific frequencies may be misleading. Data on the adverse reactions to fluid and adsorbed preparations of MassBioLogics' Td with various doses of the diphtheria and tetanus components have been reported in a series of studies (3-5,8,18). The rates of adverse reactions to MassBioLogics' Td vaccine containing 2.0 Lf of each toxoid per dose are not known. It is expected that MassBioLogics' Td vaccine may be associated with adverse reactions observed following administration of other Td vaccines. The following reactions have been associated with vaccines containing diphtheria and tetanus toxoids:

Body as a Whole: Local Reactions at the Injection Site: Pain, redness, swelling (edema), warmth, induration, nodule, abscess (20), tenderness, arthus reaction: severe local reactions starting 2 to 8 hours after an injection, subcutaneous atrophy, cellulitis.

Systemic Reactions: Irritability, fever >38°C (100.4°F), malaise, aches and pains, flushing, chills, headache, dizziness, anaphylaxis: i.e., hives, swelling of mouth, difficulty breathing, death, hypotension or shock.

Deaths have been reported in temporal association with the administration of Td vaccine.

Note: Inadvertent administration of vaccines containing aluminum adjuvant into subcutaneous tissue may increase the frequency of these more severe local reactions (19) (see DOSAGE AND ADMINISTRATION).

Cardiovascular System: Hypotension,Tachycardia, Syncope.

Digestive System: Anorexia, Vomiting, Nausea.

Hemic and Lymphatic Systems: Arthralgia, Myalgia.

Skin: Urticaria, Rash, Hives, Pruritus/Itching, Erythema multiforme, Sweating.

Nervous System: Polyneuritis - 1 in 2,500,000 doses (20), Convulsions (20), Encephalopathy (10), Transverse Myelitis (21,22), Mononeuritis, Paralysis of the radial nerve, Guillain Barre Syndrome, Polyradiculoneuropahy, Acute midbrain syndrome, EEG disturbances, Brachial plexus neuropathies (23), Accommodation pareses, Paralysis of the recurrent nerve, Paresthesia.

Respiratory System: Difficulty breathing.

Special Senses - Ear: Cochlear lesions (24).

Reporting of Adverse Events: 

If an adverse reaction to this product should occur, the Health Care Provider should report the lot number and a description of the reaction to MassBioLogics immediately (Telephone {617} 474-3000). Under the National Childhood Vaccine Injury Act (1986) health care providers are required by law to report the adverse events occurring after Td immunization described below. The adverse event must be reported to the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS) utilizing the VAERS form. VAERS forms can be obtained by writing to VAERS P.O. Box 1100 Rockville, MD 20849-1100, at www.fda.gov/vaers, or by calling the 24-hour toll free information line at 1-800-822-7967. Completed forms should be sent to VAERS at the above address. For questions regarding adverse events, the National Vaccine Injury Compensation Program office may be contacted (1-800-338-2382) .


The following adverse events must be reported to VAERS: Any events set forth in the National Childhood Vaccine Injury Act (25) or the Vaccine Injury Table, including anaphylaxis or anaphylactic shock within 7 days; brachial neuritis within 28 days; any acute complication or sequela (including death) of an illness, disability, injury, or any condition referred to above; or any event that would contraindicate further doses of vaccine, according to this package insert for Tetanus and Diphtheria Toxoids Adsorbed for Adult Use.

DOSAGE AND ADMINISTRATION

Primary Immunization:

The primary series for adults and children 7 years of age and older is three doses of 0.5 ml each given intramuscularly. The second dose is given 4-8 weeks after the first dose and the third dose is given 6-12 months after the second dose. Children who remain incompletely immunized at an age greater than 7 years should be counted as having prior exposure to tetanus and diphtheria toxoids (e.g., a child who previously received 2 doses of Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) or Diphtheria and Tetanus Toxoids Adsorbed (DT) needs only 1 dose of Tetanus and Diphtheria Toxoids Adsorbed For Adult Use to complete the primary series for tetanus and diphtheria.) If a contraindication to pertussis vaccine exists, DT should be substituted for DTaP for children less than 7 years of age. Interruption of the recommended schedule with a delay between doses does not interfere with the final immunity achieved with Td. There is no need to start the series over again, regardless of the length of time elapsed between doses. The preferred site is the deltoid muscle of the upper arm. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk. The Advisory Committee on Immunization Practices (ACIP) recommends that many of the commonly used vaccines can safely and effectively be administered simultaneously (i.e., on the same day, not at the same anatomic site) (15). In addition, in general, inactivated vaccines can be administered simultaneously at separate sites (15). Tetanus Immune Globulin (Human) or Diphtheria Antitoxin, if used, should be administered in a separate site, with a separate needle and syringe.


Booster Doses:

Routine Booster: A single injection of 0.5 ml of Tetanus and Diphtheria Toxoids Adsorbed For Adult Use is given 10 years after completion of the primary immunization and every 10 years thereafter.  If a dose is given sooner as part of wound management, the next booster dose 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.

Tetanus Prophylaxis in wound management: Available evidence shows that complete primary immunization with tetanus toxoid provides long lasting protective antitoxin levels. Additionally, protective antitoxin develops rapidly in response to a booster dose in persons who have previously received 2 or more injections of tetanus toxoid. Therefore, passive protection with Tetanus Immune Globulin (Human) need be considered only when the wound is not classified as a clean, minor wound, and the patient has less than three previous injections of tetanus toxoid (6). Documented cases of tetanus are rare in individuals with adequate primary immunization. Antitoxin persists at protective levels for at least 5 years after 4 doses of tetanus toxoid (16). Ability to react promptly to booster injections persists for a longer time. In wound management it is therefore unnecessary to use booster injections more often than every 5 years. For persons whose immunizations remain incomplete following wound management, the remainder of the recommended series should be given. If passive immunization is needed, Tetanus Immune Globulin (Human) is the product of choice. It offers the advantages of longer protection and freedom from undesirable reactions. The recommended prophylactic dose is 250 units of Tetanus Immune Globulin (Human) IM for wounds of average severity. When tetanus toxoid and immune globulin are given concurrently, separate syringes and separate sites should be used.


Administration with Diphtheria Antitoxin:

Persons 7 years of age and older who have close contact with a case of diphtheria should be immunized with Td if they have not received a booster dose of diphtheria within the last 5 years (6). If diphtheria antitoxin is also administered, it should be administered in a separate syringe and at a separate body site from Td.


Administration:

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. If these conditions exist the vaccine should not be administered.

In order to resuspend the vaccine shake the vial well before withdrawing the dose to obtain a homogenous milky white suspension. Discard the vaccine if it cannot be resuspended. Td is administered intramuscularly. Pull back on the plunger to make sure that the needle is not in a blood vessel before an injection is made. Inadvertent administration of vaccines containing aluminum adjuvant intradermally or subcutaneously may produce more severe local reactions (18). Therefore, a needle of sufficient length to ensure intramuscular administration should be selected. Do not inject more than 0.5 ml of this combined vaccine.


Recording Requirements:

All health-care providers who administer Td vaccine are required by law to record the following information in the vaccine recipient's permanent medical record (or in a permanent office file or log):

  1. the date the vaccine was given, and
  2. the manufacturer and lot number of the vaccine; and
  3. the name, address, and title of the professional administering the vaccine.


HOW SUPPLIED

NDC no. 14362-0111-3: Vial (latex free), 1 dose (10 per package)

STORAGE

Store vials at 2°C - 8°C (35.6°F - 46.4°F). DO NOT FREEZE. Do not use after expiration date.

REFERENCES

1. Latham, W.C., Bent, D.F. and Levine, L.Tetanus Toxin Production in the Absence of Protein, APP. Micro.10:146-152, 1962.

2. Wyman, L., Edsall, G., and McComb, J.A. Diphtheria Toxin Production on Modified Mueller's Media, Bacteriological Proceedings, 1950.

3. Ipsen, J.Jr., Immunization of Adults Against Diphtheria and Tetanus. NEJM. 251:459-466, 1954.

4. Edsall, G., Altman, J.S. and Gaspar, A.J. Combined Tetanus- diphtheria immunization of adults. Use of small doses of diphtheria toxoid, Am. J. Pub. Health. 44:1537-1545, 1954.

5. McComb, J.A. and Levine, L. Adult Immunization II. Dosage Reduction as a solution to Increasing Reactions to Tetanus Toxoid. NEJM. 256:1152-1158, 1961.

6. Centers for Disease Control. Diphtheria, Tetanus and Pertussis: Recommendations for vaccine use and other preventive measures: Recommendations of the Immunization Practices Advisory Committee (ACIP) MMWR 40:(No. RR-10); 1-28, 1991.

7. Federal Register Notice, Friday December 13, 1985, Vol. 50. No.240.

8. Levine, L., Ipsen J., McComb, J.A. Adult Immunization: Preparation and evaluation of combined fluid tetanus and diphtheria toxoids for adult use. Am. J. Hyg. 73:20-35, 1961.

9. Data on file: Product License - Tetanus and Diphtheria Toxoids Adsorbed For Adult Use.

10. Greco, D. Case-control study on encephalopathy associated with diphtheria-tetanus immunization in Campania, Italy Bull. WHO, 63:925-929, 1985.

11. Centers for Disease Control. General Recommendations on Immunization, Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 55: (No. RR-15); 1-48, 2006.

12. Immunization Practices Advisory Committee. Immunization of children infected with human T-lymphotropic virus type III/lymphadenopathy- associated virus. MMWR, 35:595-598, 603-606, 1986 and 37:181-183, 1988.

13. Immunization Practices Advisory Committee (ACIP). General Recommendations on Immunizations. MMWR, 38:221, 1989.

14. Centers for Disease Control. Vaccine Adverse Event Reporting System-United States. MMWR 39: (No. 41) 730- 733, 1990.

15. Gottlieb, S., McLaughlin, F.X., Levine, L., Latham, W.C., and Edsall, G. Long Term Immunity to Tetanus - A Statistical Evaluation and its Clinical Implications. Amer. Journal Public Health. 54:961 - 971, 1964.

16. Drug Information for Health Care Professional, Vol. I, USP DI, 1996, 16th Edition, p. 1246-1247.

17. Wassilak, S.G., Orenstein, W.A., Sutter, R.W., Tetanus Toxoid - Chapter 18 in Plotkin, S.A. and Orenstein, W.A. Vaccines Third Edition, W.B.Saunders, Philadelphia, 1999.

18. Levine, L., Edsall, G. Tetanus toxoid: What determines reaction proneness? J.Infect. Dis. 144:376, 1981.

19. Bernier, R.M., Frank, J.A., Jr. and Nolan, T.F. Abscesses complicating DTP vaccination. Am. J. Dis. Child., 135:826-828, 1981.

20. Rutledge, S.L. and Snead, O.C. Neurologic complications of immunizations. J. Pediatrics. 109:917-924, 1986.

21. Tezzon F., Tomelleri P., Ferrari G., Sergi A.: Acute radiculomyelitis after antitetanus vaccination. Ital. J. Neurol. Sci., 15:191-193, 1994.

22. Whittle, E., Roberton N.R.C., Transverse Myelitis after diphtheria, tetanus, and polio immunization. British Medical Journal, 6074:1450, 1977.

23. Tsaris, P.L., Duch, P,J., Mulder, D.W.: Natural history of brachial plexus neuropathy. Arch. Neurol., 27:109-117, 1972.

24. Wirth, G. Reversible Kochlearisschadigung nach Tetanol-Injektion. Munch. Med. Wschr., 107, 379-381, 1965.

25. National Childhood Vaccine Injury Act: Requirements for Permanent Vaccination Records and for Reporting at Selected events after Vaccination, MMWR 37:197-200, 1988.



Manufactured by:
MassBiologics
University of Massachusetts Medical School
Boston, MA 02130
US Government License 1779


Product information as of May 2008

Carton Label

Carton Label C0129

Vial Label

Vial Label L012801


TETANUS AND DIPHTHERIA TOXOIDS ADSORBED FOR ADULT USE 
tetanus and diphtheria toxoids adsorbed for adult use   injection
Product Information
Product TypeVACCINENDC Product Code (Source)14362-0111
Route of AdministrationINTRAMUSCULARDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
CLOSTRIDIUM TETANI ANTIGEN (CLOSTRIDIUM TETANI ANTIGEN) CLOSTRIDIUM TETANI ANTIGEN2.0   in 0.5 mL
CORYNEBACTERIUM DIPHTHERIAE ANTIGEN (CORYNEBACTERIUM DIPHTHERIAE ANTIGEN) CORYNEBACTERIUM DIPHTHERIAE ANTIGEN2.0   in 0.5 mL
Inactive Ingredients
Ingredient NameStrength
ALUMINUM PHOSPHATE 
Formaldehyde 
Product Characteristics
Colorwhite (After shaking, the vaccine appears as a homogenous milky white suspension) Score    
ShapeSize
FlavorImprint Code
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
114362-0111-310 VIAL In 1 CARTONcontains a VIAL, SINGLE-DOSE (14362-0111-3)
114362-0111-30.5 mL In 1 VIAL, SINGLE-DOSEThis package is contained within the CARTON (14362-0111-3)

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
BLABLA10132210/13/1967

Labeler - MassBiologics (019081961)
Establishment
NameAddressID/FEIOperations
MassBiologics019081961manufacture
Revised: 04/2009MassBiologics