DIPHTHERIA AND TETANUS TOXOIDS ADSORBED- corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) and clostridium tetani toxoid antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.
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DESCRIPTION
Diphtheria and Tetanus Toxoids Adsorbed is a sterile, cloudy, white, uniform suspension of diphtheria and tetanus toxoids adsorbed on aluminum phosphate and suspended in isotonic sodium chloride solution for intramuscular injection only. Diphtheria and Tetanus Toxoids Adsorbed vaccine does not contain a preservative.
Diphtheria toxoid is prepared from the toxin produced during the growth of a selected strain of Corynebacterium diphtheriae grown with aeration in submerged culture. The toxin is purified by precipitation, converted to toxoid by the addition of formalin and concentrated by ultrafiltration. The culture medium consists of a tryptic digest of casein, supplemented with cystine, maltose, uracil, inorganic salts and vitamins.
Tetanus toxoid is prepared from the toxin produced during the growth of a selected strain of Clostridium tetani. The toxin is converted to toxoid by the addition of formalin, concentrated and then purified. The culture medium consists of a tryptic digest of casein, supplemented with cystine, dextrose, uracil, inorganic salts and vitamins.
| Each dose (0.5 mL) is formulated to contain: | |
| diphtheria toxoid | 25 Lf |
| tetanus toxoid | 5 Lf |
| aluminum phosphate | 1.5 mg |
| free formaldehyde | <100 mcg |
When tested in guinea pigs, the tetanus and diphtheria components induce at least 2 neutralizing units/mL of serum. The vial stopper for this product does not contain latex.
CLINICAL PHARMACOLOGY
Diphtheria is an acute toxin-mediated disease caused by toxigenic strains of C diphtheriae. Protection against disease is due to the development of neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection, and levels of at least 0.1 IU/mL are generally regarded as protective.(1) (2)
Tetanus is an acute disease caused by an extremely potent neurotoxin produced by C tetani. Protection against disease is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of 0.01 IU/mL, measured by neutralization assay is considered the minimum protective level. (1) (3)
In a clinical study conducted in Baltimore, MD, infants received one of three lots of Diphtheria and Tetanus Toxoids Adsorbed (formulation that contained thimerosal), 0.5 mL, at 2, 4 and 6 months of age. Oral poliovirus vaccine (no longer licensed in the US) was administered concomitantly with Diphtheria and Tetanus Toxoids Adsorbed at 2 and 4 months of age. Diphtheria and tetanus antitoxin levels were evaluated at 8 months of age (see Table 1). Protective levels of diphtheria antitoxin (≥0.01 IU/mL) and tetanus antitoxin (≥0.01 IU/mL) were detected in 99% and 100%, respectively, of the Diphtheria and Tetanus Toxoids Adsorbed recipients after 3 doses. The geometric mean titres (GMT's) for diphtheria and tetanus antitoxin antibodies in recipients of the three Diphtheria and Tetanus Toxoids Adsorbed lots were not significantly different, ranging from 0.25 to 0.35 IU/mL for diphtheria antitoxin antibodies, and from 0.75 to 0.80 IU/mL for tetanus antibodies after the third dose. In a fourth group of 75 infants who received an investigational acellular pertussis vaccine simultaneously with the Diphtheria and Tetanus Toxoids Adsorbed but at separate sites with separate needles and syringes, protective diphtheria and tetanus antitoxin levels developed in 100%.
| Post Dose 3 Diphtheria and Tetanus Toxoids Adsorbed | |
|---|---|
| Diphtheria antitoxin ≥0.01 IU/mL | 99% (135/136) |
| Tetanus antitoxin ≥0.01 IU/mL | 100% (137/137) |
INDICATIONS AND USAGE
Diphtheria and Tetanus Toxoids Adsorbed is indicated for the active immunization of children, from 6 weeks of age up to age 7 years (prior to their 7th birthday) against diphtheria and tetanus in whom concomitant immunization against pertussis is not indicated.
Diphtheria and Tetanus Toxoids Adsorbed is not to be used for treatment of diphtheria or tetanus infection.
If passive immunization is required, Tetanus Immune Globulin (Human) (TIG) and equine Diphtheria Antitoxin are the products of choice for tetanus and diphtheria, respectively. (4)
CONTRAINDICATIONS
A severe allergic reaction (e.g., anaphylaxis) after a previous dose of Diphtheria and Tetanus Toxoids Adsorbed or any other diphtheria toxoid or tetanus toxoid-containing vaccine, or any other component of this vaccine is a contraindication to administration of Diphtheria and Tetanus Toxoids Adsorbed. Because of the uncertainty as to which component of the vaccine may be responsible, none of the components should be administered. Alternatively, such individuals may be referred to an allergist for evaluation if further immunizations are considered.
WARNINGS
Guillain-Barré Syndrome
A review by the Institute of Medicine found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome. (5) If Guillain-Barré syndrome occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give Diphtheria and Tetanus Toxoids Adsorbed or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.
PRECAUTIONS
General
Before administration of Diphtheria and Tetanus Toxoids Adsorbed, the patient's current health status and medical history should be reviewed in order to determine whether any contraindications exist and to assess the benefits and risks of vaccination. (See CONTRAINDICATIONS and WARNINGS.)
Epinephrine Injection (1:1000) and other appropriate agents and equipment must be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.
If Diphtheria and Tetanus Toxoids Adsorbed vaccine is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained.
Information for Vaccine Recipients and Parents/Guardians
Before administration of Diphtheria and Tetanus Toxoids Adsorbed, health-care personnel should inform the parent or guardian of the benefits and risks of the vaccine and the importance of completing the immunization series unless a contraindication to further immunization exists. Health-care personnel should inform the parent or guardian about the potential for adverse reactions that have been temporally associated with Diphtheria and Tetanus Toxoids Adsorbed or other vaccines containing similar ingredients. Health-care personnel should provide the Vaccine Information Statements (VIS), which are required by the National Childhood Vaccine Injury Act of 1986 to be given with each immunization. The parent or guardian should be instructed to report adverse reactions to their health-care provider.
Drug Interactions
Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to Diphtheria and Tetanus Toxoids Adsorbed.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Diphtheria and Tetanus Toxoids Adsorbed has not been evaluated for carcinogenicity, mutagenic potential, or impairment of fertility.
ADVERSE REACTIONS
Diphtheria and Tetanus Toxoids Adsorbed evaluated in clinical trials contained thimerosal.
In a clinical trial in Baltimore, infants received Diphtheria and Tetanus Toxoids Adsorbed at 2, 4 and 6 months of age. In a clinical trial conducted in Canada, 52 children aged 17-22 months who had previously received 3 doses of whole-cell DTP Adsorbed vaccine (not licensed in US), received Diphtheria and Tetanus Toxoids Adsorbed with either an acellular pertussis (n = 25) or a whole cell pertussis (n = 27) vaccine (neither licensed in US) given concurrently but at a separate site. The following adverse events were reported.
| BALTIMORE | CANADA | |||
|---|---|---|---|---|
| Reaction | Dose 1 (n = 155) | Dose 2 (n = 145) | Dose 3 (n = 136) | Dose 4 (n = 52) |
| Systemic Reactions | ||||
| Fever ≥38°C <39°C | 0.7 | 0.8 | 6.6 | 27 |
| Fever ≥39°C <40°C | 0 | 0 | 0 | 0 |
| Fever ≥40°C | 0 | 0 | 0 | 4 |
| Crying | 13.6 | 15.2 | 13.0 | 8 |
| Loss of Appetite | 3.9 | 6.2 | 2.9 | 26 |
| Injection Site Reactions (Diphtheria and Tetanus Toxoids Adsorbed injection site) | ||||
| Redness ≥2.5 cm | 0.7 | 0 | 3.6 | 0 |
| Slight Pain | 2.6 | 2.8 | 2.2 | 11 |
| Moderate Pain | 0.7 | 1.4 | 0 | 0 |
| Hardness ≥2.5 cm | 1.3 | 1.4 | 3.6 | 0 |
In a clinical trial conducted in Vancouver, 99 children aged 4 to 6 years old who were eligible for the preschool (fifth) dose of DTP received Diphtheria and Tetanus Toxoids Adsorbed in one arm and a whole-cell Monovalent Pertussis vaccine (not licensed in the US) in the other. The following local reactions at the Diphtheria and Tetanus Toxoids Adsorbed injection site were reported: redness ≥50 mm - 9%, swelling >50 mm - 51%, tenderness, moderate or severe - 17%, arm mobility "too sore to move" - 9%. The rates of systemic reactions were similar to the control group which received a whole-cell pertussis vaccine, DTP Adsorbed (not licensed in the US). (6)
Data from Post-marketing Experience
The following adverse events have been spontaneously reported during the post-marketing use of a Diphtheria and Tetanus Toxoids Adsorbed vaccine manufactured by Sanofi Pasteur Limited which contained thimerosal. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
The following adverse events were included based on severity, frequency of reporting or the strength of causal association with Diphtheria and Tetanus Toxoids Adsorbed:
Blood and lymphatic system disorders
- Lymphadenopathy
Gastrointestinal disorders
- Nausea
General disorders and administration site conditions
- Injection site inflammation
- Injection site hypersensitivity
- Application site oedema
- Pain
Nervous system disorders
- Convulsion
- Somnolence
- Syncope
- Headache
Skin and subcutaneous tissue disorders
- Rash
- Urticaria
Vascular disorders
- Pallor
Reporting of Adverse Events
Reporting by parents or guardians of all adverse events after vaccination should be encouraged. The National Childhood Vaccine Injury Act of 1986 requires physicians and other health-care providers who administer vaccines to maintain permanent vaccination records, including the manufacturer, lot number, date of administration, and name, address and title of the person administering the vaccine. (7) The Act further requires the health-care provider to report certain adverse events following immunization to the U.S. Department of Health and Human Services. (7) Reportable events include those listed in the Act for each vaccine and events specified in the package insert as contraindications to further doses of the vaccine. These events and other adverse events following vaccination should be reported to the U.S. Department of Health and Human Services Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or http://www.vaers.hhs.gov. Health-care providers also should report adverse events following vaccination with Diphtheria and Tetanus Toxoids Adsorbed to Sanofi Pasteur Inc. at 1-800-822-2463.
DOSAGE AND 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 product should not be administered.
Shake the vial well to distribute uniformly the suspension before withdrawing each dose. If Diphtheria and Tetanus Toxoids Adsorbed cannot be resuspended the vial should be discarded. When administering a dose from a rubber-stoppered vial, do not remove either the rubber stopper or the metal seal holding it in place.
Administer the vaccine intramuscularly. The preferred site is into the anterolateral aspect of the mid-thigh (vastus lateralis muscle) or into the deltoid muscle.
The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.
Do not inject intravenously.
Dosing Regimen
Diphtheria and Tetanus Toxoids Adsorbed is approved for administration as a 5 dose series. The recommended ages for routine vaccination of infants and children younger than 7 years of age against diphtheria and tetanus are 2, 4, 6, 15-18 months, and 4-6 years. The first dose of Diphtheria and Tetanus Toxoids Adsorbed may be administered as early as 6 weeks of age.
Concomitant Administration with Other Vaccines
No safety and immunogenicity data are available on the concomitant administration of Diphtheria and Tetanus Toxoids Adsorbed with other US licensed vaccines.
Concomitant Administration with Tetanus Immune Globulin (Human)
If passive protection against tetanus is required, TIG (Human) may be administered according to its prescribing information, concomitantly with Diphtheria and Tetanus Toxoids Adsorbed at a separate site with a separate needle and syringe.
HOW SUPPLIED
Vial 0.5 mL, 1 dose (10 per package) - NDC No. 49281-225-10
The vial stopper for this product does not contain latex.
References List
- 1
- Department of Health and Human Services, Food and Drug Administration. Biological products; bacterial vaccines and toxoids; implementation of efficacy review; proposed rule. Federal Register 1985;50(240):51002-117.
- 2
- Vitek CR, Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5th ed. Philadelphia, PA: W. B. Saunders; 2008. p. 139-56.
- 3
- Wassilak SGF, et al. Tetanus toxoid. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5th ed. Philadelphia, PA: W.B. Saunders; 2008. p. 805-39.
- 4
- Recommendations of the Advisory Committee on Immunization Practices (ACIP). Diphtheria, Tetanus, and Pertussis: Recommendations for vaccine use and other preventive measures. MMWR 1991;40:No.RR-10.
- 5
- Adverse Events Associated with Childhood Vaccines. Institute of Medicine. 1994.
- 6
- Scheifele D, et al. Role of whole-cell pertussis vaccine in severe local reactions to the preschool (fifth) dose of diphtheria-pertussis-tetanus vaccine. Can Med Assoc Journal 1994;150(1).
- 7
- CDC. National Childhood Vaccine Injury Act: requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 1988;37:197-200.
Product information as of November 2010.
Printed in Canada.
Manufactured by:
Sanofi Pasteur Limited
Toronto Ontario Canada
Distributed by:
Sanofi Pasteur Inc.
Swiftwater PA 18370 USA
R4-1110 USA
| DIPHTHERIA AND TETANUS TOXOIDS ADSORBED
corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) and clostridium tetani toxoid antigen (formaldehyde inactivated) injection, suspension |
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| Labeler - Sanofi Pasteur Inc. (086723285) |
| Establishment | |||
| Name | Address | ID/FEI | Business Operations |
| Sanofi Pasteur Limited | 208206623 | MANUFACTURE | |