NDC 49281-215 Tenivac

Clostridium Tetani Toxoid Antigen (formaldehyde Inactivated) And Corynebacterium Diphtheriae Toxoid Antigen (formaldehyde Inactivated)

NDC Product Code 49281-215

NDC CODE: 49281-215

Proprietary Name: Tenivac What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Clostridium Tetani Toxoid Antigen (formaldehyde Inactivated) And Corynebacterium Diphtheriae Toxoid Antigen (formaldehyde Inactivated) What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This vaccine is used to help prevent problems that may occur with 2 bacterial infections in children and adults (tetanus and diphtheria). Tetanus (lockjaw) and diphtheria can cause serious, sometimes fatal problems (heart problems, nerve problems, muscle paralysis). Vaccination is the best way to protect (provide immunity) against these life-threatening diseases. Vaccines work by getting the body to make its own protection (antibodies). This vaccine is recommended for all people 7 years and older. Diphtheria and tetanus toxoids combined (adult) injection should not be used in anyone younger than 7 years because they may not be fully protected by this vaccine. A vaccine for children younger than 7 years is available. Consult your child's health care professional for more information.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE CLOUDY)

NDC Code Structure

NDC 49281-215-10

Package Description: 10 VIAL, SINGLE-DOSE in 1 PACKAGE > .5 mL in 1 VIAL, SINGLE-DOSE (49281-215-58)

NDC 49281-215-15

Package Description: 10 SYRINGE in 1 PACKAGE > .5 mL in 1 SYRINGE (49281-215-88)

NDC Product Information

Tenivac with NDC 49281-215 is a a vaccine lable product labeled by Sanofi Pasteur Inc.. The generic name of Tenivac is clostridium tetani toxoid antigen (formaldehyde inactivated) and corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated). The product's dosage form is injection, suspension and is administered via intramuscular form.

Labeler Name: Sanofi Pasteur Inc.

Dosage Form: Injection, Suspension - A liquid preparation, suitable for injection, which consists of solid particles dispersed throughout a liquid phase in which the particles are not soluble. It can also consist of an oil phase dispersed throughout an aqueous phase, or vice-versa.

Product Type: Vaccine What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Tenivac Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CLOSTRIDIUM TETANI TOXOID ANTIGEN (FORMALDEHYDE INACTIVATED) 5 [Lf]/.5mL
  • CORYNEBACTERIUM DIPHTHERIAE TOXOID ANTIGEN (FORMALDEHYDE INACTIVATED) 2 [Lf]/.5mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ALUMINUM PHOSPHATE (UNII: F92V3S521O)
  • FORMALDEHYDE (UNII: 1HG84L3525)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Inactivated Clostridium Tetani Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Tetanus Toxoid - [CS]
  • Inactivated Corynebacterium Diphtheriae Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Diphtheria Toxoid - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sanofi Pasteur Inc.
Labeler Code: 49281
FDA Application Number: BLA103171 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 12-08-2010 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Tetanus, Diphtheria (Td) Vaccine

Tetanus, Diphtheria (Td) Vaccine is


...
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* Please review the disclaimer below.

Tenivac Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

TENIVAC® is a vaccine indicated for active immunization for the prevention of tetanus and diphtheria in persons 7 years of age and older.

2.1 Primary Immunization

In persons who have not been immunized previously against tetanus and diphtheria, primary immunization with TENIVAC vaccine consists of three 0.5 mL doses. The first 2 doses are administered 2 months apart and the third dose is administered 6-8 months after the second dose.TENIVAC vaccine may be used to complete the primary immunization series for tetanus and diphtheria, following one or two doses of Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (whole-cell DTP), Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP), and/or Diphtheria and Tetanus Toxoids Adsorbed (DT). However, the safety and efficacy of TENIVAC vaccine in such regimens have not been evaluated.

2.2 Routine Booster Immunization

TENIVAC vaccine may be used for routine booster immunization against tetanus and diphtheria in persons 7 years of age and older. Routine booster immunization against tetanus and diphtheria is recommended in children 11-12 years of age and every 10 years thereafter.

2.3 Diphtheria Prophylaxis For Case Contacts

TENIVAC vaccine may be used for post-exposure diphtheria prophylaxis in persons 7 years of age and older who have not completed primary vaccination, whose vaccination status is unknown, or who have not been vaccinated with diphtheria toxoid within the previous 5 years. Consult recommendations of the Advisory Committee on Immunization Practices for additional interventions for diphtheria prophylaxis in close contacts of diphtheria patients. (1)

2.4 Tetanus Prophylaxis In Wound Management

For active tetanus immunization in wound management of patients 7 years of age and older, a preparation containing tetanus and diphtheria toxoids is preferred instead of single-antigen tetanus toxoid to enhance diphtheria protection. (1) TENIVAC vaccine is approved for wound management of patients 7 years of age and older.The need for active immunization with a tetanus toxoid-containing preparation, with or without passive immunization with Tetanus Immune Globulin (TIG) (Human) depends on both the condition of the wound and the patient's vaccination history. (See Table 1.) When indicated, TIG (Human) should be administered at a separate site, with a separate needle and syringe, according to the manufacturer's package insert. If a contraindication to using tetanus toxoid-containing preparations 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 with TIG (Human) should be given. (1)Table 1: Guide for use of Tetanus and Diphtheria Toxoids Adsorbed (Td) for Tetanus Prophylaxis in Routine Wound Management in Persons 7 Years of Age and Older History of Adsorbed Tetanus Toxoid (Doses)Clean, Minor WoundsAll Other WoundsSuch as, but not limited to, wounds contaminated with dirt, puncture wounds and traumatic wounds.TdTIGTdTIGUnknown or 10 years since last dose.NoNoYes, if >5 years since last dose. (More frequent boosters are not needed and can accentuate side effects.)No

2.5 Administration

Just before use, shake the vial or syringe well until a uniform, white, cloudy suspension results. 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.When withdrawing a dose from a rubber-stoppered vial, do not remove either the rubber stopper or the metal seal holding it in place.Each 0.5 mL dose of TENIVAC vaccine is to be administered intramuscularly. The preferred site is 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 administer this product intravenously or subcutaneously.TENIVAC vaccine should not be combined through reconstitution or mixed with any other vaccine.

3 Dosage Forms And Strengths

TENIVAC vaccine is a suspension for injection available in 0.5 mL single-dose vials or syringes. [See Description (11).]

4.1 Hypersensitivity

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of TENIVAC vaccine or any other tetanus toxoid or diphtheria toxoid-containing vaccine or any other component of this vaccine is a contraindication to administration of TENIVAC vaccine. [See Description (11).] Because of 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 to be considered.

5.1 Management Of Acute Allergic Reactions

Epinephrine hydrochloride solution (1:1,000) and other appropriate agents and equipment must be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

5.2 Latex

The tip caps of the TENIVAC prefilled syringes may contain natural rubber latex, which may cause allergic reactions in latex sensitive individuals.

5.3 Frequency Of Administration

More frequent doses of TENIVAC vaccine than described in Section 2, Dosage and Administration, may be associated with increased incidence and severity of adverse reactions. [See Dosage and Administration (2.1, 2.2, 2.3, 2.4).]

5.4 Arthus Reactions

Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of a tetanus toxoid-containing vaccine usually have high serum tetanus antitoxin levels and should not receive TENIVAC vaccine more frequently than every 10 years, even for tetanus prophylaxis as part of wound management.

5.5 Guillain-Barré Syndrome And Brachial Neuritis

A review by the Institute of Medicine found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillian-Barré syndrome. (2) If Guillain-Barré syndrome occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give TENIVAC vaccine or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.

5.6 Limitations Of Vaccine Effectiveness

Vaccination with TENIVAC vaccine may not protect all individuals.

5.7 Altered Immunocompetence

If TENIVAC vaccine is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained. [See Drug Interactions (7.3).]

6.1 Data From Clinical Studies

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events. In a primary immunization study conducted in Canada, 18 participants, 8 of whom were 6 to 9 years of age and 10 of whom were 17 to 56 years of age, received three doses of TENIVAC vaccine. In four booster immunization studies conducted in either the US or Canada, TENIVAC vaccine was administered to 3,723 participants overall, ranging in age from 11 to 93 years.In one of these studies, a US multi-center booster immunization study (TDC01), 2,250 adolescents and adults ages 11-59 years of age received TENIVAC vaccine in an open-label design and adults 60 years of age and over were randomized to receive either TENIVAC vaccine (N = 700) or DECAVAC vaccine (US licensed Td manufactured by Sanofi Pasteur Inc.) (N = 701). Vaccine assignment for participants ≥60 years of age was unblinded to pharmacists and vaccination nurses, but was blinded to other study personnel and participants. Among participants who received TENIVAC vaccine, overall, 80.4% were Caucasian, 3.3% Black, 5.1% Hispanic, 4.5% Asian and 6.6% other races. Among participants ≥60 years of age, the racial distribution was similar for the TENIVAC vaccine and DECAVAC vaccine groups. Among participants who received TENIVAC vaccine, the proportion of participants who were female varied by age group (44.4% of participants 11-18 years of age, 70.1% of participants 19-59 years of age and 62.4% of participants ≥60 years of age). Among participants ≥60 years of age who received DECAVAC vaccine, 57.6% were female. Nearly all (99.8%) enrolled participants and all participants in the per-protocol immunogenicity population had a reported or documented history of previous immunization against tetanus and diphtheria and, by report, had not received a vaccine containing tetanus or diphtheria toxoid within 5 years prior to enrollment. In the US multi-center booster immunization study, solicited injection site reactions and systemic adverse events were monitored on diary cards for a subset of participants 11-59 years of age and for all participants ≥60 years of age. The incidence and severity of solicited injection site reactions and selected solicited systemic adverse events that occurred within 3 days following vaccination are shown in Table 2.Table 2: Frequency and Severity of Selected Solicited Adverse Events Within 0-3 Days Following TENIVAC Vaccine or DECAVAC Vaccine in a US StudyTENIVAC VaccineDECAVAC VaccineAdolescents11 to 18 yearsN = 491-492%Adults19 to 59 yearsN = 247%Adults≥60 yearsN = 688-695%Adults≥60 yearsN = 686-693%Injection Site Adverse ReactionsPain  Any80.174.935.329.4  ModerateModerate: interfered with activities, but did not require medical care or absenteeism.15.018.2  2.9  2.3  SevereSevere: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.  0.2  0.4  0.6  0.7Redness  Any25.615.818.118.0  ≥35 mm to <50 mm  1.2  2.4  0.7  1.3  ≥50 mm  0.4  0.4  2.3  1.9Swelling  Any  15.0  17.0  12.1  13.0  ≥35 mm to <50 mm  1.2  2.8  1.0  1.3  ≥50 mm  1.8  2.8  1.7  1.3Systemic Adverse EventsFever  ≥37.5°C  4.3  5.7  2.5  3.8  ≥38.0°C to <39°C  0.8  1.6  0.6  0.9  ≥39°C  0.0  0.0  0.1  0.1Headache  Any23.025.111.710.8  Moderate  4.3  7.3  1.6  1.4  Severe  0.6  0.8  0.0  0.3Muscle Weakness  Any32.317.4  4.9  5.9  Moderate  7.3  3.2  1.3  1.0  Severe  0.6  0.4  0.1  0.1Malaise  Any14.517.0  8.9  8.8  Moderate  3.5  3.2  2.4  1.2  Severe  0.8  0.4  0.1  0.4Pain in Joints  Any15.710.9  8.5  7.4  Moderate  2.8  1.6  2.2  1.4  Severe  0.6  0.4  0.1  0.0In the US booster immunization study, among participants ≥60 years of age, 7 (1.0%) participants in the TENIVAC vaccine group and 10 (1.4%) participants in the DECAVAC vaccine group experienced a serious adverse event within 30 days following vaccination. During this period, 2 (0.3%) participants 19-59 years of age and no participants 11-18 years of age experienced a serious adverse event following TENIVAC vaccine. Serious adverse events within 30 days following TENIVAC vaccine included localized infection, asthma, colonic polyp, cellulitis, angina pectoris, hip and wrist fracture, cholecystitis, chest pain and cerebrovascular accident. There were five deaths reported during the study. All of the reported deaths were in participants ≥60 years of age and occurred >30 days post-vaccination: three in the TENIVAC vaccine group (cardiopulmonary arrest; myocardial infarction and septic shock; and unknown cause) and two in the DECAVAC vaccine group (myocardial infarction and congestive heart failure; and liver cancer).In the primary immunization study (N = 18) in which serious adverse events were monitored for 3 days following each vaccination and in three other booster immunization studies in which serious adverse events were monitored for either four days (N = 347) or one month (N = 426) following vaccination, no serious adverse events were reported.

6.2 Data From Post-Marketing Experience

  • The following adverse events have been spontaneously reported during the post-marketing use of TENIVAC vaccine. 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 to TENIVAC vaccine:Blood and lymphatic system disorders LymphadenopathyImmune system disorders Allergic reactions (such as erythematous rash, maculopapular rash, urticaria and pruritus);anaphylactic reaction (bronchospasm and angioedema). Nervous system disorders Paresthesia, dizziness, syncope Guillain Barré syndrome Gastrointestinal disorders VomitingMusculoskeletal, connective tissue and bone disorders Myalgia, pain in extremities General disorders and administration site conditions Injection site reactions (including inflammation, mass, edema, induration, warmth, pruritus, cellulitis, discomfort)Fatigue, edema peripheral

7.1 Concomitant Vaccine Administration

No safety and immunogenicity data are available on the concomitant administration of TENIVAC vaccine with other US licensed vaccines.

7.2 Tetanus Immune Globulin (Human)

If passive protection against tetanus is required, TIG (Human) may be administered according to its prescribing information, concomitantly with TENIVAC vaccine at a separate site with a separate needle and syringe. [See Dosage and Administration (2.4).]

7.3 Immunosuppressive Treatments

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to TENIVAC vaccine. [See Warnings and Precautions (5.7).]

Teratogenic Effects

Pregnancy Category CAnimal reproduction studies have not been conducted with TENIVAC vaccine. It is also not known whether TENIVAC vaccine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. TENIVAC vaccine should be given to a pregnant woman only if clearly needed. Animal fertility studies have not been conducted with TENIVAC vaccine. The effect of TENIVAC vaccine on embryo-fetal and pre-weaning development was evaluated in one developmental toxicity study using pregnant rabbits. Animals were administered TENIVAC vaccine twice prior to gestation, during the period of organogenesis (gestation day 6) and later during pregnancy on gestation day 29, 0.5 mL/rabbit/occasion (a 17-fold increase compared to the human dose of TENIVAC vaccine on a body weight basis), by intramuscular injection. No adverse effects on pregnancy, parturition, lactation, embryo-fetal or pre-weaning development were observed. There were no vaccine related fetal malformations or other evidence of teratogenesis noted in this study.

8.3 Nursing Mothers

It is not known whether TENIVAC vaccine is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TENIVAC vaccine is administered to a nursing woman.

8.4 Pediatric Use

TENIVAC vaccine is not approved for use in infants and children younger than 7 years of age. Safety and effectiveness of TENIVAC vaccine in this age group have not been established.

8.5 Geriatric Use

In one clinical study, (TDC01) 449 participants 65 years of age and over, including 192 participants who were 75 years of age and over received a dose of TENIVAC vaccine. A lower proportion of participants 65 years of age and over had a pre-vaccination seroprotective level of antibody to tetanus toxoid and diphtheria toxin compared to adolescents and adults less than 65 years of age. The proportion of participants 65 years of age and over with a seroprotective level of antibody following TENIVAC vaccine was marginally lower for tetanus and lower for diphtheria compared to younger participants. In general, rates of solicited adverse events were not higher in participants 65 years of age and over compared to younger participants. [See Adverse Reactions (6), Clinical Pharmacology (12.1), and Clinical Studies (14.2).]

11 Description

TENIVAC vaccine, Tetanus and Diphtheria Toxoids Adsorbed, is a sterile isotonic suspension of tetanus and diphtheria toxoids adsorbed on aluminum phosphate.Each 0.5 mL dose of TENIVAC vaccine contains the following active ingredients:Tetanus Toxoid5 Lf Diphtheria Toxoid2 LfOther ingredients per 0.5 mL dose include 1.5 mg of aluminum phosphate (0.33 mg of aluminum) as the adjuvant and ≤5.0 mcg of residual formaldehyde. Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. (3) Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. Corynebacterium diphtheriae is grown in modified Mueller's growth medium. (4) After purification by ammonium sulfate fractionation, diphtheria toxin is detoxified with formaldehyde and diafiltered. Tetanus and diphtheria toxoids are individually adsorbed onto aluminum phosphate.The adsorbed tetanus and diphtheria toxoids are combined with aluminum phosphate (as adjuvant), sodium chloride and water for injection. This product contains no preservative.In the guinea pig potency test, the tetanus toxoid component induces at least 2 neutralizing units/mL of serum and the diphtheria toxoid component induces at least 0.5 neutralizing units/mL of serum.The tip caps of the prefilled syringes may contain natural rubber latex. The vial stoppers do not contain latex.

Other

TetanusTetanus 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 at least 0.01 IU/mL, measured by neutralization assay is considered the minimum protective level. (5) (6) A tetanus antitoxoid level of ≥0.1 IU/mL as measured by the ELISA used in some clinical studies of TENIVAC vaccine is considered protective.

DiphtheriaDiphtheria 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. Antitoxin levels of at least 0.1 IU/mL are generally regarded as protective. (5) A level of at least of 1.0 IU/mL has been associated with long-term protection. (7)

Product information as of April 2013.Manufactured by:Sanofi Pasteur LimitedToronto Ontario CanadaDistributed by:Sanofi Pasteur Inc.Swiftwater PA 18370 USATENIVAC® is a registered trademark of the sanofi pasteur group and its subsidiaries.R5-0413 USA

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

TENIVAC vaccine has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility.

14.1 Primary Immunization

A three-dose primary immunization series with TENIVAC vaccine was evaluated in 17 participants ages 6 to 56 years in a study conducted in Canada. [See Adverse Reactions (6.1).] The first two doses were administered two months apart, followed by a third dose six to eight months after the second dose. Serum tetanus antitoxin levels were measured by an in vivo neutralizing assay and serum diphtheria antitoxin levels were measured by an in vitro neutralizing assay. [See Clinical Pharmacology (12.1).] All 17 participants had serum tetanus and diphtheria antitoxin levels pre-vaccination and 7 days post-vaccination <0.01 IU/mL, consistent with no previous immunization. Four weeks following the second dose, all 17 participants had a serum tetanus antitoxin level >0.1 IU/mL and a serum diphtheria antitoxin level ≥0.01 IU/mL. Four weeks following the third dose, all 17 participants had a serum diphtheria antitoxin level >0.1 IU/mL.

14.2 Booster Immunization

In the US multicenter booster immunization study (TDC01) [see Adverse Reactions (6.1)], the immune response to a dose of TENIVAC vaccine was evaluated in an open-label manner in a subset of participants 11 to 59 years of age, and in comparison to DECAVAC vaccine in participants ≥60 years of age who were randomized to receive a dose of either TENIVAC vaccine or DECAVAC vaccine. Tetanus immune responses, measured by ELISA [see Clinical Pharmacology (12.1)] are presented in Table 3. Diphtheria immune responses, measured by a microneutralization assay [see Clinical Pharmacology (12.1)], are presented in Table 4.Among adults 65 years of age and over who received TENIVAC vaccine (N = 419), 94.5% (95% confidence interval 91.9, 96.5) had a post-vaccination tetanus antitoxoid level ≥0.1 IU/mL and 61.1% (95% confidence interval 56.2, 65.8) had a post-vaccination diphtheria antitoxoid level ≥0.1 IU/mL.Table 3: Tetanus Antitoxoid Levels and Booster Response Rates Following a Dose of TENIVAC Vaccine, by Age Group, and for Adults ≥60 Years of Age, Compared to DECAVAC Vaccine, per Protocol Immunogenicity PopulationTreatment GroupAge GroupTimingPercent of Participants With Specified Level of Tetanus Antitoxoid and Booster Response≥0.1 IU/mL% (95% CI)≥1.0 IU/mL% (95% CI)Booster ResponseBooster response: If pre-vaccination level ≤0.10 IU/mL, 4-fold increase and post-vaccination level ≥0.10 IU/mL. If pre-vaccination level >0.10 IU/mL and ≤2.7 IU/mL, 4-fold increase. If pre-vaccination level >2.7 IU/mL, 2-fold increase.% (95% CI)Pre- indicates pre-vaccination bleed.Post- indicates 26-42 days post-vaccination bleed.TENIVAC vaccineAdolescents11 to 18 years(N = 470)Pre-97.9(96.1, 99.0)48.7(44.1, 53.3)-Post-100.0(99.2, 100)99.8(98.8, 100)92.8(90.0, 94.9)Adults19 to 59 years(N = 237)Pre-97.5(94.6, 99.1)77.6(71.8, 82.8)-Post-100.0(98.5, 100)99.6(97.7, 100)84.0(78.7, 88.4)Adults≥60 years(N = 661)Pre-76.2(72.8, 79.4)43.7(39.9, 47.6)-Post-96.1TENIVAC vaccine non-inferior to DECAVAC vaccine [upper limit of 95% CI for difference (DECAVAC vaccine minus TENIVAC vaccine) <5%].(94.3, 97.4)90.6Non-inferiority criteria not prospectively specified for this endpoint.(88.1, 92.7)82.3TENIVAC vaccine non-inferior to DECAVAC vaccine [upper limit of 95% CI for difference (DECAVAC vaccine minus TENIVAC vaccine) <10%].(79.2, 85.1)DECAVAC vaccineAdults≥60 years(N = 658)Pre-75.2(71.7, 78.5)45.7(41.9, 49.6)-Post-97.3(95.7, 98.4)91.9(89.6, 93.9)83.7(80.7, 86.5)Table 4: Diphtheria Antitoxin Levels and Booster Response Rates Following a Dose of TENIVAC Vaccine, by Age Group, and for Adults ≥60 Years of Age, Compared to DECAVAC Vaccine, per Protocol Immunogenicity PopulationTreatment GroupAge GroupTimingPercent of Participants With Specified Level of Diphtheria Antitoxin and Booster Response≥0.01 IU/mL % (95% CI)≥0.1 IU/mL% (95% CI)≥1.0 IU/mL% (95% CI)Booster ResponseBooster response: If pre-vaccination level ≤0.10 IU/mL, 4-fold increase and post-vaccination level ≥0.10 IU/mL. If pre-vaccination level >0.10 IU/mL and ≤2.56 IU/mL, 4-fold increase. If pre-vaccination level >2.56 IU/mL, 2-fold increase.% (95% CI)Pre- indicates pre-vaccination bleed.Post- indicates 26-42 days post-vaccination bleed.TENIVAC vaccineAdolescents11 to 18 years(N = 470)Pre-99.1(97.8, 99.8)78.7(74.7, 82.3)18.5(15.1, 22.3)-Post-100.0(99.2, 100)99.8(98.8, 100)98.9(97.5, 99.7)95.7(93.5, 97.4)Adults19 to 59 years(N = 237)Pre-96.6(93.5, 98.5)73.0(66.9, 78.5)18.6(13.8, 24.1)-Post-99.2(97.0, 99.9)97.5(94.6, 99.1)91.1(86.8, 94.4)89.9(85.3, 93.4)Adults≥60 years(N = 661)Pre-61.9(58.1, 65.6)29.0(25.6, 32.7)8.5(6.5, 10.9)-Post-88.0Non-inferiority criteria not prospectively specified for this endpoint.(85.3, 90.4)71.1TENIVAC vaccine non-inferior to DECAVAC vaccine [upper limit of 95% CI for difference (DECAVAC vaccine minus TENIVAC vaccine) <10%].(67.5, 74.5)47.5(43.6, 51.4)65.5(61.7, 69.1)DECAVAC vaccineAdults≥60 years(N = 658)Pre-61.7(57.9, 65.4)32.2(28.7, 35.9)10.5(8.3, 13.1)-Post-87.4(84.6, 89.8)70.7(67.0, 74.1)45.7(41.9, 49.6)62.9(59.1, 66.6)

15 References

  • 1CDC. Diphtheria, tetanus and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(RR-10):1-28.2Stratton KR, et al, editors. Adverse events associated with childhood vaccines; evidence bearing on causality. Washington, DC: National Academy Press 1994. p. 67-117.3Mueller JH, Miller PA. Variable factors influencing the production of tetanus toxin. J Bacteriol 1954;67(3):271-7.4Stainer DW. Production of diphtheria toxin. In: Manclark CR, editor. Proceedings of an informal consultation on the World Health Organization requirements for diphtheria, tetanus, pertussis and combined vaccines. United States Public Health Services, Bethesda, MD. DHHS 91-1174. 1991. p. 7-11.5FDA. Department of Health and Human Services (DHHS). Biological products; bacterial vaccines and toxoids; implementation of efficacy review; proposed rule. Fed Reg 1985;50(240):51002-117.6Wassilak SGF, et al. Tetanus toxoid. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5th ed. Philadelphia, PA: WB Saunders Company; 2008. p. 805-39.7Vitek CR and Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 5th ed. Philadelphia, PA: W.B. Saunders Company; 2008. p. 139-56.

16 How Supplied/Storage And Handling

Vial, 1 dose - NDC No. 49281-215-58; in package of 10 vials, NDC No. 49281-215-10. Contains no latex.Syringe, 1 dose– NDC No. 49281-215-88; in package of 10 syringes, NDC No. 49281-215-15. The tip caps of the prefilled syringes may contain natural rubber latex. No other components contain latex.

Storage And Handling

TENIVAC vaccine should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Product which has been exposed to freezing should not be used. Do not use after expiration date shown on the label.

17 Patient Counseling Information

Before administration of TENIVAC vaccine health-care providers should inform the patient, parent or guardian of the benefits and risks of the vaccine and the importance of completing the primary immunization series or receiving recommended booster doses, as appropriate, unless a contraindication to further immunization exists. The health-care provider should inform the patient, parent or guardian about the potential for adverse reactions that have been temporally associated with TENIVAC vaccine or other vaccines containing similar components. The health-care provider should provide the Vaccine Information Statements (VISs) which are required by the National Childhood Vaccine Injury Act of 1986 to be given with each immunization. Patients, parents, or guardians should be instructed to report adverse reactions to their health-care provider.

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