Vaccine Information: TENIVAC (Page 2 of 3)

6.2 Postmarketing Experience

The following adverse events have been spontaneously reported during the postmarketing use of TENIVAC. 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:

  • Blood and lymphatic system disorders
    Lymphadenopathy
  • Immune 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
    Vomiting
  • Musculoskeletal, 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 DRUG INTERACTIONS

7.1 Concomitant Vaccine Administration

No safety and immunogenicity data are available on the concomitant administration of TENIVAC 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 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. [See Warnings and Precautions (5.7).]

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. There are no adequate and well-controlled studies of TENIVAC administration in pregnant women in the U.S. There are insufficient human data from TENIVAC administered during pregnancy to establish the presence or absence of a vaccine-associated risk.

A developmental toxicity study has been performed in female rabbits administered a single human dose of TENIVAC prior to mating and during gestation. This study revealed no evidence of harm to the fetus due to TENIVAC. (See Animal data)

Data

Animal data

In a developmental toxicity study, female rabbits received a single human dose (0.5 mL) of TENIVAC by intramuscular injection 17 and 10 days prior to mating, and on gestation days 6 and 29. No adverse effects on pre-weaning development up to post-natal day 35 were observed. There were no vaccine-related fetal malformations or variations observed.

8.2 Lactation

It is not known whether TENIVAC components are excreted in human milk. Data are not available to assess the effect of administration of TENIVAC on breastfed infants or on milk production/excretion.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TENIVAC and any potential adverse effects on the breastfed child from TENIVAC or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

TENIVAC is not approved for use in infants and children younger than 7 years of age. Safety and effectiveness of TENIVAC 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. 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 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, 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 contains the following active ingredients:

Tetanus Toxoid 5 Lf
Diphtheria Toxoid 2 Lf

Other 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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Tetanus

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 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 is considered protective.

Diphtheria

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. 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)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

TENIVAC has not been evaluated for carcinogenic or mutagenic potential or impairment of male fertility in animals. Vaccination of female rabbits with TENIVAC had no effects on fertility. [See Use in Specific Populations (8.1)].

14 CLINICAL STUDIES

14.1 Primary Immunization

A three-dose primary immunization series with TENIVAC 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 was evaluated in an open-label manner in a subset of participants 11 to 59 years of age, and in comparison to DECAVAC in participants ≥60 years of age who were randomized to receive a dose of either TENIVAC or DECAVAC . 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 (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, by Age Group, and for Adults ≥60 Years of Age, Compared to DECAVAC, per Protocol Immunogenicity Population
Treatment Group Age Group Timing Percent of Participants With Specified Level of Tetanus Antitoxoid and Booster Response
≥0.1 IU/mL% (95% CI) ≥1.0 IU/mL% (95% CI) Booster Response *% (95% CI)
Pre- indicates pre-vaccination bleed.
Post- indicates 26-42 days post-vaccination bleed.
*
Booster 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.
TENIVAC non-inferior to DECAVAC [upper limit of 95% CI for difference (DECAVAC minus TENIVAC) <5%].
Non-inferiority criteria not prospectively specified for this endpoint.
§
TENIVAC non-inferior to DECAVAC [upper limit of 95% CI for difference (DECAVAC minus TENIVAC) <10%].
TENIVAC Adolescents11 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- 96.1(94.3, 97.4) 90.6(88.1, 92.7) 82.3§(79.2, 85.1)
DECAVAC Adults≥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, by Age Group, and for Adults ≥60 Years of Age, Compared to DECAVAC, per Protocol Immunogenicity Population
Treatment Group Age Group Timing Percent 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 Response *% (95% CI)
Pre- indicates pre-vaccination bleed.
Post- indicates 26-42 days post-vaccination bleed.
*
Booster 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.
Non-inferiority criteria not prospectively specified for this endpoint.
TENIVAC non-inferior to DECAVAC [upper limit of 95% CI for difference (DECAVAC minus TENIVAC) <10%].
TENIVAC Adolescents11 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- 88.0(85.3, 90.4) 71.1(67.5, 74.5) 47.5(43.6, 51.4) 65.5(61.7, 69.1)
DECAVAC Adults≥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)

VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Vaccine Sections

Vaccine Information by RSS

As the leading independent provider of trustworthy vaccine information, our database comes directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. VxLabels.com provides the full vaccine subset of the FDA's repository. Vaccine information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.