Adacel TDAP

Name: Adacel TDAP

Clinical Studies

The efficacy of the tetanus toxoid and diphtheria toxoid used in Adacel vaccine was based on the immune response to these antigens compared to a US licensed Tetanus and Diphtheria Toxoids Adsorbed For Adult Use (Td) vaccine manufactured by Sanofi Pasteur Inc., Swiftwater, PA. The primary measures of immunogenicity were (a) the percentage of participants attaining an antibody level of at least 0.1 IU/mL and (b) the percentage of participants achieving a rise in antibody concentration after vaccination (booster response). The demonstration of a booster response depended on the antibody concentration to each antigen prior to immunization. Threshold or "cut-off" values for antibody concentrations to each antigen were established based on the 95th percentile of the pre-vaccination antibody concentrations observed in previous clinical trials. A booster response was defined as a four-fold rise in antibody concentration if the pre-vaccination concentration was equal to or below the cut-off value and a two-fold rise in antibody concentration if the pre-vaccination concentration was above the cut-off value.

The efficacy of the pertussis antigens used in Adacel vaccine was inferred based on a comparison of pertussis antibody levels achieved in recipients of a single booster dose of Adacel vaccine with those obtained in infants after three doses of DAPTACEL vaccine. In the Sweden I Efficacy Trial, three doses of DAPTACEL vaccine were shown to confer a protective efficacy of 84.9% (95% CI: 80.1%, 88.6%) against WHO defined pertussis (21 days of paroxysmal cough with laboratory-confirmed B pertussis infection or epidemiological link to a confirmed case). The protective efficacy against mild pertussis (defined as at least one day of cough with laboratory-confirmed B pertussis infection) was 77.9% (95% CI: 72.6%, 82.2%). (8) (9) In addition, the ability of Adacel vaccine to elicit a booster response to the pertussis antigens following vaccination was evaluated. The acellular pertussis formulations for Adacel and DAPTACEL vaccines differ only in the amount of detoxified PT (2.5 µg in Adacel vaccine versus 10 µg in DAPTACEL vaccine).

The principal immunogenicity study was a comparative, multi-center, randomized, observer-blind, controlled trial which enrolled 4,480 participants; 2,053 adolescents (11-17 years of age) and 2,427 adults (18-64 years of age). Enrollment was stratified by age to ensure adequate representation across the entire age range. Participants had not received a tetanus or diphtheria toxoid containing vaccine within the previous 5 years. After enrollment participants were randomized to receive one dose of either Adacel vaccine or Td vaccine. A total of 4,461 randomized participants were vaccinated. The per-protocol immunogenicity subset included 1,270 Adacel vaccine recipients and 1,026 Td vaccine recipients. Sera were obtained before and approximately 35 days after vaccination. (Blinding procedures for safety assessments are described in the ADVERSE REACTIONS section.)

Demographic characteristics were similar within age groups and between the vaccine groups. A total of 76% of the adolescents and 1.1% of the adults reported a history of receiving 5 previous doses of diphtheria-tetanus-pertussis containing vaccines. Anti-tetanus and anti-diphtheria seroprotection rates (≥0.1 IU/mL) and booster response rates were comparable between Adacel and Td vaccines. (See Table 1 and Table 2.) Adacel vaccine induced pertussis antibody levels that were non-inferior to those of Swedish infants who received three doses of DAPTACEL vaccine. (See Table 3.) Acceptable booster responses to each of the pertussis antigens were also demonstrated, i.e., the percentage of participants with a booster response exceeded the pre-defined lower limit. (9) (See Table 4.)

Table 1: Pre-vaccination and Post-vaccination Antibody Responses and Booster Response Rates to Tetanus Toxoid Following Adacel Vaccine as Compared to Td Vaccine
   Tetanus Antitoxin (IU/mL)
Pre-Vaccination 1 Month Post-Vaccination
Age
Group
(years)
Vaccine N* % ≥0.10
  (95% CI)
% ≥1.0
  (95% CI)
% ≥0.10
  (95% CI)
% ≥1.0
  (95% CI)
% Booster†
  (95% CI)
* N = number of participants in the per-protocol population with available data. † Booster response is defined as: A four-fold rise in antibody concentration, if the pre-vaccination concentration was equal to or below the cut-off value and a two-fold rise in antibody concentration if the pre-vaccination concentration was above the cut-off value. The cut-off value for tetanus was 2.7 IU/mL. ‡ Seroprotection rates at ≥0.10 IU/mL and booster response rates to Adacel vaccine were non-inferior to Td vaccine (upper limit of the 95% CI on the difference for Td vaccine minus Adacel vaccine <10%). § Seroprotection rates at ≥1.0 IU/mL were not prospectively defined as a primary endpoint. ¶ Tetanus and Diphtheria Toxoids Adsorbed for Adult Use manufactured by Sanofi Pasteur Inc., Swiftwater, PA.
11-17 Adacel 527 99.6
 
(98.6, 100.0)
44.6
 
(40.3, 49.0)
100.0‡
 
(99.3, 100.0)
99.6§
 
(98.6, 100.0)
91.7‡
 
(89.0, 93.9)
Td¶ 516 99.2
 
(98.0, 99.8)
43.8
 
(39.5, 48.2)
100.0
 
(99.3, 100.0)
99.4
 
(98.3, 99.9)
91.3
 
(88.5, 93.6)
18-64 Adacel 742-
743
97.3
 
(95.9, 98.3)
72.9
 
(69.6, 76.1)
100.0‡
 
(99.5, 100.0)
97.8§
 
(96.5, 98.8)
63.1‡
 
(59.5, 66.6)
Td¶ 509 95.9
 
(93.8, 97.4)
70.3
 
(66.2, 74.3)
99.8
 
(98.9, 100.0)
98.2
 
(96.7, 99.2)
66.8
 
(62.5, 70.9)
Table 2: Pre-vaccination and Post-vaccination Antibody Responses and Booster Response Rates to Diphtheria Toxoid Following Adacel Vaccine as Compared to Td Vaccine
   Diphtheria Antitoxin (IU/mL)
Pre-Vaccination 1 Month Post-Vaccination
Age
Group
(years)
Vaccine N* % ≥0.10
  (95% CI)
% ≥1.0
  (95% CI)
% ≥0.10
  (95% CI)
% ≥1.0
  (95% CI)
% Booster†
  (95% CI)
* N = number of participants in the per-protocol population with available data. † Booster response is defined as: A four-fold rise in antibody concentration, if the pre-vaccination concentration was equal to or below the cut-off value and a two-fold rise in antibody concentration if the pre-vaccination concentration was above the cut-off value. The cut-off value for diphtheria was 2.56 IU/mL. ‡ Seroprotection rates at ≥0.10 IU/mL and booster response rates to Adacel vaccine were non-inferior to Td vaccine (upper limit of the 95% CI on the difference for Td vaccine minus Adacel vaccine <10%). § Seroprotection rates at ≥1.0 IU/mL were not prospectively defined as a primary endpoint. ¶ Tetanus and Diphtheria Toxoids Adsorbed for Adult Use manufactured by Sanofi Pasteur Inc., Swiftwater, PA.
11-17 Adacel 527 72.5
 
(68.5, 76.3)
15.7
 
(12.7, 19.1)
99.8‡
 
(98.9, 100.0)
98.7§
 
(97.3, 99.5)
95.1‡
 
(92.9, 96.8)
Td¶ 515-
516
70.7
 
(66.5, 74.6)
17.3
 
(14.1, 20.8)
99.8
 
(98.9, 100.0)
98.4
 
(97.0, 99.3)
95.0
 
(92.7, 96.7)
18-64 Adacel 739-
741
62.6
 
(59.0, 66.1)
14.3
 
(11.9, 17.0)
94.1‡
 
(92.1, 95.7)
78.0§
 
(74.8, 80.9)
87.4‡
 
(84.8, 89.7)
Td¶ 506-
507
63.3
 
(59.0, 67.5)
16.0
 
(12.9, 19.5)
95.1
 
(92.8, 96.8)
79.9
 
(76.1, 83.3)
83.4
 
(79.9, 86.5)
Table 3: Ratio of Pertussis Antibody Geometric Mean Concentrations (GMCs)* Observed One Month After a Dose of Adacel Vaccine in Adolescents and Adults Compared with Those Observed in Infants One Month Following Vaccination at 2, 4 and 6 Months of Age in the Efficacy Trial with DAPTACEL Vaccine
  Adolescents Adults
Adacel†/DAPTACEL‡
GMC Ratio
(95% CIs)
Adacel§/DAPTACEL‡
GMC Ratio
(95% CIs)
* Antibody GMCs, measured in arbitrary ELISA units were calculated separately for infants, adolescents and adults. † N = 524 to 526, number of adolescents in the per-protocol population with available data for Adacel vaccine. ‡ N = 80, number of infants who received DAPTACEL vaccine with available data post-dose 3 (Sweden Efficacy I). § N = 741, number of adults in the per-protocol population with available data for Adacel vaccine. ¶ GMC following Adacel vaccine was non-inferior to GMC following DAPTACEL vaccine (lower limit of 95% CI on the ratio of GMC for Adacel vaccine divided by DAPTACEL vaccine >0.67).
Anti-PT 3.6
(2.8, 4.5)¶
2.1
(1.6, 2.7)¶
Anti-FHA 5.4
(4.5, 6.5)¶
4.8
(3.9, 5.9)¶
Anti-PRN 3.2
(2.5, 4.1)¶
3.2
(2.3, 4.4)¶
Anti-FIM 5.3
(3.9, 7.1)¶
2.5
(1.8, 3.5)¶
Table 4: Booster Response Rates to the Pertussis Antigens Observed One Month After a Dose of Adacel Vaccine in Adolescents and Adults
Adolescents Adults Pre-defined
Acceptable Rates*
%†
N‡ % (95% CI) N‡ % (95% CI)
* The acceptable response rate for each antigen was defined as the lower limit of the 95% CI for the rate being no more than 10% lower than the response rate observed in previous clinical trials. † A booster response for each antigen was defined as a four-fold rise in antibody concentration if the pre-vaccination concentration was equal to or below the cut-off value and a two-fold rise in antibody concentration if the pre-vaccination concentration was above the cut-off value. The cut-off values for pertussis antigens were established based on antibody data from both adolescents and adults in previous clinical trials. The cut-off values were 85 EU/mL for PT, 170 EU/mL for FHA, 115 EU/mL for PRN and 285 EU/mL for FIM. ‡ N = number of participants in the per-protocol population with available data.
Anti-PT 524 92.0
(89.3, 94.2)
739 84.4
(81.6, 87.0)
81.2
Anti-FHA 526 85.6
(82.3, 88.4)
739 82.7
(79.8, 85.3)
77.6
Anti-PRN 525 94.5
(92.2, 96.3)
739 93.8
(91.8, 95.4)
86.4
Anti-FIM 526 94.9
(92.6, 96.6)
739 85.9
(83.2, 88.4)
82.4

Warnings

Persons who experienced Arthus-type hypersensitivity reactions (e.g., severe local reactions associated with systemic symptoms) (12) following a prior dose of tetanus toxoid usually have high serum tetanus antitoxin levels and should not be given emergency doses of tetanus toxoid containing vaccines more frequently than every 10 years, even if the wound is neither clean nor minor. (4) (10) (11) (13)

If Guillain-Barré syndrome occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give Adacel vaccine or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks. (5) (10) (11)

In the following situations, Adacel vaccine should generally be deferred:

  • Moderate or severe acute illness with or without fever, until the acute illness resolves. (10) (11)
  • In adolescents, progressive neurologic disorder, including progressive encephalopathy, or uncontrolled epilepsy, until the condition has stabilized. (11)
  • In adults, unstable neurologic condition (e.g., cerebrovascular events and acute encephalopathic conditions), until the condition has resolved or is stabilized. (10)

Adacel TDAP Dosage and Administration

Adacel vaccine should be administered as a single injection of one dose (0.5 mL) by the intramuscular route. Adacel vaccine should not be combined through reconstitution or mixed with any other vaccine.

Just before use, shake the vial 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. (See DESCRIPTION.) If these conditions exist, the vaccine should not be administered.

When administering a dose from a rubber-stoppered vial, do not remove either the stopper or the metal seal holding it in place.

The preferred site is into the deltoid muscle. The vaccine should not be injected into the gluteal area or areas where there is a major nerve trunk.

Do NOT administer this product intravenously or subcutaneously.

Five years should have elapsed since the recipient's last dose of tetanus toxoid, diphtheria toxoid and/or pertussis containing vaccine.

There are no data to support repeat administration of Adacel vaccine.

The use of Adacel vaccine as a primary series or to complete the primary series for tetanus, diphtheria, or pertussis has not been studied.

Diphtheria Prophylaxis for Case Contacts

The ACIP has published recommendations on vaccination for diphtheria prophylaxis in individuals who have had contact with a person with confirmed or suspected diphtheria. (4)

Tetanus Prophylaxis in Wound Management

Clinicians should refer to guidelines for tetanus prophylaxis in routine wound management. (4) (13)

A thorough attempt must be made to determine whether a patient has completed primary immunization. Individuals who have completed primary immunization against tetanus and who sustain wounds that are minor and uncontaminated, should receive a booster dose of a tetanus toxoid containing preparation if they have not received tetanus toxoid within the preceding 10 years. For tetanus prone wounds (e.g., wounds contaminated with dirt, feces, soil and saliva, puncture wounds, avulsions and wounds resulting from missiles, crushing, burns or frostbite), a booster is appropriate if the patient has not received a tetanus toxoid containing preparation within the preceding 5 years. (4)

Adacel vaccine can be used as a one-time alternative to Tetanus and Diphtheria Toxoids Adsorbed for Adult Use (Td) vaccine in patients for whom the pertussis component is also indicated. (See INDICATIONS AND USAGE.)

If passive protection against tetanus is required, Tetanus Immune Globulin (Human) (TIG) may be administered at a separate site with a separate needle and syringe.

Concomitant Vaccine Administration

Safety and immunogenicity data are available on concomitant administration of Adacel vaccine with Hepatitis B (10 µg, two dose regimen) and trivalent inactivated influenza vaccines (TIV). (See CLINICAL PHARMACOLOGY and ADVERSE REACTIONS sections.)

Concomitant immunization of Adacel vaccine with Hepatitis B vaccine did not result in reduced antibody responses to any of the antigens from either vaccine. (9)

No interference in tetanus and diphtheria seroprotection rates and responses to influenza vaccine, detoxified PT, FIM or FHA were observed when Adacel vaccine was administered concomitantly with TIV compared to separate administration. A lower PRN GMC was observed when Adacel vaccine was administered concomitantly with TIV compared to separate administration. (9)

The safety and effectiveness of concomitant administration of Adacel vaccine with other vaccines has not been evaluated.

Separate injection sites and separate syringes must be used in case of concomitant administration.

How is Adacel TDAP Supplied

Syringe, without needle, 1 dose (5 per package) – Product No. 49281-400-15

Vial, 1 dose (5 per package) – Product No. 49281-400-05

Vial, 1 dose (10 per package) – Product No. 49281-400-10

Neither the vial nor the syringe for this product contain latex.

PRINCIPAL DISPLAY PANEL - Syringe Label

NDC 49281-400-15

Adolescent/Adult
Tdap

Tetanus Toxoid, Reduced
Diphtheria Toxoid and Acellular
Pertussis Vaccine Adsorbed
Adacel®
Rx only

0.5 mL Dose
IM only
Sanofi Pasteur Limited

5433

For Healthcare Professionals

Applies to diphtheria toxoid / pertussis, acellular / tetanus toxoid: intramuscular suspension

Local

Local side effects have included injection site pain, swelling, and erythema.[Ref]

Gastrointestinal

Gastrointestinal side effects have included nausea, diarrhea, and vomiting.[Ref]

Musculoskeletal

Musculoskeletal side effects have included sore and swollen joints, body aches, muscle weakness, and lymph node swelling.[Ref]

General

General side effects have included headache, fever, chills, and tiredness.[Ref]

Dermatologic

Dermatologic side effects have included rash, pruritus, and urticaria.[Ref]

Some side effects of diphtheria toxoid / pertussis, acellular / tetanus toxoid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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