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Pentacel

Pentacel

CLINICAL PHARMACOLOGY

The efficacy of Pentacel (tetanus toxoid conjugate) vaccine is based on the immunogenicity of the individual antigens compared to separately administered vaccines. Serological correlates of protection exist for diphtheria, tetanus, poliomyelitis, and invasive disease due to H influenzae type b. The efficacy against pertussis, for which there is no well established serological correlate of protection, was based, in part, on a comparison of pertussis immune responses following Pentacel (tetanus toxoid conjugate) vaccine in US children to responses following DAPTACEL vaccine (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) manufactured bySanofi Pasteur Limited) in an efficacy study conducted in Sweden (Sweden I Efficacy Trial). While Pentacel (tetanus toxoid conjugate) and DAPTACEL vaccines contain the same pertussis antigens, manufactured by the same process, Pentacel (tetanus toxoid conjugate) vaccine contains twice as much detoxified PT and four times as much FHA as DAPTACEL vaccine.

The vaccination schedules of Pentacel (tetanus toxoid conjugate) vaccine, Control vaccines, and concomitantly administered vaccines used in clinical studies of Pentacel (tetanus toxoid conjugate) vaccine that are referred to in this package insert are provided in Table 1. With the exception of Study 5A9908, which was conducted in Canada, all other studies listed in Table 1 were conducted in the US.

Table 1: Clinical Studies of Pentacel (tetanus toxoid conjugate) Vaccine: Vaccination Schedules

Study Pentacel Control Vaccines Concomitantly Administered Vaccines
494-01 2, 4, 6 and 15months HCPDT + POLIOVAX +ActHIB at 2, 4, 6, and 15 months 7-valent pneumococcal conjugate vaccine* (PCV7) at 2, 4, and 6 months in a subset of participants†
Hepatitis B vaccine at 2 and 6 months‡
P3T06 2, 4, 6, and15-16 months DAPTACEL + IPOL + ActHIB at 2, 4, and 6 months; and DAPTACEL + ActHIB at 15-16 months PCV7* at 2, 4, and 6 months
Hepatitis B vaccine at 2 and 6 months
M5A10 2, 4, and 6months DAPTACEL + IPOL + ActHIB at 2, 4, and 6 months PCV7* at 2, 4, and 6 months
Hepatitis B vaccine at 2 and 6 months
494-03 2, 4, 6, and 15-16 months None PCV7* at 2, 4, and 6 months in all participants; and at 15 months in a random subset of participants
Hepatitis B vaccine at 2 and 6 months (if a dose was previously administered) or at 2, 4,and 6 months (if no previous dose)
Measles, mumps, rubella vaccine§ (MMR) and varicella vaccine§ at 12 or 15 months in random subsets of participants
5A9908 15-18 months** None None
HCPDT: non-USlicensed DTa Pvaccine that is identicalto the DTaP component of Pentacel (tetanus toxoid conjugate) vaccine.
POLIOVAX:US licensed Poliovirus Vaccine Inactivated, Sanofi Pasteur Limited.
IPOL: US licensed Poliovirus Vaccine Inactivated, Sanofi Pasteur SA
.* PCV7 manufactured by Wyeth Laboratories.
PCV7 was introduced after the study was initiated, and thus, administered concomitantly with Pentacel (tetanus toxoid conjugate) vaccine in a subset of participants.
The first dose of hepatitis B vaccine (manufacturer not specified) was administered prior to study initiation, from birth to 21 days of age [Studies 494-01, 494-03 (subset of participants), and P3T06] or from birth to 30 days prior to Dose 1 of study vaccines (Study M5A10). Subsequent doses were with hepatitis B vaccine manufactured by Merck and Co. (Studies 494-01, 494-03, and P3T06) or manufactured either by Merck and Co. or GlaxoSmithKline Biologicals (Study M5A10).
§ MMR and varicella vaccines were both manufactured by Merck and Co.
** Study participants previously had received three doses of Pentacel (tetanus toxoid conjugate) vaccine by 8 months of age.

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. (8) Levels of 1.0 IU/mL have been associated with long term protection. (9)

The proportions of participants achieving diphtheria antitoxin seroprotective levels one month following three and four doses of Pentacel (tetanus toxoid conjugate) vaccine or DAPTACEL vaccine in Study P3T06 are provided in Table 2.

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. (8) (10) A tetanus antitoxoidlevel of ≥ 0.1 IU/mL as measured by the ELISA used in clinical studies of Pentacel (tetanus toxoid conjugate) vaccine is considered protective.

The proportions of participants achieving tetanus antitoxoid seroprotective levels one month following three and four doses of Pentacel (tetanus toxoid conjugate) vaccine or DAPTACEL vaccine in Study P3T06 are provided in Table 2.

Table 2: Study P3T06 Diphtheria Antitoxin and Tetanus Antitoxoid Responses One Month Following Dose 3 and Dose 4 of Pentacel (tetanus toxoid conjugate) Vaccine or DAPTACEL + IPOL + ActHIB Vaccines in US Children Vaccinated at 2, 4, 6, and 15-16 Months of Age

  Pentacel Vaccine DAPTACEL + IPOL + ActHIB Vaccines
Post-Dose 3
N = 331-345
N = 1,037-1,099
Diphtheria Antitoxin
  % ≥ 0.01 IU/mL* 100.0% 100.0%
  % ≥ 0.10 IU/mL 98.8% 98.5%
Tetanus Antitoxoid
  % ≥ 0.10 IU/mL 99.7% 100.0%
Post-Dose 4
N = 341-352
N = 328-334
Diphtheria Antitoxin
  % ≥ 0.10 IU/mL* 100.0% 100.0%
  % ≥ 1.0 IU/mL 96.5% 95.7%
Tetanus Antitoxoid
  % ≥ 0.10 IU/mL* 100.0% 100.0%
  % ≥ 1.0 IU/mL†‡ 92.9% 99.4%
Per Protocol Immunogenicity population. * Seroprotection rate following Pentacel (tetanus toxoid conjugate) vaccine is not inferior to DAPTACEL vaccine (upper limit of 90% CI of the difference DAPTACEL - Pentacel (tetanus toxoid conjugate) is < 10%).
Non-inferiority criteria were not pre-specified.
With the ELISA used in this study, a tetanus antitoxoid level of 1.0 IU/mL is 10 times the protective level.

Pertussis

Pertussis (whooping cough) is a respiratory disease caused by B pertussis. This Gram-negative coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of, or immunity to, pertussis has not been clearly defined.

In a clinical pertussis vaccine efficacy study conducted in Sweden during 1992-1995 (Sweden I Efficacy Trial), 2,587 infants received DAPTACEL vaccine and 2,574 infants received a non-US licensed DT vaccineas placebo at 2, 4, and 6 months of age. (11) The mean length of follow-up was 2 years after the third dose of vaccine. The protective efficacy of DAPTACEL vaccine against pertussis after 3 doses of vaccine using the World Health Organization (WHO) case definition ( 21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiologic link to a confirmed case) was 84.9% (95% confidence interval [CI] 80.1%, 88.6%). (12) (13) The protective efficacy of DAPTACEL vaccine against mild pertussis ( 1 day of cough with laboratory confirmation) was 77.9% (95% CI 72.6%, 82.2%). Protection against pertussis by DAPTACEL vaccine was sustained for the 2-year follow-up period.

Based on comparisons of the immune responses to DAPTACEL vaccine in US infants (Post-Dose 3) and Canadian children (Post-Dose 4) relative to infants who participated in the Sweden I Efficacy Trial, it was concluded that 4 doses of DAPTACEL vaccine were needed for primary immunization against pertussis in US children. (11)

In a serology bridging analysis, immune responses to FHA, PRN and FIM in a subset of infants who received three doses of DAPTACEL vaccine in the Sweden I Efficacy Trial were compared to the Post-Dose 3 and Post-Dose 4 responses in a subset of US children from Study 494-01 who received Pentacel (tetanus toxoid conjugate) vaccine (Table 3). Available stored sera from infants who received DAPTACEL vaccine in the Sweden I Efficacy Trial and sera from children who received PCV7 concomitantly with the first three doses of Pentacel (tetanus toxoid conjugate) vaccine in Study 494-01 (Table 1) were assayed in parallel. Data on levels of antibody to PT using an adequately specific assay were not available for this serology bridging analysis.

Geometric mean antibody concentrations (GMCs) and seroconversion rates for antibodies to FHA, PRN and FIM one month following Dose 3 of DAPTACEL vaccine in the subset of infants from the Sweden I Efficacy Trial and one month following Dose 3 and Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine in a subset of infants from US Study 494-01 are presented in Table 3. Seroconversion was defined as 4-fold rise in antibody level (Post-Dose 3/Pre-Dose 1 or Post-Dose 4/Pre-Dose 1). For anti-FHA and anti-FIM, the non-inferiority criteria were met for seroconversion rates, and for anti-FHA, anti-PRN, and anti-FIM, the non-inferiority criteria were met for GMCs, following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine relative to Dose 3 of DAPTACEL vaccine. The non-inferiority criterion for anti-PRN seroconversion following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine relative to Dose 3 of DAPTACEL vaccine was not met [upper limit of 95% CI for difference in rate (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) = 13.24%]. Whether the lower anti-PRNseroconversion rate following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine in US children relative to Dose 3 of DAPTACEL vaccine in Swedish infants correlates with diminished efficacy of Pentacel (tetanus toxoid conjugate) vaccine against pertussis is unknown.

Table 3: FHA, PRN and FIM Antibody Responses One Month Following Dose 3 of DAPTACEL Vaccine in a Subset of Infants Vaccinated at 2, 4, and 6 Months of Age in the Sweden I Efficacy Trial and One Month Following Dose 3 andDose 4 of Pentacel (tetanus toxoid conjugate) Vaccine in a Subset of Infants Vaccinated at 2, 4, 6, and 15-16 Months of Age in US Study 494-01

  Post-Dose 3 DAPTACEL Vaccine Sweden I Efficacy Trial Post-Dose 3 Pentacel Vaccine* US Study 494-01 Post-Dose 4 Pentacel Vaccine US Study 494-01
N = 80 N = 730-995 N = 507-554
Anti-FHA% achieving 4-foldrise GMC (EU/mL) 68.8
40.70
79.8
71.46
91.7§
129.85§
Anti-PRN% achieving 4-fold rise GMC (EU/mL) 98.8
111.26
74.4
38.11
89.2**
90.82§
Anti-FIM% achieving 4-fold rise GMC (EU/mL) 86.3
339.31
86.5
265.02
91.5§
506.57§
Analyzed sera were from subsets of the Per Protocol Immunogenicity populations in each study. Data on anti-PT levels using an adequately specific assay were not available.
* Non-inferiority criteria were not pre-specified for the comparisons of immune responses to Pentacel (tetanus toxoid conjugate) vaccine Post-Dose 3 vs. DAPTACEL vaccine Post-Dose 3.
Pre-specified non-inferiority analyses compared immune responses to Pentacel (tetanus toxoid conjugate) vaccine Post-Dose 4 vs. DAPTACEL vaccine Post-Dose 3.
Fold rise was calculated as Post-Dose 3/Pre-Dose 1 antibody level or Post-Dose 4/Pre-Dose 1 antibody level.
§ Percent achieving 4-fold rise or GMC Post-Dose 4 Pentacel (tetanus toxoid conjugate) vaccine is not inferior to Post-Dose 3 DAPTACEL vaccine [upper limit of 95% CI for difference in rates (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) < 10% and upper limit of 90% CI for GMC ratio (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) < 1.5].
** Non-inferiority criterion is not met for percent achieving 4-fold rise in anti-PRN Post-Dose 4 Pentacel (tetanus toxoid conjugate) vaccine relative to Post-Dose 3 DAPTACEL vaccine [upper limit of 95% CI for difference in rates (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) = 13.24%, exceeds the non-inferiority criterion of < 10%].

In a separate study, Study P3T06, US infants were randomized to receive either Pentacel (tetanus toxoid conjugate) vaccine or DAPTACEL + IPOL + ActHIB vaccines at 2, 4, 6, and 15-16 months of age (Table 1). The pertussis immune responses (GMCs and seroconversion rates) one month following the third and fourth doses were compared between the two vaccine groups (Table 4). Seroconversion was defined as a 4-fold rise in antibody level (Post-Dose 3/Pre-Dose 1 or Post-Dose 4/Pre-Dose 1). Data on anti-PT responses obtained from an adequately specific assay were available on only a non-random subset of study participants. The subset of study participants was representative of all study participants with regard to Pre-Dose 1, Post-Dose 3 and Post-Dose 4 GMCs of antibodies to FHA, PRN and FIM. For each of the pertussis antigens, non-inferiority criteria were met for seroconversion rates and GMCs following Dose 3 of Pentacel (tetanus toxoid conjugate) vaccine relative to Dose 3 of DAPTACEL vaccine. Following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine relative to Dose 4 of DAPTACEL vaccine, non-inferiority criteria were met for all comparisons except for anti-PRN GMCs [upper limit of 90% CI for ratio of GMCs (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) = 2.25]. Whether the lower anti-PRN GMC following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine relative to Dose 4 of DAPTACEL vaccine in US children correlates with diminished efficacy of Pentacel (tetanus toxoid conjugate) vaccine against pertussis is unknown.

Table 4: Pertussis Antibody Responses One Month Following Doses 3 and 4 of Pentacel (tetanus toxoid conjugate) Vaccine or DAPTACEL + IPOL + ActHIB Vaccines in US Infants Vaccinated at 2, 4, 6, and 15-16 Months of Age in Study P3T06

  Post-Dose 3 Pentacel Vaccine Post-Dose 3 DAPTACEL + IPOL + ActHIB Vaccines Post-Dose 4 Pentacel Vaccine Post-Dose 4 DAPTACEL + ActHIB Vaccines
  N = 143 N = 481-485 N = 113 N = 127-128
Anti-PT
% achieving 4-fold rise*
GMC (EU/mL)
95.8
102.62
87.3
61.88
93.8
107.89
91.3
100.29
  N = 218-318 N = 714-1,016 N = 230-367 N = 237-347
Anti-FHA
% achieving 4-fold rise
GMC (EU/mL)
81.9§
73.68§
60.9
29.22
88.4**
107.94
79.3
64.02
Anti-PRN
% achieving 4-fold rise
GMC (EU/mL)
74.2
36.05
75.4
43.25
92.7
93.59††
98.3
186.07
Anti-FIM
% achieving 4-fold rise
GMC (EU/mL)
91.7
268.15
86.3
267.18
93.5
553.39
91.6
513.54
Per Protocol Immunogenicity population for anti-FHA, anti-PRN, and anti-FIM.
Non-random subset of per Protocol Immunogenicity population for anti-PT. See text for further information on the subset evaluated.
* Fold rise was calculated as Post-Dose 3/Pre-Dose 1 antibody level or Post-Dose 4/Pre-Dose 1 antibody level.
Percent achieving 4-fold rise or GMC Post-Dose 3 Pentacel (tetanus toxoid conjugate) vaccine not inferior to Post-Dose 3 DAPTACEL vaccine [upper limit of 95% CI for GMC ratio (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) < 1.5 and upper limit of 95% CI for differences in rates (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) < 10%].
Percent achieving 4-fold rise or GMC Post-Dose 4 Pentacel (tetanus toxoid conjugate) vaccine not inferior to Post-Dose 4 DAPTACEL vaccine [upper limit of 95% CI for GMC ratio (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) < 1.5 and upper limit of 95% CI for differences in rates (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) < 10%].
§ Percent achieving 4-fold rise or GMC Post-Dose 3 Pentacel (tetanus toxoid conjugate) vaccine not inferior to Post-Dose 3 DAPTACEL vaccine [upper limit of 90% CI for GMC ratio (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) < 1.5 and upper limit of 90% CI for differences in rates (DAPTACEL minus Pentacel (tetanus toxoid conjugate) ) < 10%].
** Percent achieving 4-fold rise or GMC Post-Dose 4 Pentacel (tetanus toxoid conjugate) vaccine not inferior to Post-Dose 4
††Non-inferiority criterion is not met for GMC Post-Dose 4 Pentacel (tetanus toxoid conjugate) vaccine relative to Post-Dose 4 DAPTACEL vaccine [upper limit of 90% CI for GMC ratio (DAPTACEL/Pentacel (tetanus toxoid conjugate) ) = 2.25, which exceeds the non-inferiority criterion of < 1.5].

Poliomyelitis

Polioviruses, of which there are three serotypes (Types 1, 2, and 3) are enteroviruses. The presence of poliovirus type-specific neutralizing antibodies has been correlated with protection against poliomyelitis. (14)

In Study P3T06 (Table 1), in which infants were randomized to receive the first three doses of Pentacel (tetanus toxoid conjugate) vaccine or DAPTACEL + IPOL + ActHIB vaccines at 2, 4, and 6 months of age, one month following the third dose of study vaccines, ≥ 99.4% of participants in both groups (Pentacel (tetanus toxoid conjugate) :N = 338-350), (DAPTACEL + IPOL + ActHIB: N = 1,050-1,097) achieved neutralizing antibody levels of ≥ 1:8 for Poliovirus types 1, 2, and 3.

In Study 494-01 (Table 1), in which infants were randomized to receive Pentacel (tetanus toxoid conjugate) vaccine or HCPDT + POLIOVAX + ActHIB vaccines, GMTs (1/dil) of antibodies to Poliovirus types 1, 2, and 3 one month following Dose 4 of Pentacel (tetanus toxoid conjugate) vaccine (N = 851-857) were 2,304, 4,178, and 4,415, respectively, and one month following Dose 4 of POLIOVAX vaccine (N = 284-287) were 2,330, 2,840, and 3,300, respectively.

Invasive Disease Due to H influenzae Type b

H influenzae type b can cause invasive disease such as meningitis and sepsis. Anti-PRP antibody has been shown to correlate with protection against invasive disease due to H influenzae type b. Based on data from passive antibody studies (15) and an efficacy study with H influenzae type b polysaccharide vaccine in Finland, (16) a post-vaccination anti-PRP level of 0.15 µg/mL has been accepted as a minimal protective level. Data from an efficacy study with H influenzae type b polysaccharide vaccine in Finland indicate that a level > 1.0 µg/mL 3 weeks after vaccination predicts protection through a subsequent one-year period. (17) (18) These levels have been used to evaluate the effectiveness of Haemophilus b Conjugate Vaccines, including the ActHIB vaccine component of Pentacel (tetanus toxoid conjugate) vaccine.

Anti-PRP seroprotection rates and GMCs one month following Dose 3 of Pentacel (tetanus toxoid conjugate) vaccine or separately administered ActHIB vaccine in studies P3T06 and M5A10 are presented in Table 5. In Study 494-01, non-inferiority criteria were not met for the proportion of participants who achieved an anti-PRP level ≥ 1.0 µg/mL and for anti-PRP GMCs following Pentacel (tetanus toxoid conjugate) vaccine compared with separately administered ActHIB vaccine. In each of Studies P3T06 and M5A10, the non-inferiority criterion was met for the proportion of participants who achieved an anti-PRP level ≥ 1.0 µg/mL following Pentacel (tetanus toxoid conjugate) vaccine compared with separately administered ActHIB vaccine. In Study M5A10, the non-inferiority criterion was met for anti-PRP GMCs following Pentacel (tetanus toxoid conjugate) vaccine compared with separately administered ActHIB vaccine.

Table 5: Anti-PRP Seroprotection Rates and GMCs One Month Following Three Doses of Pentacel (tetanus toxoid conjugate) Vaccine or Separate DTaP + IPV + ActHIB Vaccines Administered at 2, 4, and 6 Months of Age in Studies 494-01, P3T06, and M5A10

  Study 494-01
  Pentacel Vaccine
N = 1,127
HCPDT + POLIOVAX + ActHIB Vaccines
N = 401
% achieving anti-PRP ≥ 0.15 µg/mL 95.4* 98.3
% achieving anti-PRP ≥ 1.0 µg/mL 79.1 88.8
Anti-PRP GMC (µg/mL) 3.19 6.23
  Study P3T06
  Pentacel Vaccine N = 365 DAPTACEL + IPOL +ActHIB Vaccines N = 1,128
% achieving anti-PRP ≥ 0.15 µg/mL 92.3* 93.3
% achieving anti-PRP ≥ 1.0 µg/mL 72.1* 70.8
Anti-PRP GMC (µg/mL) 2.31§ 2.29
  Study M5A10
  Pentacel Vaccine
N = 826
DAPTACEL + IPOL +ActHIB Vaccines
N = 421
% achieving anti-PRP ≥ 0.15 µg/mL 93.8** 90.3
% achieving anti-PRP ≥ 1.0 µg/mL 75.1** 74.8
Anti-PRP GMC (µg/mL) 2.52†† 2.38
Per Protocol Immunogenicity population for all studies.
IPV indicates Poliovirus Vaccine Inactivated.
* Percent achieving specified level following Pentacel (tetanus toxoid conjugate) vaccine not inferior to ActHIB vaccine [upper limit of 90% CI for difference in rates (ActHIB minus Pentacel (tetanus toxoid conjugate) ) < 10%].
Non-inferiority criterion not met for percent achieving anti-PRP 1.0 µg/mL following Pentacel (tetanus toxoid conjugate) vaccine relative to ActHIB vaccine [upper limit of 90% CI for difference in rates (ActHIB minus Pentacel (tetanus toxoid conjugate) ), 12.9%, exceeds the non-inferiority criterion < 10%].
Non-inferiority criterion not met for GMC following Pentacel (tetanus toxoid conjugate) vaccine relative to ActHIB vaccine [upper limit of 90% CI of GMC ratio (ActHIB/Pentacel (tetanus toxoid conjugate) ), 2.26, exceeds the non-inferiority criterion < 1.5]. § Non-inferiority criterion not pre-specified.
** Percent achieving specified level following Pentacel (tetanus toxoid conjugate) vaccine not inferior to ActHIB vaccine [upper limit of 95% CI for difference in rates (ActHIB minus Pentacel (tetanus toxoid conjugate) ) < 10%].
†† GMC following Pentacel (tetanus toxoid conjugate) vaccine not inferior to ActHIB vaccine [upper limit of 90% CI of GMC ratio (ActHIB/Pentacel (tetanus toxoid conjugate) ) < 1.5].

In Study 494-01, at 15 months of age prior to receipt of Dose 4 of study vaccines, 68.6% of Pentacel (tetanus toxoid conjugate) vaccine recipients (N = 829) and 80.8% of separately administered ActHIB vaccine recipients (N = 276) had an anti-PRP level ≥ 0.15 µg/mL. Following Dose 4 of study vaccines, 98.2% of Pentacel (tetanus toxoid conjugate) vaccine recipients (N = 874) and 99.0% of separately administered ActHIB vaccine recipients (N = 291) had an anti-PRP level ≥ 1.0 µg/mL.

In Study P3T06, at 15 months of age prior to receipt of Dose 4 of study vaccines, 65.4% of Pentacel (tetanus toxoid conjugate) vaccine recipients (N = 335) and 60.7% of separately administered ActHIB vaccine recipients (N = 323) had an anti-PRP level ≥ 0.15 µg/mL. Following Dose 4 of study vaccines, 97.8% of Pentacel (tetanus toxoid conjugate) vaccine recipients (N = 361) and 95.9% of separately administered ActHIB vaccine recipients (N = 340) had an anti-PRP level ≥ 1.0 µg/mL.

Concomitantly Administered Vaccines

Vaccines administered concomitantly with Pentacel (tetanus toxoid conjugate) vaccine in clinical trials are listed in Table 1.

In Study P3T06, there was no evidence for reduced antibody responses to hepatitis B vaccine (percent of participants with anti-HBsAg ≥ 10 mIU/mL and GMCs) or PCV7 (percent of participants with antibody levels ≥ 0.15 µg/mL and ≥ 0.5 µg/mL and GMCs to each serotype) administered concomitantly with Pentacel (tetanus toxoid conjugate) vaccine (N = 321-325) relative to these vaccines administered concomitantly with DAPTACEL + IPOL + ActHIB vaccines (N = 998-1,029). The immune responses to hepatitis B vaccine and PCV7 were evaluated one month following the third dose.

In Study 494-03, there was no evidence for interference in the immune response to the fourth dose of PCV7 (percent of participants with antibody levels ≥ 0.15 µg/mL and ≥ 0.5 µg/mL and GMCs to each serotype) administered at 15 months of age concomitantly with Pentacel (tetanus toxoid conjugate) vaccine (N = 155) relative to this vaccine administered concomitantly with MMR and varicella vaccines (N = 158). There was no evidence for interference in the immune response to MMR and varicella vaccines (percent of participants with pre-specified seroresponse level) administered at 15 months of age concomitantly with Pentacel (tetanus toxoid conjugate) vaccine (N = 154) relative to these vaccines administered concomitantly with PCV7 (N = 144). The immune responses to MMR, varicella vaccine and the fourth dose of PCV7 were evaluated one month post-vaccination.

REFERENCES

8. 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.

9. 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.

10. 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.

11. DAPTACEL® [full prescribing information]. Toronto, ON: Sanofi Pasteur; 2008.

12. Gustafsson L, et al. A controlled trial of a two-component acellular, a five-component acellular and a whole-cell pertussis vaccine. N Engl J Med 1996;334(6):349-55.

13. Sanofi Pasteur Inc: Data on file.

14. Sutter RW, et al. Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: Poliovirus vaccination. In: Williams JC, et al. eds. Combined vaccines and simultaneous administration. Current issues and perspectives. New York, NY: The New York Academy of Sciences. 1995:289-99.

15. Robbins JB, et al. Quantitative measurement of "natural" and immunization-induced Haemophilus influenzae type b capsular polysaccharide antibodies. Pediatr Res 1973;7:103-10.

16. Peltola H, et al. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977;60:730-7.

17. Kayhty H, et al. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1983;147:1100.

18. Anderson P. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1984;149:1034.

Last reviewed on RxList: 7/25/2008
This monograph has been modified to include the generic and brand name in many instances.

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