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Pentacel

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Pentacel

Pentacel

SIDE EFFECTS

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. 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 Studies 494-01, 494-03, 5A9908, and P3T06 (Table 1), a total of 5,980 participants received at least one dose of Pentacel (tetanus toxoid conjugate) vaccine, including 4,198 participants who were enrolled in one of three US studies that evaluated the safety of four consecutive doses of Pentacel (tetanus toxoid conjugate) vaccine administered at 2, 4, 6, and 15-16 months of age. In calculating event rates across doses and studies, one subject who received one dose of Pentacel (tetanus toxoid conjugate) vaccine followed by three doses of Control vaccines was included in the control group. Two of the US studies, Study 494-01 and Study P3T06, included a control group that received separately administered vaccines. In Study 5A9908 conducted in Canada, 1,782 participants previously vaccinated with three doses of Pentacel (tetanus toxoid conjugate) vaccine received a fourth dose at 15-18 months of age. Across the four studies, 50.8% of participants were female. Among participants in the three US studies, 64.5% were Caucasian, 9.2% were Black, 12.9% were Hispanic, 3.9% were Asian, and 9.5% were of other racial/ethnic groups. In the two controlled studies, the racial/ethnic distribution of participants who received Pentacel (tetanus toxoid conjugate) and Control vaccines was similar. In the Canadian fourth dose study, 86.0% of participants were Caucasian, 1.9% were Black, 0.8% were Hispanic, 4.3% were Asian, 2.0% were East Indian, 0.5% were Native Indian, and 4.5% were of other racial/ethnic groups.

Solicited Adverse Reactions

The incidence and severity of selected solicited injection site and systemic adverse reactions that occurred within 3 days following each dose of Pentacel (tetanus toxoid conjugate) or Control vaccines in Study P3T06 is shown in Table 6. Information on these reactions was recorded daily by parents or guardians on diary cards. In Table 6, injection site reactions are reported for the Pentacel (tetanus toxoid conjugate) vaccine and DAPTACEL vaccine injection sites.

Table 6: Number (Percentage) of Children with Selected Solicited Injection Site Reactions and Solicited Systemic Adverse Events by Severity Occurring within 0-3 days of Pentacel (tetanus toxoid conjugate) Vaccine or Control Vaccines in Study P3T06

Injection Site Reactions Pentacel Vaccine DAPTACEL Vaccine
Dose 1
N = 465-467
%
Dose 2
N = 451
%
Dose 3
N = 438-440
%
Dose 4
N = 387-396
%
Dose 1
N = 1,400-1,404
Dose 2
N = 1,358-1,359
Dose 3
N = 1,311-1,312
Dose 4
N = 376-380
%
Redness
  >5 mm 7.1 8.4 8.7 17.3 6.2 7.1 9.6 16.4
  >25 mm 2.8 1.8 1.8 9.2 1.0 0.6 1.9 7.9
  >50 mm 0.6 0.2 0.0 2.3 0.4 0.1 0.0 2.4
Swelling
  >5 mm 7.5 7.3 5.0 9.7 4.0 4.0 6.5 10.3
  >25 mm 3.0 2.0 1.6 3.8 1.6 0.7 1.1 4.0
  >50 mm 0.9 0.0 0.0 0.8 0.4 0.1 0.1 1.3
Tenderness*
  Any 47.5 39.2 42.7 56.1 48.8 38.2 40.9 51.1
  Moderate or Severe 19.6 10.6 11.6 16.7 20.7 12.2 12.3 15.8
  Severe 5.4 1.6 1.4 3.3 4.1 2.3 1.7 2.4
Increase in ArmCircumference
>5 mm _ _ _ 33.6 _ - - 30.6
>20 mm       4.7       6.9
>40 mm       0.5       0.8
Systemic Reactions Pentacel Vaccine DAPTACEL + IPOL + ActHIB Vaccines DAPTACEL + ActHIB Vaccines
Dose 1
N = 466-467
%
Dose 2
N = 451-452
%
Dose 3
N = 435-440
%
Dose 4
N = 389-398
%
Dose 1
N = 1,390-1,406
%
Dose 2
N = 1,346-1,360
%
Dose 3
N = 1,301-1,312
%
Dose 4
N = 379-381
%
Fever†‡
   ≥ 38.0°C 5.8 10.9 16.3 13.4 9.3 16.1 15.8 8.7
  >38.5°C 1.3 2.4 4.4 5.1 1.6 4.3 5.1 3.2
  >39.5°C 0.4 0.0 0.7 0.3 0.1 0.4 0.3 0.8
Decreased Activity/Lethargy§
  Any 45.8 32.7 32.5 24.1 51.1 37.4 33.2 24.1
  Moderate or Severe 22.9 12.4 12.7 9.8 24.3 15.8 12.7 9.2
  Severe 2.1 0.7 0.2 2.5 1.2 1.4 0.6 0.3
Inconsolable Crying
  Any 59.3 49.8 47.3 35.9 58.5 51.4 47.9 36.2
   ≥ 1 hour 19.7 10.6 13.6 11.8 16.4 16.0 12.2 10.5
  >3 hours 1.9 0.9 1.1 2.3 2.2 3.4 1.4 1.8
Fussiness/Irritability
  Any 76.9 71.2 68.0 53.5 75.8 70.7 67.1 53.8
   ≥ 1 hour 34.5 27.0 26.4 23.6 33.3 30.5 26.2 19.4
  >3 hours 4.3 4.0 5.0 5.3 5.6 5.5 4.3 4.5
* Any: Mild, Moderate or Severe; Mild: subject whimpers when site is touched; Moderate: subject cries when site is touched; Severe: subject cries when leg or arm is moved.
Fever is based upon actual temperatures recorded with no adjustments to the measurement route.
Following Doses 1-3 combined, the proportion of temperature measurements that were taken by axillary, rectal or other routes, or not recorded were 46.0%, 53.0%, 1.0%, and 0% respectively, for Pentacel (tetanus toxoid conjugate) vaccine and 44.8%, 54.0%, 1.0%, and 0.1%, respectively, for DAPTACEL + IPOL + ActHIB vaccines. Following Dose 4, the proportion of temperature measurements that were taken by axillary, rectal or other routes, or not recorded were 62.7%, 34.4%, 2.4% and 0.5%, respectively, for Pentacel (tetanus toxoid conjugate) vaccine, and 61.1%, 36.6%, 1.7% and 0.5%, respectively, for DAPTACEL + ActHIB vaccines.
§ Moderate: interferes with or limits usual daily activity; Severe: disabling, not interested in usual daily activity.

Hypotonic Hyporesponsive Episodes

In Study P3T06, the diary cards included questions pertaining to HHEs. In Studies 494-01, 494-03, and 5A9908, a question about the occurrence of fainting or change in mental status was asked during post-vaccination phone calls. Across these 4 studies, no HHEs, as defined in a report of a US Public Health Service workshop (22) were reported among participants who received Pentacel (tetanus toxoid conjugate) vaccine (N = 5,979), separately administered HCPDT + POLIOVAX + ActHIB vaccines (N = 1,032) or separately administered DAPTACEL + IPOL + ActHIB vaccines (N = 1,455). Hypotonia not fulfilling HHE criteria within 7 days following vaccination was reported in 4 participants after the administration of Pentacel (tetanus toxoid conjugate) vaccine (1 on the same day as the 1st dose; 3 on the same day as the 3rd dose) and in 1 participant after the administration of DAPTACEL + IPOL + ActHIB vaccines (4 days following the 1st dose).

Seizures

Across Studies 494-01, 494-03, 5A9908 and P3T06, a total of 8 participants experienced a seizure within 7 days following either Pentacel (tetanus toxoid conjugate) vaccine (4 participants; N = 4,197 for at least one of Doses 1-3; N = 5,033 for Dose 4), separately administered HCPDT + POLIOVAX + ActHIB vaccines (3 participants; N = 1,032 for at least one of Doses 1-3, N = 739 for Dose 4), separately administered DAPTACEL + IPOL + ActHIB vaccines (1 participant; N = 1,455 for at least one of Doses 1-3), or separately administered DAPTACEL + ActHIB vaccines (0 participants; N = 418 for Dose 4). Among the four participants who experienced a seizure within 7 days following Pentacel (tetanus toxoid conjugate) vaccine, one participant in Study 494-01 had an afebrile seizure 6 days after the first dose, one participant in Study 494-01 had a possible seizure the same day as the third dose, and two participants in Study 5A9908 had a febrile seizure 2 and 4 days, respectively, after the fourth dose. Among the four participants who experienced a seizure within 7 days following Control vaccines, one participant had an afebrile seizure the same day as the first dose of DAPTACEL + IPOL + ActHIBvaccines, one participant ha d an afebrile seizure the same day as the second dose of HCPDT + POLIOVAX + ActHIBvaccines, and two participants had a febrile seizure 6 and 7 days, respectively, after the fourth dose of HCPDT + POLIOVAX + ActHIBvaccines.

Serious Adverse Events

In Study P3T06, within 30 days following any of Doses 1-3 of Pentacel (tetanus toxoid conjugate) or Control vaccines, 19 of 484 (3.9%) participants who received Pentacel (tetanus toxoid conjugate) vaccine and 50 of 1,455 (3.4%) participants who received DAPTACEL + IPOL + ActHIB vaccines experienced a serious adverse event. Within 30 days following Dose 4 of Pentacel (tetanus toxoid conjugate) or Control vaccines, 5 of 431 (1.2%) participants who received Pentacel (tetanus toxoid conjugate) vaccine and 4 of 418 (1.0%) participants who received DAPTACEL + ActHIB vaccines experienced a serious adverse event. In Study 494-01, within 30 days following any of Doses 1-3 of Pentacel (tetanus toxoid conjugate) or Control vaccines, 23 of 2,506 (0.9%) participants who received Pentacel (tetanus toxoid conjugate) vaccine and 11 of 1,032 (1.1%) participants who received HCPDT + POLIOVAX + ActHIB vaccines experienced a serious adverse event. Within 30 days following Dose 4 of Pentacel (tetanus toxoid conjugate) or Control vaccines, 6 of 1,862 (0.3%) participants who received Pentacel (tetanus toxoid conjugate) vaccine and 2 of 739 (0.3%) participants who received HCPDT + POLIOVAX + ActHIB vaccines experienced a serious adverse event.

Across Studies 494-01, 494-03 and P3T06, within 30 days following any of Doses 1-3 of Pentacel (tetanus toxoid conjugate) or Control vaccines, overall, the most frequently reported serious adverse events were bronchiolitis, dehydration, pneumonia and gastroenteritis. Across Studies 494-01, 494-03, 5A9908 and P3T06, within 30 days following Dose 4 of Pentacel (tetanus toxoid conjugate) or Control vaccines, overall, the most frequently reported serious adverse events were dehydration, gastroenteritis, asthma, and pneumonia.

Across Studies 494-01, 494-03, 5A9908 and P3T06, two cases of encephalopathy were reported, both in participants who had received Pentacel (tetanus toxoid conjugate) vaccine (N = 5,979). One case occurred 30 days post-vaccination and was secondary to cardiac arrest following cardiac surgery. One infant who had onset of neurologic symptoms 8 days post-vaccination was subsequently found to have structural cerebral abnormalities and was diagnosed with congenital encephalopathy.

A total of 5 deathsoccurred during Studies 494-01, 494- 03, 5A9908 and P3T06: 4 in children who had received Pentacel (tetanus toxoid conjugate) vaccine (N = 5,979) and one in a participant who had received DAPTACEL + IPOL + ActHIB vaccines (N = 1,455). There were no deaths reported in children who received HCPDT + POLIOVAX + ActHIB vaccines (N = 1,032). Causes of death among children who received Pentacel (tetanus toxoid conjugate) vaccine were asphyxia due to suffocation, head trauma, Sudden Infant Death syndrome, and neuroblastoma (8, 23, 52 and 256 days post-vaccination, respectively). One participant with ependymoma died secondary to aspiration 222 days following DAPTACEL + IPOL + ActHIB vaccines.

Data From Post-Marketing Experience

The following additional adverse events have been spontaneously reported between 1997 and 2007 during the post-marketing use of Pentacel (tetanus toxoid conjugate) vaccine outside of the US, primarily in Canada. 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 Pentacel (tetanus toxoid conjugate) vaccine.

  • Gastrointestinal disorders
    Vomiting, diarrhea
  • General disorders and administration site conditions
    Injection site reactions (including inflammation, mass, abscess and sterile abscess), extensive swelling of the injected limb (including swelling that involved adjacent joints),vaccination failure/therapeutic response decreased (invasive H influenzae type b disease)
  • Immune system disorders
    Hypersensitivity (such as rash and urticaria)
  • Metabolism and nutrition disorders
    Decreased appetite
  • Nervous system disorders
    Somnolence, HHE, depressed level of consciousness
  • Psychiatric disorders
    Screaming
  • Apnea, cough
  • Skin and subcutaneous tissue disorders
    Erythema, skin discoloration
  • Vascular disorders
    Pallor

Reporting of Adverse Events

The National Childhood Vaccine Injury Act of 1986 requires physicians and other health-care providers who administer vaccines to maintain in the recipient's permanent medical record the manufacturer, lot number, date of administration, and the name, address and title of the person administering the vaccine. The Act further requires the health-care provider to report to the US Department of Health and Human Services the occurrence of certain adverse events following immunization. For Pentacel (tetanus toxoid conjugate) vaccine, events required to be reported are anaphylaxis or anaphylactic shock within 7 days, brachial neuritis within 2-28 days, encephalopathy or encephalitis within 7 days following vaccination, or any acute complication or sequela (including death) of these events, or any contraindicating event listed in this Pentacel (tetanus toxoid conjugate) vaccine package insert. (23) (24) These events and other suspected adverse reactions should be reported to VAERS at 1-800-822-7967 or http://www.vaers.hhs.gov and to Sanofi Pasteur Inc. at 1-800-822-2463.

Read the Pentacel (tetanus toxoid conjugate) Side Effects Center for a complete guide to possible side effects

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 Pentacel (tetanus toxoid conjugate) vaccine.

Drug/Laboratory Test Interactions

Antigenuria has been detected in some instances following receipt of ActHIB vaccine. Urine antigen detection may not have definite diagnostic value in suspected H influenzae type b disease within one week following receipt of Pentacel (tetanus toxoid conjugate) vaccine. (21)

REFERENCES

21. Rothstein EP, et al. Comparison of antigenuria after immunization with three Haemophilus influenzae type b conjugate vaccines. Pediatr Infect Dis J 1991;10:311-4.

22. Braun MM. Report of a US Public Health Service workshop on hypotonic-hyporesponsive episode (HHE) after pertussis immunization. Pediatrics 1998;102(5)1-5.

23. CDC. Current trends - national vaccine injury act: requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 1988;37(13):197-200.

24. www.hrsa.gov/vaccinecompensation/table.htm (accessed May 28, 2008)

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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