PENTACEL: Package Insert and Label Information

PENTACEL- diphtheria and tetanus toxoids and acellular pertussis adsorbed, inactivated poliovirus and haemophilus b conjugate (tetanus toxoid conjugate) vaccine
Sanofi Pasteur Inc.

1 INDICATIONS AND USAGE

Pentacel® is a vaccine indicated for active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive disease due to Haemophilus influenzae type b. Pentacel is approved for use as a four dose series in children 6 weeks through 4 years of age (prior to fifth birthday).

2 DOSAGE AND ADMINISTRATION

2.1 Immunization Series

Pentacel is to be administered as a 4 dose series at 2, 4, 6 and 15-18 months of age. The first dose may be given as early as 6 weeks of age. Four doses of Pentacel constitute a primary immunization course against pertussis. Three doses of Pentacel constitute a primary immunization course against diphtheria, tetanus, H. influenzae type b invasive disease, and poliomyelitis; the fourth dose is a booster for diphtheria, tetanus, H. influenzae type b invasive disease, and poliomyelitis immunizations. [See 14 Clinical Studies (14.1, 14.2, 14.3, 14.4, 14.5).]

Mixed Sequences of Pentacel and DTaP Vaccine

While Pentacel and DAPTACEL (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed [DTaP], Sanofi Pasteur Limited) vaccines contain the same pertussis antigens, manufactured by the same process, Pentacel contains twice the amount of detoxified pertussis toxin (PT) and four times the amount of filamentous hemagglutinin (FHA) as DAPTACEL. Pentacel may be used to complete the first 4 doses of the 5-dose DTaP series in infants and children who have received 1 or more doses of DAPTACEL and are also scheduled to receive the other antigens of Pentacel. However, data are not available on the safety and immunogenicity of such mixed sequences of Pentacel and DAPTACEL for successive doses of the primary DTaP series. Children who have completed a 4-dose series with Pentacel should receive a fifth dose of DTaP vaccine using DAPTACEL at 4-6 years of age. (1)

Data are not available on the safety and effectiveness of using mixed sequences of Pentacel and DTaP vaccine from different manufacturers.

Mixed Sequences of Pentacel and IPV Vaccine

Pentacel may be used in infants and children who have received 1 or more doses of another licensed IPV vaccine and are scheduled to receive the antigens of Pentacel. However, data are not available on the safety and immunogenicity of Pentacel in such infants and children.

The Advisory Committee on Immunization Practices (ACIP) recommends that the final dose in the 4-dose IPV series be administered at age ≥4 years. (2) When Pentacel is administered at ages 2, 4, 6, and 15-18 months, an additional booster dose of IPV vaccine should be administered at age 4-6 years, resulting in a 5-dose IPV series. (2)

Mixed Sequences of Pentacel and Haemophilus b Conjugate Vaccine

Pentacel may be used to complete the vaccination series in infants and children previously vaccinated with one or more doses of Haemophilus b Conjugate Vaccine (either separately administered or as part of another combination vaccine), who are also scheduled to receive the other antigens of Pentacel. However, data are not available on the safety and immunogenicity of Pentacel in such infants and children. If different brands of Haemophilus b Conjugate Vaccines are administered to complete the series, three primary immunizing doses are needed, followed by a booster dose.

2.2 Administration

The package contains a vial of the DTaP-IPV component and a vial of lyophilized ActHIB vaccine component.

After removing the “flip-off” caps, cleanse the DTaP-IPV and ActHIB vial stoppers with a suitable germicide. Do not remove the vial stoppers or metal seals holding them in place. Just before use, thoroughly but gently shake the vial of DTaP-IPV component, withdraw the entire liquid content and inject into the vial of the lyophilized ActHIB vaccine component. Gently swirl the vial now containing Pentacel until a cloudy, uniform, white to off-white (yellow tinge) 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, Pentacel should not be administered.

Using a sterile needle and syringe and aseptic technique, withdraw and administer a single 0.5 mL dose of Pentacel intramuscularly. Use a separate sterile needle and syringe for each injection. Changing needles between withdrawing the vaccine from the vial and injecting it into a recipient is not necessary unless the needle has been damaged or contaminated. Pentacel should be used immediately after reconstitution. Discard unused portion. Refer to Figures 1, 2, 3, 4 and 5.

Pentacel: Instructions for Reconstitution of ActHIB Vaccine Component with DTaP-IPV Component

Figure
(click image for full-size original)

In infants younger than 1 year, the anterolateral aspect of the thigh provides the largest muscle and is the preferred site of injection. In older children, the deltoid muscle is usually large enough for injection. 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.

Pentacel should not be mixed in the same syringe with other parenteral products.

3 DOSAGE FORMS AND STRENGTHS

Pentacel is a suspension for injection (0.5 mL dose) supplied as a liquid vaccine component that is combined through reconstitution with a lyophilized vaccine component, both in single-dose vials. [See Dosage and Administration (2.2) and How Supplied/Storage and Handling (16).]

4 CONTRAINDICATIONS

4.1 Hypersensitivity

A severe allergic reaction (eg, anaphylaxis) after a previous dose of Pentacel or any other diphtheria toxoid, tetanus toxoid, or pertussis-containing vaccine, inactivated poliovirus vaccine or H. influenzae type b vaccine, or any ingredient of this vaccine is a contraindication to administration of Pentacel. [See Description (11).]

4.2 Encephalopathy

Encephalopathy (eg, coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis containing vaccine that is not attributable to another identifiable cause is a contraindication to administration of any pertussis-containing vaccine, including Pentacel.

4.3 Progressive Neurologic Disorder

Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy is a contraindication to administration of any pertussis-containing vaccine including Pentacel. Pertussis vaccine should not be administered to individuals with such conditions until a treatment regimen has been established and the condition has stabilized.

5 WARNINGS AND PRECAUTIONS

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 Adverse Reactions Following Prior Pertussis Vaccination

If any of the following events occur within the specified period after administration of a pertussis vaccine, the decision to administer Pentacel should be based on careful consideration of potential benefits and possible risks.

  • Temperature of ≥40.5°C (≥105°F) within 48 hours, not attributable to another identifiable cause.
  • Collapse or shock-like state (hypotonic-hyporesponsive episode (HHE)) within 48 hours.
  • Persistent, inconsolable crying lasting ≥3 hours within 48 hours.
  • Seizures with or without fever within 3 days.

5.3 Guillain-Barré Syndrome and Brachial Neuritis

A review by the Institute of Medicine (IOM) found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome. (3) If Guillain-Barré syndrome occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the risk for Guillain-Barré syndrome may be increased following Pentacel.

5.4 Infants and Children with a History of Previous Seizures

For infants or children with a history of previous seizures, an appropriate antipyretic may be administered (in the dosage recommended in its prescribing information) at the time of vaccination with a vaccine containing acellular pertussis antigens (including Pentacel) and for the following 24 hours, to reduce the possibility of post-vaccination fever.

5.5 Limitations of Vaccine Effectiveness

Vaccination with Pentacel may not protect all individuals.

5.6 Altered Immunocompetence

If Pentacel is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained. [See Drug Interactions (7.2).]

5.7 Apnea in Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision about when to administer an intramuscular vaccine, including Pentacel, to an infant born prematurely should be based on consideration of the individual infant’s medical status and the potential benefits and possible risks of vaccination.

6 ADVERSE REACTIONS

6.1 Data from Clinical Studies

Rates of adverse reactions varied by dose number. The most frequent (>50% of participants) systemic reactions following any dose were fussiness/irritability and inconsolable crying. The most frequent (>30% of participants) injection site reactions following any dose were tenderness and increased circumference of the injected arm.

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.

The safety of Pentacel was evaluated in four clinical studies in which a total of 5,980 participants received at least one dose of Pentacel. In three of the studies, conducted in the US, a total of 4,198 participants were enrolled to receive four consecutive doses of Pentacel. In the fourth study, conducted in Canada, 1,782 participants previously vaccinated with three doses of Pentacel received a fourth dose. The vaccination schedules of Pentacel, Control vaccines, and concomitantly administered vaccines used in these studies are provided in Table 1.

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 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.

Table 1: Clinical Safety Studies of Pentacel: Vaccination Schedules
Study Pentacel Control Vaccines Concomitantly Administered Vaccines
HCPDT: non-US licensed DTaP vaccine that is identical to the DTaP component of Pentacel.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 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. Subsequent doses were with hepatitis B vaccine manufactured by Merck and Co.
§
MMR and varicella vaccines were both manufactured by Merck and Co.
Study participants previously had received three doses of Pentacel vaccine by 8 months of age.
494-01 2, 4, 6 and 15 months 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, and 15-16 months DAPTACEL + IPOL + ActHIB at 2, 4, and 6 months; and DAPTACEL + ActHIB at 15-16 months PCV7* at 2, 4, and 6 monthsHepatitis 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 participantsHepatitis 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

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 or Control vaccines in Study P3T06 is shown in Table 2. Information on these reactions was recorded daily by parents or guardians on diary cards. In Table 2, injection site reactions are reported for the Pentacel and DAPTACEL injection sites.

Table 2: Number (Percentage) of Children with Selected Solicited Adverse Reactions by Severity Occurring within 0-3 days of Pentacel or Control Vaccines in Study P3T06
*
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 vaccine and 44.8%, 54.0%, 1.0%, and 0.1%, respectively, for DAPTACEL + IPOL + ActHIB. 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 vaccine, and 61.1%, 36.6%, 1.7% and 0.5%, respectively, for DAPTACEL + ActHIB.
§
Moderate: interferes with or limits usual daily activity; Severe: disabling, not interested in usual daily activity.
Injection Site Reactions Pentacel DAPTACEL
Dose 1N = 465-467% Dose 2N = 451% Dose 3N = 438-440% Dose 4N = 387-396% Dose 1N = 1,400-1,404% Dose 2N = 1,358-1,359% Dose 3N = 1,311-1,312% Dose 4N = 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 Arm Circumference
>5 mm 33.6 30.6
>20 mm 4.7 6.9
>40 mm 0.5 0.8
Systemic Reactions Pentacel DAPTACEL + IPOL + ActHIB DAPTACEL + ActHIB
Dose 1N = 466-467% Dose 2N = 451-452% Dose 3N = 435-440% Dose 4N = 389-398% Dose 1N = 1,390-1,406% Dose 2N = 1,346-1,360% Dose 3N = 1,301-1,312% Dose 4N = 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

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 (4) were reported among participants who received Pentacel (N = 5,979), separately administered HCPDT + POLIOVAX + ActHIB (N = 1,032) or separately administered DAPTACEL + IPOL + ActHIB (N = 1,455). Hypotonia not fulfilling HHE criteria within 7 days following vaccination was reported in 4 participants after the administration of Pentacel (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 (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 (4 participants; N = 4,197 for at least one of Doses 1-3; N = 5,033 for Dose 4), separately administered HCPDT + POLIOVAX + ActHIB (3 participants; N = 1,032 for at least one of Doses 1-3, N = 739 for Dose 4), separately administered DAPTACEL + IPOL + ActHIB (1 participant; N = 1,455 for at least one of Doses 1-3), or separately administered DAPTACEL + ActHIB (0 participants; N = 418 for Dose 4). Among the four participants who experienced a seizure within 7 days following Pentacel, 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 + ActHIB, one participant had an afebrile seizure the same day as the second dose of HCPDT + POLIOVAX + ActHIB, and two participants had a febrile seizure 6 and 7 days, respectively, after the fourth dose of HCPDT + POLIOVAX + ActHIB.

Serious Adverse Events

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

Across Studies 494-01, 494-03 and P3T06, within 30 days following any of Doses 1-3 of Pentacel 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 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 (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 deaths occurred during Studies 494-01, 494-03, 5A9908 and P3T06: 4 in children who had received Pentacel (N = 5,979) and one in a participant who had received DAPTACEL + IPOL + ActHIB (N = 1,455). There were no deaths reported in children who received HCPDT + POLIOVAX + ActHIB (N = 1,032). Causes of death among children who received Pentacel 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.

Page 1 of 3 1 2 3

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

As the leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. Our material is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2020. All Rights Reserved.