DAPTACEL: Package Insert and Label Information

DAPTACEL- corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated), clostridium tetani toxoid antigen (formaldehyde inactivated), bordetella pertussis toxoid antigen (glutaraldehyde inactivated), bordetella pertussis filamentous hemagglutinin antigen (formaldehyde inactivated), bordetella pertussis pertactin antigen and bordetella pertussis fimbriae 2/3 antigen injection, suspension
Sanofi Pasteur Inc.

1 INDICATIONS AND USAGE

DAPTACEL® is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age (prior to seventh birthday).

2 DOSAGE AND ADMINISTRATION

2.1 Immunization Series

DAPTACEL is to be administered as a 5 dose series at 2, 4 and 6 months of age (at intervals of 6-8 weeks), at 15-20 months of age and at 4-6 years of age. The first dose may be given as early as 6 weeks of age. Four doses of DAPTACEL constitute a primary immunization course for pertussis. The fifth dose is a booster for pertussis immunization. Three doses of DAPTACEL constitute a primary immunization course for diphtheria and tetanus. The fourth and fifth doses are boosters for diphtheria and tetanus immunization. [See Clinical Studies (14.1, 14.2, 14.3).]

DAPTACEL should be used as the fifth dose of the DTaP series in children who initially received 4 doses of Pentacel® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) vaccine; Sanofi Pasteur Limited]. Pentacel and DAPTACEL contain the same pertussis antigens, manufactured by the same process, although Pentacel contains twice the amount of detoxified pertussis toxin (PT) and four times the amount of filamentous hemagglutinin (FHA) as DAPTACEL.

Data are not available on the safety and effectiveness of using mixed sequences of DAPTACEL and DTaP vaccines from different manufacturers for successive doses of the DTaP vaccination series. DAPTACEL may be used to complete the immunization series in infants who have received 1 or more doses of whole-cell pertussis DTP. However, the safety and efficacy of DAPTACEL in such infants have not been fully demonstrated.

If a decision is made to withhold any recommended dose of pertussis vaccine, [see Contraindications (4.2), (4.3) and Warnings and Precautions (5.2)], Diphtheria and Tetanus Toxoids Adsorbed For Pediatric Use (DT) should be administered.

2.2 Administration

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exist, the product should not be administered.

After removing the “flip-off” cap, cleanse the vaccine vial stopper with a suitable germicide. Do not remove either the rubber stopper or the metal seal holding it in place. Just before use, shake the vial well, until a uniform, white, cloudy suspension results.

Using a sterile needle and syringe and aseptic technique, withdraw and administer a single 0.5 mL dose of DAPTACEL intramuscularly. Discard unused portion. 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. 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.

DAPTACEL should not be combined through reconstitution or mixed with any other vaccine.

3 DOSAGE FORMS AND STRENGTHS

DAPTACEL is a suspension for injection in 0.5 mL single-dose vials. See Description (11) for a complete listing of ingredients.

4 CONTRAINDICATIONS

4.1 Hypersensitivity

A severe allergic reaction (e.g., anaphylaxis) after a previous dose of DAPTACEL or any other tetanus toxoid, diphtheria toxoid, or pertussis-containing vaccine, or any other component of this vaccine is a contraindication to administration of DAPTACEL. [See Description (11).] Because of uncertainty as to which component of the vaccine may be responsible, none of the components should be administered. Alternatively, such individuals may be referred to an allergist for evaluation if further immunizations are to be considered.

4.2 Encephalopathy

Encephalopathy (e.g., 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 DAPTACEL.

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 DAPTACEL. 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 whole-cell pertussis vaccine or a vaccine containing an acellular pertussis component, the decision to administer DAPTACEL should be based on careful consideration of potential benefits and possible risks. [See Dosage and Administration (2.1).]

  • 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 found evidence for a causal relation between tetanus toxoid and both brachial neuritis and Guillain-Barré syndrome. (1) 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 DAPTACEL.

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 an acellular pertussis component (including DAPTACEL) and for the following 24 hours, to reduce the possibility of post-vaccination fever.

5.5 Limitations of Vaccine Effectiveness

Vaccination with DAPTACEL may not protect all individuals.

5.6 Altered Immunocompetence

If DAPTACEL is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained. [See Immunosuppressive Treatments (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 DAPTACEL, 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.

5.8 Syncope

Syncope (fainting) has been reported following vaccination with DAPTACEL. Procedures should be in place to prevent falling injury and manage syncopal reactions.

6 ADVERSE REACTIONS

6.1 Data from Clinical Studies

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.

Approximately 18,000 doses of DAPTACEL have been administered to infants and children in 9 clinical studies. Of these, 3 doses of DAPTACEL were administered to 4,998 children, 4 doses of DAPTACEL were administered to 1,725 children, and 5 doses of DAPTACEL were administered to 485 children. A total of 989 children received 1 dose of DAPTACEL following 4 prior doses of Pentacel.

In a randomized, double-blinded pertussis vaccine efficacy trial, the Sweden I Efficacy Trial, conducted in Sweden during 1992-1995, the safety of DAPTACEL was compared with DT and a whole-cell pertussis DTP vaccine. A standard diary card was kept for 14 days after each dose and follow-up telephone calls were made 1 and 14 days after each injection. Telephone calls were made monthly to monitor the occurrence of severe events and/or hospitalizations for the 2 months after the last injection. There were fewer of the solicited common local and systemic reactions following DAPTACEL than following the whole-cell pertussis DTP vaccine. As shown in Table 1, the 2,587 infants who received DAPTACEL at 2, 4 and 6 months of age had similar rates of reactions within 24 hours as recipients of DT and significantly lower rates than infants receiving whole-cell pertussis DTP.

Table 1: Percentage of Infants from Sweden I Efficacy Trial with Local or Systemic Reactions within 24 Hours Post-Dose 1, 2 and 3 of DAPTACEL compared with DT and Whole-Cell Pertussis DTP Vaccines
Dose 1(2 MONTHS) Dose 2(4 MONTHS) Dose 3(6 MONTHS)
EVENT DAPTACELN = 2,587 DTN = 2,574 DTPN = 2,102 DAPTACELN = 2,563 DTN = 2,555 DTPN = 2,040 DAPTACELN = 2,549 DTN = 2,538 DTPN = 2,001
DT: Swedish National Biologics LaboratoriesDTP: whole-cell pertussis DTP, Sanofi Pasteur Inc.N = Number of evaluable subjects
*
p<0.001: DAPTACEL versus whole-cell pertussis DTP
p<0.0001: DAPTACEL versus DT
Rectal temperature
§
Statistical comparisons were not made for this variable
p<0.003: DAPTACEL versus whole-cell pertussis DTP
Local
Tenderness (Any) 8.0* 8.4 59.5 10.1* 10.3 60.2 10.8* 10.0 50.0
Redness ≥2 cm 0.3* 0.3 6.0 1.0* 0.8 5.1 3.7* 2.4 6.4
Swelling ≥2 cm 0.9* 0.7 10.6 1.6* 2.0 10.0 6.3* 3.9 10.5
Systemic
Fever ≥38°C (100.4°F) 7.8* 7.6 72.3 19.1* 18.4 74.3 23.6* 22.1 65.1
Fretfulness § 32.3 33.0 82.1 39.6 39.8 85.4 35.9 37.7 73.0
Anorexia 11.2* 10.3 39.2 9.1* 8.1 25.6 8.4* 7.7 17.5
Drowsiness 32.7* 32.0 56.9 25.9* 25.6 50.6 18.9* 20.6 37.6
Crying≥1 hour 1.7* 1.6 11.8 2.5* 2.7 9.3 1.2* 1.0 3.3
Vomiting 6.9* 6.3 9.5 5.2 5.8 7.4 4.3 5.2 5.5

The incidence of serious and less common selected systemic events in the Sweden I Efficacy Trial is summarized in Table 2.

Table 2: Selected Systemic Events: Rates Per 1,000 Doses after Vaccination at 2, 4 and 6 Months of Age in Sweden I Efficacy Trial
EVENT Dose 1(2 MONTHS) Dose 2(4 MONTHS) Dose 3(6 MONTHS)
DAPTACELN = 2,587 DTN = 2,574 DTPN = 2,102 DAPTACELN = 2,565 DTN = 2,556 DTPN = 2,040 DAPTACELN = 2,551 DTN = 2,539 DTPN = 2,002
DT: Swedish National Biologics LaboratoriesDTP: whole-cell pertussis DTP, Sanofi Pasteur Inc.N = Number of evaluable subjects
Rectal temperature ≥40°C (104°F) within 48 hours of vaccination 0.39 0.78 3.33 0 0.78 3.43 0.39 1.18 6.99
Hypotonic-hypo-responsive episode within 24 hours of vaccination 0 0 1.9 0 0 0.49 0.39 0 0
Persistent crying ≥3 hours within 24 hours of vaccination 1.16 0 8.09 0.39 0.39 1.96 0 0 1.0
Seizures within 72 hours of vaccination 0 0.39 0 0 0.39 0.49 0 0.39 0

In the Sweden I Efficacy Trial, one case of whole limb swelling and generalized symptoms, with resolution within 24 hours, was observed following dose 2 of DAPTACEL. No episodes of anaphylaxis or encephalopathy were observed. No seizures were reported within 3 days of vaccination with DAPTACEL. Over the entire study period, 6 seizures were reported in the DAPTACEL group, 9 in the DT group and 3 in the whole-cell pertussis DTP group, for overall rates of 2.3, 3.5 and 1.4 per 1,000 vaccinees, respectively. One case of infantile spasms was reported in the DAPTACEL group. There were no instances of invasive bacterial infection or death.

In a US study, children received 4 doses of DAPTACEL at 2, 4, 6 and 15-17 months of age. A total of 1,454 children received DAPTACEL and were included in the safety analyses. Of these, 51.7% were female, 77.2% Caucasian, 6.3% Black, 6.5% Hispanic, 0.9% Asian and 9.1% other races. The use of DAPTACEL as a fifth dose of DTaP vaccine was evaluated in 2 subsequent US clinical studies. In one study, a total of 485 children received DAPTACEL at 4-6 years of age following 4 prior doses of DAPTACEL in infancy (DAPTACEL-primed). In a separate study, a total of 989 children received DAPTACEL at 4-6 years of age following 4 prior doses of Pentacel in infancy (Pentacel-primed). The children included in these fifth dose studies were non-random subsets of participants from previous DAPTACEL or Pentacel studies. The subsets were representative of all children who received 4 doses of DAPTACEL or Pentacel in the earlier studies with regard to frequencies of solicited local and systemic adverse events following the fourth dose.

In the US 4-dose DAPTACEL study, at 2, 4, and 6 months of age, DAPTACEL was administered concomitantly with Haemophilus influenzae type b (Hib) conjugate vaccine (tetanus toxoid conjugate) (Sanofi Pasteur SA), inactivated poliovirus vaccine (IPV) (Sanofi Pasteur SA), and 7-valent pneumococcal conjugate vaccine (Wyeth Pharmaceuticals Inc.). Infants had received the first dose of hepatitis B vaccine at 0 months of age. At 2 and 6 months of age, hepatitis B vaccine (recombinant) (Merck & Co., Inc.) was also administered concomitantly with DAPTACEL. Based on random assignment, the fourth dose of DAPTACEL was administered either alone; concomitantly with Hib conjugate (tetanus toxoid conjugate) vaccine; or concomitantly with Hib conjugate (tetanus toxoid conjugate) vaccine, 7-valent pneumococcal conjugate vaccine, measles, mumps, rubella (MMR) vaccine (Merck & Co., Inc.), and varicella vaccine (Merck & Co., Inc.). In the fifth dose studies, DAPTACEL was administered concomitantly with IPV (all DAPTACEL-primed subjects and 47% of Pentacel-primed subjects) and MMR vaccine.

In the US studies, the occurrence of solicited local and systemic adverse events listed in Table 3 was recorded daily by parents or guardians for Days 0-7 following vaccination. For Days 0 and 1 following the first three doses of DAPTACEL, signs and symptoms of HHE also were solicited. Periodic telephone calls were made to inquire about adverse events. Serious adverse events were monitored during the three studies, through 6 months following the last dose of DAPTACEL.

The incidence and severity of selected solicited local and systemic adverse events that occurred within 3 days following each dose of DAPTACEL are shown in Table 3. The incidence of redness, tenderness and swelling at the DAPTACEL injection site increased with the fourth and fifth doses, with the highest rates reported after the fifth dose. The incidence of redness, tenderness and swelling at the DAPTACEL injection site was similarly increased when DAPTACEL was given as a fifth dose of DTaP vaccine in Pentacel-primed children.

Table 3: Number (Percentage) of Children from US Studies with Selected Solicited Local and Systemic Adverse Events by Severity Occurring Between 0 to 3 Days after Each Dose of DAPTACEL
Dose 1* Dose 2* Dose 3* Dose 4* Dose 5
DAPTACEL-primed * Pentacel-primed *
N = 1390-1406% N = 1346-1360% N = 1301-1312% N = 1118-1144% N = 473-481% N = 936-981%
*
In one US study, children received four doses of DAPTACEL. A non-random subset of these children received a fifth dose of DAPTACEL in a subsequent study. A non-random subset of children previously vaccinated with 4 doses of Pentacel in previous clinical studies received a dose of DAPTACEL at 4-6 years of age as the fifth dose of DTaP vaccine in another clinical study.
Doses 1-4 — Moderate: subject cries when site is touched; Severe: subject cries when leg or arm is moved.Dose 5 — Moderate: interfered with activities, but did not require medical care or absenteeism; Severe: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.
The circumference of the DAPTACEL-injected arm at the level of the axilla was monitored following the fourth and fifth doses only. Increase in arm circumference was calculated by subtracting the baseline circumference pre-vaccination (Day 0) from the circumference post-vaccination.
§
Moderate: decreased use of arm, but did not require medical care or absenteeism; Severe: incapacitating, refusal to move arm, may have/or required medical care or absenteeism.
For Doses 1-3, 53.7% of temperatures were measured rectally, 45.1% were measured axillary, 1.0% were measured orally, and 0.1% were measured by an unspecified route. For Dose 4, 35.7% of temperatures were measured rectally, 62.3% were measured axillary, 1.5% were measured orally, and 0.5% were measured by an unspecified route. For Dose 5 in DAPTACEL-primed children, 0.2% of temperatures were measured rectally, 11.3% were measured axillary, and 88.4% were measured orally. For Dose 5 in Pentacel-primed children, 0.2% of temperatures were measured rectally, 0.5% were measured tympanically, 17% were measured axillary, and 81.7% were measured orally. Fever is based upon actual temperatures recorded with no adjustments to the measurement for route.
#
Dose 1-4 — Moderate: interferes with and limits daily activity, less interactive; Severe: disabling (not interested in usual daily activity, subject cannot be coaxed to interact with caregiver).Dose 5 — Moderate: interfered with activities, but did not require medical care or absenteeism;Severe: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.
Þ
Doses 1-4 — Moderate: 1 to 3 hours inconsolable crying; Severe: >3 hours inconsolable crying.Dose 5 — Moderate: interfered with activities, but did not require medical care or absenteeism;Severe: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.
ß
Doses 1-4 — Moderate: Irritability for 1 to 3 hours; Severe: irritability for >3 hours.Dose 5 — Moderate: interfered with activities, but did not require medical care or absenteeism;Severe: incapacitating, unable to perform usual activities, may have/or required medical care or absenteeism.
Injection Site Reactions (DAPTACEL injection site)
Redness
>5 mm 6.2 7.1 9.6 17.3 35.8 20.2
25 — 50 mm 0.6 0.5 1.9 6.3 10.4 6.8
>50 mm 0.4 0.1 0.0 3.1 15.8 6.6
Swelling
>5 mm 4.0 4.0 6.5 11.7 23.9 12.0
25 — 50 mm 1.2 0.6 1.0 3.2 5.8 4.1
>50 mm 0.4 0.1 0.1 1.6 7.7 2.9
Tenderness
Any 48.8 38.2 40.9 49.5 61.5 50.0
Moderate 16.5 9.9 10.6 12.3 11.2 7.4
Severe 4.1 2.3 1.7 2.2 1.7 0.3
Increase in Arm Circumference
>5 mm - - - 30.1 38.3 28.6
20 — 40 mm 7.0 14.0 7.6
>40 mm 0.4 1.5 1.2
Interference with Normal Activity of the Arm §
Any - - - - 20.4 8.8
Moderate 5.6 1.7
Severe 0.4 0.0
Systemic Reactions
Fever
≥38.0°C 9.3 16.1 15.8 10.5 6.1 4.6
>38.5-39.5°C 1.5 3.9 4.8 2.7 2.1 2.0
>39.5°C 0.1 0.4 0.3 0.7 0.2 0.2
Decreased Activity/Lethargy #
Any 51.1 37.4 33.2 25.3 21.0 12.6
Moderate 23.0 14.4 12.1 8.2 5.8 3.6
Severe 1.2 1.4 0.6 1.0 0.8 0.4
Inconsolable Crying Þ
Any 58.5 51.4 47.9 37.1 14.1 7.2
Moderate 14.2 12.6 10.8 7.7 3.5 1.9
Severe 2.2 3.4 1.4 1.5 0.4 0.3
Fussiness/Irritability ß
Any 75.8 70.7 67.1 54.4 34.9 22.9
Moderate 27.7 25.0 22.0 16.3 7.5 5.3
Severe 5.6 5.5 4.3 3.9 0.4 0.5

In the US study in which children received 4 doses of DAPTACEL, of 1,454 subjects who received DAPTACEL, 5 (0.3%) subjects experienced a seizure within 60 days following any dose of DAPTACEL. One seizure occurred within 7 days post-vaccination: an infant who experienced an afebrile seizure with apnea on the day of the first vaccination. Three other cases of seizures occurred between 8 and 30 days post-vaccination. Of the seizures that occurred within 60 days post-vaccination, 3 were associated with fever. In this study, there were no reported cases of HHE following DAPTACEL. There was one death due to aspiration 222 days post-vaccination in a subject with ependymoma. Within 30 days following any dose of DAPTACEL, 57 (3.9%) subjects reported at least one serious adverse event. During this period, the most frequently reported serious adverse event was bronchiolitis, reported in 28 (1.9%) subjects. Other serious adverse events that occurred within 30 days following DAPTACEL include three cases of pneumonia, two cases of meningitis and one case each of sepsis, pertussis (post-dose 1), irritability and unresponsiveness.

In the US study in which DAPTACEL was administered as a fifth DTaP dose in DAPTACEL-primed subjects, within 30 days following the fifth consecutive dose of DAPTACEL, 1 (0.2%) subject reported 2 serious adverse events (bronchospasm and hypoxia). In the US study in which DAPTACEL was administered as a fifth DTaP dose in Pentacel-primed subjects, within 30 days following DAPTACEL, 4 (0.4%) subjects reported one or more serious adverse events (asthma and pneumonia; idiopathic thrombocytopenic purpura; vomiting; cellulitis not at the injection site). In these two studies, there were no reports of seizures within 30 days following DAPTACEL in either the DAPTACEL-primed subjects or Pentacel-primed subjects.

In another study (Sweden II Efficacy Trial), 3 DTaP vaccines and a whole-cell pertussis DTP vaccine, none of which are licensed in the US, were evaluated to assess relative safety and efficacy. This study included HCPDT, a vaccine made of the same components as DAPTACEL but containing twice the amount of detoxified PT and four times the amount of FHA (20 mcg detoxified PT and 20 mcg FHA). HHE was observed following 29 (0.047%) of 61,220 doses of HCPDT; 16 (0.026%) of 61,219 doses of an acellular pertussis vaccine made by another manufacturer; and 34 (0.056%) of 60,792 doses of a whole-cell pertussis DTP vaccine. There were 4 additional cases of HHE in other studies using HCPDT vaccine for an overall rate of 33 (0.047%) in 69,525 doses.

In a randomized, parallel-group, US multi-center clinical trial conducted in children 4 through 6 years of age, DAPTACEL was administered as follows: concomitantly with IPV (Sanofi Pasteur SA) followed 30 days later by Menactra® [Meningococcal (Groups A, C, Y and W-135) Polysaccharide Diphtheria Toxoid Conjugate vaccine, Sanofi Pasteur Inc.] [Group A]; concomitantly with Menactra followed 30 days later by IPV [Group B]; or 30 days after concomitant administration of Menactra and IPV [Group C]. Solicited injection site and systemic reactions were recorded in a diary card for 7 consecutive days after each vaccination. For all study groups, the most frequently reported solicited local reaction at the DAPTACEL injection site was pain: 71.7%, 69.4% and 52.1% of subjects in Groups A, B and C, respectively. For all study groups, the most frequently reported systemic reaction after DAPTACEL vaccination was myalgia: 46.2%, 37.3% and 25.8% of subjects in Groups A, B and C, respectively. Fever >39.5ºC occurred at <1.0% in all groups.

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.