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Infanrix

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Infanrix




Side Effects
Interactions

SIDE EFFECTS

Clinical Trials Experience

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. There is the possibility that broad use of INFANRIX could reveal adverse reactions not observed in clinical trials.

Approximately 95,000 doses of INFANRIX have been administered in clinical studies. In these studies, 29,243 infants have received INFANRIX in primary series studies, 6,081 children have received a fourth consecutive dose of INFANRIX, 1,764 children have received a fifth consecutive dose of INFANRIX, and 559 children have received a dose of INFANRIX following 3 doses of PEDIARIX.

Solicited Adverse Events

In a US study, 335 infants received INFANRIX, ENGERIX-B® [Hepatitis B Vaccine (Recombinant)], inactivated poliovirus vaccine (IPV, Sanofi Pasteur SA), Haemophilus b (Hib) conjugate vaccine (Wyeth Pharmaceuticals Inc.), and pneumococcal 7-valent conjugate (PCV7) vaccine (Wyeth Pharmaceuticals Inc.) concomitantly at separate sites. All vaccines were administered at 2, 4, and 6 months of age. Data on solicited local reactions and general adverse events were collected by parents using standardized diary cards for 4 consecutive days following each vaccine dose (i.e., day of vaccination and the next days) (Table 1). Among subjects, 69% were White, 16% were Hispanic, 8% were Black, 4% were Asian, and 2% were of other racial/ethnic groups.

Table 1: Solicited Local Reactions and General Adverse Events (%) Occurring Within Days of Vaccinationa With Separate Concomitant Administration of INFANRIX, ENGERIX-B, IPV, Haemophilus b (Hib) Conjugate Vaccine, and Pneumococcal Conjugate Vaccine (PCV7) (Modified Intent To Treat Cohort)

INFANRIX, ENGERIX-B, IPV, Hib Vaccine, & PCV7
Dose 1 Dose 2 Dose 3
Localb
N 335 323 315
Pain, any 31.9 30 29.8
Pain, grade 2 or 3 9 8.7 8.9
Pain, grade 3 2.7 1.5 1.3
Redness, any 18.2 32.8 39
Redness, > 20 mm 0.3 0 1.9
Swelling, any 9.6 20.4 24.8
Swelling, > 20 mm 0.6 0 1.3
General
N 333 321 311
Feverc ( ≥ 100.4°F) 19.8 30.2 23.8
Feverc ( > 101.3°F) 4.5 9.7 5.8
Feverc ( > 102.2°F) 0.3 3.1 2.3
Feverc ( > 103.1 °F) 0 0.3 0.3
N 335 323 315
Drowsiness, any 54 48.3 38.4
Drowsiness, grade 2 or 3 17.6 12.4 11.1
Drowsiness, grade 3 3.6 0.6 1.9
Irritability/Fussiness, any 61.5 61.6 56.5
Irritability/Fussiness, grade 2 or 3 19.4 21.1 19.4
Irritability/Fussiness, grade 3 3.9 3.4 3.2
Loss of appetite, any 27.8 26.6 23.8
Loss of appetite, grade 2 or 3 5.1 3.4 5.4
Loss of appetite, grade 3 0.6 0.3 0
Hib conjugate vaccine and PCV7 manufactured by Wyeth Pharmaceuticals Inc. IPV manufactured by Sanofi Pasteur SA.
Modified intent to treat cohort = all vaccinated subjects for whom safety data were available.
N = number of infants for whom at least one symptom sheet was completed; for fever, numbers exclude missing temperature recordings or tympanic measurements.
Grade 2: pain defined as cried/protested on touch; drowsiness defined as interfered with normal daily activities; irritability/fussiness defined as crying more than usual/interfered with normal daily activities; loss of appetite defined as eating less than usual/interfered with normal daily activities.
Grade 3: pain defined as cried when limb was moved/spontaneously painful; drowsiness defined as prevented normal daily activities; irritability/fussiness defined as crying that could not be comforted/prevented normal daily activities; loss of appetite defined as no eating at all.
a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b Local reactions at the injection site for INFANRIX.
c Axillary temperatures increased by 1°C and oral temperatures increased by 0.5°C to derive equivalent rectal temperature.

In a US study, the safety of a booster dose of INFANRIX was evaluated in children 15 to 18 months of age whose previous 3 DTaP doses were with INFANRIX (N = 251) or PEDIARIX (N = 559). Vaccines administered concurrently with the fourth dose of INFANRIX included measles, mumps, and rubella (MMR) vaccine (Merck & Co., Inc.), varicella vaccine (Merck & Co., Inc.), pneumococcal 7-valent conjugate (PCV7) vaccine (Wyeth Pharmaceuticals Inc.), and any US-licensed Hib conjugate vaccine; these were given concomitantly in 13.2%, 6.3%, 37.4%, and 41.2% of subjects, respectively. Data on solicited adverse events were collected by parents using standardized diary cards for 4 consecutive days following each vaccine dose (i.e., day of vaccination and the next 3 days) (Table 2). Among subjects, 85% were White, 6% were Hispanic, 6% were Black, 1% were Asian, and 2% were of other racial/ethnic groups.

Table 2: Solicited Local Reactions and General Adverse Events (%) Occurring Within 4 Days of Vaccinationa With INFANRIX Administered as the Fourth Dose Following 3 Previous Doses of INFANRIX or PEDIARIX (Total Vaccinated Cohort)

Group Primed With INFANRIXb
N = 247
Group Primed With PEDIARIXc
N = 553
Locald
Pain, any 44.5 48.3
Pain, grade 2 or 3 19 18.6
Pain, grade 3 3.6 3.4
Redness, any 48.2 49.9
Redness, > 20 mm 6.1 6
Swelling, any 32.8 32.7
Swelling, > 20 mm 3.6 5.2
Increase in mid-thigh circumference, any 33.2 26.2
Increase in mid-thigh circumference, > 40 mm 0 1.3
General
Fevere ( > 99.5°F) 8.9 15.4
Fevere ( > 100.4°F) 4.5 6.7
Fevere ( > 101.3 °F) 2 2
Drowsiness, any 35.6 31.3
Drowsiness, grade 2 or 3 9.3 6.7
Drowsiness, grade 3 2.4 1.3
Irritability, any 52.2 53.9
Irritability, grade 2 or 3 18.2 19.7
Irritability, grade 3 3.2 1.4
Loss of appetite, any 24.7 23.3
Loss of appetite, grade 2 or 3 5.3 4.9
Loss of appetite, grade 3 2.4 0.5
Total Vaccinated Cohort = all subjects who received a dose of study vaccine.
N = number of subjects for whom at least one symptom sheet was completed.
Grade 2: pain defined as cried/protested on touch; drowsiness defined as interfered with normal daily activities; irritability defined as crying more than usual/interfered with normal daily activities; loss of appetite defined as eating less than usual/no effect on normal daily activities. Grade 3: pain defined as cried when limb was moved/spontaneously painful; drowsiness defined as prevented normal daily activities; irritability defined as crying that could not be comforted/prevented normal daily activities; loss of appetite defined as eating less than usual/interfered with normal daily activities.
a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b Received INFANRIX, ENGERIX-B, IPV (Sanofi Pasteur SA), PCV7 vaccine (Wyeth Pharmaceuticals Inc.), and Hib conjugate vaccine (Wyeth Pharmaceuticals Inc.) at 2, 4, and 6 months of age.
c Received PEDIARIX, PCV7 vaccine (Wyeth Pharmaceuticals Inc.), and Hib conjugate vaccine (Wyeth Pharmaceuticals Inc.) at 2, 4, and 6 months of age or PCV7 vaccine 2 weeks later.
d Local reactions at the injection site for INFANRIX.
e Axillary temperatures.

In a US study, the safety of a fifth consecutive dose of INFANRIX coadministered at separate sites with a fourth dose of IPV (Sanofi Pasteur SA) and a second dose of MMR vaccine (Merck & Co., Inc.) was evaluated in 1,053 children 4 to 6 years of age. Data on solicited adverse events were collected by parents using standardized diary cards for 4 consecutive days following each vaccine dose (i.e., day of vaccination and the next 3 days) (Table 3). Among subjects, 43% were White, 18% Hispanic, 15% Asian, 7% Black, and 17% were of other racial/ethnic groups.

Table 3: Solicited Local Reactions and General Adverse Events (%) Occurring Within Days of Vaccinationa With a Fifth Consecutive Dose of INFANRIX When Coadministered With IPV and MMR Vaccine (Total Vaccinated Cohort)

Localb N = 1,039-1,043
Pain, any 53.3
Pain, grade 2 or 3c 12
Pain, grade 3c 0.6
Redness, any 36.6
Redness, ≥ 50 mm 20
Redness, ≥ 110 mm 4.1
Arm circumference increase, any 37.8
Arm circumference increase, > 20 mm 7.4
Arm circumference increase, > 30 mm 3.2
Swelling, any 27
Swelling, ≥ 50 mm 11.5
Swelling, ≥ 110 mm 1.8
General N = 993-1,036
Drowsiness, any 17.5
Drowsiness, grade 3 d 0.8
Fever, ≥ 99.5 °F 14.8
Fever, > 100.4°F 4.4
Fever, > 102.2°F 1.1
Fever, > 104°F 0
Loss of appetite, any 16
Loss of appetite, grade 3e 0.6
IPV manufactured by Sanofi Pasteur SA. MMR vaccine manufactured by Merck & Co., Inc.
Total Vaccinated Cohort = all vaccinated subjects for whom safety data were available.
N = number of children with evaluable data for the events listed.
a Within 4 days of vaccination defined as day of vaccination and the next 3 days.
b Local reactions at the injection site for INFANRIX.
c Grade 2 defined as painful when the limb was moved; Grade 3 defined as preventing normal daily activities.
d Grade 3 defined as preventing normal daily activities.
e Grade 3 defined as not eating at all.

In the US booster immunization studies in which INFANRIX was administered as the fourth or fifth dose in the DTaP series following previous doses with INFANRIX or PEDIARIX, large swelling reactions of the limb injected with INFANRIX were assessed.

In the fourth dose study, a large swelling reaction was defined as injection site swelling with a diameter of > 50 mm, a > 50 mm increase in the mid-thigh circumference compared to the pre-vaccination measurement, and/or any diffuse swelling that interfered with or prevented daily activities. The overall incidence of large swelling reactions occurring within 4 days (Day 0- Day 3) following INFANRIX was 2.3%.

In the fifth dose study, a large swelling reaction was defined as swelling that involved > 50% of the injected upper arm length and that was associated with a > 30 mm increase in mid­upper arm circumference within 4 days following vaccination. The incidence of large swelling reactions following the fifth consecutive dose of INFANRIX was 1.0%.

Less Common and Serious General Adverse Events

Selected adverse events reported from a double-blind, randomized Italian clinical efficacy trial involving 4,696 children administered INFANRIX or 4,678 children administered whole-cell DTP vaccine (DTwP) (manufactured by Connaught Laboratories, Inc.) as a 3-dose primary series are shown in Table 4. The incidence of rectal temperature > 104°F, hypotonic-hyporesponsive episodes and persistent crying > 3 hours following administration of INFANRIX was significantly less than that following administration of whole-cell DTP vaccine.

Table 4:Selected Adverse Events Occurring Within 48 Hours Following Vaccination With INFANRIX or Whole-Cell DTP in Ita^ ian Infants at 2, 4, or 6 Months of Age

Event INFANRIX
(N = 13,761 Doses)
Whole-Cell DTP Vaccine
(N = 13,520 Doses)
Number Rate/1,000  Doses Number Rate/1,000  Doses
Fever ( ≥ 104°F)ab 5 0.36 32 2.4
Hypotonic-hyporesponsive episodec 0 0 9 0.67
Persistent crying ≥ 3 hoursa 6 0.44 54 4
Seizuresd 1e 0.07 3f 0.22
a P < 0.001.
b Rectal temperatures.
c P = 0.002.
d Not statistically significant at P < 0.05.
e Maximum rectal temperature within 72 hours of vaccination = 103.1°F.
f Maximum rectal temperature within 72 hours of vaccination = 99.5°F, 101.3°F, and 102.2°F.

In a German safety study that enrolled 22,505 infants (66,867 doses of INFANRIX administered as a 3-dose primary series at 3, 4, and 5 months of age), all subjects were monitored for unsolicited adverse events that occurred within 28 days following vaccination using report cards. In a subset of subjects (N = 2,457), these cards were standardized diaries which solicited specific adverse events that occurred within 8 days of each vaccination in addition to unsolicited adverse events which occurred from enrollment until approximately 30 days following the third vaccination. Cards from the whole cohort were returned at subsequent visits and were supplemented by spontaneous reporting by parents and a medical history after the first and second doses of vaccine. In the subset of 2,457, adverse events following the third dose of vaccine were reported via standardized diaries and spontaneous reporting at a follow-up visit. Adverse events in the remainder of the cohort were reported via report cards which were returned by mail approximately 28 days after the third dose of vaccine. Adverse events (rates per doses) occurring within 7 days following any of the first 3 doses included: unusual crying (0.09), febrile seizure (0.0), afebrile seizure (0.13), and hypotonic-hyporesponsive episodes (0.01).

Postmarketing Experience

In addition to reports in clinical trials, worldwide voluntary reports of adverse events received for INFANRIX since market introduction are listed below. This list includes serious events and events which have a plausible causal connection to INFANRIX. These adverse events were reported voluntarily from a population of uncertain size; therefore, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccination.

Infections and Infestations: Bronchitis, cellulitis, respiratory tract infection.

Blood and Lymphatic System Disorders: Lymphadenopathy, thrombocytopenia. Immune System Disorders: Anaphylactic reaction, hypersensitivity.

Nervous System Disorders: Encephalopathy, headache, hypotonia, syncope.

Ear and Labyrinth Disorders: Ear pain.

Cardiac Disorders: Cyanosis.

Respiratory, Thoracic, and Mediastinal Disorders: Apnea, cough.

Skin and Subcutaneous Tissue Disorders: Angioedema, erythema, pruritus, rash, urticaria.

General Disorders and Administration Site Conditions: Fatigue, injection site induration, injection site reaction, Sudden Infant Death Syndrome.

Read the Infanrix (diphtheria and tetanus toxoids and acellular pertussis) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Concomitant Vaccine Administration

In clinical trials, INFANRIX was given concomitantly with Hib conjugate vaccine, pneumococcal 7-valent conjugate vaccine, hepatitis B vaccine, IPV, and the second dose of MMR vaccine [see ADVERSE REACTIONS and Clinical Studies].

When INFANRIX is administered concomitantly with other injectable vaccines, they should be given with separate syringes. INFANRIX should not be mixed with any other vaccine in the same syringe or vial.

Immunosuppressive Therapies

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to INFANRIX.

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 11/13/2015

Side Effects
Interactions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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