Infanrix

Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements. Especially tell your doctor if you use:

• immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids

This is not a complete list of Infanrix drug interactions. Ask your doctor or pharmacist for more information. 

Tell your healthcare provider if you or your child:

• had a severe allergic reaction (eg, anaphylaxis) after a previous dose of Infanrix vaccine or any other tetanus toxoid, diphtheria toxoid, or pertussis-containing vaccine, or any other component of this vaccine
• had 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
• have progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy

Tell you doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. 

In the U.S.

• Daptacel
• Infanrix
• Tripedia

Available Dosage Forms:

• Suspension

Therapeutic Class: Vaccine

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Pain where the shot was given.
• Redness or swelling where the shot is given.
• Headache.
• Feeling tired or weak.
• Fever or chills.
• Upset stomach or throwing up.
• Belly pain.
• Loose stools (diarrhea).
• Joint pain or swelling.
• Swollen gland.

Young children:

• Feeling fussy.
• Not hungry.
• Feeling sleepy.
• Crying that is not normal.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Infanrix® is indicated for active immunization against diphtheria, tetanus, and pertussis as a 5-dose series in infants and children 6 weeks to 7 years of age (prior to seventh birthday).

Preparation for Administration

Shake vigorously to obtain a homogeneous, turbid, white suspension. Do not use if resuspension does not occur with vigorous shaking. 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 exists, the vaccine should not be administered.

Dose and Schedule

A 0.5-mL dose of Infanrix is approved for intramuscular administration in infants and children 6 weeks to 7 years of age (prior to the seventh birthday) as a 5-dose series. The series consists of a primary immunization course of 3 doses administered at 2, 4, and 6 months of age (at intervals of 4 to 8 weeks), followed by 2 booster doses, administered at 15 to 20 months of age and at 4 to 6 years of age. The first dose may be given as early as 6 weeks of age.

The preferred administration site is the anterolateral aspect of the thigh for most infants younger than 12 months of age and the deltoid muscle of the upper arm for most children 12 months of age to 7 years of age.

Do not administer this product intravenously, intradermally, or subcutaneously.

Use of Infanrix With Other DTaP Vaccines

Sufficient data are not available on the safety and effectiveness of interchanging Infanrix and Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) vaccines from different manufacturers for successive doses of the DTaP vaccination series. Because the pertussis antigen components of Infanrix and PEDIARIX® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine] are the same, Infanrix may be used to complete a DTaP vaccination series initiated with PEDIARIX.

Additional Dosing Information

If any recommended dose of pertussis vaccine cannot be given [see Contraindications (4.2, 4.3) and Warnings and Precautions (5.4)], Diphtheria and Tetanus Toxoids Adsorbed (DT) For Pediatric Use should be given according to its prescribing information.

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 3 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.

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.

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.

 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 mid-upper 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.

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 1,000 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.

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.

Pregnancy

Pregnancy Category C

Animal reproduction studies have not been conducted with Infanrix. It is also not known whether Infanrix can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

Pediatric Use

Safety and effectiveness of Infanrix in infants younger than 6 weeks of age and children 7 to 16 years of age have not been established. Infanrix is not approved for use in these age groups.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Infanrix has not been evaluated for carcinogenic or mutagenic potential, or for impairment of fertility.

Applies to diphtheria and tetanus toxoids / pertussis, acellular: intramuscular suspension

Local

Local side effects have included erythema, swelling, tenderness, and pain.[Ref]

Hypersensitivity

Hypersensitivity side effects have included rare reports of anaphylactic reactions (ie, hives, swelling of the mouth, difficulty breathing, hypotension, or shock). Arthus-type hypersensitivity reactions, characterized by severe local reactions (generally starting 2 to 8 hours after an injection), may follow receipt of tetanus toxoid.[Ref]

General

General side effects have included fever greater than 101 degrees F (rectal), high-pitched cry, persistent cry, and irritability.[Ref]

Gastrointestinal

Gastrointestinal side effects have included anorexia and vomiting.[Ref]

Nervous system

Nervous system side effects have included drowsiness. A review by the Institute of Medicine (IOM) found evidence for a causal relationship between tetanus toxoid and both brachial neuritis and Guillain-Barre syndrome.[Ref]

Some side effects of Infanrix (DTaP) may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.