Infanrix Hexa

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Infanrix hexa, Powder and suspension for suspension for injection. 
Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), 
poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine 
(adsorbed). 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
After reconstitution, 1 dose (0.5 ml) contains: 
 
Diphtheria toxoid1 not less than 30 International Units (IU) 
Tetanus toxoid1 not less than 40 International Units (IU) 
Bordetella pertussis antigens 
 Pertussis toxoid (PT)1  25 micrograms 
 Filamentous Haemagglutinin (FHA)1  25 micrograms 
 Pertactin (PRN)1 8 micrograms 
Hepatitis B surface antigen (HBs)2,3 10 micrograms 
Poliovirus (inactivated) (IPV) 
 type 1 (Mahoney strain)4 40 D-antigen unit 
 type 2 (MEF-1 strain)4 8 D-antigen unit 
 type 3 (Saukett strain)4 32 D-antigen unit 
Haemophilus influenzae type b polysaccharide 10 micrograms 
(polyribosylribitol phosphate, PRP) 3 
conjugated to tetanus toxoid as carrier protein approximately 25 micrograms 
 
1adsorbed on aluminium hydroxide, hydrated (Al(OH)3) 0.5 milligrams Al3+ 
2produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
3adsorbed on aluminium phosphate (AlPO4) 0.32 milligrams Al3+ 
4propagated in VERO cells 
 
The vaccine may contain traces of formaldehyde, neomycin and polymyxin which 
are used during the manufacturing process (see section 4.3).  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and suspension for suspension for injection. 
The diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis (DTPa-HBV-IPV) 
component is a turbid white suspension. 
The lyophilised Haemophilus influenzae type b (Hib) component is a white powder. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Infanrix hexa is indicated for primary and booster vaccination of infants and toddlers against diphtheria, 
tetanus, pertussis, hepatitis B, poliomyelitis and disease caused by Haemophilus influenzae type b. 
 
The use of Infanrix hexa should be in accordance with official recommendations. 
 
4.2 Posology and method of administration 



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Posology 
 
The primary vaccination schedule consists of two or three doses (of 0.5 ml) which should be 
administered according to official recommendations (see the table below and section 5.1 for schedules 
evaluated in clinical trials). 
 
Booster doses should be given in accordance with the official recommendations, but, as a minimum, a 
dose of Hib conjugate vaccine must be administered. Infanrix hexa can be considered for the booster if 
the antigen composition is in accordance with the official recommendations. 
 
Primary vaccination Booster 

vaccination 
General considerations 

Full-term infants 
3-dose A booster dose 

must be given. 
• There should be an interval of at least 1 month 

between primary doses. 
• The booster dose should be given at least 6 months 

after the last priming dose and preferably before 18 
months of age. 

2-dose A booster dose 
must be given. 

• There should be an interval of at least 2 months 
between primary doses. 

• The booster dose should be given at least 6 months 
after the last priming dose and preferably between 
11 and 13 months of age. 

Preterm infants born after at least 24 weeks of gestational age 
3-dose A booster dose 

must be given. 
• There should be an interval of at least 1 month 

between primary doses. 
• The booster dose should be given at least 6 months 

after the last priming dose and preferably before 18 
months of age. 

 
The Expanded Program on Immunisation schedule (at 6, 10, 14 weeks of age) may only be used if a 
dose of hepatitis B vaccine has been given at birth. 
 
Where a dose of hepatitis B vaccine is given at birth, Infanrix hexa can be used as a replacement for 
supplementary doses of hepatitis B vaccine from the age of six weeks. If a second dose of hepatitis B 
vaccine is required before this age, monovalent hepatitis B vaccine should be used. 
 
Locally established immunoprophylactic measures against hepatitis B should be maintained. 
 
Paediatric population 
 
The safety and efficacy of Infanrix hexa in children over 36 months of age have not been established.  
No data are available. 
 
Method of administration 
 
Infanrix hexa is for deep intramuscular injection, preferably at alternating sites for subsequent 
injections. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or 
formaldehyde, neomycin and polymyxin. 



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Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, hepatitis B, polio or Hib 
vaccines. 
 
Infanrix hexa is contraindicated if the infant or toddlers has experienced an encephalopathy of unknown 
aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. In 
these circumstances pertussis vaccination should be discontinued and the vaccination course should be 
continued with diphtheria-tetanus, hepatitis B, polio and Hib vaccines. 
 
As with other vaccines, administration of Infanrix hexa should be postponed in subjects suffering from 
acute severe febrile illness. The presence of a minor infection is not a contraindication. 
 
4.4 Special warnings and precautions for use 
 
Vaccination should be preceded by a review of the medical history (especially with regard to previous 
vaccination and possible occurrence of undesirable events) and a clinical examination. 
 
As with any vaccine, a protective immune response may not be elicited in all vaccinees (see section 
5.1). 
 
Infanrix hexa will not prevent disease caused by pathogens other than Corynebacterium diphtheriae, 
Clostridium tetani, Bordetella pertussis, hepatitis B virus, poliovirus or Haemophilus influenzae type b. 
However, it can be expected that hepatitis D will be prevented by immunisation as hepatitis D (caused 
by the delta agent) does not occur in the absence of hepatitis B infection. 
 
If any of the following events are known to have occurred in temporal relation to receipt of pertussis-
containing vaccine, the decision to give further doses of pertussis-containing vaccines should be 
carefully considered: 

 Temperature of ≥ 40.0°C within 48 hours of vaccination, not due to another identifiable cause; 
 Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours of 

vaccination; 
 Persistent, inconsolable crying lasting ≥ 3 hours, occurring within 48 hours of vaccination; 
 Convulsions with or without fever, occurring within 3 days of vaccination. 

There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh 
possible risks. 
 
As with all injectable vaccines, appropriate medical treatment and supervision should always be readily 
available in case of a rare anaphylactic event following the administration of the vaccine. 
 
As for any vaccination, the risk-benefit of immunising with Infanrix hexa or deferring this vaccination 
should be weighed carefully in an infant or in a child suffering from a new onset or progression of a 
severe neurological disorder. 

Infanrix hexa should be administered with caution to subjects with thrombocytopenia or a bleeding 
disorder since bleeding may occur following an intramuscular administration to these subjects. 

 
Do not administer the vaccine intravascularly or intradermally. 
 
A history of febrile convulsions, a family history of convulsions or Sudden Infant Death Syndrome 
(SIDS) do not constitute a contraindication for the use of Infanrix hexa. Vaccinees with a history of 
febrile convulsions should be closely followed up as such adverse events may occur within 2 to 3 days 
post vaccination. 
 
The physician should be aware that the rate of febrile reactions is higher when Infanrix hexa is co-
administered with a pneumococcal conjugate vaccine (PCV7, PCV10, PCV13), or with a measles-
mumps-rubella-varicella (MMRV) vaccine, compared to that occurring following the administration of 



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Infanrix hexa alone. These reactions were mostly moderate (less than or equal to 39°C) and transient 
(see sections 4.5 and 4.8). 
 
Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode 
(HHE) were observed with concomitant administration of Infanrix hexa and Prevenar 13 (see section 
4.8). 
 
Prophylactic administration of antipyretics before or immediately after vaccine administration can 
reduce the incidence and intensity of post-vaccination febrile reactions. Clinical data generated with 
paracetamol and ibuprofen suggest that the prophylactic use of paracetamol might reduce the fever rate, 
while prophylactic use of ibuprofen showed a limited effect in reducing fever rate. 
The use of prophylactic antipyretic medicinal products is recommended for children with seizure 
disorders or with a prior history of febrile seizures. 
 
Antipyretic treatment should be initiated according to local treatment guidelines. 
 
Special populations 
 
HIV infection is not considered as a contraindication. The expected immunological response may not be 
obtained after vaccination of immunosuppressed patients. 
 
Clinical data indicate that Infanrix hexa can be given to preterm infants, however, as expected in this 
population, a lower immune response has been observed for some antigens (see section 4.8 and section 
5.1). 
 
The potential risk of apnoea and the need for respiratory monitoring for 48-72h should be considered 
when administering the primary immunisation series to very preterm infants (born ≤ 28 weeks of 
gestation) and particularly for those with a previous history of respiratory immaturity. 
As the benefit of the vaccination is high in these infants, vaccination should not be withheld or delayed.  
 
Interference with laboratory testing 
 
Since the Hib capsular polysaccharide antigen is excreted in the urine, a positive urine test can be 
observed within 1-2 weeks following vaccination. Other tests should be performed in order to confirm 
Hib infection during this period. 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number of 
the administered product should be clearly recorded. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Infanrix hexa can be given concomitantly with pneumococcal conjugate vaccines (PCV7, PCV10 and 
PCV13), meningococcal serogroup C conjugate vaccine (CRM197 and TT conjugates), meningococcal 
serogroups A, C, W-135 and Y conjugate vaccine (TT conjugate), meningococcal serogroup B vaccine 
(MenB), oral rotavirus vaccine and measles-mumps-rubella-varicella (MMRV) vaccine. 
 
Data have shown no clinically relevant interference in the antibody response to each of the individual 
antigens, although inconsistent antibody response to poliovirus type 2 in co-administration with 
Synflorix was observed (seroprotection ranging from 78% to 100%) and the immune response rates to 
the PRP (Hib) antigen of Infanrix hexa after 2 doses given at 2 and 4 months of age were higher if co-
administered with a tetanus toxoid conjugate pneumococcal or meningococcal vaccine (see section 5.1). 
The clinical relevance of these observations remains unknown. 
 
When Infanrix hexa was co-administered with MenB and pneumococcal conjugate vaccines, 
inconsistent results were seen across studies for responses to inactivated poliovirus type 2, 



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pneumococcal conjugate serotype 6B antigen and to the pertussis pertactin antigen but these data do not 
suggest clinically significant interference.  
 
Data from clinical studies indicate that, when Infanrix hexa is co-administered with pneumococcal 
conjugate vaccines, the rate of febrile reactions is higher compared to that occurring following the 
administration of Infanrix hexa alone. Data from one clinical study indicate that when Infanrix hexa is 
co-administered with MMRV vaccine, the rate of febrile reactions is higher compared to that occurring 
following the administration of Infanrix hexa alone and similar to that occurring following the 
administration of MMRV vaccine alone (see sections 4.4 and 4.8). The immune responses were 
unaffected. 
 
Due to an increased risk of fever, pain at the injection site, appetite lost and irritability when Infanrix 
hexa was co-administered with MenB vaccine and 7-valent pneumococcal conjugate vaccine, separate 
vaccinations can be considered when possible. 
 
As with other vaccines it may be expected that in patients receiving immunosuppressive therapy, an 
adequate response may not be achieved. 
 
4.6 Fertility, pregnancy and lactation 
 
As Infanrix hexa is not intended for use in adults, adequate human data on use during pregnancy or 
lactation and adequate animal reproduction studies are not available. 
 
4.7 Effects on ability to drive and use machines   
 
Not relevant. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
As has been observed for DTPa and DTPa-containing combinations, an increase in local reactogenicity 
and fever was reported after booster vaccination with Infanrix hexa with respect to the primary course. 
 
Tabulated summary of adverse reactions 
 
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 
 
Frequencies per dose are defined as follows: 
 
Very common: (≥1/10) 
Common: (≥1/100 to <1/10) 
Uncommon: (≥1/1,000 to <1/100) 
Rare:  (≥1/10,000 to <1/1,000) 
Very rare: (<1/10,000) 
 



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The following drug-related adverse reactions were reported in clinical studies (data from more than 
16,000 subjects) and during post-marketing surveillance. 
 
System Organ Class Frequency Adverse reactions 
Infections and infestations Uncommon Upper respiratory tract infection 
Blood and lymphatic system disorders Rare Lymphadenopathy2, thrombocytopenia2 
Immune system disorders Rare Anaphylactic reactions2, anaphylactoid 

reactions (including urticaria)2 
Allergic reactions (including pruritus)2 

Metabolism and nutrition disorders Very common Appetite lost 
Psychiatric disorders Very common Crying abnormal, irritability, restlessness 

Common Nervousness 
Nervous system disorders Very common Somnolence 

Rare Collapse or shock-like state (hypotonic-
hyporesponsive episode)2 

Very rare Convulsions (with or without fever) 
Respiratory, thoracic and mediastinal 
disorders 

Uncommon Cough 
Rare Bronchitis, apnoea2 [see section 4.4 for 

apnoea in very preterm infants (≤ 28 
weeks of gestation)] 

Gastrointestinal disorders Common Diarrhoea, vomiting 
Skin and subcutaneous tissue disorders Rare Rash, Angioedema2 

Very rare Dermatitis 
General disorders and administration site 
conditions 

Very common Fever ≥ 38°C, pain, redness, local 
swelling at the injection site (≤ 50 mm) 

Common Fever >39.5°C, injection site reactions, 
including induration, local swelling at the 
injection site (> 50 mm)1 

Uncommon Diffuse swelling of the injected limb, 
sometimes involving the adjacent joint1, 
fatigue 

Rare Swelling of the entire injected limb1, 2, 
extensive swelling reactions2, injection 
site mass2, injection site vesicles2 

1 Children primed with acellular pertussis vaccines are more likely to experience swelling reactions after 
booster administration in comparison with children primed with whole cell vaccines. These reactions 
resolve over an average of 4 days. 
2 Adverse reactions from spontaneous reporting. 
 
• Experience in co-administration: 
 
Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions (with or 
without fever) and HHE when comparing groups which reported use of Infanrix hexa with Prevenar 13 
to those which reported use of Infanrix hexa alone. 
 
In clinical studies in which some of the vaccinees received Infanrix hexa concomitantly with Prevenar 
(PCV7) as a booster (4th) dose of both vaccines, fever ≥ 38.0°C was reported in 43.4% of infants 
receiving Prevenar and Infanrix hexa at the same time as compared to 30.5% of infants receiving the 
hexavalent vaccine alone. Fever ≥39.5°C was observed in 2.6% and 1.5% of infants receiving Infanrix 
hexa with or without Prevenar, respectively (see sections 4.4 and 4.5). The incidence and severity of 
fever following co-administration of the two vaccines in the primary series was lower than that observed 
after the booster dose. 
 
Data from clinical studies show similar incidences of fever when Infanrix hexa is co-administered with 
other pneumococcal saccharide conjugated vaccine. 
 



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In a clinical study in which some of the vaccinees received a booster dose of Infanrix hexa 
concomitantly with measles-mumps-rubella-varicella (MMRV) vaccine, fever ≥ 38.0°C was reported in 
76.6% of children receiving MMRV vaccine and Infanrix hexa at the same time, as compared to 48% of 
children receiving Infanrix hexa alone and 74.7% of children receiving MMRV vaccine alone. Fever of 
greater than 39.5°C was reported in 18% of children receiving Infanrix hexa with MMRV vaccine, as 
compared to 3.3% of children receiving Infanrix hexa alone and 19.3% of children receiving MMRV 
alone (see sections 4.4 and 4.5). 
 
• Safety in preterm infants: 
 
Infanrix hexa has been administered to more than 1000 preterm infants (born after a gestation period of 
24 to 36 weeks) in primary vaccination studies and in more than 200 preterm infants as a booster dose in 
the second year of life. In comparative clinical studies, similar rates of symptoms were observed in 
preterm and full-term infants (refer to section 4.4 for information on apnoea). 
 
• Safety in infants and toddlers born to mothers vaccinated with dTpa during pregnancy 
 
In two clinical studies, Infanrix hexa has been administered to more than 500 subjects born to mothers 
vaccinated with dTpa (n=341) or placebo (n=346) during the third trimester of pregnancy (see section 
5.1). The safety profile of Infanrix hexa was similar regardless of exposure/non-exposure to dTpa during 
pregnancy. 
 
• Experience with hepatitis B vaccine: 
 
In extremely rare cases, allergic reactions mimicking serum sickness, paralysis, neuropathy, neuritis, 
hypotension, vasculitis, lichen planus, erythema multiforme, arthritis, muscular weakness, Guillain-
Barré syndrome, encephalopathy, encephalitis and meningitis have been reported. The causal 
relationship to the vaccine has not been established. 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
No case of overdose has been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code: J07CA09 
 
Immunogenicity 
 
The immunogenicity of Infanrix hexa has been evaluated in clinical studies from 6 weeks of age. The 
vaccine was assessed in 2-dose and 3-dose priming schedules, including the schedule for the Expanded 
Program on Immunisation, and as a booster dose. The results of these clinical studies are summarised in 
the tables below. 
 
After a 3-dose primary vaccination schedule, at least 95.7% of infants had developed seroprotective or 
seropositive antibody levels against each of the vaccine antigens. After booster vaccination (post-dose 
4), at least 98.4% of children had developed seroprotective or seropositive antibody levels against each 
of the vaccine antigens. 



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Percentage of subjects with antibody titres indicative of seroprotection / seropositivity one month 
after 3-dose primary and booster vaccination with Infanrix hexa 
 
Antibody 
(cut-off) 

Post-dose 3 Post-dose 4  
(Booster vaccination 

during the second 
year of life following 

a 3-dose primary 
course) 

2-3-4 
months 
N= 196 

(2 studies) 

2-4-6 
months 
N= 1693 

(6 studies) 

3-4-5 
months 
N= 1055 

(6 studies) 

6-10-14 
weeks 
N= 265 

(1 study) 

N=2009 
(12 studies) 

% % % % % 
Anti-diphtheria  
(0.1 IU/ml) † 

100.0 99.8 99.7 99.2 99.9 

Anti-tetanus  
(0.1 IU/ml) † 

100.0 100.0 100.0 99.6 99.9 

Anti-PT  
(5 EL.U/ml) 

100.0 100.0 99.8 99.6 99.9 

Anti-FHA  
(5 EL.U/ml) 

100.0 100.0 100.0 100.0 99.9 

Anti-PRN  
(5 EL.U/ml) 

100.0 100.0 99.7 98.9 99.5 

Anti-HBs  
(10 mIU/ml) † 

99.5 98.9 98.0 98.5* 98.4 

Anti-Polio type 1  
(1/8 dilution) † 

100.0 99.9 99.7 99.6 99.9 

Anti-Polio type 2  
(1/8 dilution) † 

97.8 99.3 98.9 95.7 99.9 

Anti-Polio type 3  
(1/8 dilution) † 

100.0 99.7 99.7 99.6 99.9 

Anti-PRP  
(0.15 µg/ml) † 

96.4 96.6 96.8 97.4 99.7** 

N = number of subjects 
* in a subgroup of infants not administered hepatitis B vaccine at birth, 77.7% of subjects had anti-HBs 
titres ≥ 10 mIU/ml 
** Post booster, 98.4% of subjects had anti-PRP concentration ≥ 1 µg/ml indicative of long-term 
protection 
† cut-off accepted as indicative of protection 
 
After a 2-dose primary vaccination schedule, at least 84.3% of infants had developed seroprotective or 
seropositive antibody levels against each of the vaccine antigens. After a complete vaccination 
according to a 2-dose primary and booster schedule with Infanrix hexa, at least 97.9% of the subjects 
had developed seroprotective or seropositive antibody levels against each of the vaccine antigens. 
 
According to different studies, immune response to the PRP antigen of Infanrix hexa after 2 doses given 
at 2 and 4 months of age will vary if co-administered with a tetanus toxoid conjugate vaccine. Infanrix 
hexa will confer an anti-PRP immune response (cut-off ≥ 0.15µg/ml) in at least 84% of the infants. This 
rises to 88% in case of concomitant use of pneumococcal vaccine containing tetanus toxoid as carrier 
and to 98% when Infanrix hexa is co-administered with a TT conjugated meningococcal vaccine (see 
section 4.5). 
 



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Percentage of subjects with antibody titres indicative of seroprotection / seropositivity one month 
after 2-dose primary and booster vaccination with Infanrix hexa 
 

Antibody 
(cut-off) 

Post-dose 2 
 

Post-dose 3 
 

2-4-12 months of 
age 

N=223 
(1 study) 

3-5-11 months of 
age 

N=530 
(4 studies) 

2-4-12 months of 
age 

N=196 
(1 study) 

3-5-11 months of 
age 

N=532 
(3 studies) 

% % % % 
Anti-diphtheria 
(0.1 IU/ml) † 

99.6 98.0 100.0 100.0 

Anti-tetanus 
(0.1 IU/ml) † 

100 100.0 100.0 100.0 

Anti-PT 
(5 EL.U/ml) 

100 99.5 99.5 100.0 

Anti-FHA 
(5 EL.U/ml) 

100 99.7 100.0 100.0 

Anti-PRN 
(5 EL.U/ml) 

99.6 99.0 100.0 99.2 

Anti-HBs 
(10 mIU/ml) † 

99.5 96.8 99.8 98.9 

Anti-Polio type 1 
(1/8 dilution) † 

89.6 99.4 98.4 99.8 

Anti-Polio type 2 
(1/8 dilution) † 

85.6 96.3 98.4 99.4 

Anti-Polio type 3 
(1/8 dilution) † 

92.8 98.8 97.9 99.2 

Anti-PRP 
(0.15 µg/ml) † 

84.3 91.7 100.0* 99.6* 

N = number of subjects 
† cut-off accepted as indicative of protection 
* Post booster, 94.4% of subjects in the 2-4-12 months schedule and 97.0% of subjects in the 3-5-11 
months schedule had anti-PRP concentration ≥ 1 µg/ml indicative of long-term protection. 
 
Serological correlates of protection have been established for diphtheria, tetanus, polio, Hepatitis B and 
Hib. For pertussis there is no serological correlate of protection. However, as the immune response to 
pertussis antigens following Infanrix hexa administration is equivalent to that of Infanrix (DTPa), the 
protective efficacy of the two vaccines is expected to be equivalent. 
 
Efficacy in protecting against pertussis 
 
The clinical protection of the pertussis component of Infanrix (DTPa), against WHO-defined typical 
pertussis (≥ 21 days of paroxysmal cough) was demonstrated after 3-dose primary immunisation in the 
studies tabulated below: 
 

Study Country Schedule Vaccine efficacy Considerations 

Household contact 
study (prospective 
blinded) 

Germany 3,4,5 months 88.7% Based on data collected from secondary 
contacts in households where there was an 
index case with typical pertussis 

Efficacy study 
(NIH sponsored) 

Italy 2,4,6 months 84% In a follow-up of the same cohort, the 
efficacy was confirmed up to 60 months 
after completion of primary vaccination 
without administration of a booster dose 



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of pertussis. 
 
Persistence of the immune response 
 
The persistence of the immune response to a 3-dose primary (at 2-3-4, 3-4-5 or 2-4-6 months of age) 
and booster (in the second year of life) schedule with Infanrix hexa was evaluated in children 4-8 years 
of age. Protective immunity against the three poliovirus types and PRP was observed in at least 91.0% 
of children and against diphtheria and tetanus in at least 64.7% of children. At least 25.4% (anti-PT), 
97.5% (anti-FHA) and 87.0% (anti-PRN) of children were seropositive against the pertussis 
components. 
 
Percentage of subjects with antibody titres indicative of seroprotection / seropositivity after 
primary and booster vaccination with Infanrix hexa 
 
Antibody 
(cut-off) 

Children at 4-5 years of age Children at 7-8 years of age 
N % N % 

Anti-diphtheria 
(0.1 IU/ml) 198 68.7* 51 66.7 

Anti-tetanus 
(0.1 IU/ml) 198 74.7 51 64.7 

Anti-PT 
(5 EL.U/ml) 197 25.4 161 32.3 

Anti-FHA 
(5 EL.U/ml) 197 97.5 161 98.1 

Anti-PRN 
(5 EL.U/ml) 198 90.9 162 87.0 

Anti-HBs 
(10 mIU/ml) 

250§ 
171§ 

85.3 
86.4 

207§ 
149§ 

72.1 
77.2 

Anti-Polio type 1 
(1/8 dilution) 185 95.7 145 91.0 

Anti-Polio type 2 
(1/8 dilution) 187 95.7 148 91.2 

Anti-Polio type 3 
(1/8 dilution) 174 97.7 144 97.2 

Anti-PRP 
(0.15 µg/ml) 198 98.0 193 99.5 

N = number of subjects 
* Samples tested by ELISA to have anti-diphtheria antibody concentrations < 0.1 IU/ml were re-tested 
using Vero-cell neutralisation assay (seroprotection cut-off ≥ 0.016 IU/ml): 96.5% of the subjects were 
seroprotected 
§ Number of subjects from 2 clinical studies 
 
With regards to hepatitis B, seroprotective antibody concentrations (≥10 mIU/ml) following a 3-dose 
primary and booster schedule with Infanrix hexa have been shown to persist in ≥ 85% of subjects 4-5 
years of age, in ≥72% of subjects 7-8 years of age, in ≥60% of subjects 12-13 years of age and in 53.7% 
of subjects 14-15 years of age. Additionally, following a 2-dose primary and booster schedule, 
seroprotective antibody concentrations against hepatitis B persisted in ≥ 48% of subjects 11-12 years of 
age. 
 
Hepatitis B immunological memory was confirmed in children 4 to 15 years of age. These children had 
received Infanrix hexa as primary and booster vaccination in infancy, and when an additional dose of 
monovalent HBV vaccine was administered, protective immunity was observed in at least 93% of 
subjects.  
 
Immunogenicity in infants and toddlers born to mothers vaccinated with dTpa during pregnancy 
 



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The immunogenicity of Infanrix hexa in infants and toddlers born to healthy mothers vaccinated with 
dTpa at 27-36 weeks of pregnancy was evaluated in two clinical studies.  
Infanrix hexa was co-administered with a 13-valent pneumococcal conjugate vaccine to infants at 2, 4 
and 6 months or 2, 3 and 4 months in three-dose primary vaccination schedules (n=241), or at 3 and 5 
months or 2 and 4 months in two-dose primary vaccination schedules (n=27); and to the same 
infants/toddlers from 11 to 18 months as booster dose (n=229). 
 
Post-primary and post-booster vaccination, immunological data did not show clinically relevant 
interference of maternal vaccination with dTpa on the infant’s and toddler’s responses to diphtheria, 
tetanus, hepatitis B, inactivated poliovirus, Haemophilus influenzae type b or pneumococcal antigens. 
 
Lower antibody concentrations against pertussis antigens post-primary (PT, FHA and PRN) and post-
booster (PT, FHA) vaccination were observed in infants and toddlers born to mothers vaccinated with 
dTpa during pregnancy. The fold-increases of anti-pertussis antibody concentrations from the pre-
booster to the 1-month post-booster time point were in the same range for infants and toddlers born to 
mothers vaccinated with dTpa or with placebo, demonstrating effective priming of the immune system. 
In the absence of correlates of protection for pertussis, the clinical relevance of these observations 
remains to be fully understood. However, current epidemiological data on pertussis disease following 
the implementation of dTpa maternal immunisation do not suggest any clinical relevance of this 
immune interference. 
 
Immunogenicity in preterm infants 
 
The immunogenicity of Infanrix hexa was evaluated across three studies including approximately 300 
preterm infants (born after a gestation period of 24 to 36 weeks) following a 3-dose primary vaccination 
course at 2, 4 and 6 months of age. The immunogenicity of a booster dose at 18 to 24 months of age was 
evaluated in approximately 200 preterm infants. 
 
One month after primary vaccination at least 98.7% of subjects were seroprotected against diphtheria, 
tetanus and poliovirus types 1 and 2; at least 90.9% had seroprotective antibody levels against the 
hepatitis B, PRP and poliovirus type 3 antigens; and all subjects were seropositive for antibodies against 
FHA and PRN while 94.9% were seropositive for anti-PT antibodies. 
 
One month after the booster dose at least 98.4% of subjects had seroprotective or seropositive antibody 
levels against each of the antigens except against PT (at least 96.8%) and hepatitis B (at least 88.7%). 
The response to the booster dose in terms of fold increases in antibody concentrations (15- to 235-fold), 
indicate that preterm infants were adequately primed for all the antigens of Infanrix hexa. 
 
In a follow-up study conducted in 74 children, approximately 2.5 to 3 years after the booster dose, 
85.3% of the children were still seroprotected against hepatitis B and at least 95.7% were seroprotected 
against the three poliovirus types and PRP. 
 
Post marketing experience 
 
Results of long term follow-up in Sweden demonstrate that acellular pertussis vaccines are efficacious 
in infants when administered according to the 3 and 5 months primary vaccination schedule, with a 
booster dose administered at approximately 12 months. However, data indicate that protection against 
pertussis may be waning at 7-8 years of age with this 3-5-12 month’s schedule. This suggests that a 
second booster dose of pertussis vaccine is warranted in children aged 5-7 years who have previously 
been vaccinated following this particular schedule. 
 
The effectiveness of the Hib component of Infanrix hexa was investigated via an extensive post-
marketing surveillance study conducted in Germany. Over a seven year follow-up period, the 
effectiveness of the Hib components of two hexavalent vaccines, of which one was Infanrix hexa, was 
89.6% for a full primary series and 100% for a full primary series plus booster dose (irrespective of the 
Hib vaccine used for priming). 
 



13 

Results of ongoing routine national surveillance in Italy demonstrate that Infanrix hexa is effective in 
controlling Hib disease in infants when the vaccine is administered according to the 3 and 5 months 
primary vaccination schedule, with a booster dose administered at approximately 11 months. Over a six 
year period starting in 2006, where Infanrix hexa was the principal Hib-containing vaccine in use with 
vaccination coverage exceeding 95%, Hib invasive disease continued to be well controlled, with four 
confirmed Hib cases reported in Italian children aged less than 5 years through passive surveillance. 
 
5.2 Pharmacokinetic properties 
 
Evaluation of pharmacokinetic properties is not required for vaccines. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety, specific 
toxicity, repeated dose toxicity and compatibility of ingredients.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hib powder: 
Lactose anhydrous 
 
DTPa-HBV-IPV suspension: 
Sodium chloride (NaCl) 
Medium 199 containing principally amino acids, mineral salts, vitamins 
Water for injections 
 
For adjuvants, see section 2. 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf-life 
 
3 years. 
 
After reconstitution: an immediate use is recommended. However the stability has been demonstrated 
for 8 hours at 21°C after reconstitution. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Store in the original package, in order to protect from light. 
 
Stability data indicate that the vaccine components are stable at temperatures up to 25°C for 72 hours. 
At the end of this period Infanrix hexa should be used or discarded. These data are intended to guide 
healthcare professionals in case of temporary temperature excursion only. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 



14 

Powder in a vial (type I glass) with a stopper (butyl).  
 
0.5 ml of suspension in a pre-filled syringe (type I glass) with plunger stopper (butyl).  
 
Pack sizes of 1 and 10 with or without needles and a multipack of 5 packs, each containing 10 vials and 
10 pre-filled syringes, without needles. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Upon storage, a clear liquid and white deposit may be observed in the pre-filled syringe containing the 
DTPa-HBV-IPV suspension. This is a normal observation. 
 
The pre-filled syringe should be well shaken in order to obtain a homogeneous turbid white suspension. 
 
The vaccine is reconstituted by adding the entire contents of the pre-filled syringe to the vial containing 
the powder. The mixture should be well shaken until the powder is completely dissolved prior to 
administration. 
 
The reconstituted vaccine appears as a slightly more cloudy suspension than the liquid component 
alone. This is a normal observation. 
 
The vaccine suspension should be inspected visually before and after reconstitution for any foreign 
particulate matter and/or abnormal physical appearance. If either is observed, do not administer the 
vaccine. 
 
The pre-filled syringe can be supplied with either a ceramic coated treatment (CCT) of the luer tip or 
with a plastic rigid tip cap (PRTC) luer lock adaptor.   

• Instructions for use of pre-filled syringe if supplied with a PRTC luer lock adaptor  
 

Needle 

 

 

 

 

Syringe 

 

 

 

 

1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap 
by twisting it anticlockwise. 

2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock 
(see picture). 

3. Remove the needle protector, which on occasion can be a little stiff. 
4. Reconstitute the vaccine as described above. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

Needle protector 

Syringe plunger 
Syringe barrel 

Syringe cap 



15 

 
 
7. MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l'Institut 89 
B-1330 Rixensart, Belgium 
 
 
8.  MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/152/001 
EU/1/00/152/002 
EU/1/00/152/005 
EU/1/00/152/006 
EU/1/00/152/021 
 
 
9.  DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 23 October 2000 
Date of latest renewal: 31 August 2010 
 
 
10.  DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu  
 



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 
B.  CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



17 

 
A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  
 
Name and address of the manufacturers of the biological active substances 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89, 
1330 Rixensart 
Belgium 
 
GlaxoSmithKline Biologicals s.a. 
Parc de la Noire Epine 20, rue Fleming, 
1300 Wavre 
Belgium 
 
GlaxoSmithKline Biologicals s.a.  
10, Tuas South Avenue 8 
Singapore 637421 
Singapore 
 
GSK Vaccines GmbH 
Emil-von-Behring-Str. 76, 
D-35041 Marburg 
Germany 
 
GlaxoSmithKline Biologicals Kft 
Homoki Nagy István utca 1. 
H-2100 Gödöllö 
Hungary 
 
Name and address of the manufacturer responsible for batch release 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89, 
1330 Rixensart 
Belgium 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
• Official batch release 
 
In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken by 
a state laboratory or a laboratory designated for that purpose. 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
 



18 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
• Risk management plan (RMP) 
 
Not applicable. 
 
 
 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



21 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
1 VIAL AND 1 PRE-FILLED SYRINGE WITHOUT NEEDLE 
10 VIALS AND 10 PRE-FILLED SYRINGES WITHOUT NEEDLES 
1 VIAL AND 1 PRE-FILLED SYRINGE WITH 2 NEEDLES 
10 VIALS AND 10 PRE-FILLED SYRINGES WITH 20 NEEDLES 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Infanrix hexa, Powder and suspension for suspension for injection in a pre-filled syringe 
Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), 
poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
After reconstitution, 1 dose (0.5 ml): 
Diphtheria toxoid1  ≥ 30 IU 
Tetanus toxoid1  ≥ 40 IU 
Bordetella pertussis antigens  
(Pertussis toxoid1, Filamentous haemagglutinin1, Pertactin1) 25, 25, 8 micrograms 
Hepatitis B surface antigen2 10 micrograms 
Poliovirus (inactivated) type 1, 2, 3 40, 8, 32 DU 
Haemophilus influenzae type b polysaccharide 10 micrograms 
(polyribosylribitol phosphate) 2 
conjugated to tetanus toxoid as carrier protein approximately 25 micrograms 
 
1adsorbed on Al(OH)3 0.5 milligrams Al3+ 
2 adsorbed on AlPO4 0.32 milligrams Al3+ 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose anhydrous 
Sodium chloride  
Medium 199 containing principally amino acids, mineral salts, vitamins 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and suspension for suspension for injection in a pre-filled syringe 
Vial: powder 
Pre-filled syringe: suspension 
 
1 vial and 1 pre-filled syringe 
1 dose (0.5 ml) 
 
10 vials and 10 pre-filled syringes 
10 x 1 dose (0.5 ml) 
 
1 vial and 1 pre-filled syringe + 2 needles 
1 dose (0.5 ml) 
 
10 vials and 10 pre-filled syringes + 20 needles 



22 

10 x 1 dose (0.5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intramuscular use 
Shake well before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/152/001 - 1 vial and 1 pre-filled syringe without needle  
EU/1/00/152/002 - 10 vials and 10 pre-filled syringes without needles 
EU/1/00/152/005 - 1 vial and 1 pre-filled syringe with 2 needles 
EU/1/00/152/006 - 10 vials and 10 pre-filled syringes with 20 needles 
 
 
13. BATCH NUMBER 
 
LOT: 
 



23 

 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



24 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
PACK OF 10 VIALS AND 10 PRE-FILLED SYRINGES WITHOUT NEEDLES FOR 
MULTIPACK OF 50 (5 X 10) (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Infanrix hexa, Powder and suspension for suspension for injection in a pre-filled syringe 
Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), 
poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
After reconstitution, 1 dose (0.5 ml): 
Diphtheria toxoid1  ≥ 30 IU 
Tetanus toxoid1  ≥ 40 IU 
Bordetella pertussis antigens  
(Pertussis toxoid1, Filamentous haemagglutinin1, Pertactin1) 25, 25, 8 micrograms 
Hepatitis B surface antigen2 10 micrograms 
Poliovirus (inactivated) type 1, 2, 3 40, 8, 32 DU 
Haemophilus influenzae type b polysaccharide 10 micrograms 
(polyribosylribitol phosphate) 2 
conjugated to tetanus toxoid as carrier protein approximately 25 micrograms 
 
1adsorbed on Al(OH)3 0.5 milligrams Al3+ 
2 adsorbed on AlPO4 0.32 milligrams Al3+ 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose anhydrous 
Sodium chloride  
Medium 199 containing principally amino acids, mineral salts, vitamins 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and suspension for suspension for injection in a pre-filled syringe 
Vial: powder 
Pre-filled syringe: suspension 
 
Component of a multipack comprising 5 packs, each containing 10 vials and 10 pre-filled syringes 
without needles 
 
10 vials and 10 pre-filled syringes 
10 x 1 dose (0.5 ml) 
 
Each individual pack cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intramuscular use 



25 

Shake well before use 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/152/021 - pack of 50 (5 X 10) without needles 
 
 
13. BATCH NUMBER 
 
LOT: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 



26 

Justification for not including Braille accepted. 
 
 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
MULTIPACK OF 50 (5 X 10) (OUTER WRAPPER LABEL TO BE APPLIED ON 
TRANSPARENT FOIL, INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Infanrix hexa, Powder and suspension for suspension for injection in a pre-filled syringe 
Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), 
poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine (adsorbed) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
After reconstitution, 1 dose (0.5 ml): 
Diphtheria toxoid1  ≥ 30 IU 
Tetanus toxoid1  ≥ 40 IU 
Bordetella pertussis antigens  
(Pertussis toxoid1, Filamentous haemagglutinin1, Pertactin1) 25, 25, 8 micrograms 
Hepatitis B surface antigen2 10 micrograms 
Poliovirus (inactivated) type 1, 2, 3 40, 8, 32 DU 
Haemophilus influenzae type b polysaccharide 10 micrograms 
(polyribosylribitol phosphate) 2 
conjugated to tetanus toxoid as carrier protein approximately 25 micrograms 
 
1adsorbed on Al(OH)3 0.5 milligrams Al3+ 
2 adsorbed on AlPO4 0.32 milligrams Al3+ 
 
 
3. LIST OF EXCIPIENTS 
 
Lactose anhydrous 
Sodium chloride  
Medium 199 containing principally amino acids, mineral salts, vitamins 
Water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and suspension for suspension for injection in a pre-filled syringe 
Vial: powder 
Pre-filled syringe: suspension 
 
Multipack comprising 5 packs, each containing 10 vials and 10 pre-filled syringes without needles 
50 x 1 dose (0.5 ml) 
 
Each individual pack cannot be sold separately 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Intramuscular use 
Shake well before use 
 
 



28 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: MM/YYYY 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator 
Do not freeze 
Store in the original package in order to protect from light 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/00/152/021 - pack of 50 (5 X 10) without needles 
 
 
13. BATCH NUMBER 
 
LOT: 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 



29 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
 
 



30 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
VIAL WITH HIB POWDER  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Hib for Infanrix hexa 
Powder for suspension for injection 
I.M. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP:  
 
 
4. BATCH NUMBER 
 
LOT:  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose 
 
 
6. OTHER 
 



31 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
PRE-FILLED SYRINGE WITH DTPA HBV IPV SUSPENSION 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
DTPa HBV IPV for Infanrix hexa 
Suspension for suspension for injection 
I.M. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP:  
 
 
4. BATCH NUMBER 
 
LOT:  
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 dose (0.5 ml) 
 
 
6. OTHER 
 



32 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



33 

 
 Package leaflet: Information for the user 

 
Infanrix hexa, Powder and suspension for suspension for injection in a pre-filled syringe 
Diphtheria (D), tetanus (T), pertussis (acellular, component) (Pa), hepatitis B (rDNA) (HBV), 
poliomyelitis (inactivated) (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine 

(adsorbed). 
 
Read all of this leaflet carefully before your child receives this vaccine because it contains 
important information for you. 
• Keep this leaflet. You may need to read it again. 
•  If you have any further questions, ask your doctor or pharmacist. 
•  This vaccine has been prescribed for your child only. Do not pass it on to others. 
• If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Infanrix hexa is and what it is used for 
2. What you need to know before your child receives Infanrix hexa 
3. How Infanrix hexa is given 
4. Possible side effects 
5. How to store Infanrix hexa 
6. Contents of the pack and other information 
 
 
1.   What Infanrix hexa is and what it is used for 
 
Infanrix hexa is a vaccine used to protect your child against six diseases:  
 
• Diphtheria: a serious bacterial infection that mainly affects the airways and sometimes the skin. The 

airways become swollen causing serious breathing problems and sometimes suffocation. The 
bacteria also release a poison. This can cause nerve damage, heart problems, and even death. 

 
• Tetanus: tetanus bacteria enter the body through cuts, scratches or wounds in the skin. Wounds that 

are more likely to get tetanus infection are burns, fractures, deep wounds or wounds that have soil, 
dust, horse manure or wood splinters in them. The bacteria release a poison. This can cause muscle 
stiffness, painful muscle spasms, fits and even death. The muscle spasms can be strong enough to 
cause bone fractures of the spine. 

 
• Whooping cough (Pertussis): a highly infectious illness that affects the airways. It causes severe 

coughing that may lead to problems with breathing. The coughing often has a “whooping” sound. 
The cough may last for one to two months or longer. Whooping cough can also cause ear infections, 
chest infections (bronchitis) which may last a long time, lung infections (pneumonia), fits, brain 
damage and even death.  

 
• Hepatitis B: is caused by the hepatitis B virus. It makes the liver swollen. The virus is found in body 

fluids such as in the vagina, blood, semen or spit (saliva) of infected people. 
 
• Polio: a viral infection. Polio is often only a mild illness. However, sometimes it can be very serious 

and cause permanent damage or even death. Polio can make the muscles unable to move (paralysis). 
This includes the muscles needed for breathing and walking. The arms or legs affected by the disease 
may be painfully twisted (deformed). 

 
• Haemophilus influenzae type b (Hib):  can cause brain swelling (inflammation). This can lead to 

serious problems such as mental slowness (retardation), cerebral palsy, deafness, epilepsy or partial 
blindness. It can also cause swelling of the throat. This can cause death by suffocation. Less 



34 

commonly, the bacteria can also infect the blood, heart, lungs, bones, joints, and tissues of the eyes 
and mouth. 

 
How Infanrix hexa works 
• Infanrix hexa helps your child’s body make its own protection (antibodies). This will protect your 

child against these diseases. 
• As with all vaccines, Infanrix hexa may not fully protect all children who are vaccinated. 
• The vaccine cannot cause the diseases that it protects your child from. 
 
 
2.  What you need to know before your child receives Infanrix hexa 
 
Infanrix hexa should not be given 
 
• if your child is allergic to: 

- Infanrix hexa or any of the ingredients of this vaccine (listed in section 6).  
- formaldehyde. 
- neomycin or polymyxin (antibiotics). 

Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face 
or tongue. 

• if your child has had an allergic reaction to any vaccine against diphtheria, tetanus, whooping cough, 
hepatitis B, polio or Haemophilus influenzae type b. 

• if your child has had problems of the nervous system within 7 days after previous vaccination with a 
vaccine against whooping cough 

• if your child has a severe infection with a high temperature (over 38°C).  
A minor infection such as a cold should not be a problem, but talk to your doctor first. 

 
Infanrix hexa should not be given if any of the above apply to your child. If you are not sure, talk to 
your doctor or pharmacist before your child is given Infanrix hexa. 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before your child is given Infanrix hexa: 
 
• if after previously having Infanrix hexa or another vaccine against whooping cough, your child had 

any problems, especially:  
- a high temperature (over 40°C) within 48 hours of vaccination 
- a collapse or “shock-like” state within 48 hours of vaccination 
- persistent crying lasting 3 hours or more within 48 hours of vaccination 
- fits with or without a high temperature within 3 days of vaccination 

• if your child has an undiagnosed or progressive disease of the brain or epilepsy which is not 
controlled. After control of the disease the vaccine can be given. 

• if your child has a bleeding problem or bruises easily 
• if your child tends to have fits when they have a fever, or if there is a history of this in the family. 
• if your child should become unresponsive or experience seizures (fits) after the vaccination, please 

contact your doctor immediately. See also section 4 Possible side effects.  
• if your baby was born very prematurely (at or before 28 weeks of gestation) longer gaps than normal 

between breaths may occur for 2-3 days after vaccination. These babies may require respiratory 
monitoring for 48-72h following the administration of the first two or three doses of Infanrix hexa. 

 
If any of the above apply to your child (or you are not sure), talk to your doctor or pharmacist before 
your child is given Infanrix hexa. 
 
Other medicines and Infanrix hexa 



35 

Your doctor may ask you to give your child a medicine that lowers fever (such as paracetamol) before 
or immediately after Infanrix hexa is given. This can help to lower some of the side effects (febrile 
reactions) of Infanrix hexa. 
 
Tell your doctor or pharmacist if your child is taking, has recently taken, might take any other medicines 
or has recently received any other vaccine. 
 
Infanrix hexa contains neomycin and polymyxin 
This vaccine contains neomycin and polymyxin (antibiotics). Tell your doctor if your child has had an 
allergic reaction to these ingredients.  
 
 
3.  How Infanrix hexa is given 
 
How much is given 
• Your child will have a total of two or three injections with respectively at least 2 or 1 month(s) 

between each injection. 
• You will be told by the doctor or nurse when your child should come back for their next injections. 
• If additional injections (boosters) are necessary, the doctor will tell you. 
 
How the vaccine is given 
• Infanrix hexa will be given as an injection into a muscle. 
• The vaccine should never be given into a blood vessel or into the skin. 

 
If your child misses a dose 
• If your child misses an injection which is due, it is important that you make another appointment. 
• Make sure your child finishes the complete vaccination course. If not, your child may not be 

fully protected against the diseases. 
 
 
4.  Possible side effects 
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. The following 
side effects may happen with this vaccine: 
 
Allergic reactions 
If your child has an allergic reaction, see your doctor straight away. The signs may include: 
• rashes that may be itchy or blistering 
• swelling of the eyes and face 
• difficulty in breathing or swallowing 
• a sudden drop in blood pressure and loss of consciousness. 
These signs usually start very soon after the injection has been given. Talk to a doctor straight away if 
they happen after leaving the doctor’s surgery. 
 
See your doctor straight away if your child has any of the following serious side effects: 
• collapse 
• times when they lose consciousness or have a lack of awareness 
• fits – with or without fever 
These side effects have happened very rarely with Infanrix hexa as with other vaccines against 
whooping cough. They usually happen within 2 to 3 days after vaccination. 
 
Other side effects include: 
 
Very common (these may occur with more than 1 in 10 doses of the vaccine): sleepiness, loss of 
appetite, high temperature of 38°C or higher, swelling, pain, redness where the injection was given, 
unusual crying, feeling irritable or restless. 



36 

 
Common (these may occur with up to 1 in 10 doses of the vaccine): diarrhoea, being sick (vomiting), 
high temperature of more than 39.5°C, swelling larger than 5 cm or hard lump where the injection was 
given, feeling nervous. 
 
Uncommon (these may occur with up to 1 in 100 doses of the vaccine): upper respiratory tract 
infection, tiredness, cough, large swelling at the injected limb. 
 
Rare (these may occur with up to 1 in 1,000 doses of the vaccine): bronchitis, rash, swollen glands in 
the neck, armpit or groin (lymphadenopathy), bleeding or bruising more easily than normal 
(thrombocytopenia), in babies born very prematurely (at or before 28 weeks of gestation) longer gaps 
than normal between breaths may occur for 2-3 days after vaccination, temporarily stopping breathing 
(apnoea), swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or 
breathing (angioedema), swelling of the whole injected limb, blisters. 
 
Very rare (these may happen with up to 1 in 10,000 doses of the vaccine): itching (dermatitis). 
 
Experience with hepatitis B vaccine 
 
In extremely rare cases the following side effects have been reported with hepatitis B vaccine: paralysis, 
numbness or weakness of the arms and legs (neuropathy), inflammation of some nerves, possibly with 
pins and needles or loss of feeling or normal movement (Guillain-Barré syndrome), swelling or 
infection of the brain (encephalopathy, encephalitis), infection around the brain (meningitis).  
The causal relationship to the vaccine has not been established. 
Bleeding or bruising more easily than normal (thrombocytopenia) has been reported with hepatitis B 
vaccines. 
 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5.  How to store Infanrix hexa 
 
• Keep this vaccine out of the sight and reach of children. 
• Do not use this vaccine after the expiry date which is stated on the carton. The expiry date refers to 

the last day of that month. 
• Store in a refrigerator (2°C – 8°C). 
• Store in the original package in order to protect from light. 
• Do not freeze. Freezing destroys the vaccine. 
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines your child no longer uses. These measures will help protect the 
environment. 

 
 
6.  Contents of the pack and other information 
 
What Infanrix hexa contains 
 
The active substances are: 

Diphtheria toxoid1 not less than 30 International Units (IU) 
Tetanus toxoid1 not less than 40 International Units (IU) 
Bordetella pertussis antigens 



37 

Pertussis toxoid1  25 micrograms 
Filamentous Haemagglutinin1  25 micrograms 
Pertactin1  8 micrograms 

Hepatitis B surface antigen2,3 10 micrograms 
Poliovirus (inactivated) 

type 1 (Mahoney strain)4 40 D-antigen unit 
type 2 (MEF-1 strain)4 8 D-antigen unit 
type 3 (Saukett strain)4 32 D-antigen unit 

Haemophilus influenzae type b polysaccharide 10 micrograms 
(polyribosylribitol phosphate)3 
conjugated to tetanus toxoid as carrier protein  approximately 25 micrograms 
 
1adsorbed on aluminium hydroxide, hydrated (Al(OH)3) 0.5 milligrams Al3+ 
2produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology 
3adsorbed on aluminium phosphate (AlPO4) 0.32 milligrams Al3+ 
4propagated in VERO cells 

 
The other ingredients are:  
Hib powder: lactose anhydrous 
DTPa-HBV-IPV suspension: sodium chloride (NaCl), medium 199 containing principally amino acids, 
mineral salts, vitamins and water for injections 
 
What Infanrix hexa looks like and contents of the pack 
• The diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis (DTPa-HBV-IPV) 

component is a white, slightly milky liquid presented in a pre-filled syringe (0.5 ml). 
• The Hib component is a white powder presented in a glass vial. 
• Both components are mixed together just before your child receives the injection. The mixed 

appearance is a white, slightly milky liquid. 
 
• Infanrix hexa is available in packs of 1 and 10 with or without needles, and a multipack of 5 packs, 

each containing 10 vials and 10 pre-filled syringes, without needles. 
• Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
GlaxoSmithKline Biologicals s.a. 
Rue de l’Institut 89 
B-1330 Rixensart 
Belgium 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 
 
 
България 
ГлаксоСмитКлайн ЕООД 
Тел. + 359 2 953 10 34 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel. +370 5 264 90 00 
info.lt@gsk.com 
 
Luxembourg/Luxemburg 
GlaxoSmithKline Pharmaceuticals s.a./n.v. 
Tél/Tel: + 32 10 85 52 00 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 2 22 00 11 11 
cz.info@gsk.com 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36-1-2255300 
 



38 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 

Malta 
GlaxoSmithKline (Malta) Ltd 
Tel: + 356 21 238131 
 

 
Deutschland 
GlaxoSmithKline GmbH & Co. KG 
Tel: + 49 (0)89 360448701 
produkt.info@gsk.com 
 

 
Nederland 
GlaxoSmithKline BV 
Tel: + 31 (0)33 2081100 
 

Eesti 
GlaxoSmithKline Eesti OÜ  
Tel: +372 667 6900 
estonia@gsk.com 
 
Ελλάδα 
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. 
Tηλ: + 30 210 68 82 100 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 
 
Österreich 
GlaxoSmithKline Pharma GmbH. 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com  
 

España 
GlaxoSmithKline, S.A. 
Tel: + 34 900 202 700 
es-ci@gsk.com  
 

Polska 
GSK Services Sp. z.o.o. 
Tel.: + 48 (22) 576 9000 
 

France 
Laboratoire GlaxoSmithKline 
Tél: + 33 (0) 1 39 17 84 44 
diam@gsk.com 
 

Portugal 
Smith Kline & French Portuguesa - Produtos 
Farmacêuticos, Lda. 
Tel: + 351 21 412 95 00 
FI.PT@gsk.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel.: + 385 (0)1 6051999 

România 
GlaxoSmithKline (GSK) SRL 
Tel: +40 (0)21 3028 208 

  
Ireland 
GlaxoSmithKline (Ireland) Ltd 
Tel: + 353 (0)1 495 5000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0) 1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf.  
Sími: +354 535 7000  
 
 

Slovenská republika 
GlaxoSmithKline Slovakia s.r.o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
GlaxoSmithKline S.p.A. 
Tel:+ 39 (0)45 9218 111 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 10 30 30 30 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 
 
 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 

Latvija 
GlaxoSmithKline Latvia SIA 

United Kingdom 
GlaxoSmithKline UK 



39 

Tel: + 371 67312687 
lv-epasts@gsk.com 
 

Tel: +44 (0)800 221 441 
customercontactuk@gsk.com 
 

 
This leaflet was last revised in  
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 
 
----------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
Upon storage, a clear liquid and white deposit may be observed in the pre-filled syringe containing the 
DTPa-HBV-IPV suspension. This is a normal observation. 
 
The pre-filled syringe should be well shaken in order to obtain a homogeneous turbid white suspension. 
 
The vaccine is reconstituted by adding the entire contents of the pre-filled syringe to the vial containing 
the powder. The mixture should then be well shaken until the powder is completely dissolved prior to 
administration. 
 
The reconstituted vaccine appears as a slightly more cloudy suspension than the liquid component 
alone. This is a normal observation.  
 
The vaccine suspension should be inspected visually before and after reconstitution for any foreign 
particulate matter and/or abnormal physical appearance. If either is observed, do not administer the 
vaccine. 
 
The pre-filled syringe can be supplied with either a ceramic coated treatment (CCT) of the luer tip or 
with a plastic rigid tip cap (PRTC) luer lock adaptor.   

• Instructions for use of pre-filled syringe if supplied with a PRTC luer lock adaptor  
 

Needle 

 

 

 

 

Syringe 

 

 

 

 

1. Holding the syringe barrel in one hand (avoid holding the syringe plunger), unscrew the syringe cap 
by twisting it anticlockwise. 

Needle protector 

Syringe plunger 
Syringe barrel 

Syringe cap 



40 

2. To attach the needle to the syringe, twist the needle clockwise into the syringe until you feel it lock 
(see picture). 

3. Remove the needle protector, which on occasion can be a little stiff. 
4. Reconstitute the vaccine as described above. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET