Hexyon

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Hexyon suspension for injection in pre-filled syringe 
Hexyon suspension for injection 
 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 
and Haemophilus influenzae type b conjugate vaccine (adsorbed). 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One dose1 (0.5 ml) contains: 
 
Diphtheria Toxoid not less than 20 IU2 
Tetanus Toxoid not less than 40 IU2,3 
Bordetella pertussis antigens 
 Pertussis Toxoid 25 micrograms 
 Filamentous Haemagglutinin 25 micrograms 
Poliovirus (Inactivated)4 
 Type 1 (Mahoney) 40 D antigen units5 
 Type 2 (MEF-1) 8 D antigen units5 
 Type 3 (Saukett) 32 D antigen units5 
Hepatitis B surface antigen6 10 micrograms 
Haemophilus influenzae type b polysaccharide 12 micrograms 
(Polyribosylribitol Phosphate)  
conjugated to Tetanus protein 22-36 micrograms 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
2 As lower confidence limit (p= 0.95) 
3 Or equivalent activity determined by an immunogenicity evaluation 
4 Produced on Vero cells 
5 Or equivalent antigenic quantity determined by a suitable immunochemical method 
6 Produced in yeast Hansenula polymorpha cells by recombinant DNA technology 
 
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and 
polymyxin B which are used during the manufacturing process (see section 4.3). 
 
Excipient with known effect 
Phenylalanine……………85 micrograms 
(See section 4.4) 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Suspension for injection. 
 
Hexyon is a whitish, cloudy suspension. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 



 

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Hexyon (DTaP-IPV-HB-Hib) is indicated for primary and booster vaccination of infants and toddlers 
from six weeks of age against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive 
diseases caused by Haemophilus influenzae type b (Hib). 
 
The use of this vaccine should be in accordance with official recommendations. 
 
4.2 Posology and method of administration 
 
Posology 
 
Primary vaccination: 
The primary vaccination consists of 2 doses (with an interval of at least 8 weeks) or 3 doses (with an 
interval of at least 4 weeks) in accordance with the official recommendations. 
 
All vaccination schedules including the WHO Expanded Program on Immunisation (EPI) at 6, 10, 14 
weeks of age can be used whether or not a dose of hepatitis B vaccine has been given at birth. 
 
Where a dose of hepatitis B vaccine is given at birth; 

- Hexyon can be used for supplementary doses of hepatitis B vaccine from the age of 6 weeks. If 
a second dose of hepatitis B vaccine is required before this age, monovalent hepatitis B vaccine 
should be used. 

- Hexyon can be used for a mixed hexavalent/pentavalent/hexavalent combined vaccine 
immunisation schedule in accordance with official recommendations. 

 
Booster vaccination: 
After a 2-dose primary vaccination with Hexyon, a booster dose must be given. 
After a 3-dose primary vaccination with Hexyon, a booster dose should be given. 
 
Booster doses should be given at least 6 months after the last priming dose and in accordance with the 
official recommendations. As a minimum, a dose of Hib vaccine must be administered. 
 
In addition: 
In the absence of hepatitis B vaccination at birth, it is necessary to give a hepatitis B vaccine booster 
dose. Hexyon can be considered for the booster. 
 
When a hepatitis B vaccine is given at birth, after a 3-dose primary vaccination, Hexyon or a 
pentavalent DTaP-IPV/Hib vaccine can be administered for the booster. 
 
Hexyon may be used as a booster in individuals who have previously been vaccinated with another 
hexavalent vaccine or a pentavalent DTaP-IPV/Hib vaccine associated with a monovalent hepatitis B 
vaccine. 
 
WHO-EPI schedule (6, 10, 14 weeks): 
After a WHO-EPI schedule, a booster dose should be given 

- As a minimum, a booster dose of polio vaccine should be given 
- In absence of hepatitis B vaccine at birth, a hepatitis B vaccine booster must be given 
- Hexyon can be considered for the booster 

 
Other paediatric population: 
 
The safety and efficacy of Hexyon in infants less than 6 weeks of age have not been established. No 
data are available. 
 
No data are available in older children (see sections 4.8 and 5.1) 
 
Method of administration  



 

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Immunisation must be carried out by intramuscular (IM) injection. The recommended injection sites 
are the antero-lateral area of the upper thigh (preferred site) or the deltoid muscle in older children 
(possibly from 15 months of age). 
 
For instructions on handling, see section 6.6. 
 
4.3 Contraindications 
 
History of an anaphylactic reaction after a previous administration of Hexyon. 
 
Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, to trace 
residuals (glutaraldehyde, formaldehyde, neomycin, streptomycin and polymyxin B), to any pertussis 
vaccine, or after previous administration of Hexyon or a vaccine containing the same components or 
constituents. 
 
Vaccination with Hexyon is contraindicated if the individual has experienced an encephalopathy of 
unknown aetiology, occurring within 7 days following prior vaccination with a pertussis containing 
vaccine (whole cell or acellular pertussis vaccines). 
In these circumstances pertussis vaccination should be discontinued and the vaccination course should 
be continued with diphtheria, tetanus, hepatitis B, poliomyelitis and Hib vaccines. 
 
Pertussis vaccine should not be administered to individuals with uncontrolled neurologic disorder or 
uncontrolled epilepsy until treatment for the condition has been established, the condition has 
stabilised and the benefit clearly outweighs the risk. 
 
4.4 Special warnings and precautions for use 
 
Hexyon 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. 
Hexyon will not protect against hepatitis infection caused by other agents such as hepatitis A, hepatitis 
C and hepatitis E or by other liver pathogens. 
 
Because of the long incubation period of hepatitis B, it is possible for unrecognised hepatitis B 
infection to be present at the time of vaccination. The vaccine may not prevent hepatitis B infection in 
such cases. 
 
Hexyon does not protect against infectious diseases caused by other types of Haemophilus influenzae 
or against meningitis of other origins. 
 
Prior to immunisation 
 
Immunisation should be postponed in individuals suffering from moderate to severe acute febrile 
illness or infection. The presence of a minor infection and/or low-grade fever should not result in the 
deferral of vaccination. 
 
Vaccination should be preceded by a review of the person’s medical history (in particular previous 
vaccinations and possible adverse reactions). The administration of Hexyon must be carefully 
considered in individuals who have a history of serious or severe reactions within 48 hours following 
administration of a vaccine containing similar components. 
 
Before the injection of any biological medicinal product, the person responsible for administration 
must take all precautions known for the prevention of allergic or any other reactions. As with all 
injectable vaccines, appropriate medical treatment and supervision should always be readily available 
in case of an anaphylactic reaction following administration of the vaccine. 



 

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If any of the following events are known to have occurred after receiving any pertussis containing 
vaccine, the decision to give further doses of pertussis containing vaccine should be carefully 
considered: 
• Temperature of ≥ 40°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 some circumstances, such as high incidence of pertussis, when the potential benefits 
outweigh possible risks. 
 
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 Hexyon. Individuals with a history of febrile 
convulsions should be closely followed up as such adverse events may occur within 2 to 3 days post 
vaccination. 
 
If Guillain-Barré syndrome or brachial neuritis has occurred following receipt of prior vaccine 
containing tetanus toxoid, the decision to give any vaccine containing tetanus toxoid should be based 
on careful consideration of the potential benefits and possible risks, such as whether or not the primary 
vaccination has been completed. Vaccination is usually justified for individuals whose primary 
vaccination is incomplete (i.e. fewer than three doses have been received). 
 
The immunogenicity of the vaccine may be reduced by immunosuppressive treatment or 
immunodeficiency. It is recommended to postpone vaccination until the end of such treatment or 
disease. Nevertheless, vaccination of individuals with chronic immunodeficiency such as HIV 
infection is recommended even if the antibody response may be limited. 
 
Special populations 
 
Immunogenicity data are available for 105 preterm infants. These data support the use of Hexyon in 
preterm infants. As expected in preterm infants, lower immune response has been observed for some 
antigens, when indirectly compared to term infants, although seroprotective levels have been achieved 
(see section 5.1). No safety data were collected in preterm infants (born ≤ 37 weeks of gestation) in 
clinical trials. 
 
The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 hours should be 
considered when administering the primary immunisation series to very premature infants (born ≤ 28 
weeks of gestation) and particularly for those with a previous history of respiratory immaturity. As the 
benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed. 
 
Immune responses to the vaccine have not been studied in the context of genetic polymorphism. 
 
In individuals with chronic renal failure, an impaired hepatitis B response is observed and 
administration of additional doses of hepatitis B vaccine should be considered according to the 
antibody level against hepatitis B virus surface antigen (anti-HBsAg). 
 
Precautions for use 
 
Do not administer by intravascular, intradermal or subcutaneous injection. 
 
As with all injectable vaccines, the vaccine must be administered with caution to individuals with 
thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular 
administration. 
 
Interference with laboratory testing 
 



 

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Since the Hib capsular polysaccharide antigen is excreted in the urine, a positive urine test can be 
observed within 1 to 2 weeks following vaccination. Other tests should be performed in order to 
confirm Hib infection during this period. 
 
Hexyon contains phenylalanine, potassium and sodium 
 
Hexyon contains 85 micrograms phenylalanine in each 0.5 ml dose. Phenylalanine may be harmful for 
individuals with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up 
because the body cannot remove it properly. 
Hexyon contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, 
that is to say essentially “potassium-free” and “sodium-free”. 
 
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 
 
Hexyon can be administered simultaneously with a pneumococcal polysaccharide conjugate vaccine, 
measles, mumps, rubella (MMR) containing vaccines, rotavirus vaccines, a meningococcal C 
conjugate vaccine or a meningococcal group A, C, W-135 and Y conjugate vaccine, as no clinically 
relevant interference in the antibody response to each of the antigens have been shown. 
 
There may be a clinically relevant interference in the antibody response of Hexyon and a varicella 
vaccine and these vaccines should not be administered at the same time. 
 
If co-administration with another vaccine is considered, immunisation should be carried out on 
separate injection sites. 
 
Hexyon must not be mixed with any other vaccines or other parenterally administered medicinal 
products. 
 
No significant clinical interaction with other treatments or biological products has been reported 
except in the case of immunosuppressive therapy (see section 4.4). 
 
Interference with laboratory testing: see section 4.4. 
 
4.6 Fertility, pregnancy and lactation 
 
Not applicable. This vaccine is not intended for administration to women of child-bearing age. 
 
4.7 Effects on ability to drive and use machines 
 
Not applicable. 
 
4.8 Undesirable effects 
 
a- Summary of the safety profile 
In clinical studies in individuals who received Hexyon, the most frequently reported reactions include 
injection-site pain, irritability, crying, and injection-site erythema.  
Slightly higher solicited reactogenicity was observed after the first dose compared to subsequent 
doses. 
 
The safety of Hexyon in children over 24 months of age has not been studied in clinical trials. 
 
b- Tabulated list of adverse reactions 



 

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The following convention has been used for the classification of adverse reactions; 
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) 
Not known (cannot be estimated from available data) 
 
Table 1: Adverse Reactions from clinical trials and post marketing surveillance 
 
System Organ Class Frequency Adverse Events 
Immune system disorders 
 

Uncommon Hypersensitivity reaction 
Rare Anaphylactic reaction* 

Metabolism and nutrition 
disorders 

Very common Anorexia (decreased appetite) 

Nervous system disorders 
 

Very common Crying, somnolence 
Common Abnormal crying (prolonged crying) 
Rare Convulsions with or without fever* 
Very rare  Hypotonic reactions or hypotonic-hyporesponsive 

episodes (HHE) 
Gastrointestinal disorders 
 

Very common Vomiting 
Common Diarrhoea 

Skin and subcutaneous tissue 
disorders 

Rare Rash 

General disorders and 
administration site 
conditions 
 

Very common Injection-site pain, injection-site erythema, 
injection-site swelling 
Irritability 
Pyrexia (body temperature ≥ 38.0°C) 

Common Injection-site induration 
Uncommon Injection-site nodule 

Pyrexia (body temperature ≥39.6°C) 
Rare Extensive limb swelling† 

* Adverse reactions from spontaneous reporting. 
† See section c 
 
c- Description of selected adverse reactions 
Extensive limb swelling: Large injection-site reactions (>50 mm), including extensive limb swelling 
from the injection site beyond one or both joints, have been reported in children. These reactions start 
within 24-72 hours after vaccination, may be associated with erythema, warmth, tenderness or pain at 
the injection site and resolve spontaneously within 3-5 days. The risk appears to be dependent on the 
number of prior doses of acellular pertussis containing vaccine, with a greater risk following the 4th 
dose. 
 
d- Potential adverse events (i.e. adverse events which have been reported with other vaccines 
containing one or more of the components or constituents of Hexyon and not directly with Hexyon) 
 
Nervous system disorders 
- Brachial neuritis and Guillain-Barré Syndrome have been reported after administration of a tetanus 
toxoid containing vaccine 
- Peripheral neuropathy (polyradiculoneuritis, facial paralysis), optic neuritis, central nervous system 
demyelination (multiple sclerosis) have been reported after administration of a hepatitis B antigen 
containing vaccine 
- Encephalopathy/encephalitis 
 
Respiratory, thoracic and mediastinal disorders 
Apnoea in very premature infants (≤ 28 weeks of gestation) (see section 4.4) 



 

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General disorders and administration site conditions 
Oedematous reaction affecting one or both lower limbs may occur following vaccination with 
Haemophilus influenzae type b containing vaccines. If this reaction occurs, it is mainly after primary 
injections and within the first few hours following vaccination. Associated symptoms may include 
cyanosis, redness, transient purpura and severe crying. All events should resolve spontaneously 
without sequel within 24 hours. 
 
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 cases of overdose have been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmaco-therapeutic group: Vaccines, Bacterial and viral vaccines combined, ATC code: J07CA09 
 
The immunogenicity of Hexyon in children over 24 months of age has not been studied in clinical 
trials. 
 
Results obtained for each of the components are summarised in the tables below: 
 



 

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Table 1: Seroprotection/Seroconversion rates* one month after a primary vaccination with 2 or 3 
doses of Hexyon 
 
Antibody Thresholds Two doses Three doses 

3-5 
Months 

6-10-14 
Weeks 

2-3-4 
Months 

2-4-6 
Months 

N=249** N=123 to 
220† N=322†† 

N=934 to 
1270‡ 

% % % % 

Anti-diphtheria 
( 0.01 IU/ml)  99.6 97.6 99.7 97.1 

Anti-tetanus 
( 0.01 IU/ml)  100.0 100.0 100.0 100.0 

Anti PT 
(Seroconversion‡‡)  
(Vaccine response§) 

93.4 
98.4 

93.6 
100.0 

88.3 
99.4 

96.0 
99.7 

Anti FHA 
(Seroconversion‡‡)  
(Vaccine response§) 

92.5 
99.6 

93.1 
100.0 

90.6 
99.7 

97.0 
99.9 

Anti-HBs 
( 10 mIU/ml)  

With hepatitis B 
vaccination at birth / 99.0 / 99.7 

Without hepatitis B 
vaccination at birth 97.2 95.7 96.8 98.8 

Anti-Polio type 1 
( 8 (1/dilution)) 90.8 100.0 99.4 99.9 

Anti-Polio type 2 
( 8 (1/dilution)) 95.0 98.5 100.0 100.0 

Anti-Polio type 3 
( 8 (1/dilution)) 96.7 100.0 99.7 99.9 

Anti-PRP 
( 0.15 µg/ml)  71.5 95.4 96.2 98.0 

* Generally accepted surrogates (PT, FHA) or correlates of protection (other components) 
N = Number of individuals analysed (per protocol set) 
** 3, 5 months without hepatitis B vaccination at birth (Finland, Sweden) 
† 6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa) 
†† 2, 3, 4 months without hepatitis B vaccination at birth (Finland) 
‡ 2, 4, 6 months without hepatitis B vaccination at birth (Argentina, Mexico, Peru) and with hepatitis B 
vaccination at birth (Costa Rica and Colombia) 
‡‡ Seroconversion: minimum 4-fold increase compared to pre-vaccination level (pre-dose 1) 
§ Vaccine response: If pre-vaccination antibody concentration <8 EU/ml, then the post-vaccination antibody 
concentration should be ≥ 8 EU/ml. Otherwise, post-vaccination antibody concentration should be ≥ pre-
immunisation level. 
 



 

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Table 2: Seroprotection/Seroconversion rates* one month after booster vaccination with Hexyon 
 
Antibody Thresholds Booster vaccination at 

11-12 months 
of age after a 

two doses 
primary course 

Booster vaccination during the 
second year of life following a 

three dose primary course 

3-5 
Months 

6-10-14 
Weeks 

2-3-4 
Months 

2-4-6 
Months 

N=249** N=204† N=178†† N=177 to 
396‡ 

% % % % 

Anti-diphtheria 
( 0.1 IU/ml)  100.0 100.0 100.0 97.2 

Anti-tetanus 
( 0.1 IU/ml)  100.0 100.0 100.0 100.0 

Anti-PT 
(Seroconversion‡‡)  
(Vaccine response§) 

 
94.3 
98.0 

 
94.4 
100.0 

 
86.0 
98.8 

 
96.2  
100.0 

Anti-FHA 
(Seroconversion‡‡)  
(Vaccine response§) 

 
97.6 
100.0 

 
99.4  
100.0 

 
94.3  
100.0 

 
98.4 

100.0 

Anti-HBs 
( 10 mIU/ml)  

With hepatitis B 
vaccination at birth / 100.0 / 99.7 

Without hepatitis B 
vaccination at birth 96.4 98.5 

 
98.9 99.4 

Anti-Polio type 1 
( 8 (1/dilution)) 100.0 100.0 98.9 100.0 

Anti-Polio type 2 
( 8 (1/dilution)) 100.0 100.0 100.0 100.0 

Anti-Polio type 3 
( 8 (1/dilution)) 99.6 100.0 100.0 100.0 

Anti-PRP 
( 1.0 µg/ml)  93.5 98.5 98.9 98.3 

* Generally accepted surrogates (PT, FHA) or correlates of protection (other components) 
N = Number of individuals analysed (per protocol set) 
** 3, 5 months without hepatitis B vaccination at birth (Finland, Sweden) 
† 6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa) 
†† 2, 3, 4 months without hepatitis B vaccination at birth (Finland) 
‡ 2, 4, 6 months without hepatitis B vaccination at birth (Mexico) and with hepatitis B vaccination at birth (Costa 
Rica and Colombia) 
‡‡ Seroconversion: minimum 4-fold increase compared to pre-vaccination level (pre-dose 1) 
§ Vaccine response: If pre-vaccination antibody concentration (pre-dose 1) <8 EU/ml, then the post-booster 
antibody concentration should be ≥8 EU/ml. Otherwise, post-booster antibody concentration should be ≥ pre-
immunisation level (pre-dose 1)  
 



 

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Immune responses to Hib and pertussis antigens after 2 doses at 2 and 4 months of age 
 
The immune responses to Hib (PRP) and pertussis antigens (PT and FHA) were evaluated after 2 
doses in a subset of subjects receiving Hexyon (N=148) at 2, 4, 6 months of age. The immune 
responses to PRP, PT and FHA antigens one month after 2 doses given at 2 and 4 months of age were 
similar to those observed one month after a 2-dose priming given at 3 and 5 months of age:  

- anti-PRP titers ≥ 0.15 µg/ml were observed in 73.0% of individuals,  
- anti-PT vaccine response in 97.9% of individuals, 
- anti-FHA vaccine response in 98.6% of individuals. 

 
Persistence of immune response 
 
Studies on long-term persistence of vaccine induced antibodies following varying infant / toddler 
primary series and following Hepatitis B vaccine given at birth or not have shown maintenance of 
levels above the recognized protective levels or antibody thresholds for the vaccine antigens (see 
Table 3). 
 
In addition, immunity against the hepatitis B component of the vaccine has been shown to persist up to 
9 years of age after a primary series consisting of one dose of Hepatitis B vaccine given at birth 
followed by a 3-dose infant series at 2, 4, and 6 months of age without a toddler booster where 49.3% 
of vaccinees had antibodies ≥ 10 mIU/ml with geometric mean concentrations at 13.3 (95% CI: 8.82 – 
20.0) mIU/ml. Immune memory against Hepatitis B had been demonstrated by the presence of an 
anamnestic response to a challenge Hepatitis B vaccination at the age of 9 years in 93% of vaccinees 
with development of geometric mean concentrations at 3692 (95% CI: 1886 – 7225) mIU/ml after 
vaccination. 



 

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Table 3: Seroprotection ratesa at the age of 4.5 years old after vaccination with Hexyon 

 
Antibody Thresholds Primary 6-10-14 weeks and booster at  

15-18 months  

Primary 2-4-6 months 
and booster at 12–24 

months  

Without hepatitis B 
at birth 

With hepatitis B 
at birth 

With hepatitis B at 
birth 

N=173b N=103b N=220c 

% % % 

Anti-diphtheria 
( 0.01 IU/ml)  
( 0.1 IU/ml) 

 
98.2 
75.3 

 
97 

64.4 

 
100 
57.2 

Anti-tetanus 
( 0.01 IU/ml) 
( 0.1 IU/ml) 

 
100 
89.5 

 
100 
82.8 

 
100 
80.8 

Anti-PTe 
( 8 EU/ml) 

 
42.5 

 
23.7 

 
22.2 

Anti-FHAe 
( 8 EU/ml) 

 
93.8 

 
89.0 

 
85.6 

Anti-HBs 
( 10 mIU/ml) 

 
73.3 

 
96.1 

 
92.3 

Anti-Polio type 1 
( 8 (1/dilution)) 

 
NAd 

 
NAd 

 
99.5 

Anti-Polio type 2 
( 8 (1/dilution)) 

 
NAd 

 
NAd 

 
100 

Anti-Polio type 3 
( 8 (1/dilution)) 

 
NAd 

 
NAd 

 
100 

Anti-PRP 
( 0.15 µg/ml) 

 
98.8 

 
100 

 
100 

N = Number of individuals analysed (per protocol set) 
a:   Generally accepted surrogates (PT, FHA) or correlates of protection (other components) 
b:   6, 10, 14 weeks with and without hepatitis B vaccination at birth (Republic of South Africa) 
c:   2, 4, 6 months with hepatitis B vaccination at birth (Colombia)  
d:   Due to an OPV National Immunisation Days in the country, Polio results have not been analysed 
e:   8 EU/ml corresponds to 4 LLOQ (Lower Limit Of Quantification in enzyme-linked immunosorbent assay 

ELISA). 
 LLOQ value for anti-PT and anti-FHA is 2 EU/ml 
 
Immune responses to Hexyon in preterm infants 
 
Immune responses to Hexyon antigens in preterm (105) infants (born after a gestation period of 28 to 
36 weeks), including 90 infants born to women vaccinated with Tdap vaccine during pregnancy and 
15 to women not vaccinated during pregnancy, were evaluated following a 3-dose primary vaccination 
course at 2, 3 and 4 months of age and a booster dose at 13 months of age. 
One month after primary vaccination, all subjects were seroprotected against diphtheria (≥ 0.01 
IU/mL), tetanus (≥ 0.01 IU/mL) and poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)); 89.8% of subjects 
were seroprotected against hepatitis B (≥ 10 IU/mL) and 79.4% were seroprotected against Hib 
invasive diseases (≥ 0.15 µg/mL).  
One month after the booster dose, all subjects were seroprotected against diphtheria (≥ 0.1 IU/mL), 
tetanus (≥ 0.1 IU/mL) and poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)); 94.6% of subjects were 



 

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seroprotected against hepatitis B (≥ 10 IU/mL) and 90.6% were seroprotected against Hib invasive 
diseases (≥ 1 µg/mL). 
Regarding pertussis, one month after primary vaccination 98.7% and 100% of subjects developed 
antibodies ≥ 8 EU/mL against PT and FHA antigens respectively. One month after the booster dose 
98.8% of subjects developed antibodies ≥ 8 EU/mL against both PT and FHA antigens. Pertussis 
antibody concentrations were increased by 13-fold after primary vaccination and by 6- to 14-fold after 
the booster dose. 
 
Immune responses to Hexyon in infants born to women vaccinated with Tdap during pregnancy 
 
Immune responses to Hexyon antigens in term (119) and preterm (90) infants born to women 
vaccinated with Tdap vaccine during pregnancy (between 24 and 36 weeks of gestation) were 
evaluated following a 3-dose primary vaccination course at 2, 3 and 4 months of age and a booster 
dose at 13 (preterm infants) or 15 (term infants) months of age.  
One month after primary vaccination, all subjects were seroprotected against diphtheria (≥ 0.01 
IU/mL), tetanus (≥ 0.01 IU/mL) and poliovirus types 1 and 3 (≥ 8 (1/dilution)); 97.3% of subjects 
were seroprotected against poliovirus type 2 (≥ 8 (1/dilution)); 94.6% of subjects were seroprotected 
against hepatitis B (≥ 10 IU/mL) and 88.0% were seroprotected against Hib invasive diseases (≥ 0.15 
µg/mL).  
One month after the booster dose, all subjects were seroprotected against diphtheria (≥ 0.1 IU/mL), 
tetanus (≥ 0.1 IU/mL) and poliovirus types 1, 2 and 3 (≥ 8 (1/dilution)); 93.9% of subjects were 
seroprotected against hepatitis B (≥ 10 IU/mL) and 94.0% were seroprotected against Hib invasive 
diseases (≥ 1 µg/mL). 
Regarding pertussis, one month after primary vaccination 99.4% and 100% of subjects developed 
antibodies ≥ 8 EU/mL against PT and FHA antigens respectively. One month after the booster dose 
99.4% of subjects developed antibodies ≥ 8 EU/mL against both PT and FHA antigens. Pertussis 
antibody concentrations were increased by 5- to 9-fold after primary vaccination and by 8- to 19-fold 
after the booster dose. 
 
Efficacy and effectiveness in protecting against pertussis 
 
Vaccine efficacy of the acellular pertussis (aP) antigens contained in Hexyon against the most severe 
WHO-defined typical pertussis ( 21 days of paroxysmal cough) is documented in a randomised 
double-blind study among infants with a 3 dose primary series using a DTaP vaccine in a highly 
endemic country (Senegal). The need for a toddler booster dose was seen in this study. 
The long term capability of the acellular pertussis (aP) antigens contained in Hexyon to reduce 
pertussis incidence and control pertussis disease in the childhood has been demonstrated in a 10-year 
national pertussis surveillance on pertussis disease in Sweden with the pentavalent DTaP-IPV/Hib 
vaccine using a 3, 5, 12 months schedule. Results of long term follow-up demonstrated a dramatic 
reduction of the pertussis incidence following the second dose regardless of the vaccine used. 
 
Effectiveness in protecting against Hib invasive disease 
 
The vaccine effectiveness against Hib invasive disease of DTaP and Hib combination vaccines 
(pentavalent and hexavalent including vaccines containing the Hib antigen from Hexyon) has been 
demonstrated in Germany via an extensive (over five years follow-up period) post-marketing 
surveillance study. The vaccine effectiveness was of 96.7% for the full primary series, and 98.5% for 
booster dose (irrespective of priming). 
 
5.2 Pharmacokinetic properties 
 
No pharmacokinetic studies have been performed. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional repeat dose toxicity and 
local tolerance studies. 



 

14 

 
At the injection sites, chronic histological inflammatory changes were observed, that are expected to 
have a slow recovery. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Trometamol 
Saccharose 
Essential amino acids including L-phenylalanine 
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment)  
Water for injections. 
For adsorbent: see section 2. 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this vaccine must not be mixed with other vaccines or 
medicinal products. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2C – 8C). 
Do not freeze. 
Keep the container in the outer carton 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, Hexyon should be used or discarded. These data are intended to guide 
healthcare professionals in case of temporary temperature excursion only.  
 
6.5 Nature and contents of container 
 
Hexyon in pre-filled syringes 
0.5 ml suspension in pre-filled syringe (type I glass) with plunger stopper (halobutyl) and tip cap 
(halobutyl), without needle. 
0.5 ml suspension in pre-filled syringe (type I glass) with plunger stopper (halobutyl) and tip cap 
(halobutyl), with 1 separate needle. 
0.5 ml suspension in pre-filled syringe (type I glass) with plunger stopper (halobutyl) and tip cap 
(halobutyl), with 2 separate needles. 
Pack size of 1 or 10 pre-filled syringes with or without needle. 
Pack size of 50 pre-filled syringes without needle. 
Multipack of 50 (5 packs of 10) pre-filled syringes without needle. 
 
Hexyon in vials 
0.5 ml suspension in vial (type I glass) with a stopper (halobutyl). 
Pack size of 10. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 



 

15 

 
Hexyon in pre-filled syringes 
Prior to administration, the pre-filled syringe should be shaken in order to obtain a homogeneous, 
whitish, cloudy suspension. 
 
The suspension should be visually inspected prior to administration. In the event of any foreign 
particulate matter and/or variation of physical aspect being observed, discard the pre-filled syringe. 
 
For syringes without an attached needle, the needle must be fitted firmly to the syringe, rotating it by a 
one-quarter turn. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Hexyon in vials 
Prior to administration, the vial should be shaken in order to obtain a homogeneous, whitish, cloudy 
suspension. 
 
The suspension should be visually inspected prior to administration. In the event of any foreign 
particulate matter and/or variation of physical aspect being observed, discard the vial. 
 
A dose of 0.5 ml is withdrawn using a syringe for injection. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Hexyon in pre-filled syringes 
EU/1/13/829/002 
EU/1/13/829/003 
EU/1/13/829/004 
EU/1/13/829/005 
EU/1/13/829/006 
EU/1/13/829/007 
EU/1/13/829/008 
EU/1/13/829/009 
 
Hexyon in vials 
EU/1/13/829/001 
 
 
9. DATE OF FIRST AUTHORISATION / RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 17 April 2013 
Date of latest renewal: 08 January 2018 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 



 

16 

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 



 

17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE 
SUBSTANCE(S) AND MANUFACTURER(S) 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 
 
 
 



 

18 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s) 
 
Sanofi Pasteur  
1541 avenue Marcel Mérieux 
69280 Marcy L'Etoile 
France 
 
Sanofi Pasteur  
Calle 8, N° 703 (esquina 5)  
Parque Industrial Pilar - (1629)  
Provincia de Buenos Aires 
Argentina 
 
Sanofi Pasteur 
Parc Industriel d'Incarville 
27100 Val de Reuil 
France 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Sanofi Pasteur  
Parc Industriel d'Incarville 
27100 Val de Reuil 
France 
 
Sanofi Pasteur  
1541 avenue Marcel Mérieux 
69280 Marcy L'Etoile 
France 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
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 
 
The requirements for submission of periodic safety update reports 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. 



 

19 

 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
 Risk Management Plan (RMP) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in 
the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed 
subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 



 

20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



 

21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



 

22 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Hexyon – Carton for pre-filled syringe without needle. Pack of 1, 10 or 50. 
Hexyon – Carton for pre-filled syringe with one separate needle. Pack of 1 or 10. 
Hexyon – Carton for pre-filled syringe with two separate needles. Pack of 1 or 10. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Hexyon suspension for injection in pre-filled syringe 
 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 
and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
DTaP-IPV-HB-Hib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose1 (0.5 ml) contains: 
 
 Diphtheria Toxoid ≥ 20 IU 
 Tetanus Toxoid ≥ 40 IU 
 Bordetella pertussis antigens : Pertussis Toxoid/Filamentous Haemagglutinin 25/25 µg 
 Poliovirus (Inactivated) Types 1/2/3 40/8/32 DU 
 Hepatitis B surface antigen 10 µg 
 Haemophilus influenzae type b polysaccharide 12 µg 
 conjugated to Tetanus protein 22-36 µg 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
 
 
3. LIST OF EXCIPIENTS 
 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Trometamol 
Saccharose 
Essential amino acids including L-phenylalanine 
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment) 
Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe. 
1 pre-filled syringe (0.5 ml) without needle 
10 pre-filled syringes (0.5 ml) without needle 
50 pre-filled syringes (0.5 ml) without needle 
1 pre-filled syringe (0.5 ml) with 1 needle 
10 pre-filled syringes (0.5 ml) with 10 needles 
1 pre-filled syringe (0.5 ml) with 2 needles 
10 pre-filled syringes (0.5 ml) with 20 needles 
 
 



 

23 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. 
Shake before use. 
Read the package leaflet 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. 
Keep the vaccine in the outer carton 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 
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/829/002 
EU/1/13/829/003 
EU/1/13/829/004 
EU/1/13/829/005 
EU/1/13/829/006 
EU/1/13/829/007 
EU/1/13/829/008 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 



 

24 

 
 
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:  



 

25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Hexyon – Carton for pre-filled syringe without needle. Multipack of 50 (5x10) (including blue 
box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Hexyon suspension for injection in pre-filled syringe 
 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 
and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
DTaP-IPV-HB-Hib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose1 (0.5 ml) contains: 
 
 Diphtheria Toxoid ≥ 20 IU 
 Tetanus Toxoid ≥ 40 IU 
 Bordetella pertussis antigens : Pertussis Toxoid/Filamentous Haemagglutinin 25/25 µg 
 Poliovirus (Inactivated) Types 1/2/3 40/8/32 DU 
 Hepatitis B surface antigen 10 µg 
 Haemophilus influenzae type b polysaccharide 12 µg 
 conjugated to Tetanus protein 22-36 µg 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
 
 
3. LIST OF EXCIPIENTS 
 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Trometamol 
Saccharose 
Essential amino acids including L-phenylalanine 
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment)  
Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe. 
Multipack: 50 (5 packs of 10) pre-filled syringes (0.5ml) without needle. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. 
Shake before use. 
Read the package leaflet before use. 
 



 

26 

 
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. 
Keep the vaccine in the outer carton 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 
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/829/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 



 

27 

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



 

28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Hexyon – Carton for pre-filled syringe without needle. Pack of 10 for multipack (without blue 
box) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Hexyon suspension for injection in pre-filled syringe 
 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 
and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
DTaP-IPV-HB-Hib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose1 (0.5 ml) contains: 
 
 Diphtheria Toxoid ≥ 20 IU 
 Tetanus Toxoid ≥ 40 IU 
 Bordetella pertussis antigens : Pertussis Toxoid/Filamentous Haemagglutinin 25/25 µg 
 Poliovirus (Inactivated) Types 1/2/3 40/8/32 DU 
 Hepatitis B surface antigen 10 µg 
 Haemophilus influenzae type b polysaccharide 12 µg 
 conjugated to Tetanus protein 22-36 µg 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
 
 
3. LIST OF EXCIPIENTS 
 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Trometamol 
Saccharose 
Essential amino acids including L-phenylalanine 
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment) 
Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection in pre-filled syringe. 
10 pre-filled syringes (0.5ml) without needle. 
Component of a multipack, cannot be sold separately. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. 
Shake before use. 
Read the package leaflet before use. 



 

29 

 
 
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. 
Keep the vaccine in the outer carton 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 
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/829/009 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 



 

30 

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



 

31 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Hexyon – Carton for vial. Pack of 10. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Hexyon suspension for injection 
 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 
and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
DTaP-IPV-HB-Hib 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One dose1 (0.5 ml) contains: 
 
 Diphtheria Toxoid ≥ 20 IU 
 Tetanus Toxoid ≥ 40 IU 
 Bordetella pertussis antigens : Pertussis Toxoid/Filamentous Haemagglutinin 25/25 µg 
 Poliovirus (Inactivated) Types 1/2/3 40/8/32 DU 
 Hepatitis B surface antigen 10 µg 
 Haemophilus influenzae type b polysaccharide 12 µg 
 conjugated to Tetanus protein 22-36 µg 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
 
 
3. LIST OF EXCIPIENTS 
 
Disodium hydrogen phosphate 
Potassium dihydrogen phosphate 
Trometamol 
Saccharose 
Essential amino acids including L-phenylalanine 
Sodium hydroxide, acetic acid or hydrochloric acid (for pH adjustment) 
Water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Suspension for injection. 
10 vials (0.5 ml) 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intramuscular use. 
Shake before use. 
Read the package leaflet before use. 
 
 



 

32 

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. 
Keep the vaccine in the outer carton 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 
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/13/829/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 



 

33 

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



 

34 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Label – Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Hexyon suspension for injection 
DTaP-IPV-HB-Hib 
IM 
 
 
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 
 
Sanofi Pasteur Europe 
 
 



 

35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Label – Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Hexyon suspension for injection 
DTaP-IPV-HB-Hib 
IM 
 
 
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 
 
Sanofi Pasteur Europe 
 
 



 

36 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



 

37 

 
Package leaflet: Information for the user 

 
Hexyon suspension for injection in pre-filled syringe 

 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 

and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
 
Read all of this leaflet carefully before your child is vaccinated because it contains important 
information for him/her. 
 Keep this leaflet. You may need to read it again. 
 If you have any further questions, ask your doctor, pharmacist or nurse. 
 If your child gets any side effects, talk to your doctor, pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Hexyon is and what it is used for 
2. What you need to know before Hexyon is given to your child 
3. How to use Hexyon 
4. Possible side effects 
5. How to store Hexyon 
6. Contents of the pack and other information  
 
 
1. What Hexyon is and what it is used for 
 
Hexyon (DTaP-IPV-HB-Hib) is a vaccine used to protect against infectious diseases. 
 
Hexyon helps to protect against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and serious 
diseases caused by Haemophilus influenzae type b. Hexyon is given to children from six weeks of age. 
 
The vaccine works by causing the body to produce its own protection (antibodies) against the bacteria 
and viruses that cause these different infections: 
 Diphtheria is an infectious disease that usually first affects the throat. In the throat, the infection 

causes pain and swelling which can lead to suffocation. The bacteria that cause the disease also 
make a toxin (poison) that can damage the heart, kidneys and nerves. 

 Tetanus (often called lock jaw) is usually caused by the tetanus bacteria entering a deep wound. 
The bacteria make a toxin (poison) that causes spasms of the muscles, leading to inability to 
breathe and the possibility of suffocation. 

 Pertussis (often called whooping cough) is 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 causes the liver to become swollen (inflamed). 
In some people, the virus can stay in the body for a long time, and can eventually lead to serious 
liver problems, including liver cancer. 

 Poliomyelitis (often just called polio) is caused by viruses that affect the nerves. It can lead to 
paralysis or muscle weakness most commonly of the legs. Paralysis of the muscles that control 
breathing and swallowing can be fatal. 

 Haemophilus influenzae type b infections (often just called Hib) are serious bacterial infections 
and can cause meningitis (inflammation of the outer covering of the brain), which can lead to 
brain damage, deafness, epilepsy, or partial blindness. Infection can also cause inflammation 
and swelling of the throat, leading to difficulties in swallowing and breathing, and infection can 
affect other parts of the body such as the blood, lungs, skin, bones, and joints. 

 



 

38 

Important information about the protection provided 
 
 Hexyon will only help to prevent these diseases if they are caused by the bacteria or viruses 

targeted by the vaccine. Your child could get diseases with similar symptoms if they are caused 
by other bacteria or viruses. 

 The vaccine does not contain any live bacteria or viruses and it cannot cause any of the 
infectious diseases against which it protects. 

 This vaccine does not protect against infections caused by other types of Haemophilus 
influenzae nor against meningitis due to other micro-organisms. 

 Hexyon will not protect against hepatitis infection caused by other agents such as hepatitis A, 
hepatitis C and hepatitis E. 

 Because symptoms of hepatitis B take a long time to develop, it is possible for unrecognised 
hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent 
hepatitis B infection in such cases. 

 As with any vaccine, Hexyon may not protect 100% of children who receive the vaccine. 
 
 
2. What you need to know before Hexyon is given to your child 
 
To make sure that Hexyon is suitable for your child, it is important to talk to your doctor or nurse if 
any of the points below apply to your child. If there is anything you do not understand, ask your 
doctor, pharmacist or nurse to explain. 
 
Do not use Hexyon if your child: 
 
 has had respiratory disorder or swelling of the face (anaphylactic reaction) after administration 

of Hexyon. 
 has had an allergic reaction 

- to the active substances, 
- to any of the excipients listed in section 6, 
- to glutaraldehyde, formaldehyde, neomycin, streptomycin or polymyxin B, as these 
substances are used during the manufacturing process. 
- after previous administration of Hexyon or any other diphtheria, tetanus, pertussis, 
poliomyelitis, hepatitis B or Hib containing vaccines. 

 suffered from a severe reaction affecting the brain (encephalopathy) within 7 days of a prior 
dose of a pertussis vaccine (acellular or whole cell pertussis). 

 has an uncontrolled condition or severe illness affecting the brain and nervous system 
(uncontrolled neurologic disorder) or uncontrolled epilepsy. 

 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before vaccination if your child: 
 has a moderate or high temperature or an acute illness (e.g. fever, sore throat, cough, cold or 

flu). Vaccination with Hexyon may need to be delayed until your child is better. 
 has had any of the following events after receiving a pertussis vaccine, as the decision to give 

further doses of pertussis containing vaccine will need to be carefully considered: 
- fever of 40°C or above within 48 hours of vaccination not due to another identifiable 
cause. 
- collapse or shock-like state with hypotonic-hyporesponsive episode (drop in energy) 
within 48 hours of vaccination. 
- persistent, inconsolable crying lasting 3 hours or more, occurring within 48 hours of 
vaccination. 
- fits (convulsions) with or without fever, occurring within 3 days of vaccination. 

 previously had Guillain-Barré syndrome (temporary inflammation of nerves causing pain, 
paralysis and sensitivity disorders) or brachial neuritis (severe pain and decreased mobility of 
arm and shoulder) after being given a vaccine containing tetanus toxoid (an inactivated form of 



 

39 

tetanus toxin). In this case, the decision to give any further vaccine containing tetanus toxoid 
should be evaluated by your doctor. 

 is having a treatment that suppresses her/his immune system (the body’s natural defenses) or 
has any disease that causes the weakness of the immune system. In these cases the immune 
response to the vaccine may be decreased. It is normally recommended to wait until the end of 
the treatment or disease before vaccinating. However children with long standing problems with 
their immune system such as HIV infection (AIDS) may still be given Hexyon but the 
protection may not be as good as in children whose immune system is healthy. 

 suffers from an acute or chronic illness including chronic renal insufficiency or failure (inability 
of the kidneys to work properly). 

 suffers from any undiagnosed illness of the brain or epilepsy which is not controlled. Your 
doctor will assess the potential benefit offered by vaccination. 

 has any problems with the blood that cause easy bruising or bleeding for a long time after minor 
cuts. Your doctor will advise you whether your child should have Hexyon. 

 
Other medicines or vaccines and Hexyon 
 
Tell your doctor or nurse if your child is taking, has recently taken or might take any other medicines 
or vaccines. 
Hexyon can be given at the same time as other vaccines such as pneumococcal vaccines, measles-
mumps-rubella vaccines, rotavirus vaccines or meningococcal vaccines. 
When given at the same time with other vaccines, Hexyon will be given at different injection sites. 
 
Hexyon contains phenylalanine, potassium and sodium 
 
Hexyon contains 85 micrograms phenylalanine in each 0.5 ml dose. Phenylalanine may be harmful if 
you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the 
body cannot remove it properly. 
Hexyon contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, 
that is to say essentially “potassium-free” and “sodium-free”. 
 
3. How to use Hexyon 
 
Hexyon will be given to your child by a doctor or nurse trained in the use of vaccines and who are 
equipped to deal with any uncommon severe allergic reaction to the injection (see section 4 Possible 
side effects). 
Hexyon is given as an injection into a muscle (intramuscular route IM) in the upper part of your 
child’s leg or upper arm. The vaccine will never be given into a blood vessel or into or under the skin. 
 
The recommended dose is as follows: 
 
First course of vaccination (primary vaccination) 
Your child will receive either two injections given at an interval of two months or three injections 
given at an interval of one to two months (at least four weeks apart). This vaccine should be used 
according to the local vaccination programme. 
 
Additional injections (booster) 
After the first course of injections, your child will receive a booster dose, in accordance with local 
recommendations, at least 6 months after the last dose of the first course. Your doctor will tell you 
when this dose should be given. 
 
If you forget one dose of Hexyon 
 
If your child misses a scheduled injection, it is important that you discuss with your doctor or nurse 
who will decide when to give the missed dose. 
It is important to follow the instructions from the doctor or nurse so that your child completes the 
course of injections. If not, your child may not be fully protected against the diseases. 



 

40 

 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. 
 
Serious allergic reactions (anaphylactic reaction) 
 
If any of these symptoms occur after leaving the place where your child received his/her injection, you 
must consult a doctor IMMEDIATELY: 
 difficulty in breathing 
 blueness of the tongue or lips 
 a rash 
 swelling of the face or throat  
 sudden and serious malaise with drop in blood pressure causing dizziness and loss of 

consciousness, accelerated heart rate associated with respiratory disorders 
 
When these signs or symptoms (signs or symptoms of anaphylactic reaction) occur they usually 
develop quickly after the injection is given and while the child is still in the clinic or doctor’s surgery. 
 
Serious allergic reactions are a rare possibility (may affect up to 1 in 1,000 people) after receiving this 
vaccine. 
 
Other side effects 
 
If your child experiences any of the following side effects, please tell your doctor, nurse or pharmacist. 
 Very common side effects (may affect more than 1 in 10 people) are: 

- loss of appetite (anorexia) 
- crying 
- sleepiness (somnolence) 
- vomiting 
- pain, redness or swelling at the injection site 
- irritability 
- fever (temperature 38°C or higher) 

 Common side effects (may affect up to 1 in 10 people) are: 
- abnormal crying (prolonged crying) 
- diarrhoea 
- injection site hardness (induration) 

 Uncommon side effects (may affect up to 1 in 100 people) are: 
- allergic reaction 
- lump (nodule) at the injection site 
- high fever (temperature 39.6°C or higher) 

 Rare side effects (may affect up to 1 in 1,000 people) are: 
- rash 
- large reactions at the injection site (larger than 5 cm), including extensive limb swelling from 
the injection site beyond one or both joints. These reactions start within 24-72 hours after 
vaccination, may be associated with redness, warmth, tenderness or pain at the injection site, 
and get better within 3-5 days without the need for treatment.  
- fits (convulsions) with or without fever. 

 Very rare side effects (may affect up to 1 in 10,000 people) are: 
- episodes when your child goes into a shock-like state or is pale, floppy and unresponsive for a 
period of time (hypotonic reactions or hypotonic hyporesponsive episodes HHE). 

 
Potential side effects 



 

41 

 
Other side effects not listed above have been reported occasionally with other diphtheria, tetanus, 
pertussis, poliomyelitis, hepatitis B or Hib containing vaccines and not directly with Hexyon: 
 Temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain-

Barré syndrome) and severe pain and decreased mobility of arm and shoulder (brachial neuritis) 
have been reported after administration of a tetanus containing vaccine. 

 Inflammation of several nerves causing sensory disorders or weakness of limbs 
(polyradiculoneuritis), facial paralysis, visual disturbances, sudden dimming or loss of vision 
(optic neuritis), inflammatory disease of brain and spinal cord (central nervous system 
demyelination, multiple sclerosis) have been reported after administration of a hepatitis B 
antigen containing vaccine. 

 Swelling or inflammation of the brain (encephalopathy/encephalitis). 
 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. 
 Swelling of one or both feet and lower limbs which may occur along with bluish discoloration of 

the skin (cyanosis), redness, small areas of bleeding under the skin (transient purpura) and 
severe crying following vaccination with Haemophilus influenzae type b containing vaccines. If 
this reaction occurs, it is mainly after first injections and within the first few hours following 
vaccination. All symptoms should disappear completely within 24 hours without need for 
treatment. 

 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor, pharmacist or nurse. 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 Hexyon 
 
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 and the label after EXP. The 
expiry date refers to the last day of that month. 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the vaccine in the outer carton in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Hexyon contains 
 
The active substances are per dose (0.5 ml)1: 
Diphtheria Toxoid not less than 20 IU2 
Tetanus Toxoid not less than 40 IU2,3 
Bordetella pertussis antigens 
 Pertussis Toxoid 25 micrograms 
 Filamentous Haemagglutinin 25 micrograms 
Poliovirus (Inactivated) 4 
 Type 1 (Mahoney) 40 D antigen units5 
 Type 2 (MEF-1) 8 D antigen units5 
 Type 3 (Saukett) 32 D antigen units5 
Hepatitis B surface antigen6 10 micrograms 



 

42 

Haemophilus influenzae type b polysaccharide 12 micrograms 
(Polyribosylribitol Phosphate)  
conjugated to Tetanus protein 22-36 micrograms 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
2 IU International Unit 
3 Or equivalent activity determined by an immunogenicity evaluation 
4 Produced on Vero cells 
5Equivalent antigenic quantity in the vaccine 
 6 Produced in yeast Hansenula polymorpha cells by recombinant DNA technology 
 
The other ingredients are: 
Disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, saccharose, essential 
amino acids including L-phenylalanine, sodium hydroxide and/or acetic acid and/or hydrochloric acid 
(for pH adjustment), and water for injections. 
 
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and 
polymyxin B. 
 
What Hexyon looks like and contents of the pack 
 
Hexyon is provided as a suspension for injection in pre-filled syringe (0.5 ml). 
Hexyon is available in pack containing 1,10 or 50 pre-filled syringes without attached needle. 
Hexyon is available in pack containing 1 or 10 pre-filled syringes with 1 separate needle. 
Hexyon is available in pack containing 1 or 10 pre-filled syringes with 2 separate needles. 
Hexyon is available in multipack comprising 5 cartons, each containing 10 pre-filled syringes without 
attached needle. 
 
Not all pack sizes may be marketed. 
 
After shaking, the normal appearance of the vaccine is a whitish cloudy suspension. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder:  
 
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
Manufacturer: 
Sanofi Pasteur, 1541 avenue Marcel Mérieux, 69280 Marcy l'Etoile, France 
 
Sanofi Pasteur, Parc Industriel d'Incarville, 27100 Val de Reuil, France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/ Belgique /Belgien 
Sanofi Belgium 
Tel: +32 2 710.54.00 
 

Lietuva 
Sanofi – Aventis Lietuva, UAB 
Tel: +370 5 275 5224 
 

България 
Sanofi Bulgaria EOOD  
Teл.: +359 2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium 
Tel: +32 2 710.54.00 
 



 

43 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt 
central number: +36 1 505 0000 

Danmark 
Sanofi A/S 
Tel: +45 4516 7000 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel: 0800 54 54 010 
Tel. aus dem Ausland: +49 69 305 21 130 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 20 245 4000 

Eesti 
Sanofi-Aventis Estonia OÜ 
Tel: +372 627 3488 
 

Norge 
Sanofi-aventis Norge AS 
Tel: + 47 67 10 71 00 
 

Ελλάδα 
VIANEX S.A. 
Τηλ: +30.210.8009111 
 

Österreich 
Sanofi-Aventis GmbH 
Tel: +43 (1) 80185-0. 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
Sanofi Pasteur Sp. z o.o. 
Tel: +48 22 280 05 00 
 

France 
Sanofi Pasteur Europe 
Tel: 0800 42 43 46 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o 
Tel: +385 1 6003 400 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 

Ireland 
sanofi-aventis Ireland T/A SANOFI 
Tel: + 353 (0) 1 4035 600 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor 
Tel: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l.                  
Tel: 800536389  
 

Suomi/Finland 
Sanofi Oy 
Tel: +358 (0) 201 200 300 
 

Κύπρος 
Γ. Α. Σταμάτης & Σια Λτδ. 
Τηλ.: +357 – 22 76 62 76 
 

Sverige 
Sanofi AB 
Tel: +46 8-634 50 00 

Latvija 
sanofi-aventis Latvia SIA  
Tel: +371 67332451 
 

United Kingdom 
Sanofi 
Tel: +44 845 372 7101 
 

 
 



 

44 

This leaflet was last revised in {MM/YYYY}  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
--------------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only: 
 
 For syringes without attached needle, the needle must be fitted firmly to the syringe, rotating it 

by a one-quarter turn. 
 Shake the pre-filled syringe so that the contents become homogeneous. 
 Hexyon should not be mixed with other medicinal products. 
 Hexyon must be administered intramuscularly. The recommended injection sites are the antero-

lateral area of the upper thigh (preferred site) or the deltoid muscle in older children (possibly 
from 15 months of age). 
The intradermal or intravenous routes must not be used. Do not administer by intravascular 
injection: ensure that the needle does not penetrate a blood vessel. 



 

45 

 
Package leaflet: Information for the user 

 
Hexyon suspension for injection 

 
Diphtheria, tetanus, pertussis (acellular, component), hepatitis B (rDNA), poliomyelitis (inactivated) 

and Haemophilus influenzae type b conjugate vaccine (adsorbed) 
 
 
Read all of this leaflet carefully before your child is vaccinated because it contains important 
information for him/her. 
 Keep this leaflet. You may need to read it again. 
 If you have any further questions, ask your doctor, pharmacist or nurse. 
 If your child gets any side effects, talk to your doctor, pharmacist or nurse. This includes any 

possible side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Hexyon is and what it is used for 
2. What you need to know before Hexyon is given to your child 
3. How to use Hexyon 
4. Possible side effects 
5. How to store Hexyon 
6. Contents of the pack and other information  
 
 
1. What Hexyon is and what it is used for 
 
Hexyon (DTaP-IPV-HB-Hib) is a vaccine used to protect against infectious diseases. 
 
Hexyon helps to protect against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and serious 
diseases caused by Haemophilus influenzae type b. Hexyon is given to children from six weeks of age. 
 
The vaccine works by causing the body to produce its own protection (antibodies) against the bacteria 
and viruses that cause these different infections: 
 Diphtheria is an infectious disease that usually first affects the throat. In the throat, the infection 

causes pain and swelling which can lead to suffocation. The bacteria that cause the disease also 
make a toxin (poison) that can damage the heart, kidneys and nerves. 

 Tetanus (often called lock jaw) is usually caused by the tetanus bacteria entering a deep wound. 
The bacteria make a toxin (poison) that causes spasms of the muscles, leading to inability to 
breathe and the possibility of suffocation. 

 Pertussis (often called whooping cough) is 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 causes the liver to become swollen (inflamed). 
In some people, the virus can stay in the body for a long time, and can eventually lead to serious 
liver problems, including liver cancer. 

 Poliomyelitis (often just called polio) is caused by viruses that affect the nerves. It can lead to 
paralysis or muscle weakness most commonly of the legs. Paralysis of the muscles that control 
breathing and swallowing can be fatal. 

 Haemophilus influenzae type b infections (often just called Hib) are serious bacterial infections 
and can cause meningitis (inflammation of the outer covering of the brain), which can lead to 
brain damage, deafness, epilepsy, or partial blindness. Infection can also cause inflammation 
and swelling of the throat, leading to difficulties in swallowing and breathing, and infection can 
affect other parts of the body such as the blood, lungs, skin, bones, and joints. 



 

46 

 
Important information about the protection provided 
 
 Hexyon will only help to prevent these diseases if they are caused by the bacteria or viruses 

targeted by the vaccine. Your child could get diseases with similar symptoms if they are caused 
by other bacteria or viruses. 

 The vaccine does not contain any live bacteria or viruses and it cannot cause any of the 
infectious diseases against which it protects. 

 This vaccine does not protect against infections caused by other types of Haemophilus 
influenzae nor against meningitis due to other micro-organisms. 

 Hexyon will not protect against hepatitis infection caused by other agents such as hepatitis A, 
hepatitis C and hepatitis E. 

 Because symptoms of hepatitis B take a long time to develop, it is possible for unrecognised 
hepatitis B infection to be present at the time of vaccination. The vaccine may not prevent 
hepatitis B infection in such cases. 

 As with any vaccine, Hexyon may not protect 100% of children who receive the vaccine. 
 
 
2. What you need to know before Hexyon is given to your child 
 
To make sure that Hexyon is suitable for your child, it is important to talk to your doctor or nurse if 
any of the points below apply to your child. If there is anything you do not understand, ask your 
doctor, pharmacist or nurse to explain. 
 
Do not use Hexyon if your child: 
 
 has had respiratory disorder or swelling of the face (anaphylactic reaction) after administration 

of Hexyon 
 has had an allergic reaction 

- to the active substances, 
- to any of the excipients listed in section 6, 
- to glutaraldehyde, formaldehyde, neomycin, streptomycin or polymyxin B, as these 
substances are used during the manufacturing process 
- after previous administration of Hexyon or any other diphtheria, tetanus, pertussis, 
poliomyelitis, hepatitis B or Hib containing vaccines. 

 suffered from a severe reaction affecting the brain (encephalopathy) within 7 days of a prior 
dose of a pertussis vaccine (acellular or whole cell pertussis). 

 has an uncontrolled condition or severe illness affecting the brain and nervous system 
(uncontrolled neurologic disorder) or uncontrolled epilepsy. 

 
Warnings and precautions 
 
Talk to your doctor, pharmacist or nurse before vaccination if your child: 
 has a moderate or high temperature or an acute illness (e.g. fever, sore throat, cough, cold or 

flu). Vaccination with Hexyon may need to be delayed until your child is better. 
 has had any of the following events after receiving a pertussis vaccine, as the decision to give 

further doses of pertussis containing vaccine will need to be carefully considered: 
- fever of 40°C or above within 48 hours of vaccination not due to another identifiable 
cause. 
- collapse or shock-like state with hypotonic-hyporesponsive episode (drop in energy) 
within 48 hours of vaccination. 
- persistent, inconsolable crying lasting 3 hours or more, occurring within 48 hours of 
vaccination. 
- fits (convulsions) with or without fever, occurring within 3 days of vaccination. 

 previously had Guillain-Barré syndrome (temporary inflammation of nerves causing pain, 
paralysis and sensitivity disorders) or brachial neuritis (severe pain and decreased mobility of 



 

47 

arm and shoulder) after being given a vaccine containing tetanus toxoid (an inactivated form of 
tetanus toxin). In this case, the decision to give any further vaccine containing tetanus toxoid 
should be evaluated by your doctor. 

 is having a treatment that suppresses her/his immune system (the body’s natural defenses) or 
has any disease that causes the weakness of the immune system. In these cases the immune 
response to the vaccine may be decreased. It is normally recommended to wait until the end of 
the treatment or disease before vaccinating. However children with long standing problems with 
their immune system such as HIV infection (AIDS) may still be given Hexyon but the 
protection may not be as good as in children whose immune system is healthy. 

 suffers from an acute or chronic illness including chronic renal insufficiency or failure (inability 
of the kidneys to work properly). 

 suffers from any undiagnosed illness of the brain or epilepsy which is not controlled. Your 
doctor will assess the potential benefit offered by vaccination. 

 has any problems with the blood that cause easy bruising or bleeding for a long time after minor 
cuts. Your doctor will advise you whether your child should have Hexyon. 

 
Other medicines or vaccines and Hexyon 
 
Tell your doctor or nurse if your child is taking, has recently taken or might take any other medicines 
or vaccines. 
Hexyon can be given at the same time as other vaccines such as pneumococcal vaccines, measles-
mumps-rubella vaccines, rotavirus vaccines or meningococcal vaccines.  
When given at the same time with other vaccines, Hexyon will be given at different injection sites. 
 
Hexyon contains phenylalanine, potassium and sodium 
 
Hexyon contains 85 micrograms phenylalanine in each 0.5 ml dose. Phenylalanine may be harmful if 
you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the 
body cannot remove it properly. 
Hexyon contains less than 1 mmol potassium (39 mg) and less than 1 mmol sodium (23 mg) per dose, 
that is to say essentially “potassium-free” and “sodium-free”. 
 
3. How to use Hexyon 
 
Hexyon will be given to your child by a doctor or nurse trained in the use of vaccines and who are 
equipped to deal with any uncommon severe allergic reaction to the injection (see section 4 Possible 
side effects). 
Hexyon is given as an injection into a muscle (intramuscular route IM) in the upper part of your 
child’s leg or upper arm. The vaccine will never be given into a blood vessel or into or under the skin. 
 
The recommended dose is as follows: 
 
First course of vaccination (primary vaccination) 
Your child will receive either two injections given at an interval of two months or three injections 
given at an interval of one to two months (at least four weeks apart). This vaccine should be used 
according to the local vaccination programme. 
 
Additional injections (booster) 
After the first course of injections, your child will receive a booster dose, in accordance with local 
recommendations, at least 6 months after the last dose of the first course. Your doctor will tell you 
when this dose should be given. 
 
If you forget one dose of Hexyon 
 
If your child misses a scheduled injection, it is important that you discuss with your doctor or nurse 
who will decide when to give the missed dose. 



 

48 

It is important to follow the instructions from the doctor or nurse that your child completes the course 
of injections. If not, your child may not be fully protected against the diseases. 
 
If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects  
 
Like all medicines, this vaccine can cause side effects, although not everybody gets them. 
 
Serious allergic reactions (anaphylactic reaction) 
 
If any of these symptoms occur after leaving the place where your child received his/her injection, you 
must consult a doctor IMMEDIATELY: 
 difficulty in breathing 
 blueness of the tongue or lips 
 a rash 
 swelling of the face or throat 
 sudden and serious malaise with drop in blood pressure causing dizziness and loss of 

consciousness, accelerated heart rate associated with respiratory disorders 
 
When these signs or symptoms (signs or symptoms of anaphylactic reaction) occur they usually 
develop quickly after the injection is given and while the child is still in the clinic or doctor’s surgery. 
 
Serious allergic reactions are a rare possibility (may affect up to 1 in 1,000 people) after receiving this 
vaccine. 
 
Other side effects 
 
If your child experiences any of the following side effects, please tell your doctor, nurse or pharmacist. 
 Very common side effects (may affect more than 1 in 10 people) are: 

- loss of appetite (anorexia) 
- crying 
- sleepiness (somnolence) 
- vomiting 
- pain, redness or swelling at the injection site 
- irritability 
- fever (temperature 38°C or higher) 

 Common side effects (may affect up to 1 in 10 people) are: 
- abnormal crying (prolonged crying) 
- diarrhoea 
- injection site hardness (induration) 

 Uncommon side effects (may affect up to 1 in 100 people) are: 
- allergic reaction 
- a lump (nodule) at the injection site  
- high fever (temperature 39.6°C or higher) 

 Rare side effects (may affect up to 1 in 1,000 people) are: 
- rash 
- large reactions at the injection site (larger than 5 cm), including extensive limb swelling from 
the injection site beyond one or both joints. These reactions start within 24-72 hours after 
vaccination, may be associated with redness, warmth, tenderness or pain at the injection site, 
and get better within 3-5 days without the need for treatment. 
- fits (convulsions) with or without fever 

 Very rare side effects (may affect up to 1 in 10,000 people) are: 
- episodes when your child goes into a shock-like state or is pale, floppy and unresponsive for a 
period of time (hypotonic reactions or hypotonic hyporesponsive episodes HHE). 



 

49 

 
Potential side effects 
 
Other side effects not listed above have been reported occasionally with other diphtheria, tetanus, 
pertussis, poliomyelitis, hepatitis B or Hib containing vaccines and not directly with Hexyon: 
 Temporary inflammation of nerves causing pain, paralysis and sensitivity disorders (Guillain-

Barré syndrome) and severe pain and decreased mobility of arm and shoulder (brachial neuritis) 
have been reported after administration of a tetanus containing vaccine. 

 Inflammation of several nerves causing sensory disorders or weakness of limbs 
(polyradiculoneuritis), facial paralysis, visual disturbances, sudden dimming or loss of vision 
(optic neuritis), inflammatory disease of brain and spinal cord (central nervous system 
demyelination, multiple sclerosis) have been reported after administration of a hepatitis B 
antigen containing vaccine. 

 Swelling or inflammation of the brain (encephalopathy/encephalitis). 
 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. 
 Swelling of one or both feet and lower limbs which may occur along with bluish discoloration 

of the skin (cyanosis), redness, small areas of bleeding under the skin (transient purpura) and 
severe crying following vaccination with Haemophilus influenzae type b containing vaccines. If 
this reaction occurs, it is mainly after first injections and within the first few hours following 
vaccination. All symptoms should disappear completely within 24 hours without need for 
treatment. 

 
Reporting of side effects 
 
If your child gets any side effects, talk to your doctor, pharmacist or nurse. 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 Hexyon 
 
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 and the label after EXP. The 
expiry date refers to the last day of that month. 
Store in a refrigerator (2°C - 8°C). 
Do not freeze. 
Keep the vaccine in the outer carton in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help to protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Hexyon contains 
 
The active substances are per dose (0.5 ml)1: 
Diphtheria Toxoid not less than 20 IU2 
Tetanus Toxoid not less than 40 IU2,3 
Bordetella pertussis antigens 
 Pertussis Toxoid 25 micrograms 
 Filamentous Haemagglutinin 25 micrograms 
Poliovirus (Inactivated) 4 
 Type 1 (Mahoney) 40 D antigen units5 



 

50 

 Type 2 (MEF-1) 8 D antigen units5 
 Type 3 (Saukett) 32 D antigen units5 
Hepatitis B surface antigen6 10 micrograms 
Haemophilus influenzae type b polysaccharide 12 micrograms 
(Polyribosylribitol Phosphate)  
conjugated to Tetanus protein 22-36 micrograms 
 
1 Adsorbed on aluminium hydroxide, hydrated (0.6 mg Al3+) 
2 IU International Unit 
3 Or equivalent activity determined by an immunogenicity evaluation 
4 Produced on Vero cells 
5 Equivalent antigenic quantity in the vaccine 
6 Produced in yeast Hansenula polymorpha cells by recombinant DNA technology 
 
The other ingredients are: 
Disodium hydrogen phosphate, potassium dihydrogen phosphate, trometamol, saccharose, essential 
amino acids including L-phenylalanine, sodium hydroxide and/or acetic acid and/or hydrochloric acid 
(for pH adjustment), and water for injections. 
 
The vaccine may contain traces of glutaraldehyde, formaldehyde, neomycin, streptomycin and 
polymyxin B. 
 
What Hexyon looks like and contents of the pack 
 
Hexyon is provided as a suspension for injection in vial (0.5 ml). 
Hexyon is available in pack containing 10 vials. 
 
After shaking, the normal appearance of the vaccine is a whitish cloudy suspension. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder:  
Sanofi Pasteur Europe, 14 Espace Henry Vallée, 69007 Lyon, France 
 
Manufacturer: 
Sanofi Pasteur, 1541 avenue Marcel Mérieux, 69280 Marcy l'Etoile, France 
 
Sanofi Pasteur, Parc Industriel d'Incarville, 27100 Val de Reuil, France 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/ Belgique /Belgien 
Sanofi Belgium 
Tel: +32 2 710.54.00 
 

Lietuva 
Sanofi – Aventis Lietuva, UAB 
Tel: +370 5 275 5224 
 

България 
Sanofi Bulgaria EOOD  
Teл.: +359 2 970 53 00 
 

Luxembourg/Luxemburg 
Sanofi Belgium 
Tel: +32 2 710.54.00 
 

Česká republika 
sanofi-aventis, s.r.o. 
Tel: +420 233 086 111 
 

Magyarország 
SANOFI-AVENTIS Zrt 
central number: +36 1 505 0000 



 

51 

Danmark 
Sanofi A/S 
Tel: +45 4516 7000 
 

Malta 
Sanofi S.r.l. 
Tel: +39 02 39394275 

Deutschland 
Sanofi-Aventis Deutschland GmbH 
Tel: 0800 54 54 010 
Tel. aus dem Ausland: +49 69 305 21 130 
 

Nederland 
sanofi-aventis Netherlands B.V. 
Tel: +31 20 245 4000 

Eesti 
Sanofi-Aventis Estonia OÜ 
Tel: +372 627 3488 
 

Norge 
Sanofi-aventis Norge AS 
Tel: + 47 67 10 71 00 
 

Ελλάδα 
VIANEX S.A. 
Τηλ: +30.210.8009111 
 

Österreich 
Sanofi-Aventis GmbH 
Tel: +43 (1) 80185-0. 
 

España 
sanofi-aventis, S.A.  
Tel: +34 93 485 94 00 
 

Polska 
Sanofi Pasteur Sp. z o.o. 
Tel: +48 22 280 05 00 
 

France 
Sanofi Pasteur Europe 
Tel: 0800 42 43 46 
Appel depuis l’étranger : +33 1 57 63 23 23 
 

Portugal 
Sanofi – Produtos Farmacêuticos, Lda. 
Tel: + 351 21 35 89 400 
 

Hrvatska 
sanofi-aventis Croatia d.o.o 
Tel: +385 1 6003 400 
 

România 
Sanofi Romania SRL 
Tel: +40 (0) 21 317 31 36 

Ireland 
sanofi-aventis Ireland T/A SANOFI 
Tel: + 353 (0) 1 4035 600 
 

Slovenija 
sanofi-aventis d.o.o. 
Tel: +386 1 560 48 00 
 

Ísland 
Vistor 
Tel: +354 535 7000 
 

Slovenská republika 
sanofi-aventis Pharma Slovakia s.r.o. 
Tel: +421 2 33 100 100 
 

Italia 
Sanofi S.r.l.                  
Tel: 800536389  
 

Suomi/Finland 
Sanofi Oy 
Tel: +358 (0) 201 200 300 
 

Κύπρος 
Γ. Α. Σταμάτης & Σια Λτδ. 
Τηλ.: +357 – 22 76 62 76 
 

Sverige 
Sanofi AB 
Tel: +46 8-634 50 00 

Latvija 
sanofi-aventis Latvia SIA  
Tel: +371 67332451 
 

United Kingdom 
Sanofi 
Tel: +44 845 372 7101 
 

 
 
This leaflet was last revised in {MM/YYYY}  
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 



 

52 

 
--------------------------------------------------------------------------------------------------------------------------- 
The following information is intended for healthcare professionals only: 
 
 Shake the vial so that the contents become homogeneous. 
 A dose of 0.5 ml is withdrawn using a syringe for injection 
 Hexyon should not be mixed with other medicinal products. 
 Hexyon must be administered intramuscularly. The recommended injection sites are the antero-

lateral area of the upper thigh (preferred site) or the deltoid muscle in older children (possibly 
from 15 months of age). 
The intradermal or intravenous routes must not be used. Do not administer by intravascular 
injection: ensure that the needle does not penetrate a blood vessel. 

 


	ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) ANDMANUFACTURER(S) 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