This vaccine is indicated in the joint prevention of diphtheria, tetanus, pertussis, poliomyelitis and
invasive infections caused by Haemophilus influenzae type b (such as meningitis, septicaemia,
cellulitis, arthritis, epiglottitis, etc.),
• for primary vaccination in infants from the age of 2 months,
• for booster vaccination, one year after primary vaccination during the second year of life.

This vaccine does not protect against infections caused by the other types of Haemophilus influenzae
or against meningitis due to other micro-organisms.

PENTAXIM must be administered according to the official recommendations in effect.
Posology
Paediatric population
Primary vaccination: 3 injections given at an interval of one month, i.e. according to the official
schedule, at the age of 2, 3, 4 months.
Booster vaccination: 1 injection one year after primary vaccination, i.e. usually between 16 and 18 months.
Method of administration
Administer via the intramuscular route (IM).
Administration should preferably be performed in the anterolateral side of the thigh (middle third) in infants and in the deltoid area in children.
For instructions on reconstitution of the medicine before administration, see section 6.6. Once reconstituted, the suspension is cloudy and whitish.

The immunogenicity of PENTAXIM may be reduced by immunosuppressive treatment or immunodeficiency. It is then recommended to wait until the end of the treatment or disease before vaccinating. Nevertheless, vaccination of subjects with chronic immunodeficiency such as HIV infection is recommended even if the immune response may be limited.
If Guillain-Barré syndrome or brachial neuritis has occurred in subjects 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 of vaccination. Vaccination is usually justified for infants whose primary immunization schedules are incomplete (i.e. fewer than three doses administered).
Do not inject via the intravascular route: make sure the needle does not penetrate a blood vessel. Do not inject via the intradermal route.
As with all injectable vaccines, PENTAXIM must be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.
Vaccination must be preceded by medical history screening (especially with regard to vaccination

history and any occurrence of undesirable events) and a clinical examination.
If any of the following events are known to have occurred in temporal relation to receipt of vaccine, the decision to give further doses of pertussis-containing vaccine should be carefully considered:
• Fever ≥ 40°C within 48 hours 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.
A history of febrile convulsions not related to a previous vaccine injection is not a contraindication to vaccination.
In this respect, it is particularly important to monitor the temperature in the 48 hours following vaccination and to give antipyretic treatment regularly for 48 hours.
A history of afebrile convulsions not related to a previous vaccine injection should be assessed by a specialist before deciding to vaccinate.
In the event of oedematous reactions occurring in the lower limbs after injection of a Haemophilus influenzae type b-containing vaccine, the two vaccines, diphtheria-tetanus-pertussis-poliomyelitis vaccine and the Haemophilus influenzae type b conjugate vaccine should be administered in two separate injection sites and on two different days.
As with all injectable vaccines, appropriate medical treatment must be readily available and close supervision provided should a rare anaphylactic reaction occur following administration of the vaccine.
PENTAXIM does not protect against invasive diseases caused by serotypes other than Haemophilus influenzae type b, nor against meningitis from other origins.
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 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.
Interference with laboratory tests: see section 4.5.

This vaccine can be administered simultaneously with the M-M-RVAXPRO vaccine or with the HBVAXPRO vaccine, but in two separate sites.
Interference with laboratory tests
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.

Not applicable.
PENTAXIM is intended for paediatric use only.

Not applicable.
PENTAXIM is intended for paediatric use only.

The adverse events are ranked under headings of frequency using the following convention: Very common: ≥ 10%
Common: ≥ 1% and < 10%
Uncommon: ≥ 0.1% and < 1%
Rare: ≥ 0.01% and < 0.1% Very rare: < 0.01%
Not known: cannot be estimated from the available data.
Based on spontaneous reports, certain undesirable events were very rarely reported following the use of PENTAXIM. Because events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. This is why these undesirable events are ranked under the « Not known » frequency.
In clinical studies in children who received PENTAXIM as a primary series, the most frequently reported reactions are local injection-site reactions, abnormal crying, irritability and fever.
These signs and symptoms usually occur within 48 hours following the vaccination and may continue for 48-72 hours. They resolve spontaneously without specific treatment.
The frequency of injection-site reactions tends to increase at booster vaccination compared with the frequency observed for primary series.

Immune system disorders
Reactions with a Not Known frequency
• Immediate hypersensitivity reactions such as face oedema, angioedema, Quincke’s oedema, anaphylactic reactions and shocks.
Metabolism and nutrition disorders
Very common reactions
• Loss of appetite.
Psychiatric disorders
Very common reactions
• Nervousness, irritability.
• Abnormal crying.

Common reactions
• Insomnia, sleep disturbances.
Uncommon reactions
• Prolonged inconsolable crying.
Nervous system disorders
Very common reactions
• Somnolence.
Reactions with a Not Known frequency
• Convulsions with or without fever.
• Hypotonic-hyporesponsive episodes.
Gastro-intestinal disorders
Very common reactions
• Vomiting.
Common reactions
• Diarrhoea.
Skin and subcutaneous tissue disorders
Reactions with a Not Known frequency
• Rash, erythema, urticaria.
General disorders and administration site conditions
Very common reactions
• Injection-site erythema.
• Fever ≥38°C.
• Injection-site oedema.
• Injection-site pain.
Common reactions
• Injection-site induration.
Uncommon reactions
• Fever ≥39°C.
• Injection-site redness and oedema ≥5 cm.
Rare reactions
• Fever >40°C.
OEdematous reactions on one or on both lower limbs may occur after vaccination with a Haemophilus influenzae type b conjugate-containing vaccine. These reactions generally occur after primary series, within hours of the vaccination, and resolve without sequelae within 24 hours. These reactions may be accompanied with cyanosis, erythema, transient purpura and severe crying.
Reactions with a Not Known frequency
• Large injection-site reactions (> 50 mm), including extensive limb swelling that may spread from the injection site to one or both adjacent joints. These reactions start within 24-72 hours after vaccination and may be associated with symptoms such as erythema, warmth, tenderness or pain at the injection site. They resolve spontaneously within 3-5 days. The risk appears to be dependent on the number of prior doses of acellular pertussis-containing vaccines, with a greater risk following the 4th and 5th doses.
Potential undesirable effects (i.e. that have not been reported directly with PENTAXIM, but with other vaccines containing one or more of the antigenic constituents of PENTAXIM):
• Guillain-Barré Syndrome and brachial neuritis after administration of a tetanus toxoid-containing vaccine.

Complementary information concerning specific populations
Apnoea in very premature infants (born ≤ 28 weeks of gestation) (see section 4.4).
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

To reports any side effect(s):
• Saudi Arabia:
- The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
o Toll free phone: 8002490000
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc
• Other GCC States:
- Please contact the relevant competent authority.

Not documented.

Pharmacotherapeutic group: Bacterial and viral vaccines, combined, ATC code: J07CA06.
Diphtheria and tetanus toxins are detoxified using formaldehyde and then purified.
The poliomyelitis vaccine is obtained from the propagation of poliomyelitis virus types 1, 2 and 3 on Vero cells, purified, then inactivated by formaldehyde.
The acellular pertussis components (PT and FHA) are extracted from Bordetella pertussis cultures, then purified. The pertussis toxin (PT) is detoxified by glutaraldehyde and corresponds to the pertussis toxoid (PTxd). The FHA is native. It has been shown that PTxd and FHA are two components of major importance for protection against pertussis.
The PRP capsular polysaccharide (polyribosyl ribitol phosphate: PRP) is extracted from the culture of Haemophilus influenzae type b and conjugated to the tetanus protein (T) to give the PRP-T conjugate vaccine.
The PRP capsular polysaccharide (polyribosyl ribitol phosphate: PRP) induces an anti-PRP serological response in humans. However, as for all polysaccharide antigens, the immune response is thymo-independent, characterised by a low immunogenicity in infants and by the absence of a booster effect before the age of 15 months. The covalent bond of the Haemophilus influenzae type b capsular polysaccharide to a carrier protein, the tetanus protein, enables the conjugate vaccine to behave like a thymo-dependent antigen inducing a specific anti-PRP serological response in infants and to obtain a booster effect.
Immune response after primary vaccination:
Immunogenicity studies in infants have shown that, one month after the third dose of the primary vaccination, all (100%) developed a seroprotective antibody level (> 0.01 IU/ml) to both diphtheria and tetanus antigens.
As for pertussis, one month after the third dose of the primary vaccination, 93% of infants achieved a four-fold rise in PT antibodies and more than 88% in FHA antibodies.
At least 99% of children had seroprotective antibody titres to poliomyelitis virus types 1, 2 and 3 (≥ 5

as expressed by reciprocal of dilution in seroneutralisation).
At least 97.2% of infants achieved anti PRP titres above 0.15 μg/ml one month after the third dose of the primary vaccination.
Immune response after the booster:
After the first booster dose (16-18 months), all the toddlers developed protective antibodies against diphtheria (> 0.1 IU/ml), tetanus (> 0.1 IU/ml), poliomyelitis viruses (≥ 5 as expressed by reciprocal of dilution in seroneutralisation).
The seroconversion rate in pertussis antibodies (titres higher than four-fold the pre-vaccinal titers) is at least 98% for PT (EIA) and 99% for FHA (EIA).
An antibody titre anti-PRP ≥ 1.0 μg/ml was reached in all toddlers.
A follow-up study of pertussis immunogenicity in children at 5-6 years of age has shown that the antibody titres anti-PT and anti-FHA of children vaccinated for primary course and booster with acellular combined vaccines were at least equivalent to those observed at the same age in children vaccinated with whole pertussis combined vaccines.

Not applicable.

Non-clinical data revealed no special hazard for humans based on conventional acute toxicity, repeat dose toxicity and local tolerance studies.

Concerning the adsorbent, see section 2. Suspension for injection:
• Hanks' medium (without phenol red) 0.05 ml
• Acetic acid glacial and/or sodium hydroxide (for pH adjustment)
• Formaldehyde 10 μg
• Phenoxyethanol 2.5 μl
• Ethanol 2.5 μl
• Water for injections. qs 0.5 ml
Hanks medium is a complex mixture of amino acids (including phenylalanine), mineral salts, vitamins and other components (such as glucose) diluted in water for injections.
Powder:
• Saccharose 42.5 mg
• Tromethamol 0.6 mg
• Concentrated hydrochloric acid for pH adjustment.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Store in a refrigerator (2°C - 8°C).

Do not freeze.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

• Powder in vial (type I glass) equipped with a stopper (chlorobutyl) + 0.5 ml of suspension in prefilled syringe (type I glass) equipped with a plunger-stopper (bromobutyl or chlorobutyl or bromochlorobutyl). Box of 1
Not all pack sizes may be marketed.

For syringes without attached needles, the needle must be fitted firmly to the syringe, rotating it by a one-quarter turn.
Reconstitute the solution by injecting the suspension of the combined diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine into the vial with the powder of the Haemophilus type b conjugate vaccine. Shake until complete dissolution of the powder. After reconstitution, the whitish-turbid appearance of the suspension is normal.
The vaccine must be used immediately after reconstitution.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.