Tritanrix HepB - summary of medicine characteristics

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

1 dose (0.5 ml) contains:

Diphtheria toxoid1

Tetanus toxoid1

Bordetella pertussis (inactivated)2

Hepatitis B surface antigen 2,3

Adsorbed on aluminium hydroxide, hydrated

Adsorbed on aluminium phosphate

Produced in yeast cells (Saccharomyces cerevisiae ) by recombinant DNA te

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Suspension for injection.

Turbid white suspension.

4. CLINICAL PARTICULARS4.1 Therapeutic indications

Tritanrix HepB is indicated for active immunisation against diphtheria, tetanus, pertussis and hepatitis B (HBV) in infants from 6 weeks onwards (see section 4.2).

4.2 Posology and method of administration

Posolo

Primary vaccin;

accination schedule consists of three doses within the first six months of life. Where HBV vaccine is not given at birth, the combined vaccine can be administered beginning as early as 8 weeks of age. Where there is a high endemicity of HBV, the practice to administer HBV vaccine at birth should be continued. In these circumstances, vaccination with the combined vaccine should start at 6 weeks of age.

Three vaccine doses must be administered at intervals of at least 4 weeks.

When Tritanrix HepB is given according to the 6–10–14 weeks schedule, it is recommended to administer a dose of HBV vaccine at birth to improve protection.

In the case of children born of known HBV carrier mothers the immunoprophylactic measures for hepatitis B should not be modified. This may require separate vaccination with HBV and DTPw vaccines and also include the administration of HBIg at birth.

Booster vaccination:

A booster dose with Tritanrix HepB will give rise to increased reactogenicity as would be expected for a booster during the second year of life. In consequence, boostering should follow local recommendations.

The administration of a booster dose with trivalent DTP vaccine is recommended before the end of the second year of life. For long-term protection against HBV, a booster dose of HBV vaccine could also be administered after the first year of life. However, the need for this dose is currently not established.

Method of administration

Tritanrix HepB is for deep intramuscular injection, preferably in the anterolateral thig­h.

It is recommended that in patients with thrombocytopenia or bleeding disorders the vaccine subcutaneously (see section 4.4).

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients.

Hypersensitivity after previous administration of diphtheria, tetanus, pertussis or hepatitis B vaccines.

The administration of Tritanrix HepB should be postponed in subjects suffering from acute severe febrile illness.

Tritanrix HepB is contraindicated if the child has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. In these circumstances the vaccination course should be continued with DT and HBV vaccines.

4.4 Special warnings and precautions for use

Vaccination should be preceded by a review of the medical history (especially with regard to previous

e reactions) and a clinical examination.

As with all injectable vaccines, appropriate medical treatment should always be readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccinee should remain under medical supervision for 30 minutes after vaccination.

If any of the following events occur in temporal relation to receipt of Tritanrix HepB, the decision to give subsequent doses of vaccine containing the pertussis component should be carefully considered.

Temperature of > 40.0 C within 48 hours, not due to another identifiable cause.

Collapse or shock-like state (hypotonic-hyporesponsive episode) within 48 hours.

Persistent crying lasting > 3 hours, occurring within 48 hours.

Convulsions with or without fever, occurring within 3 days.

There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks.

As for any vaccination, the risk-benefit of immunising with Tritanrix HepB or deferring this vaccination should be weighed carefully in an infant or in a child suffering from a new onset or progression of a severe neurological disorder.

A history of febrile convulsions, a family history of convulsions, a family history of SIDS (Sudden Infant Death Syndrome) and a family history of an adverse reaction following Tritanrix HepB vaccination do not constitute contra-indications.

HIV infection is not considered as a contra-indication for diphtheria, tetanus, pertussis and HBV vaccination. The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patients on immunosuppressive therapy.

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

TRITANRIX HepB SHOULD UNDER NO CIRCUMSTANCES BE ADMINISTERED INTRAVENOUSLY.

The potential risk of apnoea and the need for respiratory monitoring for 48–72h should be considered w administering the primary immunisation series to very premature infants (born < 28 weeks of gestati 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.

4.5 Interaction with other medicinal products and other forms of interaction

It is current practice in paediatric vaccination to co-administer different vaccines with injectable vaccines being administered at separate injection sites.

Tritanrix HepB can be administered simultaneously at separate sites or in any temporal relationship with other paediatric vaccines if this fits conveniently in the immunisation scheme.

In clinical studies, Tritanrix HepB has been administered simultaneously with oral polio vaccine (OPV) and Haemophilus influenzae type b (Hib) vaccine. In these studies the immune response to the oral polio vaccine has not been investigated, however, previous experience with simultaneous administration of DTP, OPV and

HBV vaccines has not shown any interference. In some clinical studies, Tritanrix HepB was used to reconstitute the lyophilised Hib vaccine (Hiberix); no interference in the immune response to any of the antigens was observed as compared to the responses observed following administration of the vaccines at separate sites (see section 6.2).

In patients receiving immunosuppressive may not be achieved.

As Tritanrix HepB is not intended for use in adults, information on the safety of the vaccine when used during pregnancy or lactation is not available.

4.7 Effects on ability to drive and use machinesNot relevan4.8 Undesirable effectsinical trials:

In clinical studies, the most commonly reported adverse events were reactions at the injection site, including redness, swelling and pain.

General reactions that may occur in temporal association with Tritanrix HepB vaccination are listed below.

Frequencies are defined as follows:

Very common (>1/10)

Common (>1/100 to <1/10)

Uncommon (>1/1,000 to <1/100)

Rare (>1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Nervous system disorders: very common: drowsiness

Respiratory, thoracic and mediastinal disorders: common: bronchitis uncommon: respiratory disorder

Gastro-intestinal disorders:

very common: feeding problems

common: gastro-intestinal symptoms such as vomiting and diarrhoea

Infections and infestations: common: otitis media, pharyngitis uncommon: pneumonia

General disorders and administration site conditions: very common: fever, swelling, pain and redness

Immune system disorders:                   <

very rare: allergic reactions including anaphylactic a like disease

In a prospective comparative study, which compared the administration of the combined DTPw-HBV vaccine with the simultaneous separate administration of DTPw and HBV vaccine, higher incidences of pain, redness, swelling and fever were reported in the group receiving the combined vaccine. The incidences are presented below:

* reported by the parents as adversely affecting the child’s daily activities

For both vaccination groups, the majority of the reactions were short lasting.

Post marketing surveillance:

Nervous system disorders:

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

Respiratory, thoracic and mediastinal disorders:

Apnoea in very premature infants (< 28 weeks of gestation) (see section 4.4)

Experience with hepatitis B vaccine:

Blood and lymphatic system disorders: Thrombocytopenia

Nervous system disorders:

Convulsions

This medicinal product contains thiomersal (an organomercuric compound) as a preservative and therefore, it is possible that sensitisation reactions may occur (see section 4.3)

4.9 Overdose

No case of overdose has been reported.

5. PHARMACOLOGICAL PROPERTIES5.1 Pharmacodynamic properties

5.2 Pharmacokinetic properties

Evaluation of pharmacokinetic properties is not required for vaccines.

5.3 Preclinical safety data

6. PHARMACEUTICAL PARTICULARS6.1 List of excipientsThiomersalSodium chloride Water for injectionsFor adjuvants, see section 2.6.2 IncompatibilitiesThis medicinal product must not be mixed with other medicinal products except those mentioned in sect 6.6.6.3 Shelf life3 years.6.4 Special precautions for storageStore in a refrigerator (2°C - 8°C).Do not freeze.Store in the original package, in order to protect from light.6.5 Nature and contents of container0.5 ml of suspension in a vial (type I glass) with a plunger stopper (rubber butyl) - pack size of 1.6.6 Special precautions for disposal and other handlingTritanrix HepB can be mixed with the lyophilised Hib vaccine (Hiberix).Upon storage, a white deposit and cleatant can be observed.The vaccine should be well shaken in order to obtain a homogeneous turbid white suspension and visually inspected for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the vaccine.Any unused productte material should be disposed of in accordance with local requirements.7. MANG AUTHORISATION HOLDER

EU/1/96/014/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 19 July 1996.