Leaflet TRITANRIX HEPB multidose injection suspension
Indicated for: active immunization
Route of administration: injectable
Substance: DTPA + HEPB combination vaccine (vaccine)
ATC: J07CA05 (Antiinfectives for systemic use | Bacterial and viral vaccines, combined)
Risk of severe allergic reaction. Seek urgent medical help if serious symptoms occur.
This medicine is subject to additional monitoring.
Store in the refrigerator as instructed in the leaflet.
Store protected from light.
The combined DTPa+HepB vaccine is used for active immunization against diphtheria, tetanus, pertussis (whooping cough), and hepatitis B. This vaccine contains acellular components of Bordetella pertussis, diphtheria and tetanus toxoids, and the hepatitis B surface antigen.
The vaccine is administered intramuscularly, usually in multiple doses, according to recommended vaccination schedules for infants and young children. It is essential for preventing serious diseases such as chronic hepatitis B, liver cirrhosis, and liver cancer, as well as complications associated with diphtheria, tetanus, and whooping cough.
Common side effects include fever, irritability, drowsiness, and pain at the injection site. In rare cases, severe allergic reactions may occur.
The combined DTPa+HepB vaccine is a crucial measure for protecting public health, helping to reduce the incidence of these infectious diseases and prevent severe complications associated with them.
General data about TRITANRIX HEPB
- Substance: DTPA + HEPB combination vaccine
- Date of latest medicines list: 01-07-2013
- Product code: W13365002
- Pharmaceutical form: multidose injection suspension
- Quantity: 1
- Product type: Generic medicine
- Prescription status: P-RF - Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Pharmaceutical forms available for DTPA + HEPB combination vaccine
Leaflet TRITANRIX HEPB
Contents of the package leaflet for the medicine TRITANRIX HEPB multidose injection suspension
1. NAME OF THE MEDICINAL PRODUCT
Tritanrix HepB, suspension for injection, multidose
Diphtheria (D), tetanus (T), pertussis (whole cell) (Pw) and hepatitis B (rDNA) (HBV) vaccine (adsorbed)
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 dose (0.5 ml) contains:
Diphtheria toxoid1 not less than 30 IU
Tetanus toxoid1 not less than 60 IU
Bordetella pertussis (inactivated)2 not less than 4 IU
Hepatitis B surface antigen2,3 10 micrograms1 Adsorbed on aluminium hydroxide, hydrated 0.26 milligrams Al3+2 Adsorbed on aluminium phosphate 0.37 milligrams Al3+3 Produced in yeast cells (Saccharomyces cerevisiae) by recombinant DNA technology
This is a multidose container. See section 6.5 for the number of doses per vial.
For a full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Suspension for injection.
Turbid white suspension.
4. CLINICAL PARTICULARS
4.1 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
The recommended dose is 0.5 ml.
Primary vaccination:The primary vaccination schedule consists of three doses within the first six months of life. Where HBVvaccine is not given at birth, the combined vaccine can be administered beginning as early as 8 weeks ofage. Where there is a high endemicity of HBV, the practice to administer HBV vaccine at birth shouldbe continued. In these circumstances, vaccination with the combined vaccine should start at 6 weeks ofage.
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 toadminister a dose of HBV vaccine at birth to improve protection.
In the case of children born of known HBV carrier mothers the immunoprophylactic measures forhepatitis B should not be modified. This may require separate vaccination with HBV and DTPwvaccines 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 abooster 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 thesecond year of life. For long-term protection against HBV, a booster dose of HBV vaccine could also beadministered after the first year of life. However, the need for this dose is currently not established.
Method of administrationTritanrix HepB is for deep intramuscular injection, preferably in the anterolateral thigh.
It is recommended that in patients with thrombocytopenia or bleeding disorders the vaccine be administeredsubcutaneously (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 severefebrile 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 thesecircumstances 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 previousvaccination and possible occurrence of adverse reactions) and a clinical examination.
As with all injectable vaccines, appropriate medical treatment should always be readily available in caseof anaphylactic reactions following the administration of the vaccine. For this reason, the vaccineeshould 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 givesubsequent 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 outweighpossible risks.
As for any vaccination, the risk-benefit of immunising with Tritanrix HepB or deferring this vaccinationshould be weighed carefully in an infant or in a child suffering from a new onset or progression of a severeneurological 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 donot 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 bleedingdisorder 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 whenadministering the primary immunisation series to very premature infants (born ≤ 28 weeks of gestation) andparticularly 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 ordelayed.
4.5 Interaction with other medicinal products and other forms of interaction
It is current practice in paediatric vaccination to co-administer different vaccines during the samesession with injectable vaccines being administered at separate injection sites.
Tritanrix HepB can be administered simultaneously at separate sites or in any temporal relationship withother 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 poliovaccine 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 HepBwas used to reconstitute the lyophilised Hib vaccine (Hiberix); no interference in the immune responseto any of the antigens was observed as compared to the responses observed following administration ofthe vaccines at separate sites. (see section 6.2.).
In patients receiving immunosuppressive therapy or patients with immunodeficiency, an adequateresponse may not be achieved.
4.6 Fertility, pregnancy and lactation
As Tritanrix HepB is not intended for use in adults, information on the safety of the vaccine when usedduring pregnancy or lactation is not available.
4.7 Effects on ability to drive and use machines
Not relevant.
4.8 Undesirable effects
* Clinical 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 listedbelow.
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: bronchitisuncommon: respiratory disorder
Gastro-intestinal disorders:very common: feeding problemscommon: gastro-intestinal symptoms such as vomiting and diarrhoea
Infections and infestations:common: otitis media, pharyngitisuncommon: pneumonia
General disorders and administration site conditions:very common: fever, swelling, pain and redness
Immune system disorders:very rare: allergic reactions including anaphylactic and anaphylactoid reactions and serum sicknesslike disease
Psychiatric disorders:very common: unusual crying, irritability
In a prospective comparative study, which compared the administration of the combined DTPw-HBVvaccine 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 arepresented below:
Group 1 Group 2
DTPw-HBV DTPw HBV(combined) (separate)
N° of symptom checklists 175 177 177
Local symptoms (%)
Pain Total 32.0 15.3 2.8
Severe* 0.0 0.0 0.0
Redness Total 38.9 27.1 5.1> 2cm 9.1 3.4 0.6
Swelling Total 30.9 21.5 4.5> 2cm 10.9 3.4 0.6
General Symptoms (%)
Fever > 38°C 53.1 35.0
Fever > 39.5° C 1.1 0.0
* 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, itis possible that sensitisation reactions may occur (see section 4.3)
4.9 Overdose
No case of overdose has been reported.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmaco-therapeutic group: Bacterial and viral vaccines combined, ATC code J07CA05.
Tritanrix HepB contains diphtheria (D), tetanus (T) toxoids, inactivated pertussis bacteria (Pw) andthe purified major surface antigen of the hepatitis B virus (HBV), adsorbed on aluminium salts.
The D and T toxoids are prepared from the toxins of cultures of Corynebacterium diphtheriae and
Clostridium tetani by formalin inactivation using established technology. The Pw component isobtained by heat inactivation of phase I culture of Bordetella pertussis bacteria.
The surface antigen of the HBV (HBsAg) is produced by culture of genetically-engineered yeast cells(Saccharomyces cerevisiae) which carry the gene coding for the major surface antigen of the HBV.
This HBsAg expressed in yeast cells is purified by several physico-chemical steps. The HBsAgassembles spontaneously, in the absence of chemical treatment, into spherical particles of 20 nm inaverage diameter containing non-glycosylated HBsAg polypeptide and a lipid matrix consistingmainly of phospholipids. Extensive tests have demonstrated that these particles display thecharacteristic properties of the natural HBsAg.
Four different schedules have been studied (6-10-14 weeks, 2-4-6 months; 3-4-5 months and 3-4½-6 months)according to routine vaccination practices in different countries with three doses administered within the firstsix months of life.
For each component of the vaccine, the following immune responses have been documented onemonth after completion of the primary vaccination schedule.
Percentage of subjects with antibody titres ≥ assay cut-off one month after primary vaccination with
Tritanrix HepB:
Antibody 6-10-14 weeks 2-4-6 months; 3-4-5 months(cut-off) and 3-4½-6 months% %
Anti-diphtheria 93.1 99.7(0.1 IU/ml) †
Anti-tetanus 100 100(0.1 IU/ml) †
Anti-B. Pertussis 97.2 97.7(vaccine response) ††
Anti-HBs 97.7* 99.2(10 mIU/ml) †
* in a subgroup of infants not administered hepatitis B vaccine at birth, 89.9% of subjects had anti-HBs titres≥ 10 mIU/ml† cut-off accepted as indicative of protection†† vaccine response: % of subjects considered to have responded to the Bordetella pertussis antigen
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on general safety studies.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Thiomersal
Sodium chloride
Water for injections
For adjuvants, see section 2.
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section6.6.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Store in the original package, in order to protect from light.
6.5 Nature and contents of container
1 ml of suspension in a vial (type I glass) for 2 doses with a plunger stopper (rubber butyl) - pack size of1.
5 ml of suspension in a vial (type I glass) for 10 doses with a plunger stopper (rubber butyl) - pack size of1.
Not all pack-sizes may be marketed
6.6 Special precautions for disposal and other handling
Tritanrix HepB can be mixed with the lyophilised Hib vaccine (Hiberix).
Upon storage, a white deposit and clear supernatant can be observed.
The vaccine should be well shaken in order to obtain a homogeneous turbid white suspension and visuallyinspected for any foreign particulate matter and/or variation of physical aspect prior to administration. Inthe event of either being observed, discard the vaccine.
When using a multidose vial, each dose should be taken with a sterile needle and syringe. As with othervaccines, a dose of vaccine should be withdrawn under strict aseptic conditions and precautions taken toavoid contamination of the contents.
Any unused product of waste material should be disposed of in accordance with local requirements.