SUMMARY OF PRODUCT CHARACTERISTICS

Transcription

1 SUMMARY OF PRODUCT CHARACTERISTICS Infanrix-IPV+Hib 1 SPC Vial + Vial

2 1. NAME OF THE MEDICINAL PRODUCT INFANRIX-IPV+Hib powder and suspension for suspension for injection Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION A 0.5 ml dose of vaccine contains: Diphtheria toxoid 1 not less than 30 International Units (IU) (25 Lf) Tetanus toxoid 1 not less than 40 International Units (IU) (10 Lf) Bordetella pertussis antigens Pertussis toxoid 1 25 µg Filamentous haemagglutinin 1 25 µg Pertactin 1 8 µg Poliovirus (inactivated) type 1 (Mahoney strain) 2 40 D-antigen unit type 2 (MEF-1 strain) 2 8 D-antigen unit type 3 (Saukett strain) 2 32 D-antigen unit Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) 10 µg conjugated to tetanus toxoid as carrier protein approximately 30 µg 1 Adsorbed on aluminium hydroxide, hydrated 0.5 milligrams Al 3+ 2 Propagated in VERO cells For the full list of excipients, see section PHARMACEUTICAL FORM Powder and suspension for suspension for injection. The diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis (DTPa-IPV) component is a turbid white suspension. The lyophilised Haemophilus influenzae type b (Hib) component is a white powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications INFANRIX-IPV+Hib is indicated for active immunisation against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b disease from the age of 2 months. 4.2 Posology and method of administration Infanrix-IPV+Hib 2 SPC Vial + Vial

3 Posology Primary vaccination: The primary vaccination schedule consists of two or three doses given in accordance with official recommendations. The minimum age at the time of the first dose is 2 months. Subsequent doses of the primary course should be separated by a minimum interval of four weeks. Booster vaccination: After primary vaccination with two doses, a booster dose of INFANRIX-IPV+Hib must be given at least 6 months after the last priming dose, preferably between 11 and 13 months of age. After primary vaccination with three doses, a booster dose of Hib conjugate vaccine (monovalent or combined) must be administered. The timing of this Hib conjugate vaccine booster dose should be in accordance with official recommendations. INFANRIX-IPV+Hib may be used for this booster dose if administration of the additional antigens at the same time is in accordance with official recommendations. INFANRIX-IPV+Hib may be used as a booster dose for children who have previously been immunised with other vaccines that contain DTP, polio and Hib antigens. Paediatric population: The safety and efficacy of INFANRIX-IPV+Hib in children over 36 months of age have not been established. No data are available. Method of administration INFANRIX-IPV+Hib is for deep intramuscular injection, in the anterolateral aspect of the thigh. It is preferable that each subsequent dose is given into alternating limbs. INFANRIX-IPV+Hib should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes. INFANRIX-IPV+Hib should under no circumstances be administered intravascularly. For instructions on reconstitution of the medicinal product before administration, see section Contraindications Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or neomycin, polymyxin and polysorbate 80. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio or Hib vaccines. INFANRIX-IPV+Hib is contra-indicated if the child has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. Infanrix-IPV+Hib 3 SPC Vial + Vial

4 As with other vaccines, the administration of INFANRIX-IPV+Hib should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, however, is not a contraindication. 4.4 Special warnings and precautions for use As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. If any of the following events have occurred in temporal relation to receipt of any DTP-containing vaccine, the decision to give subsequent doses of vaccine containing a pertussis component should be carefully considered. Temperature of 40.0 C (rectal) 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. There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks, particularly since the events are not associated with permanent sequelae. According to available clinical data, the risk of such reactions is lower with acellular pertussis vaccines than with whole cell pertussis vaccines. As for any vaccination, the risk-benefit of immunising with INFANRIX-IPV+Hib 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. The Hib component of the vaccine does not protect against diseases due to other types of Haemophilus influenzae nor against meningitis caused by other organisms. A history of febrile convulsions, a family history of convulsions, a family history of Sudden Infant Death Syndrome (SIDS) and a family history of an adverse event following DTP, IPV and/or Hib vaccination do not constitute contra-indications to administration of INFANRIX-IPV+Hib. Human Immunodeficiency Virus (HIV) infection is not considered to be a contraindication to administration of INFANRIX-IPV+Hib. The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patients on immunosuppressive therapy. Excretion of capsular polysaccharide antigen in the urine has been described following receipt of Hib vaccines. Therefore false positive antigen detection test results are possible within 1-2 weeks of vaccination. Administration of INFANRIX-IPV+Hib should be recorded in the patient s International Vaccination Certificate. 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. Infanrix-IPV+Hib 4 SPC Vial + Vial

5 As the benefit of the vaccination is high in this group of infants, vaccination should not be withheld or delayed. Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints. 4.5 Interaction with other medicinal products and other forms of interaction If INFANRIX-IPV+Hib is to be given at the same time as another injectable vaccine(s), the vaccines should always be administered at different injection sites. As with other vaccines it may be expected that, in patients receiving immunosuppressive therapy or patients with immunodeficiency, an adequate response may not be achieved. 4.6 Fertility, pregnancy and lactation As INFANRIX-IPV+Hib 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 machines Not relevant. 4.8 Undesirable effects - Clinical trials The safety profile presented below is based on data from more than 3500 subjects. As has been observed for DTPa and DTPa-containing combinations, an increase in local reactogenicity and fever was reported after booster vaccination with INFANRIX IPV+Hib with respect to the primary course. Frequencies per dose are defined as follows: Very common: (1/10) Common: ( 1/100 to < 1/10) Uncommon: ( 1/1,000 to < 1/100) Rare: ( 1/10,000 to < 1/1,000) Very rare: (< 1/10,000) Infections and infestations Uncommon: upper respiratory tract infection Blood and lymphatic system disorders Uncommon: lymphadenopathy Metabolism and nutrition disorders Very common: appetite lost Psychiatric disorders Very common: crying abnormal, irritability, restlessness Infanrix-IPV+Hib 5 SPC Vial + Vial

6 Nervous system disorders Very common: somnolence Respiratory, thoracic and mediastinal disorders Uncommon: bronchitis, cough, rhinorrhoea Gastrointestinal disorders Common: diarrhoea, vomiting Skin and subcutaneous tissue disorders Uncommon: urticaria, rash Rare: pruritus, dermatitis General disorders and administration site conditions Very common: fever (38.0 C), injection site reactions such as pain and redness, local swelling at the injection site ( 50 mm) Common: injection site reactions including induration, local swelling at the injection site (>50 mm) 1 Uncommon: diffuse swelling of the injected limb, sometimes involving the adjacent joint 1, fever 2 >39.5 C, fatigue - Post-marketing surveillance Immune system disorders Allergic reactions (including anaphylactic 3 and anaphylactoid reactions) Nervous system disorders Collapse or shock-like state (hypotonic-hyporesponsiveness episode), convulsions (with or without fever) Respiratory, thoracic and mediastinal disorders Apnoea 3 [see 4.4 for apnoea in very premature infants ( 28 weeks of gestation)] Skin and subcutaneous tissue disorders Angioneurotic oedema 3 General disorders and administration site conditions Swelling of the entire injected limb 1, injection site vesicles 3 1 Children primed with acellular pertussis vaccines are more likely to experience swelling reactions after booster administration in comparison with children primed with whole cell vaccines. These reactions resolve over an average of 4 days. 2 common with booster vaccination 3 reported with GSK s DTPa containing vaccines 4.9 Overdose Not applicable. Infanrix-IPV+Hib 6 SPC Vial + Vial

7 5. PHARMACOLOGICAL PROPERTIES. 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Bacterial and viral vaccines combined, ATC code: J07CA06 Results obtained in the clinical studies for each of the components are summarised in the tables below: Percentage of subjects with antibody titres assay cut-off after primary vaccination with INFANRIX-IPV+Hib: Antibody (cut-off) 3-5 months N= 86 (1 trial) % months N= 62 ( 1 trial) % months N= 337 ( 3 trials) % months N= 624 (6 trials) % months N= 127 (2 trials) % months N=198 (1 trial) % Anti-diphtheria (0.1 IU/ml)* Anti-tetanus 100.0** (0.1 IU/ml)* Anti-PT 99.5** (5 EL.U/ml) Anti-FHA 99.7** (5 EL.U/ml) Anti-PRN 99.0** (5 EL.U/ml) Anti-Polio type ND (1/8 dilution)* Anti-Polio type ND (1/8 dilution)* Anti-Polio type ND (1/8 dilution)* Anti-PRP (Hib) (0.15 g/ml)* Anti-PRP (Hib) (1.0 g/ml) * cut-off accepted as indicative of protection ** Post dose 2 results from studies where DTPa-HBV-IPV+Hib was administered in a schedule 3, 5 and 11 months of age. N = numbers of subjects ND = not determined Infanrix-IPV+Hib 7 SPC Vial + Vial

8 Percentage of subjects with antibody titres assay cut-off after booster vaccination with INFANRIX-IPV+Hib: Antibody (cut-off) Booster vaccination at 11/12 months of age following a 3-5 months primary course N =184 (1 trial) % Booster vaccination during the second year of life following a three dose primary course N = 1326 (9 trials) % Anti-diphtheria (0.1 IU/ml)* Anti-tetanus 99.9** 99.9 (0.1 IU/ml)* Anti-PT 99.9** 99.7 (5 EL.U/ml) Anti-FHA 99.9** 100 (5 EL.U/ml) Anti-PRN 99.5** 99.9 (5 EL.U/ml) Anti-Polio type (1/8 dilution)* Anti-Polio type (1/8 dilution)* Anti-Polio type (1/8 dilution)* Anti-PRP (Hib) (0.15 g/ml)* Anti-PRP (Hib) (1.0 g/ml) * cut-off accepted as indicative of protection ** Post dose 3 results from studies where DTPa-HBV-IPV+Hib was administered in a schedule 3, 5 and 11 months of age. N = numbers of subjects The effectiveness of the Hib component (when combined with DTPa, DTPa-IPV or DTPa-HBV- IPV) was investigated via an extensive post-marketing surveillance study conducted in Germany. Over a 4.5 year follow-up period, the effectiveness of DTPa+Hib or DTPa-IPV+Hib vaccines was 96.7% for a full primary series and 98.5% for a booster dose (irrespective of priming). Over a seven year follow-up period, the effectiveness of the Hib components of two hexavalent vaccines was 89.6% for a full primary series and 100% for a full primary series plus booster dose (irrespective of the Hib vaccine used for priming). 5.2 Pharmacokinetic properties Evaluation of pharmacokinetic properties is not required for vaccines. 5.3 Preclinical safety data Infanrix-IPV+Hib 8 SPC Vial + Vial

9 Non-clinical data reveal no special hazard for humans based on conventional studies of safety, specific toxicity and compatibility of ingredients. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Lyophilised HIB component: Lactose Liquid DTPa-IPV component: Sodium chloride Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances) Water for injections For adjuvants, see section Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life The shelf life of the vaccine components before reconstitution is 3 years. After reconstitution, the vaccine should be injected immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not be longer than 8 hours at +2 C to +8 C (in a refrigerator). 6.4 Special precautions for storage Store in a refrigerator (2C 8C). Do not freeze. Store in the original package, in order to protect from light. For storage conditions after reconstitution of the medicinal product, see section Nature and contents of container Powder in vial (type I glass) with stopper (butyl rubber). 0.5 ml of suspension in vial (type I glass) with a stopper (butyl rubber). Pack size of 1, 10, 20, 25, 40, 50 and 100. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Infanrix-IPV+Hib 9 SPC Vial + Vial

10 Upon storage of the DTPa-IPV suspension, a white deposit and clear supernatant can be observed in the vial. This is not a sign of deterioration. The DTPa-IPV suspension in the vial should be well shaken to obtain a homogeneous suspension. The DTPa-IPV suspension, the Hib powder and the reconstituted vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either is observed, the vaccine should be discarded. The vaccine is reconstituted by adding the entire contents of the vial of DTPa-IPV suspension to the vial containing the Hib powder. The mixture should then be injected immediately. The full reconstitution instructions are: 1. Shake the vial containing the DTPa-IPV suspension 2. Attach a needle to an empty syringe and withdraw the DTPa-IPV suspension into it. 3. Inject the entire contents of the syringe into the Hib vial. 4. With the needle still inserted, shake the Hib vial vigorously and examine for complete dissolution. 5. Withdraw the entire mixture back into the syringe. 6. Replace the needle with an appropriate size needle for injection and administer the vaccine. 7. If the vaccine is not administered immediately, shake the solution vigorously again before injection. 8. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 7. MARKETING AUTHORISATION HOLDER [To be completed nationally] 8. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally] 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION [To be completed nationally] 10. DATE OF REVISION OF THE TEXT [To be completed nationally] Detailed information on this medicinal product is available on the website of: {name of MS/Agency} Infanrix-IPV+Hib 10 SPC Vial + Vial

11 1. NAME OF THE MEDICINAL PRODUCT INFANRIX-IPV+Hib powder and suspension for suspension for injection Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION A 0.5 ml dose of vaccine contains: Diphtheria toxoid 1 not less than 30 International Units (IU) (25 Lf) Tetanus toxoid 1 not less than 40 International Units (IU) (10 Lf) Bordetella pertussis antigens Pertussis toxoid 1 25 µg Filamentous haemagglutinin 1 25 µg Pertactin 1 8 µg Poliovirus (inactivated) type 1 (Mahoney strain) 2 40 D-antigen unit type 2 (MEF-1 strain) 2 8 D-antigen unit type 3 (Saukett strain) 2 32 D-antigen unit Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) 10 µg conjugated to tetanus toxoid as carrier protein approximately 30 µg 1 Adsorbed on aluminium hydroxide, hydrated 0.5 milligrams Al 3+ 2 Propagated in VERO cells For the full list of excipients, see section PHARMACEUTICAL FORM Powder and suspension for suspension for injection. The diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis (DTPa-IPV) component is a turbid white suspension. The lyophilised Haemophilus influenzae type b (Hib) component is a white powder. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications INFANRIX-IPV+Hib is indicated for active immunisation against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenzae type b disease from the age of 2 months. 4.2 Posology and method of administration Posology Infanrix-IPV+Hib 11 SPC Vial + Pre-filled syringe

12 Primary vaccination: The primary vaccination schedule consists of two or three doses given in accordance with official recommendations. The minimum age at the time of the first dose is 2 months. Subsequent doses of the primary course should be separated by a minimum interval of four weeks. Booster vaccination: After primary vaccination with two doses, a booster dose of INFANRIX-IPV+Hib must be given at least 6 months after the last priming dose, preferably between 11 and 13 months of age. After primary vaccination with three doses, a booster dose of Hib conjugate vaccine (monovalent or combined) must be administered. The timing of this Hib conjugate vaccine booster dose should be in accordance with official recommendations. INFANRIX-IPV+Hib may be used for this booster dose if administration of the additional antigens at the same time is in accordance with official recommendations. INFANRIX-IPV+Hib may be used as a booster dose for children who have previously been immunised with other vaccines that contain DTP, polio and Hib antigens. Paediatric population The safety and efficacy of INFANRIX-IPV+Hib in children over 3 years of age have not been established. No data are available. Method of administration INFANRIX-IPV+Hib is for deep intramuscular injection, in the anterolateral aspect of the thigh. It is preferable that each subsequent dose is given into alternating limbs. INFANRIX-IPV+Hib should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes. INFANRIX-IPV+Hib should under no circumstances be administered intravascularly. For instructions on reconstitution of the medicinal product before administration, see section Contraindications Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 or neomycin, polymyxin and polysorbate 80. Hypersensitivity after previous administration of diphtheria, tetanus, pertussis, polio or Hib vaccines. INFANRIX-IPV+Hib is contra-indicated if the child has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. As with other vaccines, the administration of INFANRIX-IPV+Hib should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor infection, however, is not a contraindication. Infanrix-IPV+Hib 12 SPC Vial + Pre-filled syringe

13 4.4 Special warnings and precautions for use As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following the administration of the vaccine. If any of the following events have occurred in temporal relation to receipt of any DTP-containing vaccine, the decision to give subsequent doses of vaccine containing a pertussis component should be carefully considered. Temperature of 40.0 C (rectal) 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. There may be circumstances, such as a high incidence of pertussis, when the potential benefits outweigh possible risks, particularly since the events are not associated with permanent sequelae. According to available clinical data, the risk of such reactions is lower with acellular pertussis vaccines than with whole cell pertussis vaccines. As for any vaccination, the risk-benefit of immunising with INFANRIX-IPV+Hib 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. The Hib component of the vaccine does not protect against diseases due to other types of Haemophilus influenzae nor against meningitis caused by other organisms. A history of febrile convulsions, a family history of convulsions, a family history of Sudden Infant Death Syndrome (SIDS) and a family history of an adverse event following DTP, IPV and/or Hib vaccination do not constitute contra-indications to administration of INFANRIX-IPV+Hib. Human Immunodeficiency Virus (HIV) infection is not considered to be a contraindication to administration of INFANRIX-IPV+Hib. The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patients on immunosuppressive therapy. Excretion of capsular polysaccharide antigen in the urine has been described following receipt of Hib vaccines. Therefore false positive antigen detection test results are possible within 1-2 weeks of vaccination. Administration of INFANRIX-IPV+Hib should be recorded in the patient s International Vaccination Certificate. 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 the vaccination is high in this group of infants, vaccination should not be withheld or delayed. Syncope (fainting) can occur following, or even before, any vaccination as a psychogenic response to the needle injection. It is important that procedures are in place to avoid injury from faints. 4.5 Interaction with other medicinal products and other forms of interaction Infanrix-IPV+Hib 13 SPC Vial + Pre-filled syringe

14 If INFANRIX-IPV+Hib is to be given at the same time as another injectable vaccine(s), the vaccines should always be administered at different injection sites. As with other vaccines it may be expected that, in patients receiving immunosuppressive therapy or patients with immunodeficiency, an adequate response may not be achieved. 4.6 Fertility, pregnancy and lactation As INFANRIX-IPV+Hib 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 machines Not relevant. 4.8 Undesirable effects - Clinical trials The safety profile presented below is based on data from more than 3500 subjects. As has been observed for DTPa and DTPa-containing combinations, an increase in local reactogenicity and fever was reported after booster vaccination with INFANRIX IPV+Hib with respect to the primary course. Frequencies per dose are defined as follows: Very common: (1/10) Common: ( 1/100 to < 1/10) Uncommon: ( 1/1,000 to < 1/100) Rare: ( 1/10,000 to < 1/1,000) Very rare: (< 1/10,000) Infections and infestations Uncommon: upper respiratory tract infection Blood and lymphatic system disorders Uncommon: lymphadenopathy Metabolism and nutrition disorders Very common: appetite lost Psychiatric disorders Very common: crying abnormal, irritability, restlessness Nervous system disorders Very common: somnolence Respiratory, thoracic and mediastinal disorders Uncommon: bronchitis, cough, rhinorrhoea Gastrointestinal disorders Common: diarrhoea, vomiting Skin and subcutaneous tissue disorders Infanrix-IPV+Hib 14 SPC Vial + Pre-filled syringe

15 Uncommon: urticaria, rash Rare: pruritus, dermatitis General disorders and administration site conditions Very common: fever (38.0 C), injection site reactions such as pain and redness, local swelling at the injection site ( 50 mm) Common: injection site reactions including induration, local swelling at the injection site (>50 mm) 1 Uncommon: diffuse swelling of the injected limb, sometimes involving the adjacent joint 1, fever 2 >39.5 C, fatigue - Post-marketing surveillance Immune system disorders Allergic reactions (including anaphylactic 3 and anaphylactoid reactions) Nervous system disorders Collapse or shock-like state (hypotonic-hyporesponsiveness episode), convulsions (with or without fever) Respiratory, thoracic and mediastinal disorders Apnoea 3 [see 4.4 for apnoea in very premature infants ( 28 weeks of gestation)] Skin and subcutaneous tissue disorders Angioneurotic oedema 3 General disorders and administration site conditions Swelling of the entire injected limb 1, injection site vesicles 3 1 Children primed with acellular pertussis vaccines are more likely to experience swelling reactions after booster administration in comparison with children primed with whole cell vaccines. These reactions resolve over an average of 4 days. 2 common with booster vaccination 3 reported with GSK s DTPa containing vaccines 4.9 Overdose Not applicable. 5. PHARMACOLOGICAL PROPERTIES. 5.1 Pharmacodynamic properties Pharmacotherapeutic group: Bacterial and viral vaccines combined, ATC code: J07CA06 Results obtained in the clinical studies for each of the components are summarised in the tables below: Infanrix-IPV+Hib 15 SPC Vial + Pre-filled syringe

16 Percentage of subjects with antibody titres assay cut-off after primary vaccination with INFANRIX-IPV+Hib: Antibody (cut-off) 3-5 months N= 86 (1 trial) % months N= 62 ( 1 trial) % months N= 337 ( 3 trials) % months N= 624 (6 trials) % months N= 127 (2 trials) % months N=198 (1 trial) % Anti-diphtheria (0.1 IU/ml)* Anti-tetanus 100.0** (0.1 IU/ml)* Anti-PT 99.5** (5 EL.U/ml) Anti-FHA 99.7** (5 EL.U/ml) Anti-PRN 99.0** (5 EL.U/ml) Anti-Polio type ND (1/8 dilution)* Anti-Polio type ND (1/8 dilution)* Anti-Polio type ND (1/8 dilution)* Anti-PRP (Hib) (0.15 g/ml)* Anti-PRP (Hib) (1.0 g/ml) * cut-off accepted as indicative of protection ** Post dose 2 results from studies where DTPa-HBV-IPV+Hib was administered in a schedule 3, 5 and 11 months of age N = number of subjects ND = not determined Infanrix-IPV+Hib 16 SPC Vial + Pre-filled syringe

17 Percentage of subjects with antibody titres assay cut-off after booster vaccination with INFANRIX-IPV+Hib: Antibody (cut-off) Booster vaccination at 11/12 months of age following a 3-5 months primary course N =184 (1 trial) % Booster vaccination during the second year of life following a three dose primary course N = 1326 (9 trials) % Anti-diphtheria (0.1 IU/ml)* Anti-tetanus 99.9** 99.9 (0.1 IU/ml)* Anti-PT 99.9** 99.7 (5 EL.U/ml) Anti-FHA 99.9** 100 (5 EL.U/ml) Anti-PRN 99.5** 99.9 (5 EL.U/ml) Anti-Polio type (1/8 dilution)* Anti-Polio type (1/8 dilution)* Anti-Polio type (1/8 dilution)* Anti-PRP (Hib) (0.15 g/ml)* Anti-PRP (Hib) (1.0 g/ml) * cut-off accepted as indicative of protection ** Post dose 3 results from studies where DTPa-HBV-IPV+Hib was administered in a schedule 3, 5 and 11 months of age N = number of subjects The effectiveness of the Hib component (when combined with DTPa, DTPa-IPV or DTPa-HBV- IPV) was investigated via an extensive post-marketing surveillance study conducted in Germany. Over a 4.5 year follow-up period, the effectiveness of DTPa+Hib or DTPa-IPV+Hib vaccines was 96.7% for a full primary series and 98.5% for a booster dose (irrespective of priming). Over a seven year follow-up period, the effectiveness of the Hib components of two hexavalent vaccines was 89.6% for a full primary series and 100% for a full primary series plus booster dose (irrespective of the Hib vaccine used for priming). 5.2 Pharmacokinetic properties Evaluation of pharmacokinetic properties is not required for vaccines. 5.3 Preclinical safety data Non-clinical data reveal no special hazard for humans based on conventional studies of safety, specific toxicity and compatibility of ingredients. Infanrix-IPV+Hib 17 SPC Vial + Pre-filled syringe

18 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Lyophilised HIB component: Lactose Liquid DTPa-IPV component: Sodium chloride Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances) Water for injections For adjuvants, see section Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products. 6.3 Shelf life The shelf life of the vaccine components before reconstitution is 3 years. After reconstitution, the vaccine should be injected immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and should normally not be longer than 8 hours at +2 C to +8 C (in a refrigerator). 6.4 Special precautions for storage Store in a refrigerator (2C 8C). Do not freeze. Store in the original package, in order to protect from light. For storage conditions after reconstitution of the medicinal product, see section Nature and contents of container Powder in vial (type I glass) with stopper (butyl rubber). 0.5 ml of suspension in pre-filled syringe (type I glass) with a plunger stopper (butyl rubber) with or without needles. Pack size of 1, 10, 20, 25, 40, 50 and 100. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Upon storage of the DTPa-IPV suspension, a white deposit and clear supernatant can be observed in the syringe. This is not a sign of deterioration. The pre-filled syringe should be well shaken to obtain a homogeneous suspension. The DTPa-IPV suspension in the pre-filled syringe, the Hib powder in the vial and the reconstituted vaccine should be inspected visually for any foreign particulate matter and/or abnormal physical appearance prior to administration. In the event of either is observed, the vaccine should be discarded. Infanrix-IPV+Hib 18 SPC Vial + Pre-filled syringe

19 The vaccine is reconstituted by adding the entire contents of the pre-filled syringe of DTPa-IPV suspension to the vial containing the Hib powder. The mixture should then be injected immediately. The full reconstitution instructions are: 1. Shake the pre-filled syringe containing the DTPa-IPV suspension 2. Attach a needle to the pre-filled syringe of DTPa-IPV and inject the contents of the syringe into the Hib vial. 3. With the needle still inserted, shake the Hib vial vigorously and examine for complete dissolution. 4. Withdraw the entire mixture back into the syringe. 5. Replace the needle with an appropriate size needle for injection and administer the vaccine. 6. If the vaccine is not administered immediately, shake the solution vigorously again before injection. 7. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. 7. MARKETING AUTHORISATION HOLDER [To be completed nationally] 8. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally] 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION [To be completed nationally] 10. DATE OF REVISION OF THE TEXT [To be completed nationally] Detailed information on this medicinal product is available on the website of: {name of MS/Agency} Infanrix-IPV+Hib 19 SPC Vial + Pre-filled syringe

20 LABELLING 20

21 PARTICULARS TO APPEAR ON THE OUTER PACKAGING VIAL + VIAL X 1 VIAL + VIAL X 10 VIAL + VIAL X 20 VIAL + VIAL X 25 VIAL + VIAL X 40 VIAL + VIAL X 50 VIAL + VIAL X NAME OF THE MEDICINAL PRODUCT INFANRIX-IPV+Hib powder and suspension for suspension for injection Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) 2. STATEMENT OF ACTIVE SUBSTANCE(S) : Diphtheria toxoid 1 not less than 30 IU (25 Lf) Tetanus toxoid 1 not less than 40 IU (10 Lf) Bordetella pertussis antigens Pertussis toxoid 1 25 µg Filamentous haemagglutinin 1 25 µg Pertactin 1 8 µg Poliovirus (inactivated) type 1 (Mahoney strain) 2 40 D-antigen unit type 2 (MEF-1 strain) 2 8 D-antigen unit type 3 (Saukett strain) 2 32 D-antigen unit Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) 10 µg conjugated to tetanus toxoid as carrier protein approximately 30 µg 1 Adsorbed on aluminium hydroxide, hydrated 0.5 milligrams Al 3+ 2 Propagated in VERO cells 3. LIST OF EXCIPIENTS Lyophilised Hib component: Lactose Liquid DTPa-IPV component: Sodium chloride Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances) Water for injections 4. PHARMACEUTICAL FORM AND CONTENTS Infanrix-IPV+Hib 21 Labelling Vial+Vial

22 Powder and suspension for suspension for injection Vial: powder Vial: suspension 1vial+1 vial 10 vials+10 vials 20 vials+20 vials 25 vials+25 vials 40 vials+40 vials 50 vials+50 vials 100 vials+100 vials 5. METHOD AND ROUTE(S) OF ADMINISTRATION Read the package leaflet before use. Intramuscular use Shake before use 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN Keep out of the sight and reach of children. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 8. EXPIRY DATE EXP: MM/YYYY 9. SPECIAL STORAGE CONDITIONS Store in a refrigerator Do not freeze Store in the original package in order to protect from light Infanrix-IPV+Hib 22 Labelling Vial+Vial

23 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 [To be completed nationally] 12. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally] 13. BATCH NUMBER Lot: 14. GENERAL CLASSIFICATION FOR SUPPLY [To be completed nationally] 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted Infanrix-IPV+Hib 23 Labelling Vial+Vial

24 PARTICULARS TO APPEAR ON THE OUTER PACKAGING VIAL + PRE-FILLED SYRINGE X 1 VIAL + PRE-FILLED SYRINGE X 10 VIAL + PRE-FILLED SYRINGE X 20 VIAL + PRE-FILLED SYRINGE X 25 VIAL + PRE-FILLED SYRINGE X 40 VIAL + PRE-FILLED SYRINGE X 50 VIAL + PRE-FILLED SYRINGE X 100 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 1 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 10 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 20 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 25 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 40 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X 50 VIAL + PRE-FILLED SYRINGE + 2 NEEDLES X NAME OF THE MEDICINAL PRODUCT INFANRIX-IPV+Hib powder and suspension for suspension for injection Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) 2. STATEMENT OF ACTIVE SUBSTANCE(S) : Diphtheria toxoid 1 not less than 30 IU (25 Lf) Tetanus toxoid 1 not less than 40 IU (10 Lf) Bordetella pertussis antigens Pertussis toxoid 1 25 µg Filamentous haemagglutinin 1 25 µg Pertactin 1 8 µg Poliovirus (inactivated) type 1 (Mahoney strain) 2 40 D-antigen unit type 2 (MEF-1 strain) 2 8 D-antigen unit type 3 (Saukett strain) 2 32 D-antigen unit Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) 10 µg conjugated to tetanus toxoid as carrier protein approximately 30 µg 1 Adsorbed on aluminium hydroxide, hydrated 0.5 milligrams Al 3+ 2 Propagated in VERO cells 3. LIST OF EXCIPIENTS Lyophilised Hib component: Lactose Infanrix-IPV+Hib 24 Labelling Vial+Vial

25 Liquid DTPa-IPV component: Sodium chloride Medium 199 (as stabilizer containing amino acids, mineral salts, vitamins and other substances) Water for injections 4. PHARMACEUTICAL FORM AND CONTENTS Powder and suspension for suspension for injection Vial: powder Pre-filled syringe: suspension 1vial+1 pre-filled syringe 10 vials+10 pre-filled syringes 20 vials+20 pre-filled syringes 25 vials+25 pre-filled syringes 40 vials+40 pre-filled syringes 50 vials+50 pre-filled syringes 100 vials+100 pre-filled syringes 1vial+1 pre-filled syringe+2 needles 10 vials+10 pre-filled syringes+20 needles 20 vials+20 pre-filled syringes+40 needles 25 vials+25 pre-filled syringes+50 needles 40 vials+40 pre-filled syringes+80 needles 50 vials+50 pre-filled syringes+100 needles Infanrix-IPV+Hib 25 Labelling Vial+Vial

26 100 vials+100 pre-filled syringes+200 needles 5. METHOD AND ROUTE(S) OF ADMINISTRATION Read the package leaflet before use. Intramuscular use Shake before use 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN Keep out of the sight and reach of children. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 8. EXPIRY DATE EXP: MM/YYYY 9. SPECIAL STORAGE CONDITIONS Store in a refrigerator Do not freeze Store in the original package in order to protect from light 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER [To be completed nationally] 12. MARKETING AUTHORISATION NUMBER(S) [To be completed nationally] 13. BATCH NUMBER Lot: Infanrix-IPV+Hib 26 Labelling Vial+Vial

27 14. GENERAL CLASSIFICATION FOR SUPPLY [To be completed nationally] 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted Infanrix-IPV+Hib 27 Labelling Vial+Vial

28 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS VIAL WITH HIB POWDER 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION Hib for INFANRIX-IPV+Hib Powder for suspension for injection I.M. 2. METHOD OF ADMINISTRATION 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 1 dose 6. OTHER Infanrix IPV+Hib 28 Label for Vial

29 MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS PRE-FILLED SYRINGE WITH DTPa IPV SUSPENSION 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION DTPa IPV for INFANRIX-IPV+Hib Suspension for suspension for injection I.M. 2. METHOD OF ADMINISTRATION 3. EXPIRY DATE EXP 4. BATCH NUMBER Lot 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 6. OTHER Infanrix IPV+Hib 29 Label for Pre-filled syringe

30 PACKAGE LEAFLET 30

31 Package leaflet: Information for the user Infanrix-IPV+Hib vaccine Powder and suspension for suspension for injection Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed) Read all of this leaflet carefully before your child starts receiving this vaccine because it contains important information for you. Keep this leaflet. You may need to read it again. If you have any further questions, ask your doctor or pharmacist. This vaccine has been prescribed for your child only. Do not pass it on to others. If your child gets any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. What is in this leaflet 1. What Infanrix-IPV+Hib is and what it is used for 2. What you need to know before your child receives Infanrix-IPV+Hib 3. How Infanrix-IPV+Hib is given 4. Possible side effects 5. How to store Infanrix-IPV+Hib 6. Contents of the pack and other information 1. What Infanrix-IPV+Hib is and what it is used for Infanrix-IPV+Hib is a vaccine used to protect your child against 5 diseases: Diphtheria - a serious bacterial infection that mainly affects the airways and sometimes the skin. The airways become swollen causing serious breathing problems. The bacteria also release a poison. This can cause nerve damage, heart problems and even death. Tetanus - Tetanus bacteria enter the body through cuts, scratches or wounds in the skin. Wounds that are more likely to get tetanus infection are burns, fractures, deep wounds or wounds that have soil, dust, horse manure or wood splinters in them. The bacteria release a poison. This can cause muscle stiffness, painful muscle spasms, fits and even death. The muscle spasms can be strong enough to cause bone fractures of the spine. Whooping cough (pertussis) - a highly infectious disease 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 which may last a long time, lung infections, fits, brain damage and even death. Polio - a viral infection. Polio can make the muscles unable to move (paralysis of the muscles). This includes the muscles needed for breathing and walking. The arms or legs affected by the disease may be painfully twisted (deformed). Haemophilus influenzae type b (Hib) - can cause brain swelling (inflammation). This can lead to serious problems such as: mental slowness (retardation), cerebral palsy, deafness, epilepsy or partial blindness. It can also cause swelling of the throat. This can cause death by suffocation. Less commonly, the bacteria can also infect the blood, heart, lungs, bones, joints and tissues of the eyes and mouth. Infanrix-IPV+Hib is for children between 2 months and 3 years old. It is not suitable for children older than 3 years. How the vaccine works Infanrix IPV+Hib 31 Package Leaflet - Vial + Vial

32 Infanrix-IPV+Hib helps your child s body make its own protection (antibodies). This will protect your child against these diseases. About the protection from Infanrix-IPV+Hib Infanrix-IPV+Hib will only protect against infections caused by the pathogens for which the vaccine has been developed. As with all vaccines, Infanrix-IPV+Hib may not fully protect all children who are vaccinated. Children with a weakened immune system (such as due to HIV infection) may not get the full benefit from Infanrix-IPV+Hib. The vaccine cannot cause the diseases that it protects your child from. 2. What you need to know before your child receives Infanrix-IPV+Hib Infanrix-IPV+Hib should not be given if your child is allergic to Infanrix-IPV+Hib or any of the other ingredients of this medicine (listed in section 6) or neomycin, polymyxin (types of antibiotics) or Polysorbate 80. The active substances and other ingredients in Infanrix-IPV+Hib are listed at the end of the leaflet. Signs of an allergic reaction may include itchy skin, rash, shortness of breath and swelling of the face and tongue. if your child experienced problems of the nervous system within 7 days after previous vaccination with a vaccine against pertussis (whooping cough) disease. If your child has a severe infection with a high temperature (over 38 C). A minor infection such as a cold should not be a problem. However, talk to your doctor first. Infanrix-IPV+Hib should not be given if any of the above apply to your child. If you are not sure, talk to your doctor or pharmacist before your child is given Infanrix-IPV+Hib. Warnings and precautions Talk to your doctor or pharmacist before your child is given Infanrix-IPV+Hib if after previously having Infanrix-IPV+Hib or another vaccine against pertussis(whooping cough) disease, your child had any problems, especially : - a high temperature (over 40 C) within 48 hours of vaccination - a collapse or shock-like state within 48 hours of vaccination - persistent crying lasting 3 hours or more within 48 hours of vaccination - seizures/fits with or without a high temperature within 3 days of having the vaccine your child is suffering from an undiagnosed or progressive disease of the brain or uncontrolled epilepsy. After control of the disease the vaccine should be administered. if your child has a tendency to seizures/fits due to a fever, or if there is a family history of this. if your child has a bleeding problem or bruises easily. If any of the above apply to your child (or you are not sure), talk to your doctor or pharmacist before your child is given Infanrix-IPV+Hib. Fainting can occur following, or even before, any needle injection, therefore tell the doctor or nurse if your child fainted with a previous injection. Other medicines and Infanrix-IPV+Hib Tell your doctor or pharmacist if your child is taking, has recently taken or might take any other medicines. In particular tell your doctor or pharmacist if your child is taking any of the following: Infanrix IPV+Hib 32 Package Leaflet - Vial + Vial

33 medicines to fight infection that affect the immune system. Infanrix-IPV+Hib may not work as well if your child is taking these medicines. Infanrix-IPV+Hib can be given at the same time as other childhood vaccines. A different place for the injection will be used for each vaccine. Pregnancy and breast-feeding Ask your doctor or pharmacist for advice before taking any medicine. Infanrix-IPV+Hib will never be given to people who are pregnant or breast-feeding as it is only used in children. Infanrix-IPV+Hib contains neomycin, polymyxin (antibiotics) and Polysorbate 80 Please tell your doctor if your child has had an allergic reaction to these ingredients. 3. How Infanrix-IPV+Hib is given How much is given The doctor will give the recommended dose of Infanrix-IPV+Hib to your child. Usually, your child will receive two or three injections with an interval of 1 month. It depends on official recommendation. The first injection can be given from the age of 2 months. You will be informed when your child should come back for their next injection. If additional injections (boosters) are necessary, the doctor will tell you. These booster injections will be given at least 6 months after the last injection of the initial vaccination course. How the vaccine is given Infanrix-IPV+Hib is always injected into a muscle. This is usually in the thigh. The vaccine should not be given into a blood vessel. If your child misses a dose If your child misses a scheduled injection, it is important that you make another appointment. Make sure your child finishes the complete vaccination course. If not, your child may not be fully protected against the diseases. If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 4. Possible side effects Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this vaccine: Allergic reactions If your child has an allergic reaction, see your doctor straight away. The signs may include: face swelling low blood pressure difficulty breathing skin going blue loss of consciousness. Infanrix IPV+Hib 33 Package Leaflet - Vial + Vial

34 These signs usually start very soon after the injection has been given. Take your child to see a doctor straight away if they happen after leaving the clinic. Allergic reactions are very rare (these may occur with up to 1 in 10,000 doses of the vaccine). See your doctor straight away if your child has any of the following serious side effects: collapse loss of consciousness lack of awareness fits If you notice any of the above, see your doctor straight away. These effects are very rare (these may occur with up to 1 in 10,000 doses of the vaccine). Other side effects include: Very common (these may occur with 1 in 10 doses or more of the vaccine): loss of appetite high temperature of 38 C or higher swelling, pain and redness at the injection site unusual crying feeling restless feeling irritable feeling sleepy Common (these may occur with up to 1 in 10 doses of the vaccine) diarrhoea or being sick (vomiting) hard lump at the injection site large swelling at the injection site Uncommon (these may occur with up to 1 in 100 doses of the vaccine) swollen glands in the neck, armpit or groin (lymphadenopathy) coughing, chest infection (bronchitis) or runny nose upper respiratory tract infection such as a cold, tonsillitis or laryngitis rash, lumpy rash (hives) tiredness swelling of the injected limb and sometimes the nearby joint high temperature of 39.5 C or higher Rare (these may occur with up to 1 in 1,000 doses of the vaccine) skin rash itching Very rare (these may occur with up to 1 in 10,000 doses of the vaccine) in babies born very prematurely (at or before 28 weeks of gestation) longer gaps than normal between breaths may occur for 2-3 days after vaccination temporarily stopping breathing (apnoea) swelling of the whole injected limb blisters at the injection site Booster doses of Infanrix-IPV+Hib may increase the risk of reactions at the injection site. These include swelling at the place of injection, swelling of the whole injected leg or arm and sometimes swelling at the nearby joint. These reactions usually begin within 2 days of the injection and go away after 4 days. Infanrix IPV+Hib 34 Package Leaflet - Vial + Vial