Infanrix-IPV

Combined diphtheria-tetanus-acellular pertussis (DTPa) and inactivated polio.

1 dose (0.5 ml) contains: Diphtheria toxoid¹ not less than 30 International Units (IU) (25 Lf); Tetanus toxoid¹ not less than 40 International Units (IU) (10 Lf).
Bordetella pertussis antigens: Pertussis toxoid (PT)¹ 25 micrograms, Filamentous haemagglutinin (FHA)¹ 25 micrograms, Pertactin (PRN)¹ 8 micrograms.
Poliovirus (inactivated) (IPV): 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.
¹adsorbed on aluminium hydroxide, hydrated (Al(OH)3) 0.5 milligrams Al³⁺.
²propagated in VERO cells.
Upon storage, a white deposit and clear supernatant can be observed. This does not constitute a sign of deterioration.
Excipients/Inactive Ingredients: Sodium chloride, Medium 199 (as stabilizer containing amino acids, mineral salts and vitamins), water for injections.
Neomycin sulphate and polymyxin B sulphate are present as residuals from the manufacturing process.

Pharmacotherapeutic Group: Combined bacterial and viral vaccines. ATC Code: J07CA02.
Pharmacology: Pharmacodynamics: Immune response to the DT components: One month after a primary vaccination course, more than 99% of infants vaccinated with Infanrix-IPV had antibody titres of ≥ 0.1 IU/ml to both tetanus and diphtheria.
Following administration of a booster dose of Infanrix-IPV, more than 99.5% of children had antibody titres of ≥ 0.1 IU/ml for both antigens.
Immune response to the Pa component: One month after the 3-dose primary vaccination course with Infanrix-IPV, 100% of infants were seropositive for the three pertussis components (PT, FHA, pertactin), and the overall response rates for each of the three individual pertussis antigens were ≥ 94%.
A booster response was seen in the vast majority of vaccinees against the pertussis antigens; lower response rates were seen in studies where the pre-vaccination levels of antibodies were high. All subjects were seropositive 1 month after this dose.
Protective efficacy of the Pa component: As the immune response to pertussis antigens following Infanrix-IPV administration is equivalent to that of Infanrix, it can be assumed that the protective efficacy of the two vaccines will also be equivalent.
The clinical protection of the DTPa component, against WHO-defined typical pertussis (≥ 21 days of paroxysmal cough) was demonstrated in: A prospective blinded household contact study performed in Germany (3, 4, 5 months schedule). Based on data collected from secondary contacts in households where there was an index case with typical pertussis, the protective efficacy of the vaccine was 88.7%; a NIH sponsored efficacy study performed in Italy (2, 4, 6 months schedule), the vaccine efficacy was found to be 84%. In a follow-up of the same cohort, the efficacy was confirmed for up to 4 years of age.
Immune response to the IPV component: One month after the primary vaccination, the overall seropositivity for each of the three serotypes (type 1, 2 and 3) was ≥ 99.5%.
Following administration of a booster dose of Infanrix-IPV, 100% of children were seropositive for the three serotypes.
In all booster trials, vaccination induced a marked increase in antibody levels with respect to pre-booster values.
Pharmacokinetics: Evaluation of pharmacokinetic properties is not required for vaccines.

Infanrix-IPV is indicated for active immunisation in infants from the age of 2 months against diphtheria, tetanus, pertussis and poliomyelitis.
Infanrix-IPV is also indicated as a booster dose for children who have previously been immunised with diphtheria, tetanus, pertussis (DTP) and polio antigens.

Posology: The primary vaccination schedule consists of three doses in the first year of life and can start from the age of 2 months. An interval of at least 1 month should be respected between subsequent doses.
When the primary course is completed before the age of 6 months, a booster dose can be given in the second year of life. An interval of at least 6 months after completion of primary vaccination schedule should be respected. Data on the use of the vaccine as a booster has been obtained for children up to the age of 13 years.
Infanrix-IPV should be used in accordance with available official recommendations.
Method of administration: Infanrix-IPV is for deep intramuscular injection. For infants, the preferred site of injection is the anterolateral aspect of the thigh; in older children, vaccine should be administered in the deltoid.
It is preferable that each subsequent dose is given at alternate sites.
Infanrix-IPV should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramascular administration to these subjects. Firm pressure should be applied to the injection site (without rubbing) for at least two minutes.

Cases of overdose have been reported during post-marketing surveillance. Adverse events, when reported, are not specific but similar to adverse events reported with normal vaccine administration.

Infanrix-IPV should not be administered to subjects with known hypersensitivity to any component of the vaccine or to subjects having shown signs of hypersensitivity after previous administration of diphtheria, tetanus, pertussis, or inactivated polio vaccines.
Infanrix-IPV 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 should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection, however, is not a contra-indication.
It is good clinical practice that vaccination should be preceded by a review of the medical history (especially with regard to previous vaccination and possible occurrence of undesirable events) and a clinical examination.
If any of the following events occur in temporal relation to receipt of DTP-containing vaccine, the decision to give subsequent doses of vaccine containing the pertussis component should be carefully considered. 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 benefit ratio of acellular pertussis vaccine is better than the risk benefit ratio of whole cell pertussis vaccine. The following events were previously considered contra-indications for DTPw and can now be considered precautions: 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.
In children with progressive neurological disorders, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy, it is better to defer pertussis (Pa or Pw) immunization until the condition is corrected or stable. However, the decision to give pertussis vaccine must be made on an individual basis after careful consideration of the risks and benefits.
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 and/or IPV vaccination do not constitute contra-indications.
Human immunodeficiency Virus (HIV) infection is not considered as a contra-indication.
The expected immunological response may not be obtained after vaccination of immunosuppressed patients, e.g. patients on immunosuppressive therapy.
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.
Infanrix-IPV contains traces of neomycin and polymyxin. The vaccine should be used with caution in patients with known hypersensitivity to one of these antibiotics.
As with all diphtheria, tetanus, and pertussis vaccines, the vaccine should be given deep intramuscularly.
Infanrix-IPV should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.
Infanrix-IPV should under no circumstances be administered intravenously.
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.
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.
Use in Pregnancy & Lactation: Adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.
Use in Children: 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.
Effects on the Ability to Drive and Use Machines: Not applicable.

Adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Clinical trials data: The safety profile presented as follows is based on data from more than 2,200 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 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.
Blood and lymphatic system disorders: Rare: lymphadenopathy¹.
Metabolism and nutrition disorders: Very common: appetite lost.
Psychiatric disorders: Very common: restlessness, crying abnormal, irritability.
Nervous system disorders: Very common: headache¹ (age range 6-13 years old), somnolence.
Respiratory, thoracic and mediastinal disorders: Rare: bronchitis², cough².
Gastrointestinal disorders: Common: nausea¹, vomiting, diarrhoea.
Skin and subcutaneous tissue disorders: Uncommon: dermatitis allergic.
Rare: urticaria, rash^2,3.
General disorders and administration site conditions: Very common: injection site reactions such as pain, redness, local swelling at the injection site (≤ 50 mm), fever ≥ 38.0°C.
Common: local swelling at the injection site (> 50 mm)⁴, asthenia, malaise¹, injection site reactions including induration.
Uncommon: diffuse swelling of the injected limb, sometimes involving the adjacent joint⁴, fever⁵ (> 39.5°C).
Post-marketing data: Blood and lymphatic system disorders: Thrombocytopenia⁶.
Immune system disorders: Allergic reactions, including anaphylactic² and anaphylactoid reactions.
Nervous system disorders: Collapse or shock-like state (hypotonic-hyporesponsiveness episode), convulsions (with or without fever) within 2 to 3 days of vaccination.
Respiratory disorders, thoracic and mediastinal disorders: Apnoea² (see Use in Children under Precautions).
Skin and subcutaneous tissue disorders: Pruritus, angioneurotic oedema².
General disorders and administration site conditions: Swelling of the entire injected limb⁴, injection site vesicles.
¹ reported only with booster vaccination.
² reported with GSK's DTPa containing vaccines.
³ uncommonly reported with booster vaccination.
⁴ 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. Local swelling at the injection site (>50 mm) and diffuse swelling may be more frequent (very common and common, respectively) when the booster dose is administered between 4 and 6 years. These reactions resolve over an average of 4 days.
⁵ commonly reported with booster vaccination.
⁶ reported with D and T vaccines.

It is routine practice in paediatric vaccination to coadminister different vaccines during the same session, where injectable vaccines should always be given at different injection sites.
Infanrix-IPV can be administered concomitantly with measles, mumps, rubella, varicella hepatitis B, and Haemophilus influenzae type b vaccines. 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.

Incompatibilities: Infanrix-IPV should not be mixed with other vaccines in the same syringe.
Instructions for Use and Handling: Infanrix-IPV should be inspected visually for any foreign particulate matter and/or variation of physical aspect prior to administration. In the event of either being observed, discard the vaccine.
Since a white sediment may form during storage, Infanrix-IPV suspension should be well shaken.
Any unused product or waste material should be disposed of in accordance with local requirements.

Infanrix-IPV vaccine has to be stored at +2°C to +8°C.
The Infanrix-IPV vaccine should not be frozen. Discard if it has been frozen.

Vaccines, Antisera & Immunologicals

J07CA02 - diphtheria-pertussis-poliomyelitis-tetanus ; Belongs to the class of combined bacterial and viral vaccines.

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