Infanrix Hexa: Data Sheet Information

Ingredients:

Diphtheria toxoids, tetanus toxoid, pertussis toxoid, pertussis antigen, hepatitis B surface antigens, polio viruses types 1, 2 and 3, hib polysaccharides, tetanus toxoid carrier protein.  Excipients: Lactose anhydrous Sodium chloride  Medium 199 containing principally amino acids, mineral salts, vitamins Water for injections  Adsorbed aluminium phosphate, propagated on vero (monkey) cells. May contain traces of formaldehyde, neomycin and polymyxin (antibiotics),

Paediatric population

The safety and efficacy of Infanrix hexa in children over 36 months of age have not been established.  No data are available.

Contraindications:

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or formaldehyde, neomycin and polymyxin.

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

Infanrix hexa is contraindicated if the infant or toddlers has experienced an encephalopathy of unknown aetiology, occurring within 7 days following previous vaccination with pertussis containing vaccine. In these circumstances pertussis vaccination should be discontinued and the vaccination course should be continued with diphtheria-tetanus, hepatitis B, polio and Hib vaccines.

As with other vaccines, administration of Infanrix hexa should be postponed in subjects suffering from acute severe febrile illness.

These Used to Be Contraindications Rather Than Warnings:

If any of the following events are known to have occurred in temporal relation to receipt of pertussiscontaining vaccine, the decision to give further doses of pertussis-containing vaccines 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 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.

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.

As for any vaccination, the risk-benefit of immunising with Infanrix hexa 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. Infanrix hexa should be administered with caution to subjects with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration to these subjects.

Vaccinees with a history of febrile convulsions should be closely followed up as such adverse events may occur within 2 to 3 days post vaccination.

Higher Risk of Seizure with Multiple Vaccines

The physician should be aware that the rate of febrile reactions is higher when Infanrix hexa is coadministered with a pneumococcal conjugate vaccine (PCV7, PCV10, PCV13), or with a measlesmumps-rubella-varicella (MMRV) vaccine, compared to that occurring following the administration of Infanrix hexa alone. These reactions were mostly moderate (less than or equal to 39°C) and transient (see sections 4.5 and 4.8).

Increased reporting rates of convulsions (with or without fever) and hypotonic hyporesponsive episode (HHE) were observed with concomitant administration of Infanrix hexa and Prevenar 13 (see section 4.8).

Lower Immune Response and Risk of Apnea in Premature Babies

Clinical data indicate that Infanrix hexa can be given to preterm infants, however, as expected in this population, a lower immune response has been observed for some antigens (see section 4.8 and section 5.1).

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 preterm infants (born ≤ 28 weeks of gestation) and particularly for those with a previous history of respiratory immaturity.

Co-Administration, Seizures and Fevers

Data from clinical studies indicate that, when Infanrix hexa is co-administered with pneumococcal conjugate vaccine, the rate of febrile reactions is higher compared to that occurring following the administration of Infanrix hexa alone. Data from one clinical study indicate that when Infanrix hexa is
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co-administered with measles-mumps-rubella-varicella (MMRV) vaccine, the rate of febrile reactions is higher compared to that occurring following the administration of Infanrix hexa alone and similar to that occurring following the administration of MMRV vaccine alone (see sections 4.4 and 4.8). The immune responses were unaffected.

As with other vaccines it may be expected that in patients receiving immunosuppressive therapy, an adequate response may not be achieved.

4.6 Fertility, pregnancy and lactation

As Infanrix hexa is not intended for use in adults, adequate human data on use during pregnancy or lactation and adequate animal reproduction studies are not available.

Side-Effects

System Organ Class Frequency Adverse reactions Infections and infestations, Upper respiratory tract infection Blood and lymphatic system disorders, Lymphadenopathy, thrombocytopenia, Immune system disorders, Anaphylactic reactions, anaphylactoid reactions (including urticaria), Allergic reactions (including pruritus), Metabolism and nutrition disorders,  Appetite lost,  Psychiatric disorders, Crying abnormal, irritability, restlessness,  Nervousness, Nervous system disorders, Somnolence, Collapse or shock-like state (hypotonichyporesponsive episode), Convulsions (with or without fever) Respiratory, thoracic and mediastinal disorders, Cough Rare Bronchitis, apnoea, Gastrointestinal disorders, Common Diarrhoea, vomiting Skin and subcutaneous tissue disorders, Rash, Angioedema, Dermatitis, General disorders and administration site conditions, Fever ≥ 38°C, local swelling at the injection site (≤ 50 mm), fatigue, pain, redness, Fever >39.5°C, 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, Swelling of the entire injected limb, extensive swelling reactions, injection site mass, injection site vesicles, 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.

Experience with hepatitis B vaccine:

In extremely rare cases, allergic reactions mimicking serum sickness, paralysis, neuropathy, neuritis, hypotension, vasculitis, lichen planus, erythema multiforme, arthritis, muscular weakness, GuillainBarré syndrome, encephalopathy, encephalitis and meningitis have been reported. The causal relationship to the vaccine has not been established.

• Experience in co-administration:

Analysis of postmarketing reporting rates suggests a potential increased risk of convulsions (with or without fever) and HHE when comparing groups which reported use of Infanrix hexa with Prevenar 13 to those which reported use of Infanrix hexa alone.

In clinical studies in which some of the vaccinees received Infanrix hexa concomitantly with Prevenar (PCV7) as a booster (4th) dose of both vaccines, fever ≥ 38.0°C was reported in 43.4% of infants receiving Prevenar and Infanrix hexa at the same time as compared to 30.5% of infants receiving the hexavalent vaccine alone. Fever ≥39.5°C was observed in 2.6% and 1.5% of infants receiving Infanrix hexa with or without Prevenar, respectively (see sections 4.4 and 4.5). The incidence and severity of fever following co-administration of the two vaccines in the primary series was lower than that observed after the booster dose.

Data from clinical studies show similar incidences of fever when Infanrix hexa is co-administered with other pneumococcal saccharide conjugated vaccine.
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In a clinical study in which some of the vaccinees received a booster dose of Infanrix hexa concomitantly with measles-mumps-rubella-varicella (MMRV) vaccine, fever ≥ 38.0°C was reported in 76.6% of children receiving MMRV vaccine and Infanrix hexa at the same time, as compared to 48% of children receiving Infanrix hexa alone and 74.7% of children receiving MMRV vaccine alone. Fever of greater than 39.5°C was reported in 18% of children receiving Infanrix hexa with MMRV vaccine, as compared to 3.3% of children receiving Infanrix hexa alone and 19.3% of children receiving MMRV alone (see sections 4.4 and 4.5).

See full Data Sheet: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000296/WC500032505.pdf