Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile

As has been observed for DTPa and DTPa-containing combinations, an increase in local reactogenicity and fever was reported after booster vaccination with Infanrix hexa with respect to the primary course.

Tabulated summary of adverse reactions

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

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)
The following drug-related adverse reactions were reported in clinical studies (data from more than 16,000 subjects) and during post-marketing surveillance.

System Organ Class                     Frequency        Adverse reactions Infections and infestations            Uncommon         Upper respiratory tract infection Blood and lymphatic system             Rare             Lymphadenopathy2, disorders                                               thrombocytopenia2 Immune system disorders                Rare             Anaphylactic reactions2, anaphylactoid reactions (including urticaria)2
Allergic reactions (including pruritus)2
Metabolism and nutrition disorders     Very             Appetite lost common
Psychiatric disorders                  Very             Crying abnormal, irritability, common           restlessness
Common           Nervousness
Nervous system disorders                Very            Somnolence common
Rare             Collapse or shock-like state
(hypotonic- hyporesponsive episode)2
Very rare        Convulsions (with or without fever)
Uncommon         Cough

Respiratory, thoracic and              Rare            Bronchitis, Apnoea2 [see section 4.4 mediastinal disorders                                  for apnoea in very preterm infants (≤ 28 weeks of gestation)]
Gastrointestinal disorders             Common          Diarrhoea, vomiting Skin and subcutaneous tissue           Rare            Rash, Angioedema2 disorders                              Very rare       Dermatitis
General disorders and                  Very            Fever  38°C, pain, redness, local administration site conditions         common          swelling at the injection site (≤ 50 mm)
Common          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 joint1, fatigue
Rare            Swelling of the entire injected limb1,
2
, extensive swelling reactions2,
injection site mass2, injection site vesicles2
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
Adverse reactions from spontaneous reporting.

• 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.

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).

• Safety in preterm infants:

Infanrix hexa has been administered to more than 1000 preterm infants (born after a gestation period of 24 to 36 weeks) in primary vaccination studies and in more than 200 preterm infants as a booster dose in the second year of life. In comparative clinical studies, similar rates of symptoms were observed in preterm and full-term infants (refer to section 4.4 for information on apnoea).

• 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, Guillain-Barré syndrome, encephalopathy, encephalitis and meningitis have been reported. The causal relationship to the vaccine has not been established.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/ Additionally, you should also report to GSK Israel, (il.safety@gsk.com).