Adverse reactions : תופעות לוואי

4.8         Undesirable effects
Summary of the safety profile

The safety of Bexsero was evaluated in 17 studies including 10 randomised controlled clinical trials with 10565 subjects (from 2 months of age) who received at least one dose of Bexsero. Among Bexsero recipients, 6837 were infants and children (less than 2 years of age), 1051 were children (2 to 10 years of age) and 2677 were adolescents and adults.
Of the subjects who received primary infant series of Bexsero, 3285 received a booster dose in the second year of life.

In infants and children (less than 2 years of age) the most common local and systemic adverse reactions observed in clinical trials were tenderness and erythema at the injection site, fever and irritability.

In clinical studies in infants vaccinated at 2, 4 and 6 months of age, fever (≥ 38°C) was reported by 69% to 79% of subjects when Bexsero was co-administered with routine vaccines (containing the following antigens: pneumococcal 7-valent conjugate, diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenzae type b) compared with 44% to 59% of subjects receiving the routine vaccines alone. Higher rates of antipyretic use were also reported for infants vaccinated with Bexsero and routine vaccines. When Bexsero was given alone, the frequency of fever was similar to that associated with routine infant vaccines 
administered during clinical trials. When fever occurred, it generally followed a predictable pattern, with the majority resolving by the day after vaccination.

In adolescents and adults the most common local and systemic adverse reactions observed were pain at the injection site, malaise and headache.

No increase in the incidence or severity of the adverse reactions was seen with subsequent doses of the vaccination series.

Tabulated list of adverse reactions

Adverse reactions (following primary immunisation or booster dose) considered as being at least possibly related to vaccination have been categorised by frequency.

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.

In addition to reports in clinical trials, worldwide voluntary reports of adverse reactions received for Bexsero since market introduction are included in the list. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency and they are consequently listed with the frequency unknown.

Infants and children (up to 10 years of age)
Blood and lymphatic system disorders
Not known: lymphadenopathy

Immune system disorders
Not known: allergic reactions (including anaphylactic reactions)

Metabolism and nutrition disorders
Very common: eating disorders

Nervous system disorders
Very common: sleepiness, unusual crying, headache
Uncommon: seizures (including febrile seizures)
Not known: hypotonic-hyporesponsive episode , meningeal irritation (signs of meningeal irritation, such as neck stiffness or photophobia, have been sporadically reported shortly after vaccination. These symptoms have been of mild and transient nature) 
Vascular disorders
Uncommon: pallor (rare after booster)
Rare: Kawasaki syndrome

Gastrointestinal disorders
Very common: diarrhoea, vomiting (uncommon after booster)
Skin and subcutaneous tissue disorders
Very common: rash (children aged 12 to 23 months) (uncommon after booster) Common: rash (infants and children 2 to 10 years of age)
Uncommon: eczema
Rare: urticaria

Musculoskeletal and connective tissue disorders
Very common: arthralgia

General disorders and administration site conditions
Very common: fever (≥38°C), injection site tenderness (including severe injection site tenderness defined as crying when injected limb is moved), injection site erythema, injection site swelling, injection site induration, irritability
Uncommon: fever (≥40°C)
Not known: injection site reactions (including extensive swelling of the vaccinated limb, blisters at or around the injection site and injection site nodule which may persist for more than one month)

Adolescents (from 11 years of age) and adults
Blood and lymphatic system disorders
Not known: lymphadenopathy

Immune system disorders
Not known: allergic reactions (including anaphylactic reactions)

Nervous system disorders
Very common: headache
Not known: syncope or vasovagal responses to injection , meningeal irritation (signs of meningeal irritation, such as neck stiffness or photophobia, have been sporadically reported shortly after vaccination. These symptoms have been of mild and transient nature)


Gastrointestinal disorders
Very common: nausea
Skin and subcutaneous tissue disorders
Not known: rash

Musculoskeletal and connective tissue disorders
Very common: myalgia, arthralgia

General disorders and administration site conditions
Very common: injection site pain (including severe injection site pain defined as unable to perform normal daily activity), injection site swelling, injection site induration, injection site erythema, malaise
Not known: fever, injection site reactions (including extensive swelling of the vaccinated limb, blisters at or around the injection site and injection site nodule which may persist for more than one month)


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).