Adverse reactions : תופעות לוואי

4.8 Undesirable effects

Summary of the safety profile
In clinical studies, the most frequently reported reactions in subjects 4 to 60 years of age were injection site pain (50%), headache (35%), myalgia (31%), injection site erythema (27%), malaise (24%), asthenia (20%) and fever (11%).

These adverse reactions usually occurred within 2 days after the injection, were mild to moderate in severity, had a short duration (1 to 3 days) and were less frequent after the second injection of Qdenga than after the first injection.

Vaccine viremia

In clinical study DEN-205, transient vaccine viremia was observed after vaccination with Qdenga in 49% of study participants who had not been infected with dengue before and in 16% of study participants who had been infected with dengue before. Vaccine viremia usually started in the second week after the first injection and had a mean duration of 4 days. Vaccine viremia was associated with transient, mild to moderate symptoms, such as headache, arthralgia, myalgia and rash in some subjects. Vaccine viraemia was rarely detected after the second dose.
Dengue diagnostic tests may be positive during vaccine viremia and cannot be used to distinguish vaccine viremia from wild type dengue infection.


Tabulated list of adverse reactions
Adverse reactions associated with Qdenga obtained from clinical studies are tabulated below (Table 1).

The safety profile presented below is based on a pooled analysis including 14,627 study participants aged 4 to 60 years (13,839 children and 788 adults) who have been vaccinated with Qdenga. This included a reactogenicity subset of 3,830 participants (3,042 children and 788 adults).

Adverse reactions are listed according to the following frequency categories: 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

Table 1: Adverse reactions from Clinical Studies (Age 4 to 60 years)

MedDRA System Organ Class               Frequency                  Adverse Reactions Infections and infestations             Very common                Upper respiratory tract infectiona Common                     Nasopharyngitis
Pharyngotonsillitisb
Uncommon                   Bronchitis
Rhinitis
Metabolism and nutrition                Very common                Decreased appetitec disorders
Psychiatric disorders                   Very common                Irritabilityc Nervous system disorders                Very common                Headache Somnolencec
Uncommon                   Dizziness
Gastrointestinal disorders              Uncommon                   Diarrhoea Nausea
Abdominal pain
Vomiting
Skin and subcutaneous tissue            Uncommon                   Rashd disorders                                                          Prurituse Urticaria
Very rare                  Angioedema
Musculoskeletal and connective          Very common                Myalgia tissue disorders                        Common                     Arthralgia General disorders and                   Very common                Injection site pain administration site conditions                                     Injection site erythema Malaise
Asthenia
Fever
Common                     Injection site swelling
Injection site bruisinge
Injection site prurituse
Influenza like illness
Uncommon                   Injection site haemorrhagee
Fatiguee
Injection site discolouratione a
Includes upper respiratory tract infection and viral upper respiratory tract infection b
Includes pharyngotonsillitis and tonsillitis c
Collected in children below 6 years of age in clinical studies

d
Includes rash, viral rash, rash maculopapular, rash pruritic e
Reported in adults in clinical studies

Paediatric population
Paediatric data in subjects 4 to 17 years of age

Pooled safety data from clinical trials are available for 13839 children (9210 aged 4 to 11 years and 4629 aged 12 to 17 years). This includes reactogenicity data collected in 3042 children (1865 aged 4 to
11 years and 1177 aged 12 to 17 years).

Frequency, type and severity of adverse reactions in children were largely consistent with those in adults. Adverse reactions reported more commonly in children than in adults were fever (11% versus 3%), upper respiratory tract infection (11% versus 3%), nasopharyngitis (6% versus 0.6%), pharyngotonsillitis (2% versus 0.3%), and influenza like illness (1% versus 0.1%). Adverse reactions reported less commonly in children than adults were injection site erythema (2% versus 27%), nausea (0.03% versus 0.8%) and arthralgia (0.03% versus 1%).

The following reactions were collected in 357 children below 6 years of age vaccinated with Qdenga: decreased appetite (17%), somnolence (13%) and irritability (12%).


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