Adverse reactions : תופעות לוואי

4.8          Undesirable effects

The calculated frequencies are based on a pooled analysis of adverse reactions reported after the 1st vaccination (3088 subjects) from 8 clinical studies conducted with TicoVac Junior 0.25 ml (1.2 µg) in subjects aged 1-15 years of age. Rates of systemic adverse reactions observed after the 2nd and 3rd vaccination were lower than after the 1st vaccination. Comparable rates of injection site reactions are observed after the first, second and third vaccination.

The following other undesirable effects listed in this Section are given according to the recommended frequency convention:

Adverse Reactions from clinical trials
System organ class                                                          Frequency Very common                    Common                Uncommon              Rare (1/10)                (1/100 to <1/10)   (1/1,000 to <1/100)    (1/10,000 to <1/1,000)
Blood and lymphatic                                                                     Lymphadenopathy system disorders
Metabolism and nutrition                                           Decreased Appetite disorders
Psychiatric disorders                                              Restlessness1, Sleeping disorder
Nervous system disorders                                           Headache                                    Sensory abnormalities,
Dizziness
Ear and labyrinth                                                                                              Vertigo disorders
Gastrointestinal disorders                                         Nausea,              Abdominal pain         Diarrhoea, Vomiting                                    Dyspepsia
Skin and subcutaneous                                                                                          Urticaria tissue disorders
Musculoskeletal and                                                Myalgia              Arthralgia connective tissue disorders

1
Frequency is estimated based on data from children aged 1-5 years

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General disorders and                 Injection site            Pyrexia3,                   Chills                         Injection site administration site                   reactions2 e.g.,                              4                                      pruritus Fatigue, Malaise conditions
Injection site pain
Injection site reactions such as
•        Swelling
•        Induration
•        Erythema

Fever was measured rectally in children up to at least 3 years of age and orally in children 3 years of age and older. The analysis includes any fever temporally associated with vaccination whether or not causally related.

Fever is age dependent and is decreasing with the number of vaccinations.
In a safety study and dose finding studies the fever rates observed after the first vaccination were as follows: 1 to 2 year olds (n=262): mild fever (38-39°C) in 27.9%; moderate fever (39.1-40.0°C) in 3.4%; no severe fever (>40°C). 3 to 15 year olds (n=2519): mild fever in 6.8%; moderate fever in 0.6%; no severe fever (>40°C).

Fever rates reported after the second vaccination are generally lower as compared to the fever rates after the first vaccination: 15.6% (41/263) in 1 to 2 year old children and 1.9% (49/2522) in 3 to 15 year old children.

Adverse reactions from post-marketing surveillance

The following additional adverse reactions have been reported in post-marketing experience.
System organ class                                                             Frequency* Rare (1/10,000 to <1/1,000)
Immune system disorders                                      Anaphylactic reaction, hypersensitivity Nervous system disorders                                     Encephalitis, convulsion (including febrile), meningism, polyneuropathy, motor dysfunction (hemiparesis/hemiplegia facial paresis, paralysis/paresis, neuritis), Guillain-Barré syndrome
Eye disorders                                                Visual impairment, photophobia, eye pain Ear and labyrinth disorders                                  Tinnitus Respiratory, thoracic and mediastinal                        Dyspnea disorders
Skin and subcutaneous tissue disorders                       Rash (erythematous, maculopapular, vesicular), erythema, pruritus, hyperhidrosis
Musculoskeletal and connective tissue                        Neck pain, musculoskeletal stiffness (including neck stiffness), disorders                                                    pain in extremity General disorders and administration site                    Gait disturbance, influenza-like illness, asthenia, edema conditions
* The upper limit of the 95% confidence interval of the event frequency is calculated with 3/n, with n representing the number of subjects included in all clinical trials with TicoVac Junior 0.25 ml. Therefore, the calculated frequency “rare” represents the theoretical maximum frequency for these events


2
A subject may have experienced more than 1 event.
3
Fevers occurred more frequently in younger than in older children (i.e., Very common to Common, respectively). Fever rates after the second and third vaccinations are generally lower than after the first vaccination.
4
Frequency is estimated based on data from children aged 6 – 15 years.

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In a small comparative study on the immune response after intramuscular and subcutaneous administration of Ticovac in healthy adults, the subcutaneous route led to a higher local reactogenicity profile, particularly in women. No data are available in children.

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/.