Adverse reactions : תופעות לוואי

4.8       Undesirable effects

The frequencies provided in the table below are per vaccination and have been calculated based on a pooled analysis of adverse reactions from 7 clinical studies conducted with TicoVac 0.5 mL (2.4 µg) in subjects aged 16 through 65 years receiving 3 vaccinations (3512 subjects after the first vaccination, 3477 after the second vaccination, and 3274 after the third vaccination).
The ADRs 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        (1/1,000 to <1/100)           (1/10,000 to <1/10)                                           <1/1,000)
Blood and lymphatic                                                 Lymphadenopathy system disorders
Immune system                                                                                  Hypersensitivity disorders
Nervous system                                  Headache                                       Somnolence disorders
Ear and labyrinth                                                                              Vertigo1 disorders
Gastrointestinal                                Nausea              Vomiting                   Diarrhoea disorders                                                                                      Abdominal pain Musculoskeletal and                             Myalgia connective tissue                               Arthralgia disorders
General disorders       Injection site          Fatigue             Pyrexia                    Injection site reactions and administration      reactions               Malaise             Injection site             such as site conditions         e.g., Injection site                        hemorrhage                      • Erythema pain                                                                        • Induration • Swelling
• Pruritus
• Paraesthesia
• Warmth

Adverse reactions from post-marketing surveillance
1
The frequency of vertigo is based on the rate reported after the first vaccination (n=3512). Vertigo was not reported after the second or third vaccinations.

The following additional adverse reactions have been reported in post-marketing experience.

System organ class                                              Frequency* Rare (1/10,000 to <1/1,000)
Infections and infestations                          Herpes zoster (triggered in pre-exposed patients) 
Immune system disorders                              Precipitation or aggravation of autoimmune disorders (e.g.
multiple sclerosis), anaphylactic reaction
Nervous system disorders                             Demyelinating disorders (acute disseminated encephalomyelitis, guillain-barré syndrome, myelitis,
transverse myelitis), encephalitis, convulsions, aseptic meningitis, meningism, sensory abnormalities and motor dysfunction (facial palsy/paresis, paralysis/paresis, neuritis,
hypoesthesia, paresthesia), neuralgia, optic neuritis, dizziness
Eye disorders                                        Visual impairment, photophobia, eye pain 
Ear and labyrinth disorders                          Tinnitus

Cardiac disorders                                    Tachycardia
Respiratory, thoracic and mediastinal disorders      Dyspnea

Skin and subcutaneous tissue disorders                Urticaria, rash (erythematous, maculopapular), pruritus, dermatitis, erythema, hyperhidrosis
Musculoskeletal and connective tissue disorders Back pain, joint swelling, neck pain, musculoskeletal stiffness (including neck stiffness), pain in extremity
General disorders and administration site                Gait disturbance, chills, influenza-like illness, asthenia, edema, conditions                                               injection site joint movement impairment such as joint pain, nodule and inflammation
* 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 0.5 ml. Therefore, the calculated frequency “rare” represents the theoretical maximum frequency for these events

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.

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/