Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile

The safety of IXIARO was assessed in controlled and uncontrolled clinical studies in 5,021 healthy adults (from non-endemic countries) and 1,559 children and adolescents (mostly from endemic countries). Approximately 40% of treated subjects experienced systemic adverse reactions and approximately 54% experienced injection site reactions. They usually occur within the first three days after vaccination, are usually mild and resolve within a few days. No increase in the number of adverse reactions was noted between first and second doses or following a booster dose in adults.
Most commonly reported adverse reactions in adults included headache (20% of subjects), myalgia (13%), injection site pain (33%), injection site tenderness (33%) and fatigue (12.9%).

Most commonly reported adverse reactions in children and adolescents included pyrexia, diarrhoea, influenza like illness, irritability, injection site pain, injection site tenderness, and injection site redness (see table 1).

Adverse reactions are listed according to the following frequencies:
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

Adult and older adults (≥65 years) population

Blood and lymphatic system disorders
Uncommon: lymphadenopathy
Rare: thrombocytopenia

Nervous system disorders
Very common: headache
Uncommon: migraine, dizziness
Rare: paraesthesia, neuritis, dysgeusia, syncope*
Ear and labyrinth disorders
Uncommon: vertigo

Eye disorders
Rare: eyelid oedema

Cardiac disorders
Rare: palpitations, tachycardia
Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea
Gastrointestinal disorders
Common: nausea
Uncommon: vomiting, diarrhoea, abdominal pain

Skin and subcutaneous tissue disorders
Uncommon: rash, pruritus, hyperhidrosis
Rare: urticaria, erythema

Musculoskeletal and connective tissue disorders
Very common: myalgia
Uncommon: musculoskeletal stiffness, arthralgia
Rare: pain in extremity
General disorders and administration site conditions
Very common: injection site pain, injection site tenderness, fatigue
Common: influenza-like illness, pyrexia, other injection site reactions e.g. redness, hardening, swelling, itching
Uncommon: chills, malaise, asthenia
Rare: oedema peripheral

Investigations
Uncommon: hepatic enzymes increased

*reported also from post-marketing experience

Paediatric population (2 months to <18 years of age)

Table 1: Frequency of adverse reactions observed in children given the 0.25 ml dose (2 months to <3 years of age) and in children and adolescents given the 0.5 ml dose (3 years to <18 years of age)

Frequency of adverse reactions(%) by dose/age
System Organ Class                           0.25 ml                    0.5 ml Preferred Term                               N=783                      N=628 2 months to <3 years         3 to <18 years
Blood and Lymphatic System
Disorders
Lymphadenopathy                                  0.1                         0.0 Metabolism and Nutrition
Disorders
Decreased appetite                               8.2                         1.9 Nervous System Disorders
Headache                                         2.9                         6.1 Respiratory, Thoracic and
Medistinal Disorders
Cough                                            0.5                         0.3 Gastrointestinal Disorders
Diarrhoea                                        11.9                        1.4 Vomiting                                         7.3                         1.9 Nausea                                           3.9                         1.9 Abdominal pain                                   0.1                         0.0 Skin and Subcutaneous Tissue
Disorders
Rash                                             6.3                         1.4 Musculoskeletal and Connective
Tissue Disorders
Myalgia                                          3.0                         7.1 General Disorders and
Administration Site Conditions
Pyrexia                                         28.5                        10.4 Influenza-like illness                          10.9                        2.9 Irritability                                    10.9                        1.9 Fatigue                                         3.5                         3.5 Injection site redness                          10.0                        4.1 Injection site pain                             6.1                         14.1 Injection site tenderness                       4.2                         14.7 Injection site swelling                         3.6                         2.2 Injection site hardening                        1.2                         1.9 Injection site itching                          0.6                         1.6 Investigations
Hepatic enzymes increased                        0.5                         0.2 
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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@m oh.gov.il
Additionally, you can also report to Kamada Ltd. to email address: pharmacovigilance@kamada.com