Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Adverse reactions caused by human normal immunoglobulins (in decreasing frequency) encompass (see also Section 4.4):
• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain
• reversible haemolytic reactions; especially in those patients with blood groups A, B, and AB and (rarely) haemolytic anaemia requiring transfusion
• (rarely) a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration • (rarely) transient cutaneous reactions (including cutaneous lupus erythematosus - frequency unknown)
• (very rarely) thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thromboses
• cases of reversible aseptic meningitis
• cases of increased serum creatinine level and/or occurrence of acute renal failure • cases of Transfusion Related Acute Lung Injury (TRALI)

The safety of Ig VENA was evaluated in four clinical trials in which a total of 1189 infusions was administered. The CIDP study enrolled 24 patients with Chronic Inflammatory Demyelinating Poliradiculoneuropathy (CIDP) receiving Ig VENA, for a total of 840 infusions administered. In the PID study, 16 patients with Primary Immunodeficiency (PID) were enrolled and received a total of 145 infusions. The ITP study enrolled 15 subjects with Immune Thrombocytopenia (ITP) with a total of 80 infusions administered. In the ID/ITP study, 43 patients with either Immunodeficiency (ID) or ITP were enrolled and received a total of 124 infusions.

Tabulated list of adverse reactions
The tables presented below are according to the MedDRA system organ classification (SOC and Preferred Term Level).
Table 1 shows the adverse reactions from clinical trials and Table 2 shows the post-marketing adverse reactions.
Frequencies have been evaluated according to the following convention: 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).
Frequencies of undesirable effects from clinical trials are based on percentage per infusions (total 
number of infusions: 1189).
Adverse reactions from post-marketing experience are listed with unknown frequency as post- marketing reporting of adverse reactions is voluntary and from a population of uncertain size and it is not possible to reliably estimate the frequency of these reactions.

Source of the safety database (e.g. from clinical trials, post-authorisation safety studies and/or spontaneous reporting)


Table 1
Frequency of Adverse Reactions from Clinical Trials
MedDRA System Organ Class Adverse reaction Frequency per                       Frequency per (SOC)                                              patient                     infusion Nervous system disorders       Headache,           Common                      Rare somnolence
Gastrointestinal disorders        Nausea               Common                  Rare 
Musculoskeletal and connective    Back pain            Common                  Uncommon tissue disorders
Myalgia              Common                  Rare
General     disorders      and    Asthenia, fatigue,   Common                  Rare administration site conditions    pyrexia


Table 2
Post-marketing Adverse Reactions
Frequency per       Frequency per
MedDRA SOC                     Adverse reaction patient             infusion
Infections and infestations    Meningitis aseptic        Not known           Not known Blood and lymphatic system     Haemolysis,               Not known
Not known disorders                      haemolytic anaemia
Immune system disorders        Anaphylactic shock,       Not known
Not known hypersensitivity
Psychiatric disorders          Confusional state         Not known           Not known Nervous system disorders       Cerebrovascular           Not known accident, headache,
Not known dizziness, tremor,
paraesthesia
Cardiac disorders              Myocardial infarction,    Not known cyanosis, tachycardia,
Not known bradycardia,
palpitations
Vascular disorders             Deep vein thrombosis,     Not known embolism,
Not known hypotension,
hypertension, pallor
Respiratory, thoracic and      Pulmonary embolism,       Not known           Not known Table 2
Post-marketing Adverse Reactions
Frequency per   Frequency per
MedDRA SOC                        Adverse reaction patient         infusion mediastinal disorders             pulmonary oedema,
bronchospasm,
dyspnoea, cough
Gastrointestinal disorders        Vomiting, diarrhoea,         Not known nausea, abdominal                            Not known pain
Skin and subcutaneous tissue      Angioedema, urticaria,       Not known disorders                         erythema, dermatitis,
Not known rash, pruritus, eczema,
hyperhidrosis
Musculoskeletal and               Arthralgia, back pain,       Not known connective tissue disorders       myalgia, neck pain,
Not known muscoloskeletal stiffness
Renal and urinary disorders       Acute kidney injury          Not known       Not known General disorders and             Injection site phlebitis,    Not known administration site conditions    pyrexia, chills, chest
Not known pain, face oedema,
malaise
Investigations                    Blood pressure               Not known decreased, blood                             Not known creatinine increased

For safety with respect to transmissible agents, see section 4.4.

Paediatric population
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults.
Transient glycosuria has been observed after administration of Ig VENA in paediatric patients.
This event could be due to the maltose contained in Ig VENA and to the different capacity of renal tubules to reabsorb glucose, that is an age dependent mechanism.

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 Kamada Ltd. to email address: pharmacovigilance@kamada.com