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

Tabulated list of adverse reactions
Suspected Adverse Drug Reactions reported in completed clinical trials: 
Three clinical studies have been performed with Intratect 50 g/l: two in patients with primary immunodeficiencies (PID) and one in patients with immune thrombocytopenic purpura (ITP). In the two PID studies overall 68 patients were treated with Intratect 50 g/l and evaluated for safety. Treatment period was 6 and 12 months respectively. The ITP study was performed in 24 patients.

These 92 patients received a total of 830 infusions of Intratect 50 g/l, whereby a total of 51 adverse drug reactions (ADRs) were recorded.

With Intratect 100 g/l one clinical study has been performed in patients with PID. 30 patients were treated with Intratect 100 g/l over 3 to 6 months and evaluated for safety. These 30 patients received a total of 165 infusions of Intratect 100 g/l, whereof a total of 19 infusions (11.5%) were associated with adverse drug reactions (ADRs).

The majority of these ADRs was mild to moderate and self-limiting. No serious ADRs were observed during the studies.

The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).
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).

Frequency of Adverse Drug Reactions (ADRs) in clinical studies with Intratect 50 g/l, indications PID and ITP (Frequencies are calculated per infusions administered (n=830) and patients treated (n=92) respectively.)

MedDRA                     Adverse reaction                      Frequency             Frequency System Organ Class         (MedDRA preferred term (PT))          based on infusions    based on patients (SOC)                                                            administered          treated (n=830)               (n=92)
Blood and lymphatic        Haemolysis (mild)                     Uncommon              Common system disorders
Nervous system             Headache                              Common                Very Common disorders                  Dysgeusia                             Uncommon              Common Vascular disorders         Hypertension, thrombophlebitis        Uncommon              Common superficial
Gastrointestinal           Nausea, vomiting, gastrointestinal    Uncommon              Common disorders                  pain
Skin and subcutaneous      Papular rash                         Uncommon               Common tissue disorders
General disorders and      Pyrexia                              Common                 Very Common administration site        Chills, feeling hot                  Uncommon               Common conditions
Investigations             Body temperature increased,          Uncommon               Common Coombs test (indirect and direct) positive

Frequency of Adverse Drug Reactions (ADRs) in a clinical study with Intratect 100 g/l, indication PID
(Frequencies are calculated per infusions administered (n=165) and patients treated (n=30) respectively.)

MedDRA                      Adverse reaction                           Frequency            Frequency System Organ Class          (MedDRA preferred term (PT))               based on             based on (SOC)                                                                  infusions            patients treated administered         (n=30)
(n=165)
Immune system               Infusion related reaction                   Common              Common disorders                   Hypersensitivity                            Uncommon            Common Nervous system              Headache                                    Common              Common disorders                   Sensory disturbance                         Uncommon            Common Cardiac disorders           Palpitations                                Common              Common Vascular disorders          Hyperaemia, hypertension                    Uncommon            Common Gastrointestinal            Diarrhoea, abdominal pain                   Uncommon            Common disorders
Skin and subcutaneous       Pain of skin, rash                          Uncommon            Common tissue disorders
Musculoskeletal and         Arthralgia, back pain, bone pain            Common              Common connective tissue           Myalgia                                     Uncommon            Common disorders
General disorders and       Discomfort                                  Common              Very Common administration site         Fatigue, chills, hypothermia                Uncommon            Uncommon conditions

Details of further spontaneously reported adverse reactions:
Frequency: not known (cannot be estimated from the available data)
Cardiac disorders: Angina pectoris
General disorders and administrations site conditions: Rigors
Immune system disorders: Anaphylactic shock, allergic reaction
Investigations: Blood pressure decreased
Musculoskeletal and connective tissue disorders: Back pain
Respiratory, thoracic and mediastinal disorders: Dyspnoea NOS
Vascular disorders: Shock
Blood and lymphatic system disorders: leukopenia

Description of selected adverse reactions
The reported adverse reactions for Intratect 50 g/l are in the expected profile for human normal immunoglobulins.

Paediatric population
Frequency, type and severity of adverse reactions in the paediatric population are expected to be the same as in adults.

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