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
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)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Source of the safety database from clinical trials and post-authorisation safety studies in a total of 128 patients exposed to Flebogamma 5% DIF (with a total of 1318 infusions) 
Frequency       Frequency
MedDRA System Organ
Adverse reaction               per             per
Class (SOC) patient        infusion
Infections and infestations   Nasopharyngitis                  Uncommon        Uncommon Immune system disorders       Hypersensitivity                 Uncommon        Rare Psychiatric disorders         Abnormal behaviour               Uncommon        Rare Migraine                         Uncommon        Rare
Very
Nervous system disorders      Headache                                         Common Common
Dizziness                        Common          Uncommon
Tachycardia                      Common          Common
Cardiac disorders
Cardiovascular disorder          Uncommon        Rare
Hypertension                     Common          Uncommon
Diastolic hypertension           Common          Uncommon
Systolic hypertension            Uncommon        Uncommon
Vascular disorders            Hypotension                      Common          Common Diastolic hypotension            Common          Common
Blood pressure fluctuation       Uncommon        Rare
Flushing                         Uncommon        Rare
Bronchitis                       Common          Uncommon
Dyspnoea                         Uncommon        Rare
Asthma                           Uncommon        Rare
Epistaxis                        Uncommon        Rare
Respiratory, thoracic and
Productive cough                 Uncommon        Uncommon mediastinal disorders
Cough                            Uncommon        Rare
Wheezing                         Common          Uncommon
Laryngeal pain                   Uncommon        Rare
Nasal discomfort                 Uncommon        Rare
Diarrhoea                        Common          Uncommon
Vomiting                         Common          Uncommon
Gastrointestinal disorders    Abdominal pain upper             Common          Uncommon Abdominal pain                   Common          Uncommon
Nausea                           Common          Uncommon
Rash pruritic                    Uncommon        Uncommon
Dermatitis contact               Uncommon        Rare
Skin and subcutaneous         Urticaria                        Common          Uncommon tissue disorders              Pruritus                         Uncommon        Uncommon Rash                             Uncommon        Rare
Hyperhidrosis                    Uncommon        Rare
Arthralgia                       Common          Uncommon
Musculoskeletal and
Myalgia                          Common          Uncommon connective tissue disorders
Back pain                        Common          Uncommon
Frequency             Frequency
MedDRA System Organ
Adverse reaction            per                   per
Class (SOC) patient              infusion
Neck pain                         Uncommon              Rare
Pain in extremity                 Uncommon              Rare
Muscle spasms                     Uncommon              Rare
Renal and urinary disorders Urinary retention                 Uncommon              Rare Very
Pyrexia                                                 Common
Common
Chest pain                        Uncommon              Rare
Oedema peripheral                 Uncommon              Rare
Chills                            Common                Uncommon
Rigors                            Common                Uncommon
Pain                              Common                Uncommon
General disorders and       Asthenia                          Uncommon              Rare administration site         Injection site reaction           Common                Uncommon conditions                  Infusion site erythema            Uncommon              Rare Infusion site extravasation       Uncommon              Rare
Injection site pruritus           Uncommon              Rare
Infusion site inflammation        Uncommon              Rare
Injection site swelling           Uncommon              Rare
Injection site oedema             Uncommon              Rare
Infusion site pain                Uncommon              Rare
Injection site pain               Uncommon              Rare
Blood pressure increased          Uncommon              Rare
Blood pressure systolic increased Common                Uncommon
Blood pressure systolic decreased Uncommon              Uncommon
Investigations              Body temperature increased        Common                Uncommon Alanine aminotransferase
Uncommon              Rare increased
Coombs test positive              Common                Uncommon
Injury, poisoning and
Infusion related reaction         Uncommon              Uncommon procedural complications

Description of selected adverse reactions

The most reported post-marketing ADRs received since the product was authorised for both concentrations were chest pain, flushing, blood pressure increased and decreased, malaise, dyspnoea, nausea, vomiting, pyrexia, back pain, headache and chills.

Paediatric population

The safety results for 29 paediatric patients (those ≤ 17 years old) included in the PID studies were evaluated. It was observed that the proportion of headache, pyrexia, tachycardia and 
hypotension in children was higher than in adults. Assessment of vital signs in clinical trials of the paediatric population did not indicate any pattern of clinically relevant changes.

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 (www.health.gov.il) according to the National Regulation by using an online form https://sideeffects.health.gov.il