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)

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.

Frequency of Adverse Reactions (ADRs) in clinical studies with Gammaplex 
MedDRA System              Adverse reaction                 Frequency        Frequency Organ Class                                                 per patient      per infusion
(SOC)
Metabolism and             Fluid retention, dehydration     Common           Uncommon nutrition disorders                                                          Rare Decreased appetite, iron         Uncommon deficiency
Psychiatric disorders      Insomnia                         Uncommon         Rare Nervous system             Headache                         Very             Common disorders                                                   common Dizziness                        Common           Uncommon
Migraine, paraesthesia           Uncommon         Uncommon
Hypoaesthesia, lethargy          Uncommon         Rare
Ear and labyrinth          Vertigo                          Common           Uncommon disorders
Tinnitus                         Uncommon         Rare
Cardiac disorders          Palpitations, tachycardia        Common           Uncommon 

Vascular disorders      Hypertension                      Common      Common Hypotension                       Common      Uncommon
Thrombosis, hot flush             Uncommon    Rare
Respiratory, thoracic   Nasal congestion                  Common      Uncommon and mediastinal
Bronchospasm                      Uncommon    Uncommon disorders
Epistaxis, pharyngolaryngeal      Uncommon    Rare pain
Transfusion related acute lung    Not Known   Not Known injuries (TRALI)
Gastrointestinal        Vomiting, nausea, diarrhoea,      Common      Uncommon disorders               abdominal pain
Abdominal distension,             Uncommon    Rare constipation, stomatitis
Skin and                 Urticaria                        Uncommon    Uncommon subcutaneous tissue     Erythema multiforme, pruritus     Uncommon    Rare disorders
Cutaneous lupus erythematosus     Not Known   Not Known
Musculoskeletal,        Myalgia                           Common      Common connective tissue disorders and bone      Arthralgia, muscle spasms, back   Common      Uncommon disorders               pain, neck pain
Pain in extremity                 Uncommon    Uncommon

Musculoskeletal stiffness         Uncommon    Rare

General disorders and   Pyrexia                           Very        Common administration site                                       common conditions              Fatigue                           Common      Common Chills, chest discomfort/         Common      Uncommon pain, asthenia, infusion site reaction, infusion site erythema, pain
Investigations          Coombs’ direct test positive,     Common      Uncommon anaemia/haemoglobin decreased
Anti-erythrocyte antibody         Uncommon    Rare positive, white blood cell count increased, urinary haemosiderin positive,
gastric pH decreased


Description of selected adverse reactions
None of the reported adverse reactions to Gammaplex warrant separate description.

Paediatric population

Of the 50 patients in the clinical study of Gammaplex in primary immunodeficiency (GMX01), seven were aged less than 18 years (age range 9 to 17 years). A separate paediatric clinical study of Gammaplex in primary immunodeficiency (GMX04) treated 25 patients aged less than 18 years (age range 3 to 16 years). Of the 35 patients in the clinical study of Gammaplex in chronic immune thrombocytopenia (ITP) (GMX02), three were aged less than 18 years (age range 6 to 17 years). The frequency, type and severity of adverse reactions in children are similar to those in adults.

Other special populations

Certain patient groups may be at increased risk of hypersensitivity reactions, thromboembolism or acute renal failure. Caution should be exercised when infusing IVIg in obese patients or those with advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, acquired or inherited thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia, diseases which increase blood viscosity, pre-existing renal insufficiency or those receiving concomitant nephrotoxic medicinal products; see section 4.4 for details.

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