Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile
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Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain occur occasionally.
Reactions to intravenous immunoglobulins tend to be related to the dose and the rate of infusion (see section 4.4).
Rarely human normal immunoglobulins may cause a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration.
Cases of reversible aseptic meningitis and rare cases of transient cutaneous reactions have been observed with human normal immunoglobulin. Reversible haemolytic reactions have been observed in patients, especially those with blood groups A, B, and AB. Rarely, haemolytic anaemia requiring transfusion may develop after high dose IVIg treatment (see also Section 4.4).
Increase in serum creatinine level and/or acute renal failure have been observed.
Very rarely: Thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism, deep vein thromboses.
When medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens. For safety 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).
The frequencies given in the following table are derived from clinical studies that were conducted with Octagam (Frequency "common" and "uncommon") and from postmarketing experience with Octagam (Frequency "very rare"). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.


MedDRA system organ                      Adverse Reaction (Preferred    Frequency classification (SOC)                            Term Level)
Blood and lymphatic system            haemolytic anaemia,              very rare disorders                             leukopenia;                      very rare Immune system disorders (see          anaphylactic shock;              very rare section 4.4)                          hypersensitivity                 common anaphylactic reaction;           very rare anaphylactoid reaction;          very rare angioedema;                      very rare face oedema                      very rare
Metabolic and nutritional disorders   fluid overload                   very rare (pseudo)hyponatraemia            very rare
Psychiatric disorders                 confusional state                very rare agitation                        very rare anxiety                          very rare


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nervousness                           very rare
Nervous system disorders              cerebrovascular accident (see 4.4);   very rare meningitis aseptic;                   very rare loss of consciousness;                very rare speech disoder;                       very rare migraine;                             very rare headache                              common dizziness;                            very rare hypoaesthesia;                        very rare paraesthesia                          very rare photophobia;                          very rare tremor                                very rare
Eye disorders                         visual impairment                     very rare Cardiac disorders                     myocardial infarction (see 4.4);      very rare angina pectoris;                      very rare bradycardia;                          very rare tachycardia;                          very rare palpitations;                         very rare cyanosis                              very rare
Vascular disorders                    thrombosis (see 4.4);                 very rare circulatory collapse;                 very rare peripheral circulatory failure;       very rare phlebitis;                            very rare hypotension;                          very rare hypertension                          very rare pallor                                very rare
Respiratory, thoracic and mediastinal respiratory failure;                  very rare disorders                             pulmonary embolism (see 4.4);         very rare pulmonary oedema;                     very rare bronchospasm;                         very rare hypoxia;                              very rare dyspnoea;                             very rare cough;                                very rare
Gastrointestinal disorders            vomiting;                             very rare diarrhoea;                            very rare abdominal pain;                       very rare nausea                                common
Skin and subcutaneous tissue          skin exfoliation;                     very rare disorders                             urticaria;                            very rare rash;                                 very rare rash erythematous;                    very rare dermatitis;                           very rare eczema;                               uncommon pruritus;                             very rare alopecia                              very rare erythema;                             very rare
Musculoskeletal and connective        arthralgia;                           very rare tissue disorders                      myalgia                               very rare pain in extremity                     very rare back pain;                            uncommon neck pain;                            very rare muscle spasms;                        very rare muscular weakness;                    very rare musculoskeletal stiffness             very rare
Renal and urinary disorders           renal failure acute (see 4.4)         very rare renal pain                            very rare
General disorders and administration chest pain;                            uncommon site conditions                      chest discomfort;                      very rare oedema;                                very rare influenza like illness                 very rare fever;                                 common chills;                                uncommon


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hot flush;                             very rare flushing;                              very rare feeling cold;                          very rare feeling hot;                           very rare hyperhidrosis;                         very rare asthenia;                              very rare lethargy;                              very rare burning sensation;                     very rare injection site reaction;              common fatigue;                               common malaise;                               very rare
Investigations               hepatic enzyme increased;              very rare blood glucose false positive (see 4.4) very rare

Description of selected adverse reactions
For description of selected adverse events, see Section 4.4
Paediatric population
In clinical studies with OCTAGAM most adverse reactions observed in children were graded as mild and many of them responded to simple measurements such as reduction of the infusion rate or temporary discontinuation of the infusion. With respect to the type of adverse reaction, all were recognised for IVIG preparations. The most frequent adverse reaction observed in the paediatric population was headache.

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=AdversEffectMed ic@moh.gov.il