Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain may occur occasionally.



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 (including cutaneous lupus erythematosus - frequency unknown) 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, and deep vein thromboses.

Cases of Transfusion Related Acute Lung Injury (TRALI).

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 ARs.

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 available data).

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


Table 1
Frequency of Adverse Reactions (ADRs) in clinical studies with KIOVIG MedDRA
System Organ Class Adverse reaction                                   Frequency (SOC)
Bronchitis, nasopharyngitis                     Common
Table 1
Frequency of Adverse Reactions (ADRs) in clinical studies with KIOVIG MedDRA
System Organ Class Adverse reaction                                        Frequency (SOC)
Infections         and Chronic sinusitis, fungal infection, infection, Uncommon infestations           kidney infection, sinusitis, upper respiratory tract infection, urinary tract infection, bacterial urinary tract infection, meningitis aseptic
Blood and lymphatic Anaemia, lymphadenopathy                               Common system disorders
Immune          system Hypersensitivity, anaphylactic reaction             Uncommon disorders
Endocrine disorders     Thyroid disorder                                 Uncommon Metabolism          and Decreased appetite                               Common nutrition disorders
Psychiatric disorders   Insomnia, anxiety                                Common Irritability                                     Uncommon
Nervous          system Headache                                         Very common disorders               Dizziness, migraine, paresthesia, hypoesthesia   Common Amnesia, dysarthria, dysgeusia, balance          Uncommon disorder, tremor
Eye disorders           Conjunctivitis                                   Common Eye pain, eye swelling                           Uncommon
Ear and labyrinth       Vertigo, fluid in middle ear                     Uncommon disorders
Cardiac disorders       Tachycardia                                      Common Vascular disorders      Hypertension                                     Very common Flushing                                         Common
Peripheral coldness, phlebitis                   Uncommon
Respiratory, thoracic   Cough, rhinorrhoea, asthma, nasal congestion,    Common and mediastinal         oropharyngeal pain, dyspnea disorders
Oropharyngeal swelling                           Uncommon
Gastrointestinal        Nausea                                           Very common disorders               Diarrhoea, vomiting, abdominal pain, dyspepsia   Common Abdominal distension                             Uncommon
Skin and subcutaneous   Rash                                             Very common tissue disorders        Contusion, pruritus, urticaria, dermatitis,      Common erythema
Angioedema, acute urticaria, cold sweat,         Uncommon photosensitivity reaction, night sweats,
hyperhidrosis
Musculoskeletal and     Back pain, arthralgia, pain in extremity,        Common connective tissue       myalgia, muscle spasms, muscular weakness disorders
Muscle twitching                                 Uncommon
Renal and urinary       Proteinuria                                      Uncommon disorders
General disorders and   Local     reactions    (e.g.     infusion    site Very common administration site     pain/swelling/reaction/pruritus),        pyrexia, conditions              fatigue
Table 1
Frequency of Adverse Reactions (ADRs) in clinical studies with KIOVIG MedDRA
System Organ Class Adverse reaction                                     Frequency (SOC)
Chills, edema, influenza-like illness, chest Common discomfort, chest pain, asthenia, malaise, rigors
Chest tightness, feeling hot, burning sensation, Uncommon swelling
Investigations        Blood cholesterol increased, blood creatinine Uncommon increased, blood urea increased, white blood cell count decreased, alanine aminotransferase increased, haematocrit decreased, red blood cell count decreased, respiratory rate increased

Table 2
Post-Marketing Adverse Reactions (ARs)
MedDRA
System Organ Class Adverse reaction                                        Frequency (SOC)
Blood and lymphatic   Haemolysis                                          Not known system disorders
Immune system              Anaphylactic shock                             Not known disorders
Nervous system             Transient ischemic attack, cerebral vascular   Not known disorders                  accident
Cardiac disorders          Myocardial infarction                          Not known Vascular disorders         Hypotension, deep vein thrombosis              Not known Respiratory, thoracic      Pulmonary embolism, pulmonary edema            Not known and mediastinal disorders
Investigations             Coombs direct test positive, oxygen Not known saturation decreased
Injury, poisoning and      Transfusion-related acute lung injury Not known procedural complications


Description of selected adverse reactions
Muscle twitching and weakness were reported only in patients with MMN.


Paediatric population
Frequency, type and severity of adverse reactions in children are 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

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