Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of safety profile
Adverse reactions such as chills, headache, 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.
Local reactions at infusion sites: swelling, soreness, redness, induration, local heat, itching, bruising and rash.

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

Tabulated list of adverse reactions
Adverse Reactions (ARs) have been collected in Hizentra clinical trials from 8 phase III studies ,1 extension study, and 2 phase IV studies in a total of 502 patients. The ADRs reported in these clinical studies are summarised and categorised according to the MedDRA System Organ Class (SOC and Preferred Term level) and frequency below.
Frequency per patient or per infusion has been evaluated using the following criteria: 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). For spontaneous post-marketing ADRs, the reporting frequency is categorised as unknown.

Frequency of Adverse Drug Reactions (ADR) associated with Hizentra obtained from clinical studies and post-marketing surveillance, reporting rate per patient or per infusion 
System Organ                   ADRs (MedDRA Preferred Term, PT)                ADR                  ADR Class                                                                       frequency            frequency (SOC, MedDRA)                                                              category per         category per patient             infusion
Immune system       Hypersensitivity                                   Uncommon                 Rare disorders           Anaphylactic reaction                              Unknown                  Unknown Nervous system      Headache                                           Very common              Uncommon disorders           Dizziness, Migraine                                Common                   Rare Tremor (including                                  Uncommon                 Rare Psychomotor hyperactivity)
Meningitis aseptic                                 Uncommon                 Very rare 
Burning sensation                                    Unknown                  Unknown Cardiac disorders Tachycardia                                          Uncommon                 Very rare System Organ                      ADRs (MedDRA Preferred Term, PT)              ADR               ADR Class                                                                        frequency         frequency (SOC,                                                                       category per      category per MedDRA)                                                                        patient          infusion Vascular              Hypertension                                        Common              Rare disorders             Flushing                                            Uncommon            Rare Embolic and thrombotic events                       Unknown             Unknown Gastrointestinal      Diarrhoea, abdominal pain                           Common              Uncommon disorders
Nausea, Vomiting                                    Common              Rare 
Skin and              Rash                                                Very common         Uncommon subcutaneous          Pruritus, urticaria                                 Common              Rare tissue disorders
Musculoskeletal       Musculoskeletal pain, Arthralgia                    Common              Uncommon and connective tissue disorders      Muscle spasm, Muscular weakness                     Uncommon            Rare General               Infusion site reactions                             Very common         Very common disorders and administration        Fatigue (including malaise), Pyrexia                Common              Uncommon site conditions

Chest pain, Influenza like illness, Pain            Common              Rare 
Chills (including hypothermia)                      Uncommon            Rare 
Infusion site ulcer                                 Unknown             Unknown Investigations        Blood creatinine increased                          Uncommon            Rare 
Paediatric population
Clinical trials with Hizentra showed a similar overall safety profile in paediatric and adult patients with PID.


Elderly population
The same adverse reactions may occur in the elderly population. Information available from clinical trials showed no difference in the safety profile of patients ≥ 65 years of age than of younger patients.
Postmarketing experience with Hizentra in patients ≥ 65 years of age shows an overall similar safety profile in this age group as in younger patients.
Please refer to section 4.4 for details on risk factors and monitoring recommendations.

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/
 and emailed to the Registration Holder’s Patient Safety Unit at:
PV-IL@cslbehring.com