Adverse reactions : תופעות לוואי

4.8    Undesirable effects
Summary of the safety profile

The most common serious adverse reactions in clinical studies were pneumonia (5.6%) and sepsis (3.7%). The most common adverse reactions were infections (16.7%) (including pneumonia (5.6%), urinary tract infection (5.6%) and sepsis (3.7%)), infusion site pain (3.7%), infusion related reactions (3.7%), alanine aminotransferase increased (3.7%), aspartate aminotransferase increased (3.7%), myalgia (3.7%), headache (3.7%) and flushing (3.7%).

Tabulated list of adverse reactions

The adverse reactions described in this section were identified in the clinical studies (N=54).
The adverse reactions are presented according to MedDRA system organ class and frequency category. The frequency categories are defined as follows: 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).


Table 2      Adverse reactions
MedDRA system organ class            Adverse reaction/
Frequency
Very common                   Common
Infections and infestations          Bacterial and viral           Abdominal infection infection                     Adenovirus infection
Catheter site infection
Infection
Influenza
Parvovirus infection
Pneumonia
Postoperative wound infection
Sepsis
Upper respiratory tract infection
Urinary tract infection
Wound infection
Blood and lymphatic system                                         Anaemia disorders
Immune system disorders                                            Transplant rejection Nervous system disorders                                           Dizziness postural Headache
Eye disorders                                                      Scleral haemorrhage Visual impairment
Cardiac disorders                                                  Sinus tachycardia Vascular disorders                                                 Flushing Hypertension
Hypotension
Respiratory, thoracic and                                          Dyspnoea mediastinal disorders
Skin and subcutanous tissue                                        Rash disorders
Musculoskeletal and                                                Myalgia connective tissue disorders
General disorders and                                              Feeling hot administration site conditions                                     Infusion site pain Investigations                                                     Alanine aminotransferase (ALT) increased
Aspartate aminotransferase
(AST) increased
Injury, poisoning and                                              Infusion related reactions procedural complications

Description of selected adverse reactions

Infections
In the clinical studies, 16.7% of the patients experienced an infection. Nine infections were serious and assessed as related to imlifidase in the clinical studies, whereof 5 started within 30 days after imlifidase treatment. Eight of the 9 related serious infections had a duration of less than 30 days. The incidence and pattern (including infectious agent) of serious or severe infections were not different from those observed in kidney-transplanted patients in general (see section 4.4).

Infusion-related reactions
Infusion-related reactions, including dyspnoea and flushing were reported in 5.6% of the patients, one resulting in interruption of the imlifidase infusion and the patient not being transplanted. Except for 
one event of mild rash, all infusion-related reactions started on the day of imlifidase infusion and resolved within 90 minutes (see section 4.4).

Myalgia
Myalgia was reported for 2 patients (3.7%) in the clinical studies. One of the patients had severe myalgia without any findings of muscle damage.

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/