Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Summary of the safety profile

The most frequent related adverse reactions were burning sensation (<1%), headache (<1%), paraesthesia (2%), flushing (2%), feeling hot (<1%).

Tabulated summary of adverse reactions

Table 1 gives the adverse reactions observed from the combination of pooled clinical study data (489 patients) and reported adverse reactions during the Post Marketing period. The adverse reactions are presented by system organ class and frequency categories defined using 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). Within each frequency grouping undesirable effects are presented in order of decreasing seriousness

Table 1     Adverse reactions reported for glucarpidase

System organ class           Frequency                       Adverse reactions Rare                          Hypersensitivity
Immune system disorders
Very Rare                      Anaphylactic reaction
Uncommon             Burning sensation, Headache, Paraesthesia
Nervous system disorders
Rare                Hypoaesthesia, Somnolence, Tremor
Cardiac disorders           Very Rare                          Tachycardia Uncommon                             Flushing
Vascular disorders
Rare                            Hypotension
Respiratory, thoracic and
Rare                   Pleural effusion, Throat tightness mediastinal disorders
Abdominal pain upper, Diarrhoea, Nausea,
Gastrointestinal disorders         Rare
Vomiting

Skin and subcutaneous             Rare                              Pruritus, Rash tissue disorders             Very Rare                     Drug eruption, Skin reaction Renal and urinary disorders                   Very Rare                              Crystalluria* General disorders and          Uncommon                                Feeling hot administration site             Rare                            Pyrexia, Rebound effect conditions                Very Rare                          Infusion site reaction *Crystalluria is the preferred term; the adverse reaction refers to DAMPA crystalluria 
Description of selected adverse reactions
As with any intravenous protein product, infusion-related reactions or hypersensitivity reactions are possible.
It is recommended that patients are monitored for signs and symptoms of anaphylaxis and an acute allergic reaction. Medical support must be readily available when glucarpidase is administered.
As with all therapeutic proteins, there is potential for immunogenicity. 205 patients who received one (n=176), 2 (n=27), or 3 (n=2) doses of glucarpidase were evaluated for anti-glucarpidase antibodies.
Forty-three of these 205 patients (21%) had detectable anti-glucarpidase antibodies following administration, of which 32 received 1 dose and 11 received 2 or 3 doses of glucarpidase. Antibody titers were determined using a bridging enzyme-linked immunosorbent assay (ELISA) for anti- glucarpidase antibodies. Neutralizing antibodies were detected in 22 of the 43 patients who tested positive for anti-glucarpidase binding antibodies.

Paediatric population

The incidence of adverse events related to glucarpidase did not differ between paediatric and adult patients.

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/