Adverse reactions : תופעות לוואי

4.8   Undesirable effects
Summary of safety profile
The most commonly reported adverse reactions were infusion associated reactions, which occurred in 13.7% of adult patients treated with Replagal in clinical trials. Most undesirable effects were mild to moderate in severity.

Tabulated list of adverse reactions
Table 1 lists adverse reactions reported for the 344 patients treated with Replagal in clinical trials, including 21 patients with history of end stage renal disease, 30 paediatric patients (≤18 years of age) and 17 female patients, and from post-marketing spontaneous reports. Information is presented by system organ class and frequency (very common ≥1/10; common ≥1/100 to <1/10; uncommon ≥1/1,000 to <1/100). The adverse reactions categorized as incidence “not known (cannot be estimated from the available data)” are derived from post-marketing spontaneous reports. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. The occurrence of an event in a single patient is defined as uncommon in view of the number of patients treated. A single patient could be affected by several adverse reactions.
The following adverse reactions have been identified for agalsidase alfa: 

Table 1
System organ class                                                Adverse reaction 
Very common             Common                    Uncommon                 Not known 
Metabolism and                peripheral oedema nutrition disorders

Nervous system                headache, dizziness, dysgeusia,                   parosmia disorders                     neuropathic pain,     hypersomnia,
tremor, hypoesthesia,
paraesthesia
Eye disorders                                     lacrimation increased      corneal reflex decreased


Ear and labyrinth           tinnitus              tinnitus disorders                                         aggravated
Cardiac disorders           palpitations          tachycardia,               tachyarrhythmia       myocardial ischaemia, atrial                                           heart failure,
fibrillation                                     ventricular extrasystoles,



Vascular disorders                                hypertension,
hypotension, flushing
Respiratory, thoracic and   dyspnoea, cough,      hoarseness, throat         oxygen mediastinal disorders       nasopharyngitis,      tightness,                 saturation pharyngitis,          rhinorrhoea                decreased, throat secretion increased


Gastrointestinal            vomiting, nausea,     abdominal discomfort disorders                   abdominal pain, diarrhoea


Skin and subcutaneous       rash                  urticaria, erythema,       angioneurotic tissue disorders                                  pruritus, acne,            oedema, livedo hyperhidrosis              reticularis


Musculoskeletal,            arthralgia, pain in   musculoskeletal            sensation of connective tissue and       limb, myalgia, back   discomfort, peripheral     heaviness bone disorders              pain                  swelling, joint swelling 

Immune system                                     hypersensitivity           anaphylactic disorders                                                                    reaction 

General disorders and       chest pain, rigors,   chest tightness,           injection site rash administration site         pyrexia, pain,        fatigue aggravated, conditions                  asthenia fatigue      feeling hot, feeling cold, influenza like illness, discomfort,
malaise
See also section 4.4.

Description of selected adverse reactions

Infusion related reactions reported in the postmarketing setting (also see section 4.4) may include cardiac events such as cardiac arrhythmias (atrial fibrillation, ventricular extrasystoles, tachyarrhythmia), myocardial ischemia, and heart failure in patients with Fabry disease involving the heart structures. The most common infusion related reactions were mild and include rigors, pyrexia, flushing, headache, nausea, dyspnoea, tremor and pruritus. Infusion-related symptoms may also include dizziness, hyperhidrosis, hypotension, cough, vomiting and fatigue. Hypersensitivity, including anaphylaxis, has been reported.

Paediatric population

Adverse drug reactions reported in the paediatric population (children and adolescents) were, in general, similar to those reported in adults. However, infusion related reactions (pyrexia, dyspnoea, chest pain) and pain exacerbation occurred more frequently.

Other special populations

Patients with renal disease
Adverse drug reactions reported in patients with history of end stage renal disease were similar to those reported in the general patient population.

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