Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The most frequent adverse reaction associated with Actilyse is bleeding in different forms resulting in a fall in haematocrit and/or haemoglobin values.
Adverse reactions listed below are classified according to frequency and system organ class. Frequency groupings are defined 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 the available data).

Except for intracerebral/intracranial haemorrhage as adverse reaction in the indication stroke as well as for reperfusion arrhythmias in the indication acute myocardial infarction, there is no medical reason to assume that the qualitative and quantitative adverse reaction profile of Actilyse in the indications acute massive pulmonary embolism and acute ischaemic stroke is different from the profile in the indication acute myocardial infarction.

Table 1 Adverse reactions in acute myocardial infarction, acute massive pulmonary embolism and acute ischaemic stroke

System Organ Class        Adverse Reaction

Haemorrhage very common               intracerebral haemorrhage represents the major adverse reaction in the treatment of acute ischaemic stroke all haemorrhages including those in this table, e.g. ICH and non-ICH
 common                    intracerebral haemorrhage (such as cerebral haemorrhage, cerebral haematoma, haemorrhagic stroke, haemorrhagic transformation of stroke, intracranial haematoma, subarachnoid haemorrhage) in the treatment of acute myocardial infarction and acute massive pulmonary embolism
 pharyngeal haemorrhage
 gastrointestinal haemorrhage (such as gastric haemorrhage, gastric ulcer haemorrhage, rectal haemorrhage, haematemesis, melaena, mouth haemorrhage, gingival bleeding)  ecchymosis
 urogenital haemorrhage (such as haematuria, haemorrhage urinary tract)  injection site haemorrhage (puncture site haemorrhage, catheter site haematoma, catheter site haemorrhage)
 uncommon                  pulmonary haemorrhage (such as haemoptysis, hemothorax, respiratory tract haemorrhage)
 epistaxis
 ear haemorrhage rare                      eye haemorrhage
 pericardial haemorrhage
 retroperitoneal bleeding (such as retroperitoneal haematoma) not known***              bleeding in parenchymatous organs (such as hepatic haemorrhage) Actilyse                                                                     Updated Prescribing Information  20 mg, 50 mg                                                                                        Feb 2023


Immune system disorders rare                 hypersensitivity reactions (e.g. rash, urticaria, bronchospasm, angio-oedema, hypotension, shock)* very rare            serious anaphylaxis

Nervous system disorders very rare             events related to the nervous system (e.g. epileptic seizure, convulsion, aphasia, speech disorder, delirium, acute brain syndrome, agitation, confusion, depression, psychosis) often in association with concurrent ischaemic or haemorrhagic cerebrovascular events

Cardiac disorders** very common                 recurrent ischaemia / angina pectoris, hypotension and heart failure / pulmonary oedema,
common                      cardiogenic shock, cardiac arrest and reinfarction uncommon                    reperfusion arrhythmias (such as arrhythmia, extrasystoles, AV block first degree to atrioventricular block complete, atrial fibrillation / flutter, bradycardia, tachycardia, ventricular arrhythmia, ventricular tachycardia / fibrillation, electromechanical dissociation [EMD])
 mitral regurgitation, pulmonary embolism, other systemic embolism / cerebral embolism, ventricular septal defect

Vascular disorders rare                        Embolism which may lead to corresponding consequences in the organs concerned

Gastrointestinal disorders rare                    nausea not known***            vomiting

Investigations uncommon                    blood pressure decreased not known***                body temperature increased
Injury and poisoning and procedural complications not known***           fat embolism (cholesterol crystal embolisation), which may lead to corresponding consequences in the organs concerned

Surgical and medicinal procedures not known***              Blood transfusions (necessary)
* See sections 4.4 and 4.5

**Cardiac disorders
As with other thrombolytic agents, the events described above under the respective section have been reported as sequelae of myocardial infarction and / or thrombolytic administration. These cardiac events can be life- threatening and may lead to death.
***Frequency calculation
This adverse reaction has been observed in post-marketing experience. With 95 % certainty, the frequency category is not greater than “rare”, but might be lower. Precise frequency estimation is not possible as the adverse drug reaction did not occur in a clinical trial database of 8299 patients.

Death and permanent disability are reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.
Actilyse                                                                 Updated Prescribing Information  20 mg, 50 mg                                                                                    Feb 2023


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.
You can report side effects to the Ministry of Health by following the link ‘Reporting Side Effects of Drug Treatment' on the Ministry of Health home page (www.health.gov.il) which links to an online form for reporting side effects. You can also use this link: https://sideeffects.health.gov.il