Alteplase Other names: Tissue-type plasminogen activator precursor tPA t-PA t-plasminogen activator

The risk of haemorrhage is increased if coumarine derivatives, oral anticoagulants, platelet aggregation inhibitors, unfractionated heparin or LMWH or active substances which interfere with coagulation are administeredbefore, during or within the first 24 hours after treatment with alteplase.

Concomitant treatment of alteplase with ACE inhibitors may enhance the risk of suffering a hypersensitivity reaction.

Concomitant use of alteplase with GPIIb/IIIa antagonists increases the risk of bleeding.

There is limited amount of data from the use of alteplase in pregnant women. Nonclinical studies performed with alteplase in doses higher than human doses exhibited fetal immaturity and/or embryotoxicity, secondary to the known pharmacological activity of the drug. Alteplase is not considered to be teratogenic.

In cases of an acute life-threatening disease the benefit has to be evaluated against the potential risk.

It is not known if alteplase is excreted into human milk.

Fertility

Clinical data on fertility are not available for alteplase. Nonclinical studies performed with alteplase showed no adverse effect on fertility.

Not relevant.

The most frequent adverse reaction associated with alteplase 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 alteplase in the indications acute massive pulmonary embolism and acute ischaemic stroke is different from the profile in the indication acute myocardial infarction.

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

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)

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)

* 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.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.