Actilyse

Alteplase

Thrombolytic treatment in acute MI: 90 min (accelerated) dose regimen for patients in whom treatment can be started w/in 6 hr of symptom onset; 3 hr dose regimen for patients in whom treatment can be started between 6-12 hr after symptom onset. Thrombolytic treatment in acute massive pulmonary embolism w/ haemodynamic instability. Thrombolytic treatment of acute ischaemic stroke to be started w/in 4.5 hr after onset of stroke symptoms & after exclusion of intracranial haemorrhage by appropriate imaging techniques. Effect is time-dependent; earlier treatment increases the probability of a favourable outcome.

Acute MI 90 min (accelerated) dose regimen: Start w/in 6 hr after symptom onset. Patient ≥65 kg 15 mg IV bolus, immediately followed by 50 mg IV infusion over the 1st 30 min, immediately followed by 35 mg IV infusion over 60 min until max total dose of 100 mg, <65 kg Total dose should be wt adjusted w/ 15 mg IV bolus, immediately followed by 0.75 mg/kg IV infusion over the 1st 30 min (max: 50 mg), immediately followed by 0.5 mg/kg IV infusion over 60 min (max: 35 mg). 3 hr dose regimen: Start between 6 & 12 hr after symptom onset. Patient ≥65 kg 10 mg IV bolus, immediately followed by 50 mg IV infusion over the 1st hr, immediately followed by 40 mg IV infusion over 2 hr until max total dose of 100 mg, <65 kg 10 mg IV bolus, immediately followed by IV infusion over 3 hr up to max total dose of 1.5 mg/kg. Patient w/ ST-elevation MI Antithrombotic adjunctive therapy is recommended. Acute massive pulmonary embolism Patient ≥65 kg Administer total dose of 100 mg in 2 hr. Most experience available is w/ the following dose regimen: 10 mg IV bolus over 1-2 min, immediately followed by 90 mg IV infusion over 2 hr until total dose of 100 mg, <65 kg 10 mg IV bolus over 1-2 min, immediately followed by IV infusion up to max total dose of 1.5 mg/kg. Adjunctive therapy: Initiate/resume heparin therapy after Actilyse when aPTT values are <2 times the ULN. Adjust infusion to maintain aPTT between 50-70 sec. Acute ischaemic stroke Recommended total dose: Infuse 0.9 mg/kg (max: 90 mg) starting w/ 10% of total dose administered as an initial IV bolus, immediately followed by remainder of total dose infused IV over 60 min. Initiate treatment as early as possible w/in 4.5 hr of symptom onset. Adjunctive therapy: Avoid heparin IV or platelet aggregation inhibitors (eg, ASA) in the 1st 24 hr after Actilyse. If heparin is required for other indications (eg, DVT prevention) the dose should not exceed 10,000 IU daily SC.

Hypersensitivity. High risk of haemorrhage eg, significant bleeding disorder (existing or w/in past 6 mth), known haemorrhagic diathesis; patients receiving oral anticoagulants (eg, warfarin Na); history of CNS damage (ie, neoplasm, aneurysm, intracranial or spinal surgery); history, evidence or suspicion of intracranial haemorrhage including sub-arachnoid haemorrhage; severe uncontrolled arterial HTN; major surgery or significant trauma in the past 10 days (including any trauma associated w/ current acute MI), recent head or cranial trauma; prolonged or traumatic CPR (>2 min), obstetrical delivery w/in the past 10 days, recent puncture of non-compressible blood vessel (eg, subclavian or jugular vein puncture); severe hepatic dysfunction including hepatic failure, cirrhosis, portal HTN (oesophageal varices) & active hepatitis; bacterial endocarditis, pericarditis; acute pancreatitis; documented ulcerative GI disease during last 3 mth; arterial aneurysms, arterial/venous malformations; neoplasm w/ increased bleeding risk. Acute MI & massive pulmonary embolism: Haemorrhagic stroke or stroke of unknown origin at any time; ischaemic stroke or transient ischaemic attack in the preceding 6 mth except current acute ischaemic stroke w/in 4.5 hr. Acute ischaemic stroke: Symptoms of ischaemic attack began >4.5 hr prior to infusion start or when time of symptom onset is unknown; symptoms of acute ischaemic stroke that is rapidly improving or only minor before start of infusion; severe stroke; seizure at the onset of stroke; history of previous stroke or serious head trauma w/in 3 mth; combination of previous stroke & DM; administration of heparin w/in 48 hr preceding the onset of stroke w/ elevated aPTT; platelet count <100,000/mm³; systolic BP >185 mmHg or diastolic BP >110 mmHg or aggressive management (IV medication) necessary to reduce BP; blood glucose <50 or >400 mg/dL. Childn <16 yr.

Risk of hypersensitivity reactions mediated through non-immunological mechanism. Monitor for angioedema during & for up to 24 hr after infusion. Discontinue use if severe hypersensitivity reaction occurs & promptly initiate appropriate treatment. Concomitant treatment w/ ACE inhibitors. Not to be mixed w/ other drugs in the same infusion vial or venous line (not even w/ heparin). Risk of bleeding. Concomitant use of other active substances affecting coagulation or platelet function. Avoid use of rigid catheters, IM inj & non-essential handling of patient during treatment. Discontinue fibrinolytic therapy if serious bleeding (particularly cerebral haemorrhage) occur & immediately terminate concomitant heparin administration. Dose >100 mg should not be given in acute MI & pulmonary embolism; 90 mg in acute ischaemic stroke due to increased intracranial bleeding. Recent IM inj or small recent traumas (eg, biopsies, major vessel puncture, cardiac massage for resuscitation). Conditions w/ increased haemorrhagic risk. Patients receiving oral anticoagulants. Acute MI & pulmonary embolism: Systolic BP >160 mmHg. May increase risk of intracerebral haemorrhage in advanced age. Acute MI: Coronary thrombolysis may result in arrhythmia-associated w/ reperfusion. Concomitant use of glycoprotein IIb/IIIa receptor antagonists. Increased risk of thromboembolic events in patients w/ left heart thrombus (eg, mitral stenosis or atrial fibrillation). Acute ischaemic stroke: All situations involving high risk of haemorrhage; late time-to-treatment onset; pre-treatment w/ ASA. Not to be initiated >4.5 hr after symptom onset. Monitor BP during treatment & up to 24 hr. Reduced therapeutic benefit in patients who have had a prior stroke or in whom uncontrolled diabetes exists. Patients w/ extensive infarctions. Decreased likelihood of favourable outcome & increased likelihood of severe disability & death or symptomatic intracranial bleeding w/ prolonged treatment. Reperfusion of the ischaemic area may induce cerebral oedema in the infarcted zone. Pregnancy & lactation. Childn ≥16 yr. Elderly >80 yr.

Haemorrhage (eg, haematoma); intracranial haemorrhage (eg, cerebral haemorrhage & haematoma, haemorrhagic & transformation stroke, intracranial haematoma, subarachnoid haemorrhage). Resp tract haemorrhage (eg, pharyngeal haemorrhage); GI haemorrhage (eg, gastric, gastric ulcer, rectal & mouth haemorrhage, haematemesis, melena, gingival bleeding); ecchymosis; urogenital haemorrhage (eg, haematuria, urinary tract haemorrhage); inj & puncture site haemorrhage (eg, catheter site haematoma & haemorrhage).

May increase risk of bleeding prior to, during or after therapy w/ medicinal products affecting coagulation or altering platelet function. May enhance risk of hypersensitivity reaction w/ ACE inhibitors.

Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)

B01AD02 - alteplase ; Belongs to the class of enzymes. Used in the treatment of thrombosis.

POM