Alteplase


Generic Medicine Info
Indications and Dosage
Intravenous
Acute myocardial infarction
Adult: Accelerated (90 minutes) dose regimen (for patients in whom treatment may be initiated within 6 hours post symptom onset): Patients weighing <65 kg: 15 mg as IV bolus, immediately followed by 0.75 mg/kg (Max: 50 mg) via infusion over 30 minutes, then 0.5 mg/kg (Max: 35 mg) via infusion over 60 minutes. ≥65 kg: 15 mg as IV bolus, immediately followed by 50 mg via infusion over 30 minutes, then 35 mg via infusion over 60 minutes. Max total dose: 100 mg. 3-hour dose regimen (for patients in whom treatment may be initiated between 6-12 hours post symptom onset): Patients weighing <65 kg: 10 mg as IV bolus, immediately followed by an IV infusion up to a total dose of 1.5 mg/kg over 3 hours. ≥65 kg: 10 mg as IV bolus, immediately followed by 50 mg via infusion over 1 hour, then 40 mg via infusion over 2 hours. Max total dose: 100 mg (1.5 mg/kg in patients <65 kg).

Intravenous
Acute massive pulmonary embolism
Adult: Patients weighing <65 kg: 10 mg as IV bolus over 1-2 minutes, immediately followed by an IV infusion up to a total dose of 1.5 mg/kg over 2 hours. ≥65 kg: 10 mg as IV bolus over 1-2 minutes, immediately followed by 90 mg via infusion over 2 hours. Max total dose: 100 mg (1.5 mg/kg in patients <65 kg).

Intravenous
Acute ischaemic stroke
Adult: Initiate treatment as early as possible within 3-4.5 hours of symptom onset. Recommended total dose: 0.9 mg/kg (Max: 90 mg). Initially, 10% of the total dose is given as an IV bolus over 1 minute, immediately followed by the remainder of the total dose given via infusion over 60 minutes. Dose may vary according to weight, refer to specific product guidelines for further dosing information.

Parenteral
Clearance of central venous lines
Adult: For the restoration of function in central venous access devices: As 1 mg/mL solution: Patients weighing <30 kg: Instil the volume of reconstituted solution into the occluded central venous access device corresponding to 110% of the internal lumen volume of the device. ≥30 kg: Instil 2 mg into the occluded central venous access device. Doses may be repeated after 120 minutes (2 hours) as necessary. Max total dose: 4 mg (2 mg for each instillation). Refer to detailed product guidelines for specific instructions of administration.
Child: Same as adult dose.
Hepatic Impairment
Intravenous:
Severe: Contraindicated.
Reconstitution
Preparation for IV administration: Reconstitute vials labelled as 10 mg, 20 mg, or 50 mg with 10 mL, 20 mL, or 50 mL sterile water for inj, respectively, up to a final concentration of 1 mg/mL. Gently swirl to mix; do not shake. May further dilute the reconstituted solution with 0.9% NaCl solution for inj to a minimal concentration of 0.2 mg/mL. Preparation for inj/catheter instillation: Reconstitute vial labelled as 2 mg with 2.2 mL of sterile water for inj to a final concentration of 1 mg/mL. Gently swirl to mix; do not shake. Instructions for reconstitution will vary depending on the formulation used and intended indication. Refer to specific product guidelines for further instructions on reconstitution.
Incompatibility
Increased risk of precipitation with 5% dextrose (particularly if used during further dilution). Incompatible with dopamine, dobutamine, heparin, and bacteriostatic water for inj.
Contraindications
Hypersensitivity to alteplase or any component of the formulation. Significant bleeding disorder (at present or within the past 6 months), known haemorrhagic diathesis, known history or evidence of or suspected intracranial haemorrhage (including subarachnoid haemorrhage); history of CNS damage (e.g. neoplasm, aneurysm, intracranial or spinal surgery); recent (<10 days) traumatic or prolonged CPR (>2 minutes), obstetrical delivery; recent puncture of non-compressible blood-vessel (e.g. subclavian or jugular vein puncture); severe uncontrolled arterial hypertension, acute pancreatitis, bacterial endocarditis, pericarditis, aortic dissection; history of ulcerative gastrointestinal disease (within the last 3 months), oesophageal varices, arterial aneurysm, arterial/venous malformations; neoplasms that predispose to bleeding; major surgery or significant trauma in the past 10 days (including any trauma associated with the current MI), recent head or cranial trauma. Severe hepatic impairment (including hepatic failure, cirrhosis, portal hypertension, and active hepatitis). Patient receiving effective oral anticoagulant (e.g. warfarin) therapy (INR >1.3). Acute MI and pulmonary embolism additional contraindications: Known history of haemorrhagic stroke or stroke of unknown origin, known history of ischaemic stroke or TIA in the preceding 6 months (except for current acute ischaemic stroke within 4.5 hours). Acute ischaemic stroke additional contraindications: Symptoms of ischaemic attack presenting >4.5 hours before the start of infusion or when time of symptom onset is unknown; minor neurological deficit or symptoms rapidly improving prior to infusion, severe stroke as determined clinically (e.g. National Institutes of Health Stroke Scale [NIHSS] >25) and/or by appropriate imaging techniques; recent intracranial or intraspinal surgery, stroke or serious head trauma (within the last 3 months); seizure at onset of stroke, history of stroke and concomitant diabetes, platelet count <100,000/mm3; systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg, hypertension requiring aggressive management (IV pharmacotherapy); blood glucose <50 mg/dL or >400 mg/dL; administration of heparin within 48 hours preceding the onset of stroke with high aPTT at presentation.
Special Precautions
Patient with small recent traumas (e.g. biopsies, IM injections, puncture of major vessels); extensive infarctions, left heart thrombus (e.g. mitral stenosis, atrial fibrillation), systolic blood pressure >160 mmHg, uncontrolled diabetes, other conditions with high risks of haemorrhage (which are not mentioned under contraindications). For clearance of central venous lines: Patients with thrombocytopenia, other haemostatic defects, or any condition for which bleeding poses a significant hazard or would cause difficult management due to location, or those at risk for embolic complications (e.g. venous thrombosis in the region of the catheter), known or suspected catheter infection; patients who have active internal bleeding or have had surgery, obstetrical delivery, percutaneous biopsy of viscera or deep tissues, or puncture of non-compressible vessels within 48 hours before instillation. Avoid excessive pressure during instillation into the catheter. Appropriate formulation of alteplase should be chosen and used according to the intended indication. Children (when used for clearance of central venous lines) and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Increased risk of thromboembolic events (in patients with left heart thrombus).
Eye disorders: Rarely, eye haemorrhage.
Gastrointestinal disorders: Gingival bleeding.
Nervous system disorders: Cerebral oedema (in the infarcted zone).
Renal and urinary disorders: Haematuria.
Respiratory, thoracic and mediastinal disorders: Pulmonary oedema, epistaxis.
Skin and subcutaneous tissue disorders: Ecchymosis.
Vascular disorders: Hypotension.
Potentially Fatal: Internal bleeding (e.g. intracranial/intracerebral, retroperitoneal, respiratory, gastrointestinal, genitourinary), external bleeding (particularly at arterial and venous puncture sites); sepsis (in patients with infected catheters); recurrent ischaemia or angina pectoris, heart failure, cardiac arrest, cardiogenic shock, reinfarction, mitral regurgitation, reperfusion arrhythmias (which may also lead to cardiac arrest). Rarely, hypersensitivity reactions (e.g. anaphylaxis, angioedema, urticaria), cholesterol embolisation.
IV/Parenteral: C
Monitoring Parameters
Monitor vital signs, neurological exam, head CT, prothrombin time/INR, glucose, and ECG before, during, and after therapy; blood pressure during and for 24 hours after therapy; infusion site (including other potential bleeding sites). Assess for haemorrhage during and 24 hours after therapy. Closely monitor for hypersensitivity reactions during and for several hours after infusion. For central venous catheter clearance: Evaluate catheter function by attempting to aspirate blood.
Overdosage
Symptoms: Significant reduction in blood coagulation components (e.g. fibrinogen); may increase the risk of intracranial bleeding. Management: Awaiting the physiological regeneration of the factors after treatment discontinuation may be sufficient. In case of severe bleeding, administer fresh frozen plasma; administration of synthetic antifibrinolytics may be done as necessary.
Drug Interactions
Increased risk of haemorrhage with oral anticoagulants, platelet aggregation inhibitors, unfractionated heparin or LMWH, glycoprotein IIb/IIIa inhibitors. May increase the risk of intracerebral haemorrhage in aspirin pre-treated patients (particularly if alteplase treatment is delayed). May increase the risk of hypersensitivity reactions (particularly angioedema) with ACE inhibitors.
Lab Interference
Alteplase alters the results of coagulation and fibrinolytic tests.
Action
Description: Alteplase, a recombinant human tissue-type plasminogen activator, is a thrombolytic agent. It is a glycoprotein that binds to fibrin in a thrombus which causes activation and the eventual induction of conversion of plasminogen to plasmin, thereby causing fibrin clot dissolution.
Duration: Fibrinolytic activity: Up to 1 hour (after discontinuation of infusion).
Pharmacokinetics:
Metabolism: Primarily metabolised in the liver.
Excretion: Elimination half-life: 4-5 minutes (initial); approx 40 minutes (terminal).
Storage
Intact vials: Store below 30°C or between 2-8°C (IV preparations); store between 2-8°C (preparations for inj/catheter instillation). Protect from light. Reconstituted solution: Store between 2-8°C for 24 hours or at 30°C for 8 hours. Storage recommendations may vary among countries and individual products. Refer to specific product guidelines.
MIMS Class
Anticoagulants, Antiplatelets & Fibrinolytics (Thrombolytics)
ATC Classification
B01AD02 - alteplase ; Belongs to the class of enzymes. Used in the treatment of thrombosis.
References
Actilyse 10 mg, 20 mg, and 50 mg Powder and Solvent for Injection and Infusion (Boehringer Ingelheim International GmbH). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2022.

Actilyse Cathflo 2 mg Powder for Solution for Injection and Infusion (Boehringer Ingelheim International GmbH). MHRA. https://products.mhra.gov.uk. Accessed 01/07/2022.

Actilyse Treatment-set 50 mg/vial (Boehringer Ingelheim [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 15/08/2022.

Actilyse Treatment-set 50 mg/vial (Boehringer Ingelheim Singapore Pte Ltd). MIMS Singapore. http://www.mims.com/singapore. Accessed 01/07/2022.

Activase (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/07/2022.

Anon. Alteplase. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 01/07/2022.

Anon. Alteplase. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/07/2022.

Boehringer Ingelheim (N.Z.). Actilyse 10 mg, 20 mg, and 50 mg Powder and Solvent for Solution for Injection and Infusion data sheet 14 July 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 01/07/2022.

Buckingham R (ed). Alteplase. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2022.

Cathflo Activase Injection, Powder, Lyophilized, for Solution (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 01/07/2022.

Joint Formulary Committee. Alteplase. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2022.

Disclaimer: This information is independently developed by MIMS based on Alteplase from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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