Actilyse

alteplase (tissue plasminogen activator, recombinant)

Actilyse (UK), Activase, Activase rt-PA (CA), Cathflo Activase

Pharmacologic class: Plasminogen activator

Therapeutic class: Thrombolytic

Pregnancy risk category C

Action

Converts plasminogen to plasmin, which in turn breaks down fibrin and fibrinogen, thereby dissolving thrombus

Availability

Injection: 2-mg single-patient vials; 50-mg, 100-mg vials

Indications and dosages

Lysis of thrombi obstructing coronary arteries in acute myocardial infarction (MI)

3-hour infusion-

Adults: 100 mg I.V. over 3 hours as follows: 60 mg over first hour (give 6 to 10 mg as bolus over first 1 to 2 minutes), then 20 mg I.V. over second hour, then 20 mg I.V. over third hour

Adults weighing less than 65 kg (143 lb): 1.25 mg/kg I.V. in divided doses over 3 hours, not to exceed 100 mg Accelerated infusion-

Adults weighing more than 67 kg (147 lb): Give total dosage of 100 mg as follows: 15 mg I.V. bolus over 1 to 2 minutes, then 50 mg I.V. over next 30 minutes, then 35 mg I.V. over next 60 minutes.

Adults weighing 67 kg (147 lb) or less: 15 mg I.V. bolus over 1 to 2 minutes, followed by 0.75 mg/kg I.V. over next 30 minutes (not to exceed 50 mg), followed by 0.5 mg/kg I.V. over next hour, not to exceed 35 mg

Acute ischemic cerebrovascular accident (CVA)

Adults: 0.9 mg/kg I.V. over 1 hour, to a maximum dosage of 90 mg, with 10% of total dosage given as I.V. bolus within first minute

Acute massive pulmonary embolism

Adults: 100 mg I.V. over 2 hours, followed by heparin

Restoration of function of central venous access device

Adults weighing 30 kg (66 lb) or more:Cathflo Activase-2 mg/2-ml concentration instilled in dysfunctional catheter. If catheter function isn't restored in 120 minutes after first dose, may give second dose.

Adults weighing 10 kg (22 lb) to less than 30 kg:Cathflo Activase-Use 110% of catheter lumen volume not to exceed 2 mg/2-ml concentration instilled in dysfunctional catheter. If catheter function isn't restored in 120 minutes after first dose, may give second dose.

Off-label uses

• Small-vessel occlusion by microthrombi
• Peripheral arterial thromboembolism

Contraindications

• Hypersensitivity to drug or its components (Cathflo Activase)
• Seizures, stroke, aneurysm, intracranial neoplasm, bleeding diathesis

Precautions

Use cautiously in:
• hypersensitivity to anistreplase or streptokinase
• GI or genitourinary bleeding, ophthalmic hemorrhage, organ biopsy, severe hepatic or renal disease
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

Be aware that intracranial hemorrhage must be ruled out before therapy begins.

To treat acute ischemic CVA, give within 3 hours of initial signs or symptoms.

If uncontrolled bleeding occurs, stop infusion and notify prescriber immediately.
• Give I.V. only, using controlled-infusion pump.
• Reconstitute with unpreserved sterile water for injection. May be further diluted with normal saline solution or D5W.

Adverse reactions

CNS: cerebral hemorrhage, cerebral edema, CVA (with accelerated infusion)

CV: hypotension, bradycardia, recurrent ischemia, pericardial effusion, pericarditis, mitral regurgitation, electromechanical dissociation, arrhythmias, cardiogenic shock, heart failure, cardiac arrest, cardiac tamponade, myocardial rupture, embolization, venous thrombosis

GI: nausea, vomiting, GI bleeding

GU: GU tract bleeding

Hematologic: spontaneous bleeding, bone marrow depression

Musculoskeletal: musculoskeletal pain

Respiratory: pulmonary edema

Skin: bruising, flushing

Other: fever, edema, phlebitis or bleeding at I.V. site, hypersensitivity reaction (including rash, anaphylactic reaction, laryngeal edema), sepsis

Interactions

Drug-drug.Aspirin, drugs affecting platelet activity (such as abciximab, heparin, dipyridamole, oral anticoagulants, vitamin K antagonists): increased risk of bleeding

Drug-diagnostic tests.Blood urea nitrogen: elevated level

Patient monitoring

• Monitor vital signs, ECG, and neurologic status.
• Maintain strict bed rest.
• Watch for signs and symptoms of bleeding tendency and hemorrhage.
• Monitor patient on Cathflo Activase for GI bleeding, venous thrombosis, and sepsis.
• Evaluate results of clotting studies.

Patient teaching

• As appropriate, explain therapy and monitoring to patient and family.

Actilyse

A brand name for the fibrin-dissolving (fibrinolytic) TISSUE PLASMINOGEN ACTIVATOR drug ALTEPLASE.
References in periodicals archive ?
CEO Robert Hubert said that in the ULTIMA study, 50 patients with pulmonary embolism and enlarged right hearts will be randomised to receive either standard of care anti-coagulation or Actilyse (Boehringer Ingleheim) delivered via the EKOS EkoSonic Endovascular Device.
The company anticipates that delivery of Actilyse directly into the pulmonary embolism in the presence of the ultrasound generated by the EkoSonic Device will result in complete dissolution of the obstructing embolism with restoration of right heart function and a reduction in the number of patients with long-term side effects from their pulmonary embolism, further said Hubert.
5 mg Actilyse per ml) were added to a Hellige thrombelastograph cuvette containing platelet-free and platelet-rich plasma samples (prepared by differential centrifugation).
Given the high rate of pipeline attrition in this market, investigators also remain focused on improving the utility of recombinant tissue plasminogen activator (rt-PA; alteplase [Genentech's Activase, Boehringer Ingelheim's Actilyse, Kyowa Hakko Kirin's Activacin, Mitsubishi Tanabe Pharma's Grtpa]), the current standard of care in acute ischemic stroke, through new research, including the use of advanced imaging to expand the treatment window beyond the currently-accepted 4.
While this study showed an unexpected low overall mortality compared to previous stroke clinical trials, it failed to show a statistically significant clinical benefit in stroke patients treated with Actilyse (the European tradename for Alteplase, recombinant) compared to placebo.