Reteplase (Monograph)

Brand name: Retavase
Drug class: Thrombolytic Agents
- Tissue-type Plasminogen Activator (Recombinant)
- t-PA (Recombinant)
Chemical name: 173-l-Serine-174-l-lysine-175-l-glutamine-173-527-plasminogen activator (human tissue-type)
Molecular formula: C₁₇₃₆H₂₆₅₃N₄₉₉O₅₂₂S₂₂
CAS number: 133652-38-7

Medically reviewed by Drugs.com on Oct 13, 2022. Written by ASHP.

Introduction

Thrombolytic agent; biosynthetic (recombinant DNA origin) form of human tissue-type plasminogen activator (t-PA).

Uses for Reteplase

Acute MI

Used for reperfusion therapy in patients with acute MI, in conjunction with appropriate anticoagulant (e.g., heparin) and antiplatelet (e.g., aspirin and clopidogrel) therapies.

Current standard of care in patients with ST-segment-elevation MI (STEMI) is timely reperfusion (with primary PCI or thrombolytic therapy). The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guideline states that reperfusion therapy should be administered to all eligible patients with STEMI and onset of ischemic symptoms within the previous 12 hours. Select the appropriate reperfusion method based on a risk-benefit analysis, considering the time from onset of MI symptoms, patient's clinical and hemodynamic status, comorbidities (e.g., severe heart failure), bleeding risk, contraindications, and availability (and timeliness) of PCI.

Primary PCI is preferred when it can be performed in a timely manner. Thrombolytic therapy is recommended when it is anticipated that PCI cannot be performed within 120 minutes of first medical contact.

Benefits of thrombolytic therapy in patients with STEMI are well established; resulting reperfusion with reteplase shown to improve ventricular function and reduce incidence of heart failure, cardiogenic shock, and death.

Clinical benefit diminishes as the time period from symptom onset to initiation of therapy increases; administer as soon as possible after onset of MI symptoms. ACCF and AHA recommend administration within 30 minutes of hospital arrival.

Acute PE

Has been used for the treatment of acute PE^{† [off-label]}.

The American College of Chest Physicians (ACCP) generally recommends against the use of systemic thrombolytic therapy in most patients with acute PE; however, in patients with acute PE associated with hypotension (e.g., systolic BP<90 mmHg), thrombolytic therapy may provide some benefit in terms of mortality reduction and is suggested as a possible treatment in patients without high risk of bleeding.

Reteplase Dosage and Administration

General

• Institute therapy as soon as possible after acute MI. (See Acute MI under Uses.)

Administration

IV Administration

For drug compatibility information, see Drug Compatibility under Stability.

Administer IV.

Do not add other IV substances, additives, or other drugs to reteplase solution and do not infuse anything else simultaneously through the same IV line.

If administered via an IV administration set that is used for infusing heparin, flush line with 0.9% sodium chloride or 5% dextrose solution prior to and following drug administration.

Reconstitution

Reconstitute with 10 mL of sterile water for injection without preservatives to provide a solution containing 1 unit/mL. Use dispensing pin and diluent provided by the manufacturer.

If foaming (usually slight) occurs, leave the vial undisturbed for several minutes. Gently swirl until the contents are completely dissolved; avoid shaking.

Rate of Administration

Administer over 2 minutes.

Dosage

Expressed in reteplase-specific units, but also may be expressed in mg; each reteplase-specific unit is equivalent to 1.74 mg.

Adults

Acute MI

IV

Total dose is 20 units, given as two 10-unit IV injections 30 minutes apart.

Lower doses of reteplase (two 5-unit doses 30 minutes apart) have been used in conjunction with a platelet glycoprotein (GP IIb/IIIa)-receptor inhibitor, heparin, and aspirin. (See Interactions.)

Cautions for Reteplase

Contraindications

• Active internal bleeding.

• History of cerebrovascular accident.

• Recent intracranial or intraspinal surgery or trauma.

• Intracranial neoplasm.

• Intracranial vascular disease (i.e., arteriovenous malformation, aneurysm).

• Known bleeding diathesis.

• Severe uncontrolled hypertension.

Warnings/Precautions

Warnings

Effects on Hemostasis

Possible bleeding, including internal bleeding at intracranial or retroperitoneal sites or bleeding from the GI, GU, or respiratory tract. Superficial or surface bleeding at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or sites of recent surgical intervention also may occur.

Weigh increased risks of therapy against anticipated benefits in patients with recent major surgery (e.g., CABG), obstetric delivery, organ biopsy, previous puncture of noncompressible vessels, cerebrovascular disease, hypertension (SBP ≥180 mm Hg and/or DBP ≥110 mm Hg), hemostatic defects (e.g., secondary to severe hepatic or renal disease), recent GI (e.g., active peptic ulcer) or GU bleeding, or recent trauma. Also, weigh risks against benefits of therapy in patients with diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions. Weigh risks against benefits in patients receiving concurrent oral anticoagulant therapy (e.g., warfarin). Weigh risks against benefits in patients with any condition in which bleeding constitutes a substantial hazard or would be particularly difficult to manage because of its location.

Initiate therapy only after careful screening for contraindications.

Minimize risk of bleeding by carefully selecting patients and monitoring all potential bleeding sites (e.g., sites of all venous cutdowns, arterial and venous punctures, needle punctures). Avoid IM injections and nonessential handling of patient. Perform invasive venous procedures carefully and as infrequently as possible. Minimize arterial punctures. Avoid arterial and venous invasive procedures in areas that are inaccessible to manual compression (e.g., internal jugular or subclavian punctures). Use of an artery in an upper extremity is preferred if an arterial puncture is essential. Apply pressure to the puncture site for ≥30 minutes followed by a pressure dressing and frequent inspection of the puncture site for bleeding.

If serious bleeding occurs, immediately discontinue anticoagulant therapy; heparin anticoagulation can be reversed with protamine sulfate. Do not administer a second injection of reteplase if serious bleeding occurs with the first injection.

Cardiovascular Effects

Possible fatal cardiogenic shock, heart failure, cardiac arrest, recurrent myocardial ischemia or infarction, myocardial rupture, AV block, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, hypotension, pulmonary edema, or thromboembolism.

Weigh risks against anticipated benefits of therapy in patients with a high likelihood of left heart thrombus (e.g., mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, septic thrombophlebitis, or an occluded arteriovenous cannula at a seriously infected site.

Cholesterol Embolization

Possibly fatal cholesterol crystal embolization associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or thrombolytic agents. Clinical features of cholesterol embolism include livedo reticularis, acute renal failure, gangrenous digits/purple toe syndrome, hypertension, pancreatitis, MI, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.

Arrhythmias

Possible reperfusion-related arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, VPCs, VT).

Have appropriate antiarrhythmic therapy available during and after administration.

Sensitivity Reactions

Sensitivity Reactions

Allergic-type (e.g., pruritus, rash, urticaria) or anaphylactoid reactions (e.g., dyspnea, hypotension) reported rarely.

Institute appropriate therapy if an anaphylactoid reaction occurs.

Readministration

Repeat courses not systematically studied. Do not administer second dose if anaphylaxis occurs with first dose.

Specific Populations

Pregnancy

Category C.

Increases risk of therapy in pregnant women; weigh risks against benefits of therapy in pregnant women.

Lactation

Not known whether reteplase is distributed into milk. Caution if used in nursing women.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Geriatric Use

Intracranial hemorrhage more common. Weigh risks of drug against potential benefits.

Hepatic Impairment

Weigh the risks of therapy against the potential benefits in patients with severe hepatic impairment.

Renal Impairment

Weigh the risks of therapy against the potential benefits in patients with severe renal impairment.

Common Adverse Effects

Bleeding.

Interactions for Reteplase

Specific Drugs

Reteplase Pharmacokinetics

Distribution

Extent

Not known whether reteplase is distributed into human milk.

Elimination

Metabolism

Cleared by the liver and kidney.

Half-life

13–16 minutes.

Stability

Storage

Parenteral

Powder for Injection

2–25°C; protect from light.

Reconstituted solutions contain no preservative. Preferably use solution immediately after preparation; may be used up to 4 hours after reconstitution if stored at 2–30°C. Discard any unused solution after 4 hours.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Drug Compatibility

Reteplase is incompatible with heparin.

Actions

• Binds to fibrin and converts plasminogen to plasmin. Plasmin degrades the fibrin matrix of the thrombus.

• Decreased fibrin affinity compared with alteplase.

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or recent surgery.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Frequently asked questions

• Is Activase the same as tPA?

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