Reteplase (Monograph)

Brand name: Retavase
Drug class: Thrombolytic Agents

Medically reviewed by Drugs.com on Sep 10, 2024. 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 ST-segment-elevation MI (STEMI), in conjunction with appropriate anticoagulant (e.g., heparin) and antiplatelet (e.g., aspirin and clopidogrel) therapies, to reduce risk of death or heart failure.

Manufacturer states that risk of stroke may outweigh benefit of thrombolytic therapy in patients whose STEMI places them at low risk for death or heart failure.

Current standard of care in patients with 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.

Pulmonary Embolism

Has been used for the treatment of acute pulmonary embolism^{† [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.

ACCP also recommends systemic thrombolytic therapy in selected patients with acute pulmonary embolism who clinically deteriorate after starting anticoagulant therapy but have yet to develop hypotension and who have an acceptable bleeding risk.

Reteplase Dosage and Administration

General

Patient Monitoring

Monitor patients for hypersensitivity reactions and treat appropriately.

Dispensing and Administration Precautions

Based on the Institute for Safe Medication Practices (ISMP), reteplase is a high-alert medication that has a heightened risk of causing significant patient harm when used in error.

Other General Considerations

Institute therapy as soon as possible after acute MI.

Administration

IV Administration

Administer IV.

Incompatible with heparin; do not administer through an IV line containing heparin.

Reconstitution

Supplied as a kit containing components (e.g., sterile water for injection diluent in prefilled syringe, reconstitution spike, vial containing lyophilized drug, syringe plunger, empty sterile syringe) for reconstitution. Insert the reconstitution spike provided by the manufacturer into the vial containing lyophilized reteplase powder. Using the prefilled syringe provided by manufacturer, inject 10 mL of sterile water for injection without preservatives into vial labeled as containing 10 units of lyophilized drug to provide a solution containing 1 unit/mL.

If foaming (usually slight) occurs, leave the vial undisturbed for several minutes. Gently swirl until the contents are completely dissolved (may take up to 2 minutes); avoid shaking. Withdraw the dose of reteplase using the empty, sterile syringe supplied by the manufacturer.

Rate of Administration

Administer over 2 minutes.

Dosage

Expressed in reteplase-specific units.

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.

Special Populations

Geriatric Patients

Based on results of a trial with tenecteplase showing that an excess of intracranial hemorrhage in patients ≥75 years of age with acute MI was reduced after reducing the tenecteplase dosage by 50%, some clinicians suggest considering a 50% reduction in the dosage of reteplase in patients ≥75 years of age receiving the drug for acute MI.

Cautions for Reteplase

Contraindications

Active internal bleeding.
Recent stroke.
Recent (within 3 months) intracranial or intraspinal surgery or serious head trauma.
Intracranial conditions that increase bleeding risk (e.g., neoplasms, arteriovenous malformation, aneurysm).
Bleeding diathesis.
Current severe uncontrolled hypertension.

Warnings/Precautions

Bleeding

Possible bleeding can occur, which may be serious and/or fatal.

Avoid IM injections and other trauma to patient and minimize venipunctures. Avoid puncturing noncompressible veins (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 frequent inspection of the puncture site for bleeding.

If serious bleeding occurs, immediately discontinue concomitant anticoagulant therapy. Do not administer a second injection of reteplase if serious bleeding occurs with the first injection.

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash, pruritis, erythema, glossal edema, hypotension, respiratory distress) reported.

If anaphylactoid reaction occurs, withhold second dose of reteplase (if not yet administered) and initiate appropriate therapy.

Cholesterol Embolization

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

Drug/Laboratory Test Interactions

Reteplase remains active under in vitro conditions when present in blood at pharmacologic concentrations; can result in degradation of fibrinogen in blood samples. Therefore, coagulation tests and measures of fibrinolytic activity are unreliable during reteplase therapy unless specific precautions are taken to prevent in vitro artifacts.

Specific Populations

Pregnancy

Insufficient data to inform a drug-associated risk of adverse developmental outcomes.

Increased risk of bleeding with thrombolytic therapy in pregnant women.

Lactation

Not known whether reteplase is distributed into human milk. Effects on breast-fed infant or milk production also not known.

Pediatric Use

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

Geriatric Use

Intracranial hemorrhage more common in geriatric patients >70 years of age in one trial.

Some clinicians suggest considering a 50% reduction in the dosage of reteplase in patients ≥75 years of age receiving the drug for acute MI.

Common Adverse Effects

Common adverse effects (reported in >5% of patients): Bleeding.

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Abciximab	Increased risk of hemorrhage
Aspirin	Increased risk of hemorrhage	Monitor carefully for bleeding, especially at arterial puncture sites
Dipyridamole	Increased risk of hemorrhage
Heparin	Increased risk of hemorrhage	Monitor carefully for bleeding, especially at arterial puncture sites
Tests, coagulation or fibrinolytic activity	Reteplase can result in degradation of fibrinogen in blood samples unless take precautions to prevent in vitro artifacts
Warfarin	Increased risk of hemorrhage	Weigh risks against anticipated benefits

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. Use solution immediately after preparation. Discard any unused solution.

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

Stress importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses or recent surgery.
Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Reteplase
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV use only	10 units	Retavase (with reconstitution kit containing sterile water for injection diluent and sterile reconstitution spike)	Chiesi USA