Usage
Reteplase is prescribed for the thrombolytic treatment of acute ST-elevation myocardial infarction (STEMI) to reduce the risk of death and heart failure. Its pharmacological classification is thrombolytic (fibrinolytic). It works by converting plasminogen to plasmin, which degrades fibrin, the primary component of blood clots, thereby dissolving the clot and restoring blood flow.
Alternate Names
Reteplase is also known as recombinant tissue plasminogen activator (rt-PA). Brand names include Retavase and Rapilysin.
How It Works
Pharmacodynamics: Reteplase promotes fibrinolysis by catalyzing the conversion of plasminogen to plasmin, primarily in the presence of fibrin within a thrombus. This leads to the degradation of fibrin, the main constituent of blood clots, thereby dissolving the clot. Reteplase dose-dependently decreases plasma fibrinogen levels (60-80%), which typically return to normal within 2 days.
Pharmacokinetics: Reteplase is administered intravenously. It has a short half-life (13-16 minutes), allowing for bolus administration. The initial half-life is approximately 14 minutes, while the terminal elimination half-life is around 1.6 hours in patients with acute myocardial infarction. Reteplase is eliminated through both renal and hepatic pathways.
Mode of Action: Reteplase binds to fibrin within the thrombus and activates plasminogen, which is also bound to fibrin. The activated plasmin then degrades the fibrin meshwork, leading to thrombolysis. It does not directly inhibit enzymes or modulate neurotransmitters.
Dosage
Standard Dosage
Adults:
- Acute Myocardial Infarction: 10 units IV bolus over 2 minutes, followed by a second 10-unit bolus 30 minutes later. The total dose is 20 units.
Children:
The safety and effectiveness of reteplase have not been established in pediatric patients.
Special Cases:
- Elderly Patients: While no specific dosage adjustments are recommended, elderly patients may have an increased risk of bleeding. Careful monitoring is essential.
- Patients with Renal Impairment: Use with caution due to a potential increased risk of bleeding. No specific dosage adjustment guidelines are available.
- Patients with Hepatic Dysfunction: Use with caution due to a potential increased risk of bleeding. No specific dosage adjustment guidelines are available.
- Patients with Comorbid Conditions: Patients with conditions that increase bleeding risk require careful evaluation and monitoring.
Clinical Use Cases
The primary clinical use case for reteplase is acute ST-elevation myocardial infarction (STEMI). Off-label uses include acute peripheral arterial thromboembolism and restoring patency of occluded IV catheters or AV cannulas. Dosage in these settings varies.
Dosage Adjustments
Dosage adjustments may be necessary for patients with certain comorbid conditions or those at increased risk of bleeding. However, specific guidelines are limited, and clinical judgment is crucial. Concurrent anticoagulant therapy should be managed carefully.
Side Effects
Common Side Effects
- Bleeding (e.g., at injection site, gastrointestinal, genitourinary)
- Nausea
- Vomiting
- Fever
Rare but Serious Side Effects
- Intracranial hemorrhage
- Stroke
- Severe hypotension
- Allergic reactions (including angioedema and anaphylaxis)
Long-Term Effects
Long-term effects are rare as reteplase is administered acutely. However, potential long-term complications can result from bleeding or stroke if they occur.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include major bleeding events (e.g., intracranial hemorrhage, gastrointestinal bleeding) and allergic reactions.
Contraindications
- Active internal bleeding
- Recent stroke (within 3 months)
- Recent intracranial or intraspinal surgery or trauma (within 3 months)
- Intracranial conditions that increase bleeding risk (e.g., neoplasms, arteriovenous malformation, aneurysm)
- Bleeding diathesis
- Severe uncontrolled hypertension
Drug Interactions
Reteplase interacts with anticoagulants (e.g., heparin, warfarin), antiplatelet agents (e.g., aspirin, clopidogrel), and other drugs affecting coagulation. These interactions can increase the risk of bleeding. Heparin and reteplase are physically incompatible and should not be administered through the same IV line. Consult a comprehensive drug interaction resource for a complete list.
Pregnancy and Breastfeeding
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Pregnancy: Reteplase is Pregnancy Category C. Animal studies show potential abortifacient effects. Use only if the potential benefit outweighs the risk.
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Breastfeeding: It is unknown if reteplase is excreted in breast milk. Exercise caution when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Converts plasminogen to plasmin, leading to fibrin degradation and thrombolysis.
- Side Effects: Bleeding, nausea, vomiting, fever. Rarely, stroke, severe hypotension, allergic reactions.
- Contraindications: Active bleeding, recent stroke/trauma/surgery, intracranial lesions, bleeding disorders, uncontrolled hypertension.
- Drug Interactions: Anticoagulants, antiplatelet agents.
- Pregnancy & Breastfeeding: Category C; use with caution in breastfeeding.
- Dosage: 20 units total (two 10-unit boluses 30 minutes apart).
- Monitoring Parameters: Signs of bleeding, ECG, blood pressure, complete blood count, coagulation tests.
Popular Combinations
Reteplase is often used in conjunction with heparin and aspirin in the treatment of acute myocardial infarction, despite the lack of extensive studies on combined use. The rationale is to reduce the risk of re-thrombosis. However, careful monitoring for bleeding is crucial due to the increased risk with combination therapy.
Precautions
- Screen for contraindications and risk factors for bleeding before administration.
- Avoid intramuscular injections.
- Monitor closely for bleeding complications.
- Have appropriate resources available to manage bleeding or allergic reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Reteplase?
A: The recommended dose for adults with acute myocardial infarction is 20 units total, administered as two 10-unit IV boluses 30 minutes apart.
Q2: How is Reteplase administered?
A: Reteplase is administered as an intravenous bolus injection over 2 minutes for each dose.
Q3: What is the mechanism of action of Reteplase?
A: Reteplase converts plasminogen to plasmin, which degrades fibrin, leading to thrombolysis.
Q4: What are the major side effects of Reteplase?
A: The most common side effect is bleeding. Rare but serious side effects include stroke, severe hypotension, and allergic reactions.
Q5: What are the contraindications to Reteplase use?
A: Contraindications include active bleeding, recent stroke/trauma/surgery, intracranial lesions, bleeding disorders, and uncontrolled hypertension.
Q6: Can Reteplase be used in pregnant or breastfeeding women?
A: Reteplase is Pregnancy Category C and should be used during pregnancy only if the potential benefit outweighs the risk. Caution is advised in breastfeeding women as it’s unknown if the drug is excreted in breast milk.
Q7: What are the key drug interactions with Reteplase?
A: Reteplase interacts with anticoagulants and antiplatelet agents, increasing the risk of bleeding. Heparin is incompatible with reteplase in solution.
Q8: What monitoring is required during Reteplase therapy?
A: Monitor for signs of bleeding, changes in vital signs (especially blood pressure), ECG, complete blood count, and coagulation tests.
Q9: How should bleeding complications be managed during Reteplase therapy?
A: Discontinue reteplase and any concomitant anticoagulant therapy. Provide supportive care, including blood product transfusions if necessary. Consult hematology if needed.
