Reteplase

Reteplase
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

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Overview

Reteplase is a tissue plasminogen activator that is FDA approved for the {{{indicationType}}} of acute myocardial infarction. Common adverse reactions include bleeding.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acute Myocardial Infarction

• Reteplase is indicated for use in the management of acute myocardial infarction (AMI) in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure and the reduction of mortality associated with AMI.
• Treatment should be initiated as soon as possible after the onset of AMI symptoms
• Dosing Information

• First dose: 10 unit IV bolus' over 2 minutes
• Second dose (30 minutes after first bolus): 10 unit IV bolus' over 2 minutes

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in adult patients.

Non–Guideline-Supported Use

Vascular Graft Thrombosis

• Dosing Information

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Pulmonary Embolism

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Acute Peripheral Ischemia

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Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Reteplase FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Reteplase in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Reteplase in pediatric patients.

Contraindications

• Active internal bleeding

• History of cerebrovascular accident

• Recent intracranial or intraspinal surgery or trauma

• Intracranial neoplasm, arteriovenous malformation, or aneurysm

• Known bleeding diathesis

• Severe uncontrolled hypertension

Warnings

Bleeding

• The most common complication encountered during reteplase therapy is bleeding. The sites of bleeding include both internal bleeding sites (intracranial, retroperitoneal, gastrointestinal, genitourinary, or respiratory) and superficial bleeding sites (venous cutdowns, arterial punctures, sites of recent surgical intervention).
• The concomitant use of heparin anticoagulation may contribute to bleeding.
• In clinical trials some of the hemorrhage episodes occurred one or more days after the effects of reteplase had dissipated, but while heparin therapy was continuing.
• As fibrin is lysed during reteplase therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites, and needle puncture sites).
• Noncompressible arterial puncture must be avoided andinternal jugular and subclavian venous punctures should be avoided to minimize bleeding from noncompressible sites.

• Should an arterial puncture be necessary during the administration of reteplase, it is preferable to use an upper extremity vessel that is accessible to manual compression.
• Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
• Intramuscular injections and nonessential handling of the patient should be avoided during treatment with reteplase.
• Venipunctures should be performed carefully and only as required.
• Should serious bleeding (not controllable by local pressure) occur, concomitant anticoagulant therapy should be terminated immediately.
• In addition, the second bolus of reteplase should not be given if serious bleeding occurs before it is administered.
• Each patient being considered for therapy with reteplase should be carefully evaluated and anticipated benefits weighed against the potential risks associated with therapy.
• In the following conditions, the risks of reteplase therapy may be increased and should be weighed against the anticipated benefits:

• Recent major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy
• Previous puncture of noncompressible vessels
• Cerebrovascular disease
• Recent gastrointestinal or genitourinary bleeding
• Recent trauma
• Hypertension: systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg
• High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
• Acute pericarditis
• Subacute bacterial endocarditis
• Hemostatic defects including those secondary to severe hepatic or renal disease
• Severe hepatic or renal dysfunction
• Pregnancy
• Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions
• Septic thrombophlebitis or occluded AV cannula at a seriously infected site
• Advanced age
• Patients currently receiving oral anticoagulants, e.g., warfarin sodium
• Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location

Cholesterol Embolization

• Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown.
• This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
• Clinical features of cholesterol embolism may include livedo reticularis, "purple toe syndrome” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis,myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.

Arrhythmias

• Coronary thrombolysis may result in arrhythmias associated with reperfusion.
• These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) are not different from those often seen in the ordinary course of acute myocardial infarction and should be managed with standard antiarrhythmic measures.
• It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available when reteplase is administered.

Adverse Reactions

Clinical Trials Experience

Bleeding

• The most frequent adverse reaction associated with reteplase is bleeding.
• The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.

Intracranial hemorrhage

• In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with reteplase was 0.8% (23 of 2,965 patients).
• As seen with reteplase and other thrombolytic agents, the risk for intracranial hemorrhage is increased in patients with advanced age or with elevated blood pressure.

Other types of hemorrhage

• The incidence of other types of bleeding events in clinical studies of reteplase varied depending upon the use of arterial catheterization or other invasive procedures and whether the study was performed in Europe or the USA.
• The overall incidence of any bleeding event in patients treated with reteplase in clinical studies (n = 3,805) was 21.1%.
• The rates for bleeding events, regardless of severity, for the 10 + 10 unit reteplase regimen from controlled clinical studies are summarized in Table 3.

File:Reteplase hemorrahge rates.JPG

• In these studies the severity and sites of bleeding events were comparable for reteplase and the comparison thrombolytic agents.

• Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, any concomitant heparin should be terminated immediately.
• In addition, the second bolus of reteplase should not be given if the serious bleeding occurs before it is administered.
• Death and permanent disability are not uncommonly reported in patients who have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.

• Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during reteplase therapy.
• Therefore, reteplasetherapy requires careful attention to potential bleeding sites (e.g., catheter insertion sites, arterial puncture sites).

Allergic Reactions

• Among the 2,965 patients receiving reteplase in the INJECT trial, serious allergic reactions were noted in 3 patients, with one patient experiencing dyspnea and hypotension.
• No anaphylactoid reactions were observed among the 3,856 patients treated with reteplase in initial clinical trials.
• In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving reteplase.

Other Adverse Reactions

• Patients administered reteplase as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to reteplase therapy.
• These events includecardiogenic shock, arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation), AV block, pulmonary edema,heart failure, cardiac arrest, recurrent ischemia, reinfarction, myocardial rupture, mitral regurgitation, pericardial effusion, pericarditis, cardiac tamponade, venous thrombosisand embolism, and electromechanical dissociation.
• These events can be life-threatening and may lead to death.
• Other adverse events have been reported, including nausea and/or vomiting, hypotension, and fever.

Postmarketing Experience

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Use in Specific Populations

Pregnancy

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Labor and Delivery

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Nursing Mothers

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Pediatric Use

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Geriatic Use

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Race

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Renal Impairment

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Hepatic Impairment

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Females of Reproductive Potential and Males

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Immunocompromised Patients

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Others

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Administration and Monitoring

Administration

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Monitoring

Condition 1

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Condition 2

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Condition 3

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IV Compatibility

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Not Tested

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Y-Site

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Admixture

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Syringe

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TPN/TNA

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Overdosage

Acute Overdose

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Management

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Chronic Overdose

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Pharmacology

Reteplase
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Mechanism of Action

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Structure

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Clinical Studies

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How Supplied

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Storage

There is limited information regarding Reteplase Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

(Patient Counseling Information)

Precautions with Alcohol

Alcohol-Reteplase interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Reteplase Brand Names in the drug label.

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Drug Shortage

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References

The contents of this FDA label are provided by the National Library of Medicine.