Retavase^®

(reteplase, recombinant)

Description:
Retavase^® (reteplase recombinant) is a non-glycosylated deletion mutein of tissue plasminogen activator (tPA), containing the kringle 2 and the protease domains of human tPA. Retavase^® contains 355 of the 527 amino acids of native tPA (amino acids 1-3 and 176-527). Retavase^® is produced by recombinant DNA technology in E. coli. The protein is isolated as inactive inclusion bodies from E. coli, converted into its active form by an in vitro folding process and purified by chromatographic separation. The molecular weight of reteplase is 39,571 daltons.

Indication:
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.

Additional information about Retavase is available at www.retavase.com

Full Prescribing Information

Important Safety Information
Thrombolytic therapy increases the risk of bleeding, therefore Retavase (reteplase, recombinant) is contraindicated patients with: active internal bleeding, a history of cerebrovascular accident, recent intracranial or intraspinal surgery or trauma, intracranial neoplasm, arteriovenous malformation, or aneurysm, known bleeding diathesis, and severe uncontrolled hypertension.

The most common complication encountered during Retavase^® 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, and sites of recent surgical intervention). The concomitant use of heparin anticoagulation may contribute to bleeding.

As fibrin is lysed during Retavase^® therapy, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful attention to all potential bleeding sites. Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from noncompressible sites.

If serious bleeding occurs, concomitant anticoagulant therapy should be terminated immediately. In addition, the second bolus of Retavase^® should not be given if 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.

Each patient being considered for therapy with Retavase^® should be carefully evaluated and anticipated benefits weighed against the potential risks associated with therapy.

Cholesterol embolism, which can be lethal, has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown.

Coronary thrombolysis may result in arrhythmias associated with reperfusion. It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available when Retavase^® is administered.

Reteplase should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There are no adequate and well controlled studies in pregnant women. The most common complication of thrombolytic therapy is bleeding and certain conditions, including pregnancy, can increase this risk.

Patients administered Retavase^® as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to Retavase^® therapy. These events include cardiogenic 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 thrombosis and embolism, and electromechanical dissociation. These events can be life-threatening and may lead to death.

Retavase^® is a registered trademark of EKR Therapeutics, Inc., Bedminster, NJ, USA.