reteplase, recombinant
Retavase

Available forms
Available by prescription only
Injection: 10.8 units (18.8 mg)/vial (supplied in kit with components for reconstitution and administration of two single-use vials)

Indications and dosages
 Management of acute MI. Adults: Double-bolus injection of 10 + 10 units. Give each bolus I.V. over 2 minutes. If no complications occur after first bolus, such as serious bleeding or anaphylactoid reactions, give second bolus 30 minutes after start of first bolus. Start treatment soon after onset of symptoms of acute MI. There’s no experience of repeat courses with reteplase.

Pharmacodynamics
Thrombolytic action: Drug catalyzes the cleavage of plasminogen to generate plasmin, which leads to fibrinolysis.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Cleared from plasma at 250 to 450 ml/minute.
Metabolism: Metabolized primarily by the liver and kidney.
Excretion: Plasma half-life of drug is 13 to 16 minutes.

Contraindications and precautions
Contraindicated in patients with active internal bleeding, bleeding diathesis, history of CVA, recent intracranial or intraspinal surgery or trauma, severe uncontrolled hypertension, intracranial neoplasm, arteriovenous malformation, or aneurysm.
  Use cautiously in pregnant patients, patients age 75 and older, and patients with recent (within 10 days) major surgery, obstetric delivery, organ biopsy, or trauma; previous puncture of noncompressible vessels; cerebrovascular disease; recent GI or GU bleeding; hypertension (systolic pressure 180 mm Hg or more or diastolic pressure 110 mm Hg or more); likelihood of left-sided heart thrombus; subacute bacterial endocarditis; acute pericarditis; hemostatic defects; diabetic hemorrhagic retinopathy; septic thrombophlebitis; and other conditions in which bleeding would be difficult to manage.

Interactions
Drug-drug. Heparin; oral anticoagulants; platelet inhibitors, such as abciximab, aspirin, and dipyridamole; vitamin K antagonists: May increase risk of bleeding. Use together cautiously.

Adverse reactions
CNS: intracranial hemorrhage.
CV: arrhythmias, cholesterol embolization.
GI: hemorrhage.
GU: hematuria.
Hematologic: anemia, bleeding tendency, bleeding at puncture site.

Effects on lab test results
• May decrease plasminogen and fibrinogen levels.

Overdose and treatment
No information available. Monitor patient for increased bleeding.

Special considerations
• Reconstitute drug according to manufacturer’s instructions using items provided in the kit.
• Drug is administered I.V. as a double-bolus injection. If bleeding or anaphylactoid reactions occur after first bolus; second bolus may be withheld.
• Don’t give drug with other I.V. drugs through same I.V. line. Heparin and reteplase are incompatible in solution.
• Potency is expressed in units specific to reteplase and not comparable to other thrombolytics.
• Avoid use of noncompressible sites during therapy. If an arterial puncture is needed, use a vessel in the arm. Apply pressure for at least 30 minutes; then apply a pressure dressing. Check site frequently.
• Monitor patient for bleeding. Avoid I.M. injections, invasive procedures, and nonessential handling of patient. Bleeding is the most common adverse reaction and may occur internally or at puncture sites. If local measures don’t control serious bleeding, discontinue concurrent anticoagulation therapy. Withhold second bolus of reteplase.
• Carefully monitor ECG during treatment. Coronary thrombolysis may result in reperfusion arrhythmias. Be prepared to treat bradycardia or ventricular irritability.
• Drug may alter coagulation studies; it remains active in vitro and can lead to degradation of fibrinogen in sample. Collect blood samples in the presence of PPACK (chloromethylketone) at 2-μM concentrations.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Use cautiously because risk of intracranial hemorrhage increases with age.

Patient education
• Tell patient to report adverse reactions, such as bleeding or allergic reaction, immediately.
• Advise patient about proper dental care to avoid excessive gum trauma.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use