Generic Name: Reteplase
Class: Thrombolytic Agents
Chemical Name: 173-l-Serine-174-l-lysine-175-l-glutamine-173-527-plasminogen activator (human tissue-type)
Molecular Formula: C1736H2653N499O522S22
CAS Number: 133652-38-7
Medically reviewed on Oct 23, 2017
Thrombolytic agent; biosynthetic (recombinant DNA origin) form of human tissue-type plasminogen activator (t-PA).1
Uses for Retavase
Current standard of care in patients with ST-segment-elevation MI (STEMI) is timely reperfusion (with primary PCI or thrombolytic therapy).527 994 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.527 994 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.527
Primary PCI is preferred when it can be performed in a timely manner.527 994 Thrombolytic therapy is recommended when it is anticipated that PCI cannot be performed within 120 minutes of first medical contact.527
Benefits of thrombolytic therapy in patients with STEMI are well established;527 resulting reperfusion with reteplase shown to improve ventricular function and reduce incidence of heart failure, cardiogenic shock, and death.1 2 7 8
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.1 3 527 ACCF and AHA recommend administration within 30 minutes of hospital arrival.527
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.1005
Retavase Dosage and Administration
For drug compatibility information, see Drug Compatibility under Stability.
Do not add other IV substances, additives, or other drugs to reteplase solution and do not infuse anything else simultaneously through the same IV line.1
If administered via an IV administration set that is used for infusing heparin, flush line with 0.9% sodium chloride or 5% dextrose solution prior to and following drug administration.1
Rate of Administration
Administer over 2 minutes.1
Expressed in reteplase-specific units, but also may be expressed in mg; each reteplase-specific unit is equivalent to 1.74 mg.1
Total dose is 20 units, given as two 10-unit IV injections 30 minutes apart.1
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.13 14 (See Interactions.)
Cautions for Retavase
Effects on Hemostasis
Possible bleeding, including internal bleeding at intracranial or retroperitoneal sites or bleeding from the GI, GU, or respiratory tract.1 Superficial or surface bleeding at vascular puncture and access sites (e.g., venous cutdowns, arterial punctures) or sites of recent surgical intervention also may occur.1
Weigh increased risks of therapy against anticipated benefits in patients with recent major surgery (e.g., CABG), obstetric delivery, organ biopsy, previous puncture of noncompressible vessels, cerebrovascular disease, hypertension (SBP ≥180 mm Hg and/or DBP ≥110 mm Hg), hemostatic defects (e.g., secondary to severe hepatic or renal disease), recent GI (e.g., active peptic ulcer) or GU bleeding, or recent trauma.1 Also, weigh risks against benefits of therapy in patients with diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions.1 Weigh risks against benefits in patients receiving concurrent oral anticoagulant therapy (e.g., warfarin).1 Weigh risks against benefits in patients with any condition in which bleeding constitutes a substantial hazard or would be particularly difficult to manage because of its location.1
Initiate therapy only after careful screening for contraindications.1
Minimize risk of bleeding by carefully selecting patients and monitoring all potential bleeding sites (e.g., sites of all venous cutdowns, arterial and venous punctures, needle punctures).1 Avoid IM injections and nonessential handling of patient.1 Perform invasive venous procedures carefully and as infrequently as possible.1 Minimize arterial punctures.1 Avoid arterial and venous invasive procedures in areas that are inaccessible to manual compression (e.g., internal jugular or subclavian punctures).1 Use of an artery in an upper extremity is preferred if an arterial puncture is essential.1 Apply pressure to the puncture site for ≥30 minutes followed by a pressure dressing and frequent inspection of the puncture site for bleeding.1
If serious bleeding occurs, immediately discontinue anticoagulant therapy; heparin anticoagulation can be reversed with protamine sulfate.1 Do not administer a second injection of reteplase if serious bleeding occurs with the first injection.1
Possible fatal cardiogenic shock, heart failure, cardiac arrest, recurrent myocardial ischemia or infarction, myocardial rupture, AV block, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, hypotension, pulmonary edema, or thromboembolism.1
Weigh risks against anticipated benefits of therapy in patients with a high likelihood of left heart thrombus (e.g., mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, septic thrombophlebitis, or an occluded arteriovenous cannula at a seriously infected site.1
Possibly fatal cholesterol crystal embolization associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or thrombolytic agents.1 Clinical features of cholesterol embolism include livedo reticularis, acute renal failure, gangrenous digits/purple toe syndrome, hypertension, pancreatitis, MI, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.1
Have appropriate antiarrhythmic therapy available during and after administration.1
Institute appropriate therapy if an anaphylactoid reaction occurs.1
Increases risk of therapy in pregnant women; weigh risks against benefits of therapy in pregnant women.1
Weigh the risks of therapy against the potential benefits in patients with severe hepatic impairment.1
Weigh the risks of therapy against the potential benefits in patients with severe renal impairment.1
Common Adverse Effects
Interactions for Retavase
Monitor carefully for bleeding, especially at arterial puncture sites1
Monitor carefully for bleeding, especially at arterial puncture sites1
Increased risk of hemorrhage1
Weigh risks against anticipated benefits1
Not known whether reteplase is distributed into human milk.1
Cleared by the liver and kidney.1
Powder for Injection
2–25°C; protect from light.1
Reconstituted solutions contain no preservative.1 Preferably use solution immediately after preparation; may be used up to 4 hours after reconstitution if stored at 2–30°C.1 Discard any unused solution after 4 hours.1
For information on systemic interactions resulting from concomitant use, see Interactions.
Reteplase is incompatible with heparin.1
Advice to Patients
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or recent surgery.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
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.
For IV use only
10.4 units (18.1 mg)
Retavase (with reconstitution kit containing sterile water for injection diluent and sterile dispensing pin)
AHFS DI Essentials. © Copyright 2018, Selected Revisions October 23, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
1. PDL BioPharma, Inc. Retavase (reteplase, recombinant) injection prescribing information. Freemont, CA; 2006 Jan.
2. Topol EJ, Ohman M, Armstrong PW et al. Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III trial. Circulation. 2000; 102:1761-5. http://www.ncbi.nlm.nih.gov/pubmed/11023929?dopt=AbstractPlus
3. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators. A comparison of reteplase with alteplase for acute myocardial infarction. N Engl J Med. 1997; 337:118-23.
7. International Joint Efficacy Comparison of Thrombolytics. Randomised, double-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction (INJECT): trial to investigate equivalence. Lancet. 1995; 346:329-36. http://www.ncbi.nlm.nih.gov/pubmed/7623530?dopt=AbstractPlus
8. Smalling RW, Bode C, Kalbfleisch J et al et al. More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. Circulation. 1995; 91:2725-32. http://www.ncbi.nlm.nih.gov/pubmed/7758177?dopt=AbstractPlus
9. Bode C, Smalling RW, Berg G et al et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. Circulation. 1996; 94:891-8. http://www.ncbi.nlm.nih.gov/pubmed/8790022?dopt=AbstractPlus
10. Tebbe U, von Essen R, Smolarz A et al. Open, noncontrolled dose-finding study with a novel recombinant plasminogen activator (BM 06.022) given as a double bolus in patients with acute myocardial infarction. Am J Cardiol. 1993; 72:518-24. http://www.ncbi.nlm.nih.gov/pubmed/8362764?dopt=AbstractPlus
11. Neuhaus KL, von Essen R, Vogt A et al. Dose finding with a novel recombinant plasminogen activator (BM 06.022) in patients with acute myocardial infarction: results of the German recombinant plasminogen activator study. J Am Coll Cardiol. 1994; 24:55-60. http://www.ncbi.nlm.nih.gov/pubmed/8006283?dopt=AbstractPlus
12. Boehringer Mannheim Corporation, Gaithersburg, MD: Personal communication.
13. Centocor Inc., Malvern, PA: Personal communication.
14. Topol EJ, GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combinaiton reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomized trial. Lancet. 2001; 357: 1905-14. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3372408&blobtype=pdf
20. Konstantinides S. Clinical practice. Acute pulmonary embolism. N Engl J Med. 2008; 359:2804-13. http://www.ncbi.nlm.nih.gov/pubmed/19109575?dopt=AbstractPlus
527. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; 127:e362-425. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3695607&blobtype=pdf
803. Lamas GA, Escolar E, Faxon DP. Examining treatment of ST-elevation myocardial infarction: the importance of early intervention. J Cardiovasc Pharmacol Ther. 2010; 15:6-16. http://www.ncbi.nlm.nih.gov/pubmed/20061507?dopt=AbstractPlus
805. Reed GW, Rossi JE, Cannon CP. Acute myocardial infarction. Lancet. 2017; 389:197-210. http://www.ncbi.nlm.nih.gov/pubmed/27502078?dopt=AbstractPlus
807. Smith JN, Negrelli JM, Manek MB et al. Diagnosis and management of acute coronary syndrome: an evidence-based update. J Am Board Fam Med. 2015 Mar-Apr; 28:283-93.
994. Levine GN, Bates ER, Blankenship JC et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011; 58:e44-122. http://www.ncbi.nlm.nih.gov/pubmed/22070834?dopt=AbstractPlus
1005. Kearon C, Akl EA, Comerota AJ et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e419S-94S. http://www.ncbi.nlm.nih.gov/pubmed/22315268?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3278049&blobtype=pdf
1013. Monagle P, Chan AK, Goldenberg NA et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl):e737S-801S. http://www.ncbi.nlm.nih.gov/pubmed/22315277?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3278066&blobtype=pdf
1100. Amsterdam EA, Wenger NK, Brindis RG et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 130:e344-426. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4676081&blobtype=pdf
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