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Medically reviewed on Nov 15, 2018


(RE ta plase)

Index Terms

  • r-PA
  • Recombinant Plasminogen Activator

Pharmacologic Category

  • Thrombolytic Agent


Reteplase is a nonglycosylated form of tPA produced by recombinant DNA technology using E. coli; it initiates local fibrinolysis by binding to fibrin in a thrombus (clot) and converts entrapped plasminogen to plasmin


Feces and urine

Clearance: Plasma: 250-450 mL/minute

Onset of Action

Thrombolysis: 30-90 minutes

Half-Life Elimination

13-16 minutes

Use: Labeled Indications

Management of ST-elevation myocardial infarction (STEMI) for the improvement of ventricular function, the reduction of the incidence of CHF, and the reduction of mortality following STEMI

Recommended criteria for treatment of STEMI (ACCF/AHA; O’Gara, 2013): Ischemic symptoms within 12 hours of treatment or evidence of ongoing ischemia 12-24 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability.

STEMI ECG definition: New ST-segment elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous precordial leads or limb leads on ECG. New or presumably new left bundle branch block (LBBB) may interfere with ST-elevation analysis and should not be considered diagnostic in isolation.

At non-PCI-capable hospitals, the ACCF/AHA recommends thrombolytic therapy administration when the anticipated first medical contact (FMC)-to-device time at a PCI-capable hospital is >120 minutes due to unavoidable delays.


Active internal bleeding; history of cerebrovascular accident; recent (ie, within 2 months) intracranial or intraspinal surgery or trauma; intracranial neoplasm, arteriovenous malformations, or aneurysm; known bleeding diathesis; severe uncontrolled hypertension

Additional contraindications (ACCF/AHA [O’Gara, 2013]): Ischemic stroke within 3 months; prior intracranial hemorrhage; active bleeding (excluding menses); suspected aortic dissection; significant closed head or facial trauma within 3 months

Dosing: Adult

Note: Retavase and Retavase Half-Kit have been discontinued in the US for more than 1 year.

STEMI: IV: 10 units IV over 2 minutes, followed by a second dose 30 minutes later of 10 units IV over 2 minutes; withhold second dose if serious bleeding or anaphylaxis occurs.

Note: Thrombolytic should be administered within 30 minutes of hospital arrival. Generally, there is only a small trend for benefit of therapy after a delay of 12 to 24 hours from symptom onset, but thrombolysis may be considered for selected patients with ongoing ischemic pain and extensive ST elevation; however, primary PCI is preferred in these patients. Administer concurrent aspirin, clopidogrel, and anticoagulant therapy (ie, unfractionated heparin, enoxaparin, or fondaparinux) with reteplase (O’Gara, 2013).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer’s labeling. However, risks of reteplase therapy may be increased.

Hemodialysis: Dialyzable: Unknown, but unlikely (NCS/SCCM [Frontera 2016])

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer’s labeling. However, risks of reteplase therapy may be increased.


Reteplase should be reconstituted using the diluent, syringe, needle, and dispensing pin provided with each kit. Do not shake while reconstituting; swirl gently. Once reconstituted, use within 4 hours.


IV: Reconstituted dose should be administered IV over 2 minutes; no other medication should be added to the injection solution.


Dosage kits should be stored at 2°C to 25°C (36°F to 77°F) and remain sealed until use in order to protect from light.

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Consider therapy modification

Dabigatran Etexilate: Thrombolytic Agents may enhance the anticoagulant effect of Dabigatran Etexilate. Management: Carefully monitor for bleeding. Dabigatran Canadian labeling recommends avoiding use with thrombolytic agents. Consider avoiding alteplase treatment of acute ischemic stroke in patients receiving dabigatran (see full drug monograph for details). Monitor therapy

Desirudin: Thrombolytic Agents may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with thrombolytic agents prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Consider therapy modification

Limaprost: May enhance the adverse/toxic effect of Thrombolytic Agents. The risk for bleeding may be increased. Monitor therapy

Prostacyclin Analogues: Thrombolytic Agents may enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Monitor therapy

Test Interactions

Altered results of coagulation and fibrinolytic activity tests

Adverse Reactions

Bleeding is the most frequent adverse effect associated with reteplase. Heparin and aspirin have been administered concurrently with reteplase in clinical trials. The incidence of adverse events is a reflection of these combined therapies, and is comparable to comparison thrombolytics.

>10%: Local: Bleeding at injection site (5% to 49%)

1% to 10%:

Gastrointestinal: Gastrointestinal hemorrhage (2% to 9%)

Hematologic & oncologic: Hemorrhage (genitourinary: 1% to 10%), anemia (1% to 3%)

<1%, postmarketing, and/or case reports: Anaphylactoid reaction, atheromatous embolism, hypersensitivity reaction, intracranial hemorrhage


Concerns related to adverse effects:

• Anaphylaxis: Rare anaphylactic reactions can occur.

• Arrhythmias: Coronary thrombolysis may result in reperfusion arrhythmias.

• Bleeding: Monitor all potential bleeding sites. If serious bleeding occurs, the infusion of reteplase and heparin should be stopped.

Disease-related concerns:

• Conditions that increase bleeding risk: For the following conditions the risk of bleeding is higher with use of reteplase and should be weighed against the benefits of therapy: recent (within 10 days) major surgery (eg, CABG, obstetrical delivery, organ biopsy), recent puncture of noncompressible vessels, cerebrovascular disease, recent gastrointestinal or genitourinary bleeding, recent trauma including CPR, hypertension (systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg), high likelihood of left heart thrombus (eg, mitral stenosis with atrial fibrillation), acute pericarditis, subacute bacterial endocarditis, hemostatic defects including ones caused by severe renal or hepatic dysfunction, significant hepatic or renal dysfunction, diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions, septic thrombophlebitis or occluded AV cannula at seriously infected site, or any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of location.

• Myocardial infarct (MI): Appropriate use: Follow standard management for MI while infusing reteplase.

Concurrent drug therapy issues:

• Anticoagulants: Use with caution in patients receiving oral anticoagulants; increased risk of bleeding. Adjunctive use of parenteral anticoagulants (eg, enoxaparin, heparin, or fondaparinux) is recommended to improve vessel patency and prevent reocclusion (ACCF/AHA; O’Gara, 2013); however, these may also contribute to bleeding; monitor for bleeding.

Special populations:

• Elderly: Use with caution in patients with advanced age (eg, >75 years); increased risk of bleeding.

Other warnings/precautions:

• Administration: Intramuscular injections and nonessential handling of the patient should be avoided. Venipunctures should be performed carefully and only when necessary. If arterial puncture is necessary, use an upper extremity vessel that can be manually compressed.

Monitoring Parameters

Monitor for signs of bleeding (hematuria, GI bleeding, gingival bleeding); CBC, PTT; ECG monitoring

Pregnancy Risk Factor


Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. The risk of bleeding may be increased in pregnant women.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), blue/black/purple skin discoloration, change in amount of urine passed, severe headache, severe dizziness, passing out, angina, vision changes, muscle pain, dark urine, severe abdominal pain, back pain, nausea, vomiting, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.