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Reteplase

Medically reviewed by Drugs.com. Last updated on Jun 22, 2019.

Pronunciation

(RE ta plase)

Index Terms

  • r-PA
  • Recombinant Plasminogen Activator

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Intravenous [preservative free]:

Retavase: 2 X 10 UNIT [contains polysorbate 80]

Retavase Half-Kit: 1 X 10 UNIT [contains polysorbate 80]

Brand Names: U.S.

  • Retavase
  • Retavase Half-Kit

Pharmacologic Category

  • Thrombolytic Agent

Pharmacology

Reteplase is a recombinant plasminogen activator which catalyzes the cleavage of endogenous plasminogen to generate plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

Excretion

Feces and urine

Clearance: Plasma: 250 to 450 mL/minute

Onset of Action

Thrombolysis: 30 to 90 minutes

Half-Life Elimination

13 to 16 minutes

Use: Labeled Indications

ST-elevation myocardial infarction, acute: Use in acute ST-elevation myocardial infarction (STEMI) to reduce the risk of death and heart failure

Limitation of use: The risk of stroke may outweigh the benefit produced by thrombolytic therapy in patients whose STEMI puts them at low risk for death or heart failure.

Contraindications

Active internal bleeding; recent stroke; intracranial or intraspinal surgery or serious head trauma within 3 months; intracranial conditions that increase the risk of bleeding (eg, neoplasm, arteriovenous malformations, or aneurysm); bleeding diathesis; severe uncontrolled hypertension

Additional contraindications (ACCF/AHA [O’Gara 2013]): Ischemic stroke within 3 months; any prior intracranial hemorrhage; active bleeding (excluding menses); suspected aortic dissection; significant closed head or facial trauma within 3 months with radiographic evidence of bony fracture or brain injury

Dosing: Adult

ST-elevation myocardial infarction (STEMI), acute: IV: 10 units IV over 2 minutes, followed by a second dose 30 minutes later of 10 units IV over 2 minutes

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 (ACCF/AHA [O’Gara 2013]).

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Reconstitute using the supplied 10 mL syringe and 10 mL SWFI. Do not shake when reconstituting. Slight foaming is normal and will dissipate if left standing for several minutes. The reconstituted solution is 1 unit/mL. Use immediately after reconstitution.

Administration

IV: For IV use only; do not administer IM. Administer reconstituted dose over 2 minutes; no other medication should be added to the injection solution.

Storage

Store at 2°C to 25°C (36°F to 77°F); keep sealed until use 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

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

1% to 10%:

Gastrointestinal: Gastrointestinal hemorrhage (9%)

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

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

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: Coronary thrombolysis may result in reperfusion arrhythmias (eg, sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia). Antiarrhythmic therapy should be available during therapy (Miller 1986).

• Bleeding: Internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding (especially at arterial and noncompressible venous puncture sites) may occur (may be fatal). Monitor all potential bleeding sites. If serious bleeding occurs, the infusion of reteplase and any other concurrent anticoagulants (eg, heparin) should be stopped and the patient should be treated appropriately.

• Cholesterol embolization: Has been reported rarely in patients treated with thrombolytic agents; may present as livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, or rhabdomyolysis and can be fatal.

• Hypersensitivity reactions: Have been reported, including glossal edema, hypotension, and respiratory distress. If anaphylactoid reaction occurs, withhold second dose of reteplase and initiate appropriate therapy.

• Thromboembolic events: Use may increase risk of thromboembolic events in patients with high probability of left heart thrombus (eg, patients with mitral stenosis or atrial fibrillation).

Disease-related concerns:

• Conditions that increase bleeding risk: For the following conditions the risk of bleeding is higher with use of thrombolytics and should be weighed against the benefits of therapy: History of chronic, severe, poorly controlled hypertension; significant hypertension on presentation (systolic BP >180 mm Hg or diastolic BP >110 mm Hg); history of prior ischemic stroke >3 months; dementia; traumatic or prolonged CPR (>10 minutes); major surgery (<3 weeks); recent internal bleeding (within 2 to 4 weeks); noncompressible vascular punctures; active peptic ulcer; oral anticoagulant therapy (ACC/AHA [O’Gara 2013]); lumbar puncture within 10 days (ASRA [Horlocker 2010]).

• STEMI: Appropriate use: Follow standard management for STEMI while infusing reteplase.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

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

Dosage form specific issues:

Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Other warnings/precautions:

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

Monitoring Parameters

CBC, aPTT; signs/symptoms of bleeding; ECG monitoring

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; blood in the urine; 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, chest pain, 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.

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