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What is the most important information I should know about Reteplase?
Because thrombolytic therapy increases the risk of bleeding, Reteplase is contraindicated in the following situations:
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What are the possible side effects of Reteplase?
The most frequent adverse reaction associated with Reteplase® is bleeding. The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.
In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with Reteplase® was 0.8% (23 of 2,965 patients). As seen with Reteplase® and other thrombolytic agents, the risk for intracranial hemorrhage is increased in patients with advanced age or with elevated blood pressure.
The incidence of other types of bleeding events in clinical studies of Reteplase® varied depending upon the use of arterial catheterization or other invasive procedures and whether the study was performed in Europe or the USA. The overall incidence of any bleeding event in patients treated with Reteplase® in clinical studies (n = 3,805) was 21.1%. The rates for bleeding events, regardless of severity, for the 10 + 10 unit Reteplase® regimen from controlled clinical studies are summarized in Table 3.
Table 3 : Reteplase Hemorrhage Rates
| Bleeding Site | INJECT Europe n = 2,965 | RAPID 1 and RAPID 2 | |
| USA n = 210 | Europe n =113 | ||
| Injection Site* | 4.6% | 48.6% | 19.5% |
| Gastrointestinal | 2.5% | 9.0% | 1.8% |
| Genitourinary | 1.6% | 9.5% | 0.9% |
| Anemia, site unknown | 2.6% | 1.4% | 0.9% |
| *includes the arterial catheterization site (all patients in the RAPID studies underwent arterial catheterization). |
In these studies the severity and sites of bleeding events were comparable for Reteplase® and the comparison thrombolytic agents.
Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, any concomitant heparin should be terminated immediately. In addition, the second bolus of Reteplase® should not be given if the 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.
Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during Reteplase® therapy. Therefore, Reteplase® therapy requires careful attention to potential bleeding sites (e.g., catheter insertion sites, arterial puncture sites).
Allergic ReactionsAmong the 2,965 patients receiving Reteplase® in the INJECT trial, serious allergic reactions were noted in 3 patients, with one patient experiencing dyspnea and hypotension. No anaphylactoid reactions were observed among the 3,856 patients treated with Reteplase® in initial clinical trials. In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving Reteplase®.
Other Adverse ReactionsPatients administered Reteplase® as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to Reteplase® 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. Other adverse events have been reported, including nausea and/or vomiting, hypotension, and fever.
Reteplase® (Reteplase) is indicated 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.
Reteplase is a thrombolytic (THROM-bo-LIT-ik) drug that is used to dissolve blood clots.
Reteplase is used to improve heart function and prevent congestive heart failure or death in people who have had a heart attack.
Reteplase may also be used for purposes not listed in this medication guide.
Human tissue plasminogen activator, purified, glycosylated, 355 residues purified from CHO cells. Reteplase is considered a "third-generation" thrombolytic agent, genetically engineered to retain and delete certain portions of human tPA. Reteplase is a deletion mutein of human tPA formed by deleting various amino acids present in endogenous human tPA. Reteplase contains 355 of the 527 amino acids of native human tPA (amino acids 1-3 and 176-527), and retains the activity-related kringle-2 and serine protease domains of human tPA. Three domains are deleted from Reteplase - kringle-1, finger, and epidermal growth factor (EGF).
Use Reteplase as directed by your doctor. Check the label on the medicine for exact dosing instructions.
Ask your health care provider any questions you may have about how to use Reteplase.
There are specific as well as general uses of a drug or medicine. A medicine can be used to prevent a disease, treat a disease over a period or cure a disease. It can also be used to treat the particular symptom of the disease. The drug use depends on the form the patient takes it. It may be more useful in injection form or sometimes in tablet form. The drug can be used for a single troubling symptom or a life-threatening condition. While some medications can be stopped after few days, some drugs need to be continued for prolonged period to get the benefit from it.Reteplase is used to improve heart function and prevent congestive heart failure or death in people who have had a heart attack.
Reteplase® (Reteplase) is for intravenous administration only. Reteplase® is administered as a 10 + 10 unit double-bolus injection. Two 10 unit bolus injections are required for a complete treatment. Each bolus is administered as an intravenous injection over 2 minutes. The second bolus is given 30 minutes after initiation of the first bolus injection. Each bolus injection should be given via an intravenous line in which no other medication is being simultaneously injected or infused. No other medication should be added to the injection solution containing Reteplase®. There is no experience with patients receiving repeat courses of therapy with Reteplase®. Heparin and Reteplase® are incompatible when combined in solution. Do not administer heparin and Reteplase® simultaneously in the same intravenous line.
If Reteplase® is to be injected through an intravenous line containing heparin, a normal saline or 5% dextrose (D5W) solution should be flushed through the line prior to and following the Reteplase injection.
Although the value of anticoagulants and antiplatelet drugs during and following administration of Reteplase® has not been studied, heparin has been administered concomitantly in more than 99% of patients. Aspirin has been given either during and/or following heparin treatment. Studies assessing the safety and efficacy of Reteplase® without adjunctive therapy with heparin and aspirin have not been performed.
Reconstitution – Reteplase® Kit and Reteplase® Half-KitReconstitution should be carried out using the diluent and dispensing pin provided with Reteplase®. It is important that Reteplase® be reconstituted only with the supplied Sterile Water for Injection, USP (without preservatives). The reconstituted preparation results in a colorless solution containing Reteplase® 1 unit/mL. Slight foaming upon reconstitution is not unusual; allowing the vial to stand undisturbed for several minutes is usually sufficient to allow dissipation of any large bubbles.
Because Reteplase® contains no antibacterial preservatives, it should be reconstituted immediately before use. When reconstituted as directed, the solution may be used within 4 hours when stored at 2- 30°C (36-86°F). Prior to administration, the product should be visually inspected for particulate matter and discoloration.
Reconstitution Instructions – Reteplase® Kit and Reteplase® Half-KitUse aseptic technique throughout.
Step 1: Withdraw 10 mL of Sterile Water for Injection, USP (SWFI) from the supplied vial into a sterile 10 mL syringe.
Step 2: Open the package containing the dispensing pin.
Remove the protective cap from the luer lock port of the dispensing pin and connect the sterile 10mL syringe to the dispensing pin.
Remove the protective flip-cap from one vial of Reteplase®.
Step 3: Remove the protective cap from the spike end of the dispensing pin, and insert the spike into the vial of Reteplase® until the security clips lock onto the vial.
Transfer the 10 mL of SWFI through the dispensing pin into the vial of Reteplase®.
Step 4: With the dispensing pin and syringe still attached to the vial, swirl the vial gently to dissolve the Reteplase®. DO NOT SHAKE.
Step 5: Withdraw 10 mL of Reteplase® reconstituted solution back into the syringe. A small amount of solution will remain in the vial due to overfill.
Step 6: Detach the syringe from the dispensing pin, and attach a sterile needle.
Step 7: The 10 mL bolus dose is now ready for administration.
Safely discard all used reconstitution components and the empty Reteplase® vial according to institutional procedures.
How supplied| Reteplase® Kit | NDC 24477-041-02 |
| Reteplase® Half-Kit | NDC 24477-040-01 |
Reteplase®, is supplied as a sterile, preservative-free, lyophilized powder in 10.4 unit (equivalent to 18.1 mg Reteplase®) vials without a vacuum, in the following packaging configurations:
Reteplase® Kit: 2 single-use Reteplase® vials 10.4 units (18.1 mg), 2 single-use diluent vials for reconstitution (10 mL Sterile Water for Injection, USP), 2 sterile 10 mL syringes, 2 sterile dispensing pins, 4 sterile needles, 2 alcohol swabs and a package insert;
Reteplase® Half-Kit: 1 single-use Reteplase® vial 10.4 units (18.1 mg), 1 single-use diluent vial for reconstitution (10 mL Sterile Water for Injection, USP), a sterile dispensing pin and a package insert.
StorageStore Reteplase® at 2-25°C (36-77°F). The box should remain sealed until use to protect the lyophilisate from exposure to light. Do not use beyond the expiration date printed on the box.
Manufactured by: EKR Therapeutics, Inc. Bedminster, NJ 07921. Manufactured at: Hospira, Inc., McPherson, KS 67460. Revised: Jan 2010
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What other drugs will affect Reteplase?
The interaction of Reteplase® with other cardioactive drugs has not been studied. In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as aspirin, dipyridamole, and abciximab) may increase the risk of bleeding if administered prior to or after Reteplase® therapy.
Drug/Laboratory Test InteractionsAdministration of Reteplase® may cause decreases in plasminogen and fibrinogen. During Reteplase® therapy, if coagulation tests and/or measurements of fibrinolytic activity are performed, the results may be unreliable unless specific precautions are taken to prevent in vitro artifacts. Reteplase® is an enzyme that when present in blood in pharmacologic concentrations remains active under in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis. Collection of blood samples in the presence of PPACK (chloromethylketone) at 2 μM concentrations was used in clinical trials to prevent in vitro fibrinolytic artifacts.
Use Of AntithromboticsHeparin and aspirin have been administered concomitantly with and following the administration of Reteplase® in the management of acute myocardial infarction. Because heparin, aspirin, or Reteplase® may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.
