Retavase half-kit

Contraindications

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What is the most important information I should know about Retavase Half-Kit?

Because thrombolytic therapy increases the risk of bleeding, Retavase Half-Kit is contraindicated in the following situations:

• Active internal bleeding
• History of cerebrovascular accident
• Recent intracranial or intraspinal surgery or trauma
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diathesis
• Severe uncontrolled hypertension

Undesirable effects

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What are the possible side effects of Retavase Half-Kit?

The most frequent adverse reaction associated with Retavase Half-Kit® is bleeding. The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.

• Intracranial hemorrhage

  In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with Retavase Half-Kit® was 0.8% (23 of 2,965 patients). As seen with Retavase Half-Kit® and other thrombolytic agents, the risk for intracranial hemorrhage is increased in patients with advanced age or with elevated blood pressure.

• Other types of hemorrhage

  The incidence of other types of bleeding events in clinical studies of Retavase Half-Kit® 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 Retavase Half-Kit® in clinical studies (n = 3,805) was 21.1%. The rates for bleeding events, regardless of severity, for the 10 + 10 unit Retavase Half-Kit® regimen from controlled clinical studies are summarized in Table 3.

Table 3 : Retavase Half-Kit Hemorrhage Rates

In these studies the severity and sites of bleeding events were comparable for Retavase Half-Kit® 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 Retavase Half-Kit® 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 Retavase Half-Kit® therapy. Therefore, Retavase Half-Kit® therapy requires careful attention to potential bleeding sites (e.g., catheter insertion sites, arterial puncture sites).

Among the 2,965 patients receiving Retavase Half-Kit® 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 Retavase Half-Kit® in initial clinical trials. In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving Retavase Half-Kit®.

Patients administered Retavase Half-Kit® as treatment for myocardial infarction have experienced many events which are frequent sequelae of myocardial infarction and may or may not be attributable to Retavase Half-Kit® 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.

Therapeutic indications

Retavase Half-Kit® (Retavase Half-Kit) 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.

Retavase Half-Kit is a thrombolytic (THROM-bo-LIT-ik) drug that is used to dissolve blood clots.

Retavase Half-Kit is used to improve heart function and prevent congestive heart failure or death in people who have had a heart attack.

Retavase Half-Kit may also be used for purposes not listed in this medication guide.

Name of the medicinal product

Qualitative and quantitative composition

Human tissue plasminogen activator, purified, glycosylated, 355 residues purified from CHO cells. Retavase Half-Kit is considered a "third-generation" thrombolytic agent, genetically engineered to retain and delete certain portions of human tPA. Retavase Half-Kit is a deletion mutein of human tPA formed by deleting various amino acids present in endogenous human tPA. Retavase Half-Kit 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 Retavase Half-Kit - kringle-1, finger, and epidermal growth factor (EGF).

Special warnings and precautions for use

Use Retavase Half-Kit Half-Kit as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Retavase Half-Kit Half-Kit is usually administered as an injection at your doctor's office, hospital, or clinic.
• If you miss a dose of Retavase Half-Kit Half-Kit, contact your doctor immediately.

Ask your health care provider any questions you may have about how to use Retavase Half-Kit Half-Kit.

Retavase Half-Kit is used to improve heart function and prevent congestive heart failure or death in people who have had a heart attack.

Dosage (Posology) and method of administration

Retavase Half-Kit® (Retavase Half-Kit) is for intravenous administration only. Retavase Half-Kit® 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 Retavase Half-Kit®. There is no experience with patients receiving repeat courses of therapy with Retavase Half-Kit®. Heparin and Retavase Half-Kit® are incompatible when combined in solution. Do not administer heparin and Retavase Half-Kit® simultaneously in the same intravenous line.

If Retavase Half-Kit® 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 Retavase Half-Kit injection.

Although the value of anticoagulants and antiplatelet drugs during and following administration of Retavase Half-Kit® 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 Retavase Half-Kit® without adjunctive therapy with heparin and aspirin have not been performed.

Reconstitution should be carried out using the diluent and dispensing pin provided with Retavase Half-Kit®. It is important that Retavase Half-Kit® be reconstituted only with the supplied Sterile Water for Injection, USP (without preservatives). The reconstituted preparation results in a colorless solution containing Retavase Half-Kit® 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 Retavase Half-Kit® 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.

Use 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 Retavase Half-Kit®.

Step 3: Remove the protective cap from the spike end of the dispensing pin, and insert the spike into the vial of Retavase Half-Kit® until the security clips lock onto the vial.

Transfer the 10 mL of SWFI through the dispensing pin into the vial of Retavase Half-Kit®.

Step 4: With the dispensing pin and syringe still attached to the vial, swirl the vial gently to dissolve the Retavase Half-Kit®. DO NOT SHAKE.

Step 5: Withdraw 10 mL of Retavase Half-Kit® 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 Retavase Half-Kit® vial according to institutional procedures.

Retavase Half-Kit®, is supplied as a sterile, preservative-free, lyophilized powder in 10.4 unit (equivalent to 18.1 mg Retavase Half-Kit®) vials without a vacuum, in the following packaging configurations:

Retavase Half-Kit® Kit: 2 single-use Retavase Half-Kit® 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;

Retavase Half-Kit® Half-Kit: 1 single-use Retavase Half-Kit® 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.

Store Retavase Half-Kit® 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

Interaction with other medicinal products and other forms of interaction

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What other drugs will affect Retavase Half-Kit?

The interaction of Retavase Half-Kit® 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 Retavase Half-Kit® therapy.

Administration of Retavase Half-Kit® may cause decreases in plasminogen and fibrinogen. During Retavase Half-Kit® 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. Retavase Half-Kit® 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.

Heparin and aspirin have been administered concomitantly with and following the administration of Retavase Half-Kit® in the management of acute myocardial infarction. Because heparin, aspirin, or Retavase Half-Kit® may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.