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Bleeding: The most frequent adverse reaction associated with Retavase® is bleeding (see WARNINGS).The types of bleeding events associated with thrombolytic therapy may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.
- Intracranial hemorrhage (see CLINICAL PHARMACOLOGY)
In the INJECT clinical trial the rate of in-hospital, intracranial hemorrhage among all patients treated with Retavase® (reteplase) was 0.8% (23 of 2,965 patients). As seen with Retavase® (reteplase) 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® (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 Retavase® (reteplase) in clinical studies (n = 3,805) was 21.1%. The rates for bleeding events, regardless of severity, for the 10 + 10 unit Retavase® (reteplase) regimen from controlled clinical studies are summarized in Table 3.
Table 3: Retavase® (reteplase) Hemorrhage Rates
|Bleeding Site||INJECT||RAPID 1 and RAPID 2|
n = 2,965
n = 210
|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 Retavase® (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 Retavase® (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 Retavase® (reteplase) therapy. Therefore, Retavase® (reteplase) therapy requires careful attention to potential bleeding sites (e.g.,catheter insertion sites, arterial puncture sites).
Allergic Reactions: Among the 2,965 patients receiving Retavase® (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 Retavase® (reteplase) in initial clinical trials. In an ongoing clinical trial two anaphylactoid reactions have been reported among approximately 2,500 patients receiving Retavase® (reteplase) .
Other Adverse Reactions: Patients administered Retavase® (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 Retavase® (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.
Read the Retavase (reteplase) Side Effects Center for a complete guide to possible side effects
The interaction of Retavase® (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 Retavase® (reteplase) therapy.
Drug/Laboratory Test Interactions: Administration of Retavase® (reteplase) may cause decreases in plasminogen and fibrinogen. During Retavase® (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.Retavase® (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 ÁM concentrations was used in clinical trials to prevent in vitro fibrinolytic artifacts.6
Use of Antithrombotics: Heparin and aspirin have been administered concomitantly with and following the administration of Retavase® (reteplase) in the management of acute myocardial infarction. Because heparin,aspirin, or Retavase® (reteplase) may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.
6. Martin U, Gärtner D, Markl HJ, et al.D-PHE-PRO-ARGCHLOROMETHYLKETONE prevents in vitro fibrinogen reduction by the novel recombinant plasminogen activator BM 06.022. Ann Hematol. 1992;64(suppl)A47.
Last reviewed on RxList: 9/15/2008
This monograph has been modified to include the generic and brand name in many instances.
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