Retavase Side Effects, and Drug Interactions - Reteplase

Retavase Side Effects, and Drug Interactions - Reteplase

SIDE EFFECTS

Bleeding

The most frequent adverse reaction associated with RetavaseŽ 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 RetavaseŽ was 0.8% (23 of 2,965 patients). As seen with RetavaseŽ 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 RetavaseŽ varied depending upon the use of arterial catheterization of 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 RetavaseŽ in clinical studies (n = 3,805) was 21.1%. The rates for bleeding events, regardless of severity, for the 10 + 10 U RetavaseŽ regimen from controlled clinical studies are summarized in Table 3.

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

Allergic Reactions

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

Other Adverse Reactions

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

The interaction of RetavaseŽ 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 RetavaseŽ therapy.