Retavase Half-Kit Side Effects
Generic Name: reteplase
Note: This document contains side effect information about reteplase. Some of the dosage forms listed on this page may not apply to the brand name Retavase Half-Kit.
For the Consumer
Applies to reteplase: intravenous kit, intravenous powder for solution
Along with its needed effects, reteplase (the active ingredient contained in Retavase Half-Kit) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor or nurse immediately if any of the following side effects occur while taking reteplase:
- Bleeding at injection site
- bleeding from the bladder, blood in urine
- bloody or black, tarry stools
- severe stomach pain
- vomiting of blood or material that looks like coffee grounds
- Pale skin
- troubled breathing with exertion
- unusual bleeding or bruising
- unusual tiredness or weakness
- Blurred vision
- difficult or labored breathing
- difficulty swallowing
- dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
- fast heartbeat
- puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
- shortness of breath
- skin rash
- tightness in chest
For Healthcare Professionals
Applies to reteplase: intravenous kit
Hematologic side effects have been the most frequently reported side effects. In the INJECT trial, the overall incidence of bleeds from any site was 15.0%, of which 4.6% were clinically significant. Transfusion requirements have ranged from 1.0% (INJECT trial) to 12.4% (RAPID-2 trial). The types of bleeds associated with this drug (and thrombolytic therapy, in general) may be broadly categorized as either intracranial hemorrhage or other types of hemorrhage.
The overall incidence of intracranial hemorrhage has averaged 0.8%. This risk is increased in patients with advanced age or hypertension. The incidence of transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) in the INJECT trial averaged 0.20%, and the incidence of frank stroke in the RAPID-2 trial averaged 1.8%. The average incidence of nonintracranial hemorrhage ranged from 1.9% to 9.0%, depending on the trial, use of arterial catheterization, and whether the study was performed in the US or Europe.
The incidence of IV site bleeding ranged from 4.6% to 48.6%. Arterial and venous punctures should be minimized. Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, or pericardial) occur, any concomitant heparin should be terminated immediately, and the second bolus of reteplase (the active ingredient contained in Retavase Half-Kit) should be withheld.[Ref]
The incidences of bleeding have been reported in the following sites within the following clinical trials, respectively (European INJECT study [n=2965], US RAPID-1 study [n=210], European RAPID-2 study [n=113]: injection site 4.6%, 48.6%, 19.5%; intracranial 1.2% (stroke), 0%, 1.8% (stroke); gastrointestinal 2.5%, 9.0%, 1.8%; genitourinary 1.6%, 9.5%, 0.9%; anemia 2.6%; 1.4%, 0.9%).
Since reteplase causes lysis of the fibrin plug, which is necessary to stop bleeding at puncture sites, careful attention should be paid to potential sites of bleeding during therapy (injection site, arterial puncture sites, catheter insertion sites, etc.).[Ref]
Cholesterol embolization--sometimes fatal--has been reported rarely in patients treated with thrombolytic agents. The exact incidence is unknown. Its relationship with lytic therapy might be coincidental as there is such risk associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.
Reperfusion arrhythmias during thrombolytic therapy can be a sign of successful lytic therapy. These arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, ventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) may also be seen during the natural course of acute myocardial infarction, and they should be treated with standard antiarrhythmic measures, as indicated. It is recommended that antiarrhythmic therapy for bradycardia and/or ventricular irritability be available during reteplase (the active ingredient contained in Retavase Half-Kit) therapy.[Ref]
Cardiovascular side effects are probably sequelae of myocardial infarction and not due to reteplase. These side effects have included hypotension, cardiogenic shock, arrhythmias (e.g., sinus bradycardia, accelerated idioventricular rhythm, premature ventricular depolarizations, supraventricular tachycardia, ventricular tachycardia, and 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.[Ref]
Serious hypersensitivity reactions to reteplase (the active ingredient contained in Retavase Half-Kit) have been rare. Among the 2,965 patients in the INJECT trial, such reactions were noted in 3 patients, with 1 patient experiencing dyspnea and hypotension. No cases of anaphylaxis were reported among the 3,856 patients treated with reteplase in initial clinical trials, but 2 cases of anaphylaxis were associated with the use of reteplase among approximately 2,500 patients in ongoing clinical trials.[Ref]
There are no data to demonstrate the formation of anti-reteplase antibodies among the approximately 2,400 patients who have been tested for the presence of such antibodies. Nevertheless, the use of reteplase (including the second bolus of reteplase) is not recommended if anaphylaxis has occurred with any prior use of reteplase in a given patient.[Ref]
Fever, a general body side effect, has been reported.[Ref]
1. Smalling RW, Bode C, Kalbfleisch J, Sen S, Limbourg P, Forycki F, Habib G, Feldman R, Hohnloser S, Seals A "More rapid, complete, and stable coronary thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute myocardial infarction. RAPID Investigators." Circulation 91 (1995): 2725-32
2. Tebbe U, Graf A, Kamke W, Zahn R, Forycki F, Kratzsch G, Berg G "Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism." Am Heart J 138 (1999): 39-44
3. International Joint Efficacy Comparison of Thrombolytics "Randomised, souble-blind comparison of reteplase double-bolus administration with streptokinase in acute myocardial infarction(INJECT): trial to investigate equivalence." Lancet 346 (1995): 329-6
4. Amsterdam EA "Controlled trials comparing reteplase with alteplase and streptokinase in patients with acute myocardial infarction." Pharmacotherapy 16 (1996): s137-40
5. Bode C, Smalling RW, Berg G, et al. "Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (Recombinant Plasminogen Activator) and front-loaded, accelerated alteplase (Recombinat Tissue Plasminogen Activator) in patients with acute myocardial infarction." Circulation 94 (1996): 891-8
6. "Product Information. Retavase (reteplase)." Boehringer Mannheim, Gaithersburg, MD.
7. Martin U, Dorge L, Fischer S "Comparison of desulfatohirudin (REVASC) and heparin as adjuncts to thrombolytic therapy with reteplase in a canine model of coronary thrombosis." Br J Pharmacol 118 (1996): 271-6
Some side effects may not be reported. You may report them to the FDA.