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Side Effects



The most frequent adverse reaction associated with Activase (alteplase) in all approved indications is bleeding (see WARNINGS).15,16

Should serious bleeding in a critical location (intracranial, gastrointestinal, retroperitoneal, pericardial) occur, Activase (alteplase) therapy should be discontinued immediately, along with any concomitant therapy with heparin. Death and permanent disability are not uncommonly reported in patients that have experienced stroke (including intracranial bleeding) and other serious bleeding episodes.

In the GUSTO trial for the treatment of acute myocardial infarction, using the accelerated infusion regimen the incidence of all strokes for the Activase (alteplase) treated patients was 1.6%, while the incidence of nonfatal stroke was 0.9%. The incidence of hemorrhagic stroke was 0.7%, not all of which were fatal. The incidence of all strokes, as well as that for hemorrhagic stroke, increased with increasing age (see CLINICAL PHARMACOLOGY: Accelerated Infusion in AMI Patients). Data from previous trials utilizing a 3 hour infusion of < 100 mg indicated that the incidence of total stroke in six randomized double blind placebo-controlled trials2,7-11,17 was 1.2% (37/3161) in Alteplase treated patients compared with 0.9% (27/3092) in placebo- treated patients.

For the 3-hour infusion regimen, the incidence of significant internal bleeding (estimated as > 250 cc blood loss) has been reported in studies in over 800 patients. These data do not include patients treated with the Alteplase accelerated infusion.

  Total Dose ≤ 100 mg
gastrointestinal 5%
genitourinary 4%
ecchymosis 1%
retroperitoneal < 1%
epistaxis < 1%
gingival < 1%

The incidence of intracranial hemorrhage (ICH) in acute myocardial infarction patients treated with Activase (alteplase) is as follows:

Dose Number of Patients ICH (%)
100 mg, 3-hour 3272 0.4
≤ 100 mg, accelerated 10,396 0.7
150 mg 1779 1.3
1-1.4 mg/kg 237 0.4

These data indicate that a dose of 150 mg of Activase (alteplase) should not be used in the treatment of AMI because it has been associated with an increase in intracranial bleeding.18

For acute massive pulmonary embolism, bleeding events were consistent with the general safety profile observed with Activase (alteplase) in acute myocardial infarction patients receiving the 3-hour infusion regimen.

The incidence of ICH, especially symptomatic ICH, in patients with acute ischemic stroke was higher in Activase (alteplase) -treated patients than placebo patients (see CLINICAL PHARMACOLOGY).

A study of another alteplase product, Actilyse, in acute ischemic stroke, suggested that doses greater than 0.9 mg/kg may be associated with an increased incidence of ICH.19 Doses greater than 0.9 mg/kg (maximum 90 mg) should not be used in the management of acute ischemic stroke.

Bleeding events other than ICH were noted in the studies of acute ischemic stroke and were consistent with the general safety profile of Activase (alteplase) . In The NINDS t-PA Stroke Trial (Parts 1 and 2), the frequency of bleeding requiring red blood cell transfusions was 6.4% for Activase (alteplase) -treated patients compared to 3.8% for placebo (p=0.19, using Mantel-Haenszel Chi-Square).

Fibrin which is part of the hemostatic plug formed at needle puncture sites will be lysed during Activase (alteplase) therapy. Therefore, Activase (alteplase) therapy requires careful attention to potential bleeding sites, e.g., catheter insertion sites, and arterial puncture sites.

Allergic Reactions

Allergic-type reactions, e.g., anaphylactoid reaction, laryngeal edema, orolingual angioedema, rash, and urticaria have been reported. A cause and effect relationship to Activase (alteplase) therapy has not been established. When such reactions occur, they usually respond to conventional therapy. There have been post-marketing reports of orolingual angioedema associated with the use of Activase (alteplase) . Most reports were of patients treated for acute ischemic stroke, some reports were of patients treated for acute myocardial infarctions (see PRECAUTIONS: General). Many of these patients received concomitant angiotensin-converting enzyme inhibitors (see PRECAUTIONS: DRUG INTERACTIONS). Most cases resolved with prompt treatment; there have been rare fatalities as a result of upper airway hemorrhage from intubation trauma.

Other Adverse Reactions

The following adverse reactions have been reported among patients receiving Activase (alteplase) in clinical trials and in post-marketing experience. These reactions are frequent sequelae of the underlying disease and the effect of Activase (alteplase) on the incidence of these events is unknown. Use in Acute Myocardial Infarction: Arrhythmias, AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia, myocardial reinfarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema. These events may be life threatening and may lead to death. Nausea and/or vomiting, hypotension and fever have also been reported.

Use in Pulmonary Embolism: Pulmonary reembolization, pulmonary edema, pleural effusion, thromboembolism, hypotension. These events may be life threatening and may lead to death. Fever has also been reported.

Use in Acute Ischemic Stroke: Cerebral edema, cerebral herniation, seizure, new ischemic stroke. These events may be life threatening and may lead to death.

Read the Activase (alteplase) Side Effects Center for a complete guide to possible side effects


The interaction of Activase (alteplase) with other cardioactive or cerebroactive drugs has not been studied. In addition to bleeding associated with heparin and vitamin K antagonists, drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole and Abciximab) may increase the risk of bleeding if administered prior to, during, or after Activase (alteplase) therapy. There have been post-marketing reports of orolingual angioedema associated with the use of Activase (alteplase) . Many patients, primarily acute ischemic stroke patients, were receiving concomitant Angiotensin-converting enzyme inhibitors. (See PRECAUTIONS: General and ADVERSE REACTIONS: Allergic Reactions).

Use of Antithrombotics

Aspirin and heparin have been administered concomitantly with and following infusions of Activase (alteplase) in the management of acute myocardial infarction or pulmonary embolism. Because heparin, aspirin, or Activase (alteplase) may cause bleeding complications, careful monitoring for bleeding is advised, especially at arterial puncture sites.

The concomitant use of heparin or aspirin during the first 24 hours following symptom onset were prohibited in The NINDS t-PA Stroke Trial. The safety of such concomitant use with Activase (alteplase) for the management of acute ischemic stroke is unknown.

Blood Pressure Control

Blood pressure should be monitored frequently and controlled during and following Activase (alteplase) administration in the management of acute ischemic stroke. In The NINDS t-PA Stroke Trial, blood pressure was actively controlled ( ≤ 185/110 mm Hg) for 24 hours. Blood pressure was monitored during the hospital stay.


2.   Topol EJ, Morriss DC, Smalling RW, et al. A multicenter, randomized, placebo-controlled trial of a new form of intravenous recombinant tissue type plasminogen activator (Activase® (alteplase) ) in acute myocardial infarction. J Am Coll Cardiol. 1987;9:1205-13.

7.   Guerci AD, Gerstenblith G, Brinker JA, et al. A randomized trial of intravenous tissue plasminogen activator for acute myocardial infarction with subsequent randomization to elective coronary angioplasty. New Engl J Med. 1987;317:1613-18.

8.   O'Rourke M, Baron D, Keogh A, et al. Limitation of myocardial infarction by early infusion of recombinant tissue plasminogen activator. Circulation. 1988;77:1311-15.

11. Van de Werf F, Arnold AER, et al. Effect of intravenous tissue-plasminogen activator on infarct size, left ventricular function and survival in patients with acute myocardial infarction. Br Med J. 1988;297:1374-9.

15. Califf RM, Topol EJ, George BS, et al. Hemorrhagic complications associated with the use of intravenous tissue plasminogen activator in treatment of acute myocardial infarction. Am J Med. 1988;85:353-9.

16.  Bovill EG, Terrin ML, Stump DC, et al. Hemorrhagic events during therapy with recombinant tissue type plasminogen activator, heparin, and aspirin for acute myocardial infarction: results from the thrombolysis in myocardial infarction (TIMI), Phase II trial. Ann Int Med. 1991;115(4):256-65.

17. National Heart Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial infarction salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet. 1988;1:203-7.

18. Gore JM, Sloan M, Price TR, et al. and the TIMI Investigators. Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the thrombolysis in myocardial infarction study. Circulation. 1991;83:448-59.

19.  Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. for the ECASS Study Group. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA. 1995;274:1017-25.

Read the Activase Drug Interactions Center for a complete guide to possible interactions

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 5/9/2008

Side Effects

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