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Activase Side Effects

Generic name: alteplase

Medically reviewed by Drugs.com. Last updated on Dec 11, 2023.

Note: This document contains side effect information about alteplase. Some dosage forms listed on this page may not apply to the brand name Activase.

Applies to alteplase: intravenous powder for solution.

Serious side effects of Activase

Along with its needed effects, alteplase (the active ingredient contained in Activase) 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 alteplase:

More common

Rare

Incidence not known

For Healthcare Professionals

Applies to alteplase: injectable powder for injection, intravenous powder for injection.

Hematologic

The hematologic side effect, bleeding, is the most common adverse event in all approved indications.

The incidence of bleeding among patients with acute myocardial infarction who received alteplase (the active ingredient contained in Activase) (often with aspirin and heparin) ranged from 8% to 77% (0.5% to 10% serious). Blood loss of greater than 250 mL occurred in up to 5% of patients, and typically affected the gastrointestinal tract (5%) or genitourinary tract (4%). Ecchymosis, epistaxis, gingival, or retroperitoneal bleeding occurred in up to 1% of patients.

The incidence of alteplase-associated intracranial hemorrhagic (ICH) in patients with acute myocardial infarction is dose-related and has averaged about 1%. Administration of 100 mg over 3 hours resulted in an incidence of stroke of 0.4%, at 100 mg over 90 minutes the rate was 0.7%, and at 150 mg over 90 minutes the rate of ICH was 1.3%. ICH in patients with acute ischemic stroke was significantly greater in patients receiving alteplase (15.4%) compared to placebo (6.4%). Symptomatic ICH (defined as sudden clinical worsening followed by subsequent CT verification of ICH) occurred in 8% (6.4% within 36 hours of receiving alteplase).

Stroke occurred in 1.2% to 1.6% of patients experiencing an AMI and receiving alteplase as a 3 hour infusion or an accelerated infusion, respectively.

Rare cases of atheroembolic events have been associated with the use of this drug and other lytic agents.

If bleeding occurs during therapy with alteplase and cannot be controlled by pressure, it is recommended that alteplase (and heparin, if applicable) should be discontinued immediately. Arterial punctures are of particular concern and an upper extremity accessible to manual compression is preferred. The usual precautions and procedures following arterial catheterization are extremely important. It is recommended that other invasive procedures be avoided or minimized. Non-compressible venous sites should be avoided.[Ref]

The incidence of major hemorrhagic events among heparinized patients with acute myocardial infarction who underwent cardiac catheterization in the Thrombolysis in Myocardial Infarction (TIMI) study significantly increased with age, averaging 8.7% and 24.7% for patients less than 65 years and 70 to 76 years old, respectively. These values agree with GISSI-2 data, where the overall incidence of bleeding associated with alteplase with and without heparin was 8.5% (0.5% major, 8.0% minor). Concomitant administration of heparin did not increase the incidence of stroke, although the incidence of major bleeding was greater in patients who received both thrombolytic (alteplase or streptokinase) and heparin therapy.

In one large study of 139 patients with acute thrombotic or embolic stroke, the incidence of hemorrhagic infarction averaged 20.2%. Parenchymal hematoma was observed in 10.6% of patients in this study, and neurological worsening accompanied by either hemorrhagic infarction or brain parenchymal hematoma was observed in 9.6% of patients. Limited data in which 100 mg of alteplase was given to 32 patients with documented middle cerebral artery and/or intracranial internal carotid artery occlusion reveal an incidence of hemorrhagic infarction without clinical deterioration in 28%, fatal parenchymal hemorrhage in 9%, and serious puncture site hemorrhage in 6% of patients.

In general, the overall incidence of alteplase-induced symptomatic intracerebral hemorrhage (ICH) in most studies has ranged between 3% and 7%. It appears that the overall risk of symptomatic ICH with the use of IV alteplase therapy is dependent on the expertise of the treating clinician. In one report, the risk of symptomatic ICH was 4% if protocol guidelines were strictly followed, but more than 10% when deviating from protocol guidelines. Other studies have confirmed these findings. The risk of ICH appears to be higher in elderly patients treated with thrombolytics for acute MI. An alternative reperfusion strategy (i.e., angioplasty) may be considered in this patient population.[Ref]

Cardiovascular

The mortality rate among patients in the Thrombolysis in Myocardial Infarction (TIMI) study significantly increased with age, averaging 3.5% and 12% for patients less than 65 years and 70 to 76 years old, respectively. Risk factors for death were female gender, diabetes mellitus, extensive coronary artery disease, history of congestive heart failure, persistent chest pain after alteplase (the active ingredient contained in Activase) administration, low systolic blood pressure at presentation, and advanced age.[Ref]

Cardiovascular-related side effects may occur more frequently in patient with an acute myocardial infarction (AMI) or pulmonary embolism. These events may be a sequelae of the disease and their relationship to the drug is not always clear. Reperfusion arrhythmias, including sinus bradycardia, accelerated idioventricular rhythm, premature ventricular depolarizations, or ventricular tachycardia commonly have occurred. Alteplase has been shown to significantly reduce the incidence of in-hospital mortality, left ventricular failure, postinfarction angina, reinfarction, and all ischemic events in patients with AMI.

Alteplase-associated cases of recurrent thrombosis or reinfarction have been reported. Rarely, reinfarction may be due to embolization of partially lysed thrombi. Reformation of thrombi may be due to elevated thrombin-antithrombin-III levels during alteplase therapy. Theoretically, adjunctive therapy with continuous heparin will significantly decrease the risk of an alteplase-induced hypercoagulable state.

Angioedema has also been reported (1% to 2%) during alteplase therapy in patients with acute ischemic stroke, particularly when alteplase was used in combination with an angiotensin-converting enzyme inhibitor. Orolingual angioedema has, in most cases, been mild, transient, and spontaneously reversible; however, it can be rapidly progressive requiring urgent intubation.

Recurrent hemopericardium, cardiac tamponade, massive hemorrhagic MI and death from cardiogenic shock have been associated with the use of some thrombolytic agents.

Rarely, cholesterol embolization syndrome presenting as peripheral cyanosis has been associated with alteplase therapy.[Ref]

Nervous system

A potentially life-threatening nervous system side effect, hemorrhagic stroke, has occurred in approximately 1% of patients with an acute myocardial infarction. Administration of 100 mg over 3 hours resulted in a 0.4% incidence of stroke, at 100 mg over 90 minutes the incidence was 0.7%, and at 150 mg over 90 minutes the rate of ICH was 1.3%. The incidence is significantly increased in patients with thrombotic stroke, with reports as high as 31% (4% to 10% experience worsening neurologic status). See "Hematologic" side effects. Rare cases of intracerebral hemorrhage associated with the use of t-PA in patients with cerebral amyloid angiopathy and cases of headache or subdural hematoma have been associated with alteplase (the active ingredient contained in Activase)

Recurrent intracerebral embolization following alteplase has been reported in a patient with dilated cardiomyopathy. Alteplase may promote lysis and embolization of detached intracranial thrombi.

Stroke has occurred in 1.2% to 1.6% of patients experiencing an AMI and receiving alteplase as a 3 hour infusion or an accelerated infusion, respectively.

Rare cases of atheroembolic events have been associated with the use of this drug and other lytic agents.[Ref]

A retrospective meta-analysis of patients with intracranial hemorrhage (ICH) who had received alteplase (n = 88) versus no alteplase (n = 148) revealed the following independent predictors for ICH (odds ratio): age over 65 years (2.2), body weight below 70 kg (2.1), and hypertension on admission (2.0). Furthermore, the probability of ICH increased with the number of risk factors present. Other studies have corroborated these data, with some finding a higher Killip classification and the occurrence of anterior myocardial infarction as additional risk factors. These data do not account for other possible risk factors, such as extensive peripheral vascular disease, diabetes, or the use of oral anticoagulants.[Ref]

Hypersensitivity

Hypersensitivity reactions have occurred in less than 0.02% of patients. A cause-and-effect relationship between anaphylaxis and alteplase (the active ingredient contained in Activase) has not been clearly established.[Ref]

A 69-year-old beekeeper with acute myocardial infarction developed urticaria and gross facial, tongue, and neck edema within 25 minutes following administration of glyceryl trinitrate, nifedipine, aspirin, and alteplase. Investigations revealed normal complement (qualitative and quantitative measurements), the absence of circulating immune complexes, normal levels of circulating IgE, and absence of t-PA antibodies by ELISA. Intradermal skin testing with each drug revealed no allergic response. This anaphylactoid reaction did not appear to be due to an antibody-antigen or direct chemical reaction. This patient had a history of atopy. The authors suggested that clinicians who administer alteplase to strongly atopic individuals consider the possibility of an anaphylactoid reaction and have resuscitative measures available.

A 51-year-old woman with systemic lupus erythematosus and deep vein thrombosis developed throat tightness, dyspnea and dysphagia within 24 hours after receiving alteplase therapy. Subconjunctival bullous edema of the left eye and angioedema of the tongue, face, neck and upper lip were also observed. Associated laboratory findings included markedly decreased C4 and C1 esterase inhibitor levels relative to baseline. The patient's angioedema resolved within six hours after discontinuation of alteplase and initiation of steroid and antihistamine therapy.

A separate report documented two cases of anaphylactic reactions following treatment of 105 consecutive patients receiving alteplase for the treatment of ischemic stroke.[Ref]

Gastrointestinal

Gastrointestinal (GI) side effects generally have been limited to GI bleeding.[Ref]

Renal

Renal biopsy in a 76-year-old man with a history of angina, hypertension, and hypercholesterolemia who developed acute renal failure after alteplase (the active ingredient contained in Activase) therapy for an acute myocardial infarction revealed needle-shaped cholesterol crystals in small artery intima. There was mild focal segmental mesangial cell proliferation, tubular atrophy, and interstitial fibrosis. The patient required maintenance hemodialysis.[Ref]

Rare cases of cholesterol crystal embolization syndrome-associated renal failure have occurred during alteplase therapy.[Ref]

General

Bleeding has been the most frequent side effect noted with alteplase (the active ingredient contained in Activase) therapy. Arterial punctures are of particular concern and an upper extremity accessible to manual compression is preferred if arterial puncture is required. The usual precautions and procedures following arterial catheterization are extremely important. It is recommended that other invasive procedures be avoided or minimized. Non-compressible venous sites should be avoided.[Ref]

Hepatic

Hepatic side effects have been limited to rare (at least two cases) reports of hepatic cholesterol embolization syndrome.[Ref]

Local

Local inflammation and/or ecchymosis may occur with extravasation during alteplase (the active ingredient contained in Activase) infusion.[Ref]

Frequently asked questions

References

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