July 30, 2016
Recommended Topic Related To:

Activase

"A new state-of-the-art facility dedicated to pediatric cardiac imaging and intervention, co-established by the National Institutes of Health and Children's National Medical Center, was opened with a special dedication ceremony today. The new faci"...

A A A

Activase

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Bleeding

Activase can cause internal bleeding (intracranial, retroperitoneal, gastrointestinal, genitourinary, respiratory) or external bleeding, especially at arterial and venous puncture sites. Avoid intramuscular injections and trauma to the patient while on Activase. Perform venipunctures carefully and only as required. To minimize bleeding from noncompressible sites, avoid internal jugular and subclavian venous punctures. If an arterial puncture is necessary during Activase infusion, use an upper extremity vessel that is accessible to manual compression, apply pressure for at least 30 minutes, and monitor the puncture site closely.

Because of the higher risk of intracranial hemorrhage in patients treated for acute ischemic stroke, limit treatment to facilities that can provide timely access to appropriate evaluation and management of intracranial hemorrhage.

Fatal cases of hemorrhage associated with traumatic intubation in patients administered Activase have been reported.

Aspirin and heparin have been administered concomitantly with and following infusions of Activase in the management of acute myocardial infarction and pulmonary embolism, but the concomitant administration of heparin and aspirin with and following infusions of Activase for the treatment of acute ischemic stroke during the first 24 hours after symptom onset has not been investigated. Because heparin, aspirin, or Activase may cause bleeding complications, carefully monitor for bleeding, especially at arterial puncture sites. Hemorrhage can occur 1 or more days after administration of Activase, while patients are still receiving anticoagulant therapy. If serious bleeding occurs, terminate the Activase infusion.

In the following conditions, the risks of bleeding with Activase therapy for all approved indications are increased and should be weighed against the anticipated benefits:

  • Recent major surgery or procedure, (e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels)
  • Cerebrovascular disease
  • Recent intracranial hemorrhage
  • Recent gastrointestinal or genitourinary bleeding
  • Recent trauma
  • Hypertension: systolic BP above 175 mm Hg or diastolic BP above 110 mm Hg
  • High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
  • Acute pericarditis
  • Subacute bacterial endocarditis
  • Hemostatic defects including those secondary to severe hepatic or renal disease
  • Significant hepatic dysfunction
  • Pregnancy
  • Diabetic hemorrhagic retinopathy, or other hemorrhagic ophthalmic conditions
  • Septic thrombophlebitis or occluded AV cannula at seriously infected site
  • Advanced age [see Use In Specific Populations]
  • Patients currently receiving anticoagulants (e.g., warfarin sodium)
  • Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.

Orolingual Angioedema

Orolingual angioedema has been observed during and up to 2 hours after Activase infusion in patients treated for acute ischemic stroke and acute myocardial infarction [see ADVERSE REACTIONS]. In many cases, patients received concomitant angiotensin-converting enzyme inhibitors [see DRUG INTERACTIONS]. Monitor patients treated with Activase during and for several hours after infusion for orolingual angioedema. If angioedema develops, discontinue the Activase infusion and promptly institute appropriate therapy (e.g., antihistamines, intravenous corticosteroids, epinephrine).

Cholesterol Embolization

Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents; the true incidence is unknown. Cholesterol embolism may present with livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, or rhabdomyolysis and can be fatal. It is associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy.

Reembolization Of Deep Venous Thrombi during Treatment For Acute Massive Pulmonary Embolism

Activase has not been shown to treat adequately underlying deep vein thrombosis in patients with PE. Consider the possible risk of reembolization due to the lysis of underlying deep venous thrombi in this setting.

Coagulation Tests May Be Unreliable During Activase Therapy

Coagulation tests and measures of fibrinolytic activity may be unreliable during Activase therapy, unless specific precautions are taken to prevent in vitro artifacts. When present in blood at pharmacologic concentrations, Activase remains active under in vitro conditions, which can result in degradation of fibrinogen in blood samples removed for analysis.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential or the effect on fertility. Short-term studies, which evaluated tumorigenicity of Activase and effect on tumor metastases in rodents, were negative.

Studies to determine mutagenicity (Ames test) and chromosomal aberration assays in human lymphocytes were negative at all concentrations tested. Cytotoxicity, as reflected by a decrease in mitotic index, was evidenced only after prolonged exposure and only at the highest concentrations tested.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Activase is embryocidal in rabbits when intravenously administered in doses of approximately two times (3 mg/kg) the human dose for AMI. No maternal or fetal toxicity was evident at 0.65 times (1 mg/kg) the human dose in pregnant rats and rabbits dosed during the period of organogenesis. There are no adequate and well-controlled studies in pregnant women.

Nursing Mothers

It is not known whether Activase is excreted in human milk. Many drugs are excreted in human milk.

Pediatric Use

Safety and effectiveness of Activase in pediatric patients have not been established.

Geriatric Use

Acute Ischemic Stroke

In exploratory, multivariate analyses of Studies 1 and 2, age greater than 77 years was one of several interrelated baseline characteristics associated with an increased risk of intracranial hemorrhage. Efficacy results suggest a reduced but still favorable clinical outcome for Activase-treated elderly [see Clinical Studies].

Acute Myocardial Infarction

In a large trial of accelerated-infusion Activase that enrolled 41,021 patients with AMI to one of four thrombolytic regimens [seeClinical Studies], patients over 75 years of age, a predefined subgroup, comprised 12% of enrollment. In these patients, the incidence of stroke was 4.0% for the Activase accelerated infusion group, 2.8% for streptokinase IV [SK (IV)], and 3.2% for streptokinase SQ [SK (SQ)]. The incidence of combined 30-day mortality or nonfatal stroke was 20.6% for accelerated infusion of Activase, 21.5% for SK (IV), and 22.0% for SK (SQ).

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

Last reviewed on RxList: 7/12/2016

Warnings
Precautions

Additional Activase Information

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Heart Health

Get the latest treatment options.

Atrial Fibrillation Quiz