High Risk Patients: Carefully evaluate each patient being considered for therapy and weigh anticipated benefits against potential risks associated with therapy.In the following conditions, the risk of therapy may be increased and should be weighed against the anticipated benefits: Recent (within 10 days) major surgery (eg, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels) Recent (within 10 days) serious gastrointestinal bleeding Recent (within 10 days) trauma including cardiopulmonary resuscitation Hypertension (systolic BP more than 180 mm Hg and/or diastolic BP more than 110 mm Hg) Likelihood of left heart thrombus (eg, mitral stenosis with atrial fibrillation) Subacute bacterial endocarditis Cerebrovascular disease Hemostatic defects including secondary to severe hepatic or renal disease Pregnancy Age over 75 years Diabetic hemorrhagic retinopathy Septic thrombophlebitis or occluded AV cannula at a seriously infected site Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location Arrhythmias: Rapid lysis of coronary thrombi has been shown to cause reperfusion atrial or ventricular dysrhythmias requiring immediate treatment. Carefully monitor for arrhythmias during and immediately following administration of Streptokinase for AMI. Occasionally, tachycardia and bradycardia have been observed.Hypotension: Sometimes severe hypotension, not secondary to bleeding or anaphylaxis, may occur during or soon after IV Streptokinase (1% to 10%). Closely monitor patients and, if symptomatic or alarming hypotension occurs, administer appropriate treatment. This may include a decrease in the IV Streptokinase infusion rate. Smaller hypotensive effects are common and have not required treatment.Injection sites: If an arterial puncture is necessary, upper extremity vessels are preferable. Apply pressure for at least 30 minutes. Apply a pressure dressing and check puncture site frequently.Respiratory: There have been reports of respiratory depression in patients receiving Streptokinase. In some cases, it was not possible to determine whether the respiratory depression was associated with Streptokinase or was a symptom of the underlying process. If respiratory depression is associated with Streptokinase, the occurrence is believed to be rare.Noncardiogenic pulmonary edema: Noncardiogenic pulmonary edema has been reported rarely in patients treated with Streptokinase. The risk of this appears greatest in patients who have large MIs undergoing thrombolytic therapy by the intracoronary route.Polyneuropathy: Rarely polyneuropathy has been temporally related to the use of Streptokinase, with some cases described as Gaillain-Barre syndrome.Anticoagulant and antiplatelets after treatment for MI: In the treatment of AMI, aspirin has been shown to reduce the incidence of reinfarction and stroke. The addition of aspirin to Streptokinase causes a minimal increase in the risk of minor bleeding (3.9% vs 3.1%) but does not appear to increase the incidence of major bleeding. In the treatment of AMI, aspirin, when not otherwise contraindicated, should be administered with Streptokinase. The use of anticoagulants following Streptokinase administration increases the risk of bleeding but has not been shown to be of unequivocal clinical benefit. Therefore, whereas the use of aspirin is recommended unless otherwise contraindicated, the use of anticoagulants should be decided by the treating physician.Anticoagulation after IV treatment for other indications: Continuous IV infusion of heparin, without a loading dose, has been recommended following termination of Streptokinase, infusion for treatment of PE or DVT to prevent rethrombosis. The effect of Streptokinase on thrombin time (TT) and activated partial thromboplastin time (aPTT) usually will diminish within 3 to 4 hours after Streptokinase therapy. Heparin therapy without a loading dose can be initiated when the TT or the aPTT is less than twice the normal control value for Streptokinase.Cholesterol embolism: Cholesterol embolism has occurred rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (eg, cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, Ml, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.PE: If PE or recurrent PE occur during Streptokinase therapy, complete the planned course of treatment in an attempt to lyse the embolus. While PE may occasionally occur during Streptokinase treatment, the incidence is no greater than when patients are treated with heparin alone. In addition to PE, embolization to other sites during Streptokinase treatment has been observed.Hypersensitivity reactions: Anaphylactic and anaphylactoid reactions ranging in severity from minor breathing difficulty to bronchospasm, periorbital swelling, or angioneurotic edema have been observed rarely in patients treated with IV Streptokinase. Fever and shivering, occurring in 1% to 4% of patients, are the most commonly reported allergic reactions with IV Streptokinase in AMI. Other milder allergic effects, such as urticaria, itching, flushing, nausea, headache, and musculoskeletal pain, have been observed, as have delayed hypersensitivity reactions such as vasculitis and interstitial nephritis.
