warnings and cautions
5 WARNINGS AND PRECAUTIONS Bleeding: Increases the risk of bleeding. Avoid intramuscular injections. Monitor for bleeding. ( 5.1 ) Thromboembolism: The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus. ( 5.2 ) Cholesterol Embolization: Has been reported rarely in patients treated with all types of thrombolytic agents. ( 5.3 ) Arrhythmias: It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered. ( 5.4 ) Use with Percutaneous Coronary Intervention (PCI): In patients with large ST segment elevation myocardial infarction, physicians should choose either thrombolysis or PCI as the primary treatment strategy for reperfusion. Rescue PCI or subsequent elective PCI may be performed after administration of thrombolytic therapies if medically appropriate. ( 5.5 ) Hypersensitivity: Monitor patients treated with TNKase during and for several hours after infusion. If symptoms of hypersensitivity occur, initiate appropriate therapy (e.g. antihistamines, corticosteroids). ( 5.6 ) General Each patient being considered for therapy with TNKase should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy. In the following conditions, the risk of TNKase therapy may be increased and should be weighed against the anticipated benefits: Recent major surgery, e.g., coronary artery bypass graft, obstetrical delivery, organ biopsy, previous puncture of noncompressible vessels Cerebrovascular disease Recent gastrointestinal or genitourinary bleeding Recent trauma Hypertension: systolic BP ≥ 180 mm Hg and/or diastolic BP ≥ 110 mm Hg Acute pericarditis Subacute bacterial endocarditis Hemostatic defects, including those secondary to severe hepatic or renal disease Severe hepatic dysfunction Pregnancy Diabetic hemorrhagic retinopathy or other hemorrhagic ophthalmic conditions Septic thrombophlebitis or occluded AV cannula at seriously infected site Advanced age [see Geriatric Use (8.5) ] Patients currently receiving oral anticoagulants, e.g., warfarin sodium Recent administration of GP IIb/IIIa inhibitors Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location 5.1 Bleeding The most common complication encountered during TNKase therapy is bleeding. Sites of bleeding include both internal and superficial bleeding sites. Intracranial hemorrhage has been observed in patients treated with TNKase [see Adverse Reactions (6) ] . Heparin and aspirin have been administered with TNKase in clinical trials and heparin may play a role in serious bleeding incidence. The safety of the use of TNKase with other antiplatelets has not been adequately studied [see Drug Interactions (7.1) ] . Careful monitoring for bleeding is advised. Should serious bleeding (not controlled by local pressure) occur, discontinue any concomitant heparin or antiplatelet agents immediately and treat appropriately. Avoid intramuscular injections and nonessential handling of the patient for the first few hours following treatment with TNKase. Perform arterial and venous punctures 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 TNKase infusion, use an upper extremity vessel that is accessible to manual compression. Apply pressure for at least 30 minutes. Check the pressure dressing applied, and the puncture site frequently for evidence of bleeding. 5.2 Thromboembolism The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation. 5.3 Cholesterol Embolization Cholesterol embolism has been reported 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 (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. 5.4 Arrhythmias Coronary thrombolysis may result in arrhythmias associated with reperfusion. These arrhythmias (such as sinus bradycardia, accelerated idioventricular rhythm, ventricular premature depolarizations, ventricular tachycardia) may be managed with standard anti-arrhythmic measures. It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered. 5.5 Use with Percutaneous Coronary Intervention (PCI) In patients with large ST segment elevation myocardial infarction, physicians should choose either thrombolysis or PCI as the primary treatment strategy for reperfusion. Rescue PCI or subsequent elective PCI may be performed after administration of thrombolytic therapies if medically appropriate; however, the optimal use of adjunctive antithrombotic and antiplatelet therapies in this setting is unknown. 5.6 Hypersensitivity Hypersensitivity, including urticarial / anaphylactic reactions, have been reported after administration of TNKase (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Monitor patients treated with TNKase during and for several hours after infusion. If symptoms of hypersensitivity occur, initiate appropriate therapy (e.g. antihistamines, corticosteroids).