"SILVER SPRING, MD â€” The US Food and Drug Administration (FDA) is warning of several treatment-related serious adverse events in association with implantable left ventricular assist devices (LVADs) in heart-failure patients.
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Bleeding: Following intravenous high-dose brief-duration Streptokinase therapy in acute myocardial infarction, severe bleeding complications requiring transfusion are extremely rare (0.3-0.5%), and combined therapy with low dose aspirin does not appear to increase the risk of major bleeding. The addition of aspirin to Streptokinase may cause a slight increase in the risk of minor bleeding (3.1% without aspirin vs. 3.9% with) (2) .
Streptokinase will cause lysis of hemostatic fibrin deposits such as those occurring at sites of needle punctures, particularly when infused over several hours, and bleeding may occur from such sites. In order to minimize the risk of bleeding during treatment with Streptokinase, venipunctures and physical handling of the patient should be performed carefully and as infrequently as possible, and intramuscular injections must be avoided.
Should an arterial puncture be necessary during intravenous therapy, upper extremity vessels are preferable. Pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
In the following conditions the risks of therapy may be increased and should be weighed against the anticipated benefits.
- Recent (within 10 days) major surgery, 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 >180 mm Hg and/or diastolic BP >110 mm Hg
- High likelihood of left heart thrombus, e.g., mitral stenosis with atrial fibrillation
- Subacute bacterial endocarditis
- Hemostatic defects including those secondary to severe hepatic or renal disease
- Age >75 years
- Cerebrovascular disease
- Diabetic hemorrhagic retinopathy
- Septic thrombophlebitis or occluded AV cannula at seriously infected site
- Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location.
Should serious spontaneous bleeding (not controllable by local pressure) occur, the infusion of Streptase, Streptokinase, should be terminated immediately and treatment instituted as described under ADVERSE REACTIONS.
Arrhythmias: Rapid lysis of coronary thrombi has been shown to cause reperfusion atrial or ventricular dysrhythmias requiring immediate treatment. Careful monitoring for arrhythmia is recommended during and immediately following administration of Streptase, Streptokinase, for acute myocardial infarction. Occasionally, tachycardia and bradycardia have been observed.
Hypotension: Hypotension, sometimes severe, not secondary to bleeding or anaphylaxis has been observed during intravenous Streptase, Streptokinase, infusion in 1% to 10% of patients. Patients should be monitored closely and, should symptomatic or alarming hypotension occur, appropriate treatment should be administered. This treatment may include a decrease in the intravenous Streptokinase infusion rate. Smaller hypotensive effects are common and have not required treatment.
Cholesterol Embolism: 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. Clinical features of cholesterol embolism may include livedo reticularis, "purple toe" syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction, and rhabdomyolysis.
Other: Non-cardiogenic pulmonary edema has been reported rarely in patients treated with Streptase, Streptokinase. The risk of this appears greatest in patients who have large myocardial infarctions and are undergoing thrombolytic therapy by the intracoronary route.
Rarely, polyneuropathy has been temporally related to the use of Streptase, Streptokinase, with some cases described as Guillain Barr© Syndrome.
Should pulmonary embolism or recurrent pulmonary embolism occur during Streptase, Streptokinase, therapy, the originally planned course of treatment should be completed in an attempt to lyse the embolus. While pulmonary embolism may occasionally occur during Streptokinase treatment, the incidence is no greater than when patients are treated with heparin alone. In addition to pulmonary embolism, embolization to other sites during Streptase (streptokinase) treatment, has been observed.
Formulation with Albumin (Human): This product contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
General: There have been rare cases where Streptase, Streptokinase, has been administered for suspected AMI subsequently diagnosed as pancreatitis. Fatalities have occurred under these circumstances.
Repeated Administration -- Because of the increased likelihood of resistance due to antistreptokinase antibody, Streptase, Streptokinase, may not be effective if administered between five days and twelve months of prior Streptokinase or Anistreplase administration, or streptococcal infections, such as streptococcal pharyngitis, acute rheumatic fever, or acute glomerulonephritis secondary to a streptococcal infection.
Intravenous or Intracoronary Infusion for Myocardial Infarction -- Intravenous administration of Streptase, Streptokinase, will cause marked decreases in plasminogen and fibrinogen and increases in thrombin time (TT), activated partial thromboplastin time (APTT), and prothrombin time (PT), which usually normalize within 12-24 hours. These changes may also occur in some patients with intracoronary administration of Streptokinase.
Intravenous Infusion for Other Indications -- Before commencing thrombolytic therapy, it is desirable to obtain an activated partial thromboplastin time (APTT), a prothrombin time (PT), a thrombin time (TT), or fibrinogen levels, and a hematocrit and platelet count. If heparin has been given, it should be discontinued and the TT or APTT should be less than twice the normal control value before thrombolytic therapy is started.
During the infusion, decreases in plasminogen and fibrinogen levels and an increase in the level of FDP (the latter two causing a prolongation in the clotting times of coagulation tests) will generally confirm the existence of a lytic state. Therefore, lytic therapy can be confirmed by performing the TT, APTT, PT, or fibrinogen levels approximately 4 hours after initiation of therapy. If heparin is to be (re)instituted following the Streptase, Streptokinase, infusion, the TT or APTT should be less than twice the normal control value (see manufacturer's prescribing information for proper use of heparin).
Drug Interactions: See DRUG INTERACTIONS Section
Use of Anticoagulants and Antiplatelet Agents -- Streptase, Streptokinase, alone or in combination with antiplatelet agents and anticoagulants, may cause bleeding complications. Therefore, careful monitoring is advised. In the treatment of acute MI, aspirin, when not otherwise contraindicated, should be administered with Streptokinase ( see below ).
Anticoagulation and Antiplatelets After Treatment for Myocardial Infarction -- In the treatment of acute myocardial infarction, the use of 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 (see ADVERSE REACTIONS ) (2) . The use of anticoagulants following administration of Streptokinase increases the risk of bleeding, but has not yet 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 intravenous infusion of heparin, without a loading dose, has been recommended following termination of Streptase, Streptokinase, infusion for treatment of pulmonary embolism or deep vein thrombosis to prevent rethrombosis. The effect of Streptokinase on thrombin time (TT) and activated partial thromboplastin time (APTT) will usually diminish within 3 to 4 hours after Streptokinase therapy, and heparin therapy without a loading dose can be initiated when the TT or the APTT is less than twice the normal control value.
Pregnancy Category C -- Animal reproduction studies have not been conducted with Streptase, Streptokinase. It is also not known whether Streptokinase can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Streptokinase should be given to a pregnant woman only if clearly needed.
Controlled clinical studies have not been conducted in children to determine safety and efficacy in the pediatric population. The evidence of clinical benefits and risks is solely based on anecdotal reports in patients ranging in age from <1 month to 16 years. The largest number of patient reports have pertained to the use of streptokinase in arterial occlusions. For arterial occlusions the most frequently used loading dose was 1000 IU/kg; fewer numbers of patients received 3000 IU/kg. Loading dose durations have typically ranged from 5 minutes to 30 minutes. Continuous infusion doses were frequently 1000 IU/kg/hr; fewer were at 1500 IU/kg/hr. Infusions were maintained for = 12 hours in approximately half of the published cases; a smaller proportion were between 12 hours and 24 hours. Reported adverse events associated with the use of streptokinase in the pediatric population are similar in nature to those associated with its use in adults. Rates of all bleeding complications have been variable, and as high as 50% at catheter sites in some studies. Occasionally bleeding has required transfusion. Careful monitoring of patient status is necessary.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/7/2008
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