No

Thrombolytic Agent

Thrombolytic agent used in treatment of recent severe or massive deep vein thrombosis, pulmonary emboli, myocardial infarction, and occluded arteriovenous cannulas

C

Hypersensitivity to anistreplase or streptokinase; active internal bleeding; history of CVA; recent (within 2 months) intracranial or intraspinal surgery or trauma; intracranial neoplasm, arteriovenous malformation, or aneurysm; known bleeding diathesis; severe uncontrolled hypertension

Avoid I.M. injections; use with caution in patients >75 years of age, patients with a history of cardiac arrhythmias, septic thrombophlebitis or occluded A-V cannula at seriously infected site, patients with a high likelihood of left heart thrombus, (eg, mitral stenosis with atrial fibrillation), major surgery within last 10 days, GI bleeding, diabetic hemorrhagic retinopathy, subacute bacterial endocarditis, cerebrovascular disease, recent trauma including cardiopulmonary resuscitation, or severe hypertension (systolic BP >180 mm Hg and/or diastolic BP >110 mm Hg); antibodies to streptokinase remain for 3-6 months after initial dose, use another thrombolytic enzyme (ie, alteplase) if thrombolytic therapy is indicated in patients with prior streptokinase therapy

As with all drugs which may affect hemostasis, bleeding is the major adverse effect associated with streptokinase. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the dosage administered, concurrent use of multiple agents which alter hemostasis, and patient predisposition (including hypertension). Rapid lysis of coronary artery thrombi by thrombolytic agents may be associated with reperfusion-related atrial and/or ventricular arrhythmias.

Cardiovascular: Hypotension

Local: Injection site bleeding

1% to 10%:

Central nervous system: Fever (1% to 4%)

Dermatologic: Bruising, rash, pruritus

Gastrointestinal: Gastrointestinal hemorrhage, nausea, vomiting

Genitourinary: Genitourinary hemorrhage

Hematologic: Anemia

Miscellaneous: Diaphoresis

Neuromuscular and skeletal: Muscle pain

Ocular: Eye hemorrhage, periorbital edema

Respiratory: Bronchospasm, epistaxis

<1%: Intracranial hemorrhage, retroperitoneal hemorrhage, pericardial hemorrhage, gingival hemorrhage, epistaxis, allergic reactions, anaphylaxis, anaphylactic shock, angioneurotic edema, anaphylactoid reactions, laryngeal edema, urticaria, back pain (during infusion), elevated transaminases, respiratory depression, morbilliform, erysipelas-like rash, hemarthrosis

Case reports: Guillain-Barré syndrome, Parsonage-Turner syndrome, splenic rupture, acute tubular necrosis, cholesterol embolization, ARDS

Additional cardiovascular events associated with use in myocardial infarction: AV block, cardiogenic shock, heart failure, cardiac arrest, recurrent ischemia/infarction, myocardial rupture, electromechanical dissociation, pericardial effusion, pericarditis, mitral regurgitation, cardiac tamponade, thromboembolism, pulmonary edema, asystole, ventricular tachycardia

Symptoms of overdose include epistaxis, bleeding gums, hematoma, spontaneous ecchymoses, oozing at catheter site

If uncontrollable bleeding occurs, discontinue infusion; whole blood or blood products may be used to reverse bleeding

Aminocaproic acid (antifibrinolytic agent) may decrease effectiveness.

Drugs which affect platelet function (eg, NSAIDs, dipyridamole, ticlopidine, clopidogrel, IIb/IIIa antagonists) may potentiate the risk of hemorrhage; use with caution.

Heparin and aspirin: Use with aspirin and heparin may increase bleeding over aspirin and heparin alone. However, aspirin and heparin were used concurrently in the majority of patients in some major clinical studies of streptokinase.

Warfarin or oral anticoagulants: Risk of bleeding may be increased during concurrent therapy.

Streptokinase, a white lyophilized powder, may have a slight yellow color in solution due to the presence of albumin; intact vials should be stored at room temperature; reconstituted solutions should be refrigerated and are stable for 24 hours

Activates the conversion of plasminogen to plasmin by forming a complex, exposing plasminogen-activating site, and cleaving a peptide bond that converts plasminogen to plasmin; plasmin degrades fibrin, fibrinogen and other procoagulant proteins into soluble fragments; effective both outside and within the formed thrombus/embolus

Onset of action: Activation of plasminogen occurs almost immediately

Duration: Fibrinolytic effects last only a few hours, while anticoagulant effects can persist for 12-24 hours

Half-life: 83 minutes

Elimination: By circulating antibodies and via the reticuloendothelial system

I.V.:

Clotted catheter: 25,000 units, clamp for 2 hours then aspirate contents and flush with normal saline.

Adults: Antibodies to streptokinase remain for at least 3-6 months after initial dose: Administration requires the use of an infusion pump.

An intradermal skin test of 100 units has been suggested to predict allergic response to streptokinase. If a positive reaction is not seen after 15-20 minutes, a therapeutic dose may be administered.

Guidelines for acute myocardial infarction (AMI): 1.5 million units over 60 minutes

Administration:

Dilute two 750,000 unit vials of streptokinase with 5 mL dextrose 5% in water (D₅W) each, gently swirl to dissolve.

Add this dose of the 1.5 million units to 150 mL D₅W.

This should be infused over 60 minutes; an in-line filter greater than or equal to 0.45 micron should be used.

Monitor for the first few hours for signs of anaphylaxis or allergic reaction. Infusion should be slowed if lowering of 25 mm Hg in blood pressure or terminated if asthmatic symptoms appear.

Begin heparin 5000-10,000 unit bolus followed by 1000 units/hour approximately 3-4 hours after completion of streptokinase infusion or when PTT is <100 seconds.

Guidelines for acute pulmonary embolism (APE): 3 million unit dose over 24 hours

Administration:

Dilute four 750,000 unit vials of streptokinase with 5 mL dextrose 5% in water (D₅W) each, gently swirl to dissolve.

Add this dose of 3 million units to 250 mL D₅W, an in-line filter greater than or equal to 0.45 micron should be used.

Administer 250,000 units (23 mL) over 30 minutes followed by 100,000 units/hour (9 mL/hour) for 24 hours.

Monitor for the first few hours for signs of anaphylaxis or allergic reaction. Infusion should be slowed if blood pressure is lowered by 25 mm Hg or if asthmatic symptoms appear.

Begin heparin 1000 units/hour about 3-4 hours after completion of streptokinase infusion or when PTT is <100 seconds.

Monitor PT, PTT, and fibrinogen levels during therapy.

Thromboses: 250,000 units to start, then 100,000 units/hour for 24-72 hours depending on location.

Cannula occlusion: 250,000 units into cannula, clamp for 2 hours, then aspirate contents and flush with normal saline.

Blood pressure, PT, APTT, platelet count, hematocrit, fibrinogen concentration, signs of bleeding

Partial thromboplastin time (PTT) activated: 20.4-33.2 seconds

Prothrombin time (PT): 10.9-13.7 seconds (same as control)

Fibrinogen: 200-400 mg/dL

It is important that when using thrombolytic therapy in an institution, the protocol for that institution be followed closely, particularly in terms of dosage, adjunctive heparin therapy, and standard myocardial infarction therapy (aspirin, beta-blockers, ACE inhibitor). It is important that consideration of preceding recent thrombolytic therapy be taken into account when invasive procedures, particularly intravascular procedures, are undertaken. It is important that close clinical monitoring be carried out to ensure efficacy of therapy. Failure of therapy may require emergent cardiac catheterization and interventional therapy. Reperfusion after successful thrombolysis may be associated with rapid resolution of EKG changes and restoration of cardiac function. However, reperfusion arrhythmias may also manifest.

Antibodies to streptokinase persist for up to 6 months after the initial dose. Therefore, an alternative thrombolytic approach (tissue plasminogen activator) should be used if thrombolytic therapy is needed. Furthermore, patients who have had a recent streptococcal infection (within 6 months) may also manifest hypersensitivity to streptokinase. Patients who have previously received streptokinase therapy will not necessarily develop a hypersensitivity response to urokinase.

None reported

None reported

No information available to require special precautions

No effects or complications reported

Following infusion, absolute bedrest is important; call for assistance changing position. You will have increased tendency to bleed; avoid razors, scissors or sharps, and use soft toothbrush or cotton swabs. Report back pain, abdominal pain, muscle cramping, acute onset headache, or chest pain. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant or suspect you might be pregnant. Consult prescriber if breast-feeding.

For I.V. or intracoronary use only; monitor for bleeding every 15 minutes for the first hour of therapy; do not mix with other drugs

Powder for injection: 250,000 units (5 mL, 6.5 mL); 600,000 units (5 mL); 750,000 units (6 mL, 6.5 mL); 1,500,000 units (6.5 mL, 10 mL, 50 mL)

Andrew M, Brooker L, Leaker M, et al,"Fibrin Clot Lysis by Thrombolytic Agents Is Impaired in Newborns Due to a Low Plasminogen Concentration," Thromb Haemost, 1992, 68(3):325-30.

Blum A and Shohat B, "CD-4 Lymphopenia Induced by Streptokinase," Circulation, 1995, 91(6):1899.

David M and Andrew M, "Venous Thromboembolic Complications in Children," J Pediatr, 1993, 123(3):337-46.

de Boer A and van Griensven JM, "Drug Interactions With Thrombolytic Agents. Current Perspectives," Clin Pharmacokinet, 1995, 28(4):315-26.

Dehmer GJ, Gresalfi N, Daly D, et al, "Impairment of Fibrinolysis by Streptokinase, Urokinase, and Recombinant Tissue-Type Plasminogen Activator in the Presence of Radiographic Contrast Agents," J Am Coll Cardiol, 1995, 25(5):1069-75.

Fears R, "Biochemical Pharmacology and Therapeutic Aspects of Thrombolytic Agents," Pharmacol Rev, 1990, 42(3):201-21.

Geraets DR, Hoehns JD, Burke TG, et al, "Thrombolytic-Associated Cholesterol Emboli Syndrome: Case Report and Literature Review," Pharmacotherapy, 1995, 15(4):441-50.

Hommel M, Boissel JP, Cornu C, et al, "Termination of Trial of Streptokinase in Severe Acute Ischaemic Stroke," Lancet, 1995, 345(8941):57.

Kalish SC, Gurwitz JH, Krumholz HM, et al, "A Cost-Effectiveness Model of Thrombolytic Therapy for Acute Myocardial Infarction," J Gen Intern Med, 1995, 10(6):321-30.

Kothari SS, Varma S, and Wasir HS, "Thrombolytic Therapy in Infants and Children," Am Heart J, 1994, 127(3):651-7.

Krammer B, Steiner M, Burstein C, et al, "Spontaneous, Massive Liver Hemorrhage as a Complication of Thrombolysis With Ultra-high Dose Streptokinase in Deep Thrombophlebitis," Vasa, 1994, 23(4):373-6.

Krumholz HM, Pasternak RC, Weinstein MC, et al, "Cost Effectiveness of Thrombolytic Therapy With Streptokinase in Elderly Patients With Suspected Acute Myocardial Infarction," N Engl J Med, 1992, 327:7-13.

Lee HS, "How Safe Is the Readministration of Streptokinase," Drug Saf, 1995, 13(2):76-80.

Lee HS, Quinn T, and Boyle RM, "Safety of Thrombolytic Treatment in Patients With Central Venous Cannulation," Br Heart J, 1995, 73(4):359-62.

Lee TH, "Cost Effectiveness of Tissue Plasminogen Activator," N Engl J Med, 1995, 332(21):1443-4.

Marcus DM and Frederick AR, Jr, "Streptokinase-Induced Tenon's Hemorrhage After Retinal Detachment Surgery," Am J Ophthalmol, 1994, 118(6):815-7.

Mark DB, Hlatky MA, Califf RM, et al, "Cost Effectiveness of Thrombolytic Therapy With Tissue Plasminogen Activator as Compared With Streptokinase for Acute Myocardial Infarction," N Engl J Med, 1995, 332(21):1418-24.

Michelson AD, Bovill E, Monagle P, et al, "Antithrombotic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Petch MC, "Dangers of Thrombolysis," BMJ, 1990, 300(6723):483-4.

Ruble K, Long C, and Connor K, "Pharmacologic Treatment of Catheter-Related Thrombus in Pediatrics," Pediatr Nurs, 1994, 20(6):553-7.

Taylor BV, Mastaglia FL, and Stell R, "Guillain-Barré Syndrome Complicating Treatment With Streptokinase," Med J Aust, 1995, 162(4):214-5.

Welik RA, Josselson J, Shey SY, et al, "Repeated Low-Dose Streptokinase Infusions Into Occluded Permanent, Central-Venous Hemodialysis Catheters," Kidney Int, 1987, 31(5):1210-2.