CSL Behring


Full Prescribing Info
Streptase contains stabilized pure streptokinase, derived from the culture filtrate of β-haemolytic streptococci of Lancefield group C. It is presented as a white powder and contains stabilizers.
It also contains human albumin, sodium-L-hydrogen glutamate monohydrate, sodium dihydrogenphosphate dihydrate, disodium hydrogenphosphate dihydrate.
Pharmacotherapeutic Group: Antithrombotic agents, enzymes. ATC Code: B01A D01.
Systemic Administration: Acute transmural myocardial infarction (not older than 12 hrs), with persistent ST-segment elevation or recent left bundle-branch block; deep vein thromboses (not older than 14 days); acute massive pulmonary embolism; acute and subacute thromboses of peripheral arteries; chronic occlusive arterial diseases (not older than 6 weeks); occlusion of central retinal artery or vein (arterial occlusions not older than 6-8 hrs, venous occlusions not older than 10 days).
Local Administration: Acute myocardial infarction for re-opening of coronary vessels (not older than 12 hrs); acute, subacute and chronic thromboses, as well as embolisms of peripheral venous and arterial vessels.
No statement on therapy outcome can be made for administration beyond the time windows indicated.
Dosage/Direction for Use
When thrombolytic therapy is necessary or a high antibody concentration against streptokinase is present, or recent streptokinase therapy has been given (>5 days and <1 year previously), homologous fibrinolytics should be used (see Precautions).
Acute Transmural Myocardial Infarction with Persistent ST-Segment Elevation or Recent Left-bundle Branch Block: Systemic Administration: In short-term lysis for the treatment of myocardial infarction, Streptase 1.5 MIU are given within 60 min.
Local Administration: In acute myocardial infarction, patients are given an intracoronary bolus of Streptase 20,000 IU on average and a maintenance dose of 2,000-4,000 IU/min over 30-90 min.
Acute, Subacute and Chronic Thromboses/Embolisms of Peripheral Venous and Arterial Vessels and Chronic Occlusive Arterial Diseases: Systemic Administration: In short-term thrombolysis, adults with peripheral venous and arterial vessel occlusions/embolisms receive an initial dose of Streptase 250,000 IU within 30 min, followed by a maintenance dose of 1.5 MIU/hr over a maximum of 6 hrs. The 6-hr Streptase infusion can be repeated on the following day, depending on the therapeutic success of lysis. However, repetition of treatment must on no account be conducted later than 5 days after the 1st course.
As an alternative to short-term lysis, a long-term lysis for the treatment of peripheral occlusions may be considered. An initial dose of Streptase 250,000 IU is given within 30 min, followed by a maintenance dose of 100,000 IU/hr. The duration of therapy depends on the extension and localisation of the vessel occlusion. In peripheral vessel occlusion, the maximum duration is 5 days.
Local Administration: Patients with acute, subacute and chronic peripheral thromboses and embolisms receive Streptase 1,000-2,000 IU in intervals of 3-5 min. The duration of administration depends on the length and localisation of the vessel occlusion and amounts up to 3 hrs at a total dose of maximum Streptase 120,000 IU.
A percutaneous transluminal angioplasty (mechanical vessel dilatation) can be performed simultaneously, if necessary.
Occlusions of Central Retinal Artery or Vein: Systemic Administration: In case of thromboses of the central retinal vessels, lysis of arterial occlusions should be limited to maximum 24 hrs, in venous occlusions to maximum 72 hrs. If continuation of thrombolysis is indicated due to extensive thrombotic occlusions, therapy should be interrupted for 1 day, followed by administration of a homologous fibrinolytic.
Control of Therapy: Systemic Administration: In case of short-term lysis over 6 hrs heparin should be administered during or following Streptase infusion when the thrombin time (TT) or partial thromboplastin time (aPTT) have reached less than twice or 1.5 times the normal control value, respectively. The TT and aPTT should be prolonged to 2- to 4-fold and 1.5- to 2.5-fold the normal value, respectively, in order to ensure sufficient protection against rethrombosis (reocclusion of the vessel).
If the Streptase infusion is not repeated, the heparin therapy is instituted simultaneously with the administration of oral anticoagulants (see Follow-Up Treatment as follows).
The long-term lysis is controlled with the TT. A 2- to 4-fold prolongation of the TT which is considered as a sufficient anticoagulant protection has to be aimed at. Therefore, a simultaneous administration of heparin may become necessary from the 16th hour of treatment. If the TT after the 16th hour is still prolonged to >4-fold the normal control value, the maintenance dose of Streptase has to be doubled for several hours until the TT recedes.
Local Administration: As is usual with angiographies (x-ray of the vessels with the help of contrast media), heparin is administered, if necessary, prior to the angiography as a safeguard against catheter-induced thromboses. The success of therapy can be determined by the angiography. With a sufficient blood flow of >15 min, the therapy can be considered successful and then can be terminated.
Follow-up Treatment: After every course of streptokinase therapy, a follow-up treatment with anticoagulants or platelet aggregation inhibitors (drugs which inhibit platelet-induced clot formation), can be instituted as a prevention of rethromboses. With heparin therapy, in particular, an increased risk of haemorrhage must be considered. The heparin therapy is controlled individually with the TT or aPTT. A 2- to 4-fold prolongation of the TT and 1.5- to 2.5-fold prolongation of the aPTT is aimed at. For long term prophylaxis oral anticoagulants eg, coumarin derivatives or platelet aggregation inhibitors can be applied.
Administration: Streptase is administered IV or intra-arterially. The duration of therapy depends on the nature and extension of the vessel occlusion and differs according to the indication.
Streptase is presented as a white lyophilisate. Upon reconstitution, with physiological saline, a colorless to yellowish, clear solution is obtained.
To ensure that the contents of the vial are rapidly and completely reconstituted, 5 mL of physiological saline should be injected into the vacuum Streptase vial and the residual vacuum abolished by briefly loosening the needle from the syringe.
For administration with an infusion pump, physiological saline, Ringer lactate solution, glucose or laevulose 5% solution can be used as diluent.
Streptase must not be used in case of severe allergic reactions.
Because of the increased risk of haemorrhage (bleeding) under thrombolytic therapy, Streptase must not be given in the following situations: Existing or recent internal haemorrhages, all forms of reduced blood coagulability, in particular spontaneous fibrinolysis and extensive clotting disorders, recent cerebrovascular insultus (stroke, cerebral haemorrhage), intracranial (in the skull) or intraspinal (spinal cord) surgery, intracranial neoplasm (tumour), recent head trauma, arteriovenous malformation or aneurysm (expansion of an arterial vessel), known neoplasm with risk of haemorrhage, acute pancreatitis, uncontrollable hypertension with systolic values above 200 mmHg and/or diastolic values above 100 mmHg or hypertensive retinal changes grades III/IV (changes to the fundus of the eye due to high blood pressure), recent implantation of a vessel prosthesis, simultaneous treatment with oral anticoagulants (drugs which inhibit the coagulation) (INR>1.3), severe liver or kidney damages, endocarditis (inflammation of the inner membrane of the heart) or pericarditis (inflammation of the heart sac). Isolated cases of a pericarditis, misdiagnosed as acute myocardial infarction and treated with Streptase have resulted in pericardial effusions, including tamponade (overloading of the heart sac with liquid), known bleeding tendency, recent major operations (6th-10th postoperative day, depending on the severity of surgical intervention), invasive operations eg, recent organ biopsy (removal of tissue specimen), long-term (traumatic) closed-chest cardiac massage.
Local Administration: Also in local administration, a systemic effect is possible. Therefore, the contraindications mentioned, should also be considered for local administration.
Special Precautions
Individual Benefit/Risk Assessment: The risk of therapy in case of life-threatening thromboembolic events, in particular that of haemorrhages, must be weighed against the anticipated benefit in cases such as: Recent severe gastrointestinal bleeding eg, active peptic ulcer, risk of severe local haemorrhage eg, in case of aortography by lumbar route (angiography of principal artery of the lumbar vertebrae section), recent trauma (severe injury) and cardiopulmonary resuscitation, invasive operations eg, recent intubation, puncture of noncompressible vessels, IM injections, recent delivery, abortion (including miscarriage), diseases of the urogenital tract with existing or potential sources of bleeding (implanted bladder catheter), known septic thrombotic disease (formation of clots in case of blood poisoning), severe atherosclerotic vessel degeneration, cerebrovascular diseases, cavernous diseases (eg, open tuberculosis), mitral valve (heart valve) defects or atrial fibrillation.
Local Administration: A systemic effect is also possible during local administration. Therefore, the special warnings mentioned should also be considered in local administration.
Antistreptokinase Antibodies: Because of the increased likelihood of resistance due to antistreptokinase antibodies, re-treatment with Streptase or streptokinase-containing products may not be effective if administered >5 days, particularly between 5 days and 12 months, after initial treatment.
Likewise, the therapeutic effect may be reduced in patients with recent streptococcal infections eg, streptococcal pharyngitis (bacterial inflammation of the throat), acute rheumatic fever, acute glomerulonephritis (inflammation of the kidney).
Infusion Rate and Corticosteroid Prophylaxis: At the beginning of therapy, fall in blood pressure, increase in heart rate or decrease in heart rate (in individual cases reaching as far as shock) are commonly observed. Therefore, at the beginning of therapy, the infusion should be performed slowly. Furthermore, corticosteroids can be administered prophylactically.
Pre-Treatment with Heparin or Coumarin Derivatives: If the patient is under active heparinization, it should be neutralized by the administration of protamine sulphate before the start of the thrombolytic therapy. The thrombin time should not be more than twice the normal control value before thrombolytic therapy is started. In patients previously treated with coumarin derivatives, the international normalized ratio (INR) must be <1.3 before starting the streptokinase infusion.
Simultaneous Treatment with Acetylsalicylic Acid: A positive, mutually reinforcing effect of acetylsalicylic acid and streptokinase on the life expectancy of patients with suspected myocardial infarction has been observed. The administration of acetylsalicylic acid should commence prior to the streptokinase therapy and be continued for at least 1 month.
Arterial Puncture: Should an arterial puncture be necessary during IV therapy, upper extremity vessels are preferable. After the puncture, pressure should be applied for at least 30 min by a compression bandage and the puncture site should be checked frequently for evidence of bleeding.
Use in pregnancy & lactation: Due to the risk for the foetus, Streptase should only be given during pregnancy after careful benefit-risk consideration. In the first 18 weeks of pregnancy, the use of streptokinase must be restricted to vital indications only.
Information on the use of Streptase during breastfeeding is not available.
Use in children: Sufficient experience with Streptase therapy in children is not yet available. The benefit of treatment has to be evaluated against the potential risks which may aggravate an acute life-threatening situation.
Use In Pregnancy & Lactation
Due to the risk for the foetus, Streptase should only be given during pregnancy after careful benefit-risk consideration. In the first 18 weeks of pregnancy, the use of streptokinase must be restricted to vital indications only.
Information on the use of Streptase during breastfeeding is not available.
Adverse Reactions
If the patient experience reactions, especially which are not mentioned, inform the physician or pharmacist.
The following adverse reactions based on experience from clinical trials and on post-marketing experience. The following standard categories of frequency are used: Very common: >1/10; common: >1/100 and <1/10; uncommon: >1/1,000 and <1/100; rare: >1/10,000 and <1/1,000; very rare: <1/10,000 (including reported single cases).
Blood Disorders: Common: Haemorrhages at the injection site and ecchymoses (small-area skin bleedings). Gastrointestinal or urogenital bleedings, epistaxis (nosebleeding). Uncommon: Cerebral haemorrhages with their complications and possible fatal outcome, retinal haemorrhages, severe haemorrhages (also with fatal outcome), including liver haemorrhages, retroperitoneal (in the back of the abdomen) bleedings, splenic rupture. Blood transfusions are rarely required. Very Rare: Haemorrhages into the pericardium (heart sac), including myocardial rupture (tearing of the heart muscle) during the thrombolytic (clot dissolving) treatment of acute myocardial infarction.
In severe haemorrhagic complications, the Streptase therapy is discontinued and a proteinase inhibitor eg, aprotinin, administered in the following dosage: Initially, 500,000 KIU (Kallikrein inactivator unit), if necessary up to 1 million KIU, followed by 50,000 KIU/hr by IV drip until the bleeding stops. In addition, combination with synthetic antifibrinolytics is recommended. If necessary, coagulation factors can be administered. Additional administration of synthetic antifibrinolytics was reported to be efficient in single cases of bleeding episodes.
Immune System Disorders: Very Common: Development of antistreptokinase antibodies (see Precautions). Common: Allergic-anaphylactic reactions with rash, flushing (skin reddening with heat sensation), itching, urticaria, angioneurotic edema, dyspnoea, bronchospasm (constriction of airways) or fall in blood pressure. Very Rare: Delayed allergic reactions eg, serum sickness, arthritis (inflammation of the joints with pain, swelling and loss of motion), vasculitis (inflammation of a vessel wall), nephritis (inflammation of the kidney) and neuroallergic (concerning the nerves) symptoms [polyneuropathy (disease concerning several nerves) eg, Guillain Barre syndrome], severe allergic reactions up to shock including respiratory arrest.
Mild or moderate allergic reactions may be managed with concomitant antihistamine and/or corticosteroid therapy. If a severe allergic/anaphylactic reaction occurs, the administration of Streptase has to be discontinued immediately and an appropriate treatment should be initiated. The current medical standards for shock treatment should be observed. Lysis therapy should be continued with homologous fibrinolytics.
Nervous System Disorders: Rare: Neurologic symptoms eg, dizziness, confusion, paralysis, hemiparesis (paralysis of the left or right part of the body), restlessness or convulsions (cramps) in the context of cerebral haemorrhages or cardiovascular (relating to the heart and circulation) disorders with hypoperfusion (reduced blood flow) of the brain.
Cardiac Complications and Vascular Disorders: Common: At the beginning of therapy, fall in blood pressure, tachycardia or bradycardia (see Precautions: Infusion Rate and Corticosteroid Prophylaxis). Very Rare: Crystal cholesterol embolism.
In the setting of fibrinolytic (clot dissolving) therapy with Streptase in patients with myocardial infarction the following events have been reported as complications of myocardial infarction and/or symptoms of reperfusion (re-opening of occluded blood vessels): Very Common: Fall in blood pressure, heart rate and rhythm disorders, angina pectoris. Common: Recurrent ischaemia (depletion of blood), heart failure, reinfarction (repeated infarction), cardiogenic (triggered by heart failure) shock, pericarditis, pulmonary oedema. Uncommon: Cardiac arrest (leading to respiratory arrest), mitral (heart valve) insufficiency, pericardial effusion (seropurulent liquid accumulation in the heart sac), cardiac tamponade (liquid load in the heart sac), myocardial rupture, pulmonary or peripheral embolism.
These cardiovascular complications can be life-threatening and may lead to death.
During local lysis of peripheral arteries, distal (away from the heart) embolization cannot be excluded.
Respiratory Disorders: Very Rare: Noncardiogenic (not triggered by heart failure) pulmonary edema after intracoronary thrombolytic therapy in patients with extensive myocardial infarction.
Gastrointestinal Disorders: Common: Nausea, diarrhoea, epigastric (upper abdomen) pain and vomiting.
General Disorders: Common: Headache and back pain, muscle pain, chills and/or rise in temperature, as well as faintness/weariness.
Investigations: Common: Transient elevations of serum transaminases (liver function parameters), as well as of bilirubin.
Drug Interactions
Simultaneous or previous treatment with anticoagulants (drugs which inhibit the coagulation eg, heparin) and substances which inhibit the platelet formation or function (eg, platelet aggregation inhibitors, dextrans) may increase the danger of haemorrhage.
Before starting long-term systemic lysis (lysis=clot dissolving treatment) of deep vein thromboses and arterial occlusions with streptokinase, the effects of drugs which act upon platelet formation or function should be allowed to subside (see Precautions).
Incompatibilities: Not known.
For further dilution of the reconstituted solution, special infusion solutions are recommended (see Dosage & Administration).
Store at 2-25°C.
Once reconstituted with physiological saline, the physicochemical stability has been demonstrated for 24 hrs at 2-8°C. From a microbiological point of view and as Streptase contains no preservative, the reconstituted product should be used immediately. If it is not administered immediately, storage shall not exceed 24 hrs at 2-8°C.
ATC Classification
B01AD01 - streptokinase ; Belongs to the class of enzymes. Used in the treatment of thrombosis.
Powd for inj 1.5 MIU (vial, white, lyophilised powder) x 1's.
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