Israel - English - Ministry of Health
Streptase 750 000:
Active ingredient: Stabilized pure streptokinase, derived from the culture ﬁltrate of beta-
haemolytic streptococci of Lanceﬁeld group C. It is presented as a white powder and contains
QUALITATIVE AND QUANTITATIVE COMPOSITION
Streptase 1 500 000:
1 injection vial with 147 to 192 mg dried substance contains 1 500 000 IU streptokinase.
1 injection vial with 139 to 182 mg dried substance contains 750 000 IU streptokinase.
Human albumin, Sodium-L-hydrogen glutamate monohydrate, Sodium dihydrogenphosphate
dihydrate, Disodium hydrogenphosphate dihydrate.
PHARMACEUTICAL FORM AND PRESENTATIONS
Powder for intravenous or intraarterial administration after reconstitution with physiological saline.
Streptase 1 500 000
1 vial of 1 500 000 IU streptokinase
Streptase 750 000
1 vial of 750 000 IU streptokinase
Streptokinase (antithrombotic agents, enzymes).
ATC-code: B01A D01
Streptase 750,000 IU: Acute myocardial infarction, deep vein thrombosis, pulmonary embolism,
acute or subacute thrombosis of peripheral arteries and chronic occlusive arterial diseases,
occlusion of central retinal artery or vein.
Streptase 1,500,000 IU:
Systemic administration: in deep vein thromboses, lung embolism, acute myocardial infarction for re-
opening of coronary vessels. In acute and subacute thromboses of peripheral arteries and chronic
occlusive arterial diseases, occlusion of central retinal artery or vein.
Local administration: in acute myocardial infarction for re-opening of coronary vessels, in acute,
subacute and chronic thromboses as well as embolisms of peripheral arteries.
Streptase must not be used in case of severe allergic reactions to the product.
Because of the increased risk of haemorrhage 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
recent cerebrovascular insultus, intracranial or intraspinal surgery
recent head trauma
arteriovenous malformation or aneurysm
known neoplasm with risk of haemorrhage
uncontrollable hypertension with systolic values above 200 mmHg and/or diastolic values
above 100 mmHg or hypertensive retinal changes grades III/IV
recent implantation of a vessel prothesis
simultaneous treatment with oral anticoagulants (drugs which inhibit the coagulation) (INR>1.3)
severe liver or kidney damages
endocarditis or pericarditis. Isolated cases of a pericarditis, misdiagnosed as acute
myocardial infarction and treated with Streptase, have resulted in pericardial effusions
known bleeding tendency
recent major operations (6
postoperative day, depending on the severity of surgical
invasive operations, e.g. recent organ biopsy, long-term closed-chest cardiac massage.
Also in local administration a systemic effect is possible. Therefore, the contraindications
mentioned above should also be considered for local administration.
Pregnancy and lactation
Due to the risk for the fetus, 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 breast-feeding is not available.
SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE
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, e.g. active peptic ulcer
risk of severe local haemorrhage, e.g. in case of aortography by lumbar route (angiography of
principal artery of the lumbar vertebrae section)
recent trauma and cardiopulmonary resuscitation
invasive operations, e.g. recent intubation
puncture of non-compressible vessels, intramuscular injections
recent delivery, abortion (including miscarriage)
diseases of the urogenital tract with existing or potential sources of bleeding (implanted
known septic thrombotic disease
severe atherosclerotic vessel degeneration, cerebrovascular diseases
cavernous diseases (e.g. open tuberculosis)
mitral valve defects or atrial ﬁbrillation.
A systemic effect is also possible during local administration. Therefore, the special warnings
mentioned above should also be considered for local administration.
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 more
than 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
such as streptococcal pharyngitis, acute rheumatic fever, acute glomerulonephritis.
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 INR (International Normalized Ratio) must be
less than 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 one month.
Should an arterial puncture be necessary during intravenous therapy, upper extremity vessels are
preferable. After the puncture, pressure should be applied for at least 30 minutes by a compression
bandage, and the puncture site should be checked frequently for evidence of bleeding.
Simultaneous or previous treatment with anticoagulants or substances which inhibit the platelet
formation or function (e.g. platelet aggregation inhibitors, dextrans) may increase the danger of
Before starting long-term systemic lysis 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 “Special warnings and precautions for use”).
For further dilution of the reconstituted solution special infusion solutions are recommended (see
DOSAGE AND ADMINISTRATION
streptokinase is present, or recent streptokinase therapy has been given (more than 5 days
and less than one year previously), homologous ﬁbrinolytics should be used (see also “Special
warnings and precautions for use”).
Acute transmural myocardial infarction with persistent ST-segment elevation or recent left bundle-
In short-term lysis for the treatment of acute myocardial infarction 1.5 Mio IU Streptase are given
within 60 min.
In acute myocardial infarction patients are given an intracoronary bolus of 20 000 IU Streptase on
average and a maintenance dose of 2000 IU to 4000 IU per min over 30 to 90 min.
Acute, subacute and chronic thromboses/embolisms of peripheral venous and arterial vessels
and chronic occlusive arterial diseases:
In short-term thrombolysis, adults with peripheral venous and arterial vessel occlusions/ embolism,
receive an initial dose of 250 000 IU Streptase within 30 min, followed by a maintenance dose
of 1.5 Mio IU per hour over a maximum of six hours. The six-hour 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 ﬁrst 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 250 000 IU Streptase is given within 30 min, followed by
a maintenance dose of 100 000 IU per hour. The duration of therapy depends on the extension
and localisation of the vessel occlusion. In peripheral vessel occlusion the maximum duration is
Patients with acute, subacute and chronic peripheral thromboses and embolisms receive 1000 IU
to 2000 IU Streptase in intervals of 3 to 5 min. The duration of administration depends on the
length and localisation of the vessel occlusion and amounts up to 3 hours at a total dose of max.
120 000 IU Streptase.
A percutaneous transluminal angioplasty can be performed simultaneously, if necessary.
Occlusions of central retinal artery or vein:
In case of thromboses of the central retinal vessels, lysis of arterial occlusions should be limited
to max. 24 hours and in venous occlusions to max. 72 hours. If continuation of thrombolysis
is indicated due to extensive thrombotic occlusions, therapy should be interrupted for one day,
followed by administration of a homologous ﬁbrinolytic.
Dosage for neonates, infants and 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-
Control of therapy
In case of short-term lysis over six hours 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.
If the Streptase infusion is not repeated the heparin therapy is instituted simultaneously with the
administration of oral anticoagulants (see Follow-up treatment).
The long-term lysis is controlled with the thrombin time (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 16
hour of treatment.
If the TT after the 16
hour is still prolonged to more than 4 fold the normal control value, the
maintenance dose of Streptase has to be doubled for several hours until the TT recedes.
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 more than 15 minutes the therapy can be considered successful and then terminated.
After every course of streptokinase therapy a follow-up treatment with anticoagulants or platelet
aggregation inhibitors 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
coumarin derivatives or platelet aggregation inhibitors can be applied.
Streptase is administered intravenously or intraarterially. The duration of therapy depends on
the nature and extension of the vessel occlusion and differs according to the indication (see
Streptase is presented as a white lyophilisate. Upon reconstitution with physiological saline, a
colourless 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 Streptase vacuum 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, 5%
glucose or laevulose solution can be used as diluent. For higher dilutions, especially when good
stability is required over longer periods, polygeline can be used as diluent.
If you experience reactions, especially those which are not mentioned in this package insert,
please inform your doctor or pharmacist.
The following adverse reactions are based on experience from clinical trials and on postmarketing
experience. The following standard categories of frequency are used:
1/100 and < 1/10
1/1,000 and < 1/100
1/10,000 and < 1/1,000
1/10,000 (including reported single cases)
: Haemorrhages at the injection site and ecchymoses. Gastrointestinal or urogenital
Uncommon: Cerebral haemorrhages with their complications and possible fatal outcome, retinal
haemorrhages, severe haemorrhages (also with fatal outcome) including liver haemorrhages,
retroperitoneal bleedings, splenic rupture. Blood transfusions are rarely required.
Very rare: Haemorrhages into the pericardium including myocardial rupture during thrombolytic
treatment of acute myocardial infarction.
In severe haemorrhagic complications the Streptase therapy is discontinued and a proteinase
inhibitor, e.g. aprotinin, administered in the following dosage: Initially 500 000 KIU , if necessary
up to 1 million KIU, followed by 50 000 KIU per hour by intravenous 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 also “Special warnings and
special precautions for use”).
Common: Allergic-anaphylactic reactions with rash, ﬂushing, itching, urticaria, angioneurotic
edema, dyspnoea, bronchospasm or fall in blood pressure.
Very rare: Delayed allergic reactions, such as serum sickness, arthritis, vasculitis, nephritis
and neuroallergic symptoms, polyneuropathy,( e.g. Guillain Barré 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 (e.g. dizziness, confusion, paralysis, hemiparesis, restlessness
or convulsions in the context of cerebral haemorrhages or cardiovascular disorders with
hypoperfusion of the brain.
Cardiac complication and vascular disorders
Common: At the beginning of therapy fall in blood pressure, tachycardia or bradycardia (see also
“Special warnings and special precautions for use”, subheading “Infusion rate and corticosteroid
Very rare: Crystal cholesterol embolism.
In the setting of ﬁbrinolytic therapy with Streptase in patients with myocardial infarction the
following events have been reported as complications of myocardial infarction and/or symptoms
Very common: Fall in blood pressure, heart rate and rhythm disorders, angina pectoris
Common: Recurrent ischaemia (depletion of blood), heart failure, reinfarction, cardiogenic
shock, pericarditis, pulmonary oedema.
These cardiovascular complications can be life-threatening and may lead to death.
During local lysis of peripheral arteries, distal embolization cannot be excluded.
Very rare: Non-cardiogenic pulmonary edema after intracoronary thrombolytic therapy in
patients with extensive myocardial infarction.
Common: Nausea, diarrhoea, epigastric pain and vomiting.
Common: Headache and back pain, muscle pain, chills and/or rise in temperature as well as
Common: Transient elevations of serum transaminases (liver function parameters) as well as
STORAGE AND STABILITY
Streptase is to be stored at +2 to +25 °C.
Once reconstituted with physiological saline, the physico-chemical stability has been demonstrated
for 24 hours at +2 to +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 hours at +2 to +8 °C.
Streptase must not be used after the expiry date given on the pack and container.
Keep out of the reach of children!
CSL Behring GmbH, Germany
Genmedix, 12 Beit Harishonim St. Emek-Hefer 38777
The format of this leaﬂet has been determined by the Ministry of Health and its content has been
examined and approved in November 2012.
SH Z550051009999B/STR OCT14