Summary of Product Characteristics Updated 11-Aug-2015 | Beacon Pharmaceuticals
AdultsDeep vein thrombosisAn initial dose of 250 000 IU streptokinase should be infused into a peripheral vein over 30 minutes. A maintenance infusion of 100 000 IU/hour for 72 hours should follow.Pulmonary embolismInfuse 1 500 000 IU streptokinase into a peripheral vein preferably over a short time of 1-2 hours.As an alternative, an initial dose of 250 000 IU streptokinase should be infused into a peripheral vein over 30 minutes. A maintenance infusion of 100 000 IU/hour for 24 hours should follow.Occlusive peripheral arterial diseasesAdminister streptokinase with a local intra-arterial catheter-directed infusion using one of the following regimes:- Gradual infusion: 1000 to 2500 IU streptokinase at an interval of 3 to 5 minutes for a maximum of 10 hours and a total maximum dose of 250 000 IU- Prolonged continuous low-dose infusion (using an infusion pump): 5000 to 10,000 IU streptokinase per hour for up to 5 days maximum. A percutaneous transluminal angioplasty can be performed simultaneously, if necessary.As an alternative for difficult arterial access or multiple occlusions, an initial dose of 250 000 IU streptokinase should be infused over 30 minutes. A maintenance infusion of 100 000 IU/hour for a maximum of 5 days should follow.Central retinal vessel occlusionAn initial dose of 250 000 IU streptokinase should be infused into a peripheral vein over 30 minutes. A maintenance infusion of 100 000 IU/hour for 12 hours should follow.
Paediatric populationThe safety and efficacy of Biofactor Streptokinase have not been sufficiently established in children. Due to low levels of plasminogen in newborns and in children with acquired plasminogen deficiency and due to the potential of streptokinase for allergic/anaphylactic reactions, it is not recommended in neonates, infants and children.
Control of TherapyBefore commencing thrombolytic therapy, it is desirable to obtain a thrombin time (TT), activated partial thromboplastin time (aPTT), haematocrit and platelet count to obtain the haemostatic status of the patient. If heparin has been given it should be discontinued, and the TT or aPTT should be less than twice the normal control value before the thrombolytic therapy is started. In patients previously treated with coumarin derivatives, the INR (international normalised ratio) should be below 1.3 before starting therapy with streptokinase.
Method of AdministrationThe administration of streptokinase may be by systemic intravenous infusion or by local intra-arterial catheter-directed infusion.For instructions on reconstitution of the medicinal product before administration, see section 6.6.Upon reconstitution with physiological saline a clear solution, colourless to yellowish, is obtained.Note: When thrombolytic therapy is necessary and a high antibody concentration against streptokinase is present or when recent streptokinase therapy has been given (more than 5 days and less than one year previously), homologous fibrinolytics should be used (see sections 4.4 and 4.8).
Systemic AdministrationDuring the infusion, decreases in the plasminogen and fibrinogen levels and an increase in the level of fibrin degradation product (FDP) (the latter two serving to prolong the clotting time of coagulation tests) will generally confirm the existence of a thrombolytic state. Therefore, therapy can be monitored by performing the TT or aPTT approximately 4 hours after initiation of therapy.A 2 to 4 fold prolongation of the TT should be aimed for and is considered a sufficient anticoagulation protection. If the thrombin time or any other parameter of lysis after 4 hours of therapy is less than approximately 1.5 times the normal control value, discontinue Biofactor Streptokinase as excessive resistance to streptokinase is present.
Local administrationAs is usual with angiographies, 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 stopped.
Follow-up treatmentAfter every course of streptokinase therapy, follow-up treatment with anticoagulants or platelet aggregation inhibitors can be instituted as prevention of rethromboses. With heparin therapy, in particularly, an increased risk of haemorrhage must be considered.
AntistreptokinaseRepeat treatment with streptokinase administered more than 5 days and less than 12 months after initial treatment may not be effective. This is because of the increased likelihood of resistance due to antistreptokinase antibodies.Also, the therapeutic effect may be reduced in patients with recent streptococcal infections such as streptococcal pharyngitis, acute rheumatic fever and acute glomerulonephritis.
Infusion rate and corticosteroid prophylaxisAt the beginning of therapy, a fall in blood pressure, tachycardia or bradycardia (in individual cases going as far a shock) are commonly observed. Therefore, at the beginning of therapy the infusion should be performed slowly. Corticosteroids can be administered prophylactically to reduce the likelihood of infusion-related allergic reactions.
Pre-treatment with heparin or coumarin derivativesIf the patient is under active heparinization, it should be neutralised by administering 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.
Arterial punctureShould 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. The puncture site should be checked frequently for evidence of bleeding.Streptokinase is not indicated for restoration of patency of intravenous catheters.
|Very common||more than1/10|
|Common||more than 1/100; less than 1/10|
|Uncommon||more than 1/1000; less than 1/100|
|Rare||more than 1/10,000; less than 1/1000|
|Very Rare||less than1/10,000 (including isolated cases)|
Blood and lymphatic system disordersCommon: haemorrhage at the injection site, ecchymoses, gastrointestinal bleeding, genitourinary bleeding, epistaxisUncommon: cerebral haemorrhages with their complications and possible fatal outcome, retinal haemorrhages, severe haemorrhages (also with fatal outcome), liver haemorrhages, retroperitoneal bleeding, bleeding into joints, splenic rupture. Blood transfusions are rarely required. Very rare: haemorrhage into the pericardium including myocardial rupture during thrombolytic treatment of acute myocardial infarctionIn serious haemorrhagic complications, streptokinase therapy should be discontinued and a proteinase inhibitor, e.g., aprotinin, should be given as follows. Initially 500 000 KIU (Kallikrein Inactivator Unit) up to one million KIU by slow intravenous injection or infusion. If necessary this should be followed by 200,000 KIU every four hours by intravenous drip until the bleeding stops. In addition, combination with synthetic antifibrinolytics is recommended. If necessary, clotting factors can be substituted. Additional administration of synthetic antifibrinolytics has been reported to be efficient in single cases of bleeding episodes.
Immune system disordersVery Common: development of antistreptokinase antibodies (see also 4.4)Common: allergic anaphylactic reactions, e.g. rash, flushing, itching, urticaria, angioneurotic oedema, dyspnoea, bronchospasm, hypotensionVery Rare: delayed allergic reactions, e.g. serum sickness, arthritis, vasculitis, nephritis, neuroallergic symptoms (polyneuropathy, e.g. Guillain Barré syndrome), severe allergic reactions up to shock including respiratory arrest. Moderate or mild allergic reactions can be managed with concomitant antihistamine and/or corticosteroid therapy. If a severe allergic reaction occurs the infusion of streptokinase should be discontinued immediately and the patient given the appropriate treatment. The current medical standards for shock treatment should be observed. Lysis therapy should be continued with homologous fibrinolytics, such as Urokinase or tPA.
Nervous system disordersRare: neurologic symptoms (e.g. dizziness, confusion, paralysis, hemiparesis, agitation, convulsion) in the context of cerebral haemorrhages or cardiovascular disorders with hypoperfusion of the brain
Eye disordersVery rare: iritis/uveitis/iridocyclitis
Cardiac and vascular disordersCommon: at the start of therapy, hypotension, tachycardia, bradycardiaVery rare: crystal cholesterol embolismDuring fibrinolytic therapy with streptokinase in patients with myocardial infarction, the following events have been reported as complications of myocardial infarction and/or symptoms of reperfusion:Very common: hypotension, heart rate and rhythm disorders, angina pectorisCommon: recurrent ischaemia, heart failure, reinfarction, cardiogenic shock, pericarditis, pulmonary oedemaUncommon: cardiac arrest (leading to respiratory arrest), mitral insufficiency, pericardial effusion, cardiac tamponade, myocardial rupture, pulmonary or peripheral embolismThese cardiovascular complications can be life-threatening and may lead to death. During local lysis of peripheral arteries, distal embolization cannot be excluded.
Respiratory DisordersVery rare: non-cardiogenic pulmonary oedema after intracoronary thrombolytic therapy in patients with extensive myocardial infarction
Gastrointestinal disordersCommon: nausea, diarrhoea, epigastric pain, vomiting
General disorders and administration site conditionsCommon: headache, back pain, musculoskeletal pain, chills, fever, asthenia, malaise
TestingCommon: Transient elevations of serum transaminases and bilirubin
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.
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