SYNER-KINASE

Syner-KINASE® must be restricted to hospital use only. Adequate diagnostic and monitoring techniques should be available. Posology The dose of Syner-KINASE may be adjusted individually depending on the clinical condition and response to treatment.

Thrombosed intravascular catheters and cannula 5,000 to 25,000 IU Syner- KINASE® should be dissolved in the volume of solvent required to completely fill the lumen of the catheter or cannula and locked for a duration of 20 to 60 minutes.

The lysate is then aspirated and the procedure repeated if necessary. Alternatively, an infusion of up to 250,000 IU Syner-KINASE® can be administered into the catheter or cannula over a period of 90 to 180 minutes using a solution of 1,000 to 2,500 IU/ml in the solvent.

Extensive acute proximal deep vein thrombosis An initial loading dose of 4,400 IU/kg body weight dissolved in 15 ml solvent should be infused in a peripheral vein over 10 minutes followed by 4,400 IU/kg/hour for 12- 24 hours. Acute massive pulmonary embolism An initial loading dose of 4,400 IU/kg body weight dissolved in 15 ml solvent should be infused in a peripheral vein over 10 minutes followed by 4,400 IU/kg/hour for 12 hours.

Alternatively, a bolus injection into the pulmonary artery repeated for up to 2 times at 24-hour intervals may be used. An initial dosage of 15,000 IU/kg body weight may be adjusted if necessary for subsequent injections depending on the plasma fibrinogen concentration produced by the previous injection.

Acute occlusive peripheral arterial disease with limb threatening ischaemia A solution of 2,000 IU/ml (500,000 IU Syner-KINASE® dissolved in 250 ml solvent) should be infused into the clot with angiographic monitoring of progress of treatment.

It is recommended that the rate of infusion should be 4,000 IU/minute for 2 hours when angiography should be repeated. Following this, the catheter should be advanced into the occluded segment of vessel and Syner-KINASE® infused at the same rate of 4,000 IU/minute for another 2 hours.

The process can be repeated up to 4 times if flow has not been achieved. Once a channel has been created through the blocked segment, the catheter may be withdrawn until it lies proximal to the remaining thrombus. Infusion should continue at the rate of 1,000 IU/minute until the clot has completely lysed.

Usually, a dose of 500,000 IU over 8 hours should be sufficient. If the length of the clot has not been reduced by more than 25% after the initial dose of 500,000 IU and further reductions of 10% by subsequent infusions of 500,000 IU, discontinuation of treatment should be considered.

Special populations Elderly Available data are limited in patients over 65 years and it is not known whether they respond differently from younger subjects. The initial dosage should be the same as in adults but it may be adjusted subsequently depending on response.

4). 2). In these cases, the fibrinogen level should not fall below 100 mg/dl. Paediatric population There is very limited experience with urokinase in children with thromboembolic occlusive vascular disease and urokinase should not be used in this indication.

Syner-KINASE® may be used in children of all ages for the treatment of thrombosed central venous catheters using the same lock procedure as in adults. Method of administration The route of administration is by intravenous infusion, intra-arterial injection or local instillation.

It must not be given as a subcutaneous or intramuscular injection. 6.

There are limited data available on the adverse effects of urokinase from controlled clinical trials. The adverse reactions described below reflect the available data from these clinical trials and the clinical use of urokinase in the general population, where it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.

Haemorrhage The most frequent and severe adverse effect of urokinase therapy is haemorrhage. Severe spontaneous bleeding, including fatalities resulting from cerebral haemorrhage, has occurred during urokinase therapy. Less severe spontaneous bleeding has occurred approximately twice as frequently as that occurring during heparin therapy.

Patients with pre-existing haemostatic defects have the greatest risk of spontaneous bleeding. Moderate decreases in haematocrit not accompanied by clinically detectable bleeding have been reported in approximately 20% of patients receiving urokinase.

Embolism Embolic episodes may occur after fragments of clot have been released. Cholesterol embolisms have also been reported. Hypersensitivity reactions Urokinase is reportedly non-antigenic but mild hypersensitivity reactions including urticaria, rash, bronchospasm and very rare cases of fatal anaphylaxis have been reported.

Infusion reactions Infusion reactions including fever and shaking chills (rigors) have been reported. Symptomatic treatment is usually sufficient to alleviate discomfort caused by urokinase-induced fever, however, acetylsalicylic acid should not be used.

Other infusion reactions include dyspnoea, cyanosis, hypoxemia, acidosis, back pain, and nausea and/or vomiting; these reactions generally occurred within one hour of beginning urokinase infusion. The following frequency convention was used as a basis for the evaluation of undesirable effects: Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1,000 to < 1/100) Rare (≥ 1/10,000 to < 1/1,000) Very rare (< 1/10,000) Immune system disorders Rare Hypersensitivity reactions, including urticaria, dyspnoea, hypotension, flushing, rash Very rare Anaphylaxis Nervous system disorders Common Stroke Vascular disorders Very common Haemorrhage, including from puncture site and wound Epistaxis, gingival bleeding Thromboembolism Embolism, including pulmonary embolism Haematuria (microscopic) Common Gastrointestinal haemorrhage, intracranial haemorrhage, retroperitoneal haemorrhage, urogenital haemorrhage, muscle haemorrhage Artery dissection Cholesterol embolism Uncommon Intrahepatic haemorrhage Rare Vascular pseudoaneurysm Haematuria (macroscopic) Renal and urinary disorders Uncommon Renal failure General disorders and administration site conditions Common Fever, chills Investigations Very common Decrease in haematocrit without clinically detectable haemorrhage Transient increase in transaminases Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

g. g. implanted bladder catheter) - Known septic thrombotic disease - Elderly patients, especially those over 75 years of age When bleeding occurs in patients receiving urokinase, it may be difficult to control. ) are also subject to lysis, and bleeding from such sites may result.

Oozing of blood from sites of percutaneous trauma occurs frequently. The possibility of bruising or haematoma formation, especially after intramuscular injections, is high during urokinase therapy. Intramuscular injections and unnecessary handling of the patient should be avoided.

Venipuctures and invasive venous procedures should be performed as infrequently as possible and with care to minimise bleeding. If bleeding from an invasive site is not serious, urokinase therapy may be continued while closely observing the patient; local measures such as application of pressure should be initiated immediately.

Arterial invasive procedures must be avoided before and during urokinase treatment to minimise bleeding. If an arterial puncture is absolutely essential, it should be performed by a physician experienced in the procedure, using a radial or brachial rather than a femoral artery.

Direct pressure should be applied at the puncture site for at least 30 minutes, a pressure dressing applied, and the site checked frequently for evidence of bleeding. 9). 5). 5) Syner-KINASE® contains highly purified urokinase which is obtained from human urine.

Products manufactured from human source materials have the potential to transmit infectious agents. Procedures to control such risks strongly reduce but cannot completely eliminate the risk of transmitting infectious agents. Therapeutic monitoring Before thrombolytic therapy the following laboratory tests are indicated: thrombin time (TT), activated partial thromboplastin time (aPTT), prothrombin time (PT), haematocrit and platelet count.

If heparin has been given it should be discontinued (unless the patient is receiving haemodialysis) and the TT or aPTT should be less than twice the normal control value before thrombolytic therapy is started. Therapeutic monitoring should consist of circulating fibrinogen levels and fibrinogen degradation products.

However, these tests do not reliably predict efficacy and bleeding complications. After fibrinolytic therapy has been completed, suitable anticoagulant therapy should be considered provided that the TT or aPTT is less than twice the normal control value.

Excipients This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-free’.

1. g. g. within 2 months) - Severe hypertension - Severe hepatic or renal insufficiency unless the patient is receiving renal replacement therapy - Blood coagulation defects and severe thrombocytopenia - Aneurysm and arteriovenous malformation - Intracranial neoplasm or other neoplasm with risk of haemorrhage - Acute pancreatitis or pericarditis or bacterial endocarditis or sepsis - Recent obstetric delivery