SYNER-KINASE Powder for solution for injection or infusion Ref.[9391] Active ingredients: Urokinase

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 Once a channel has been created through the blocked segment, the catheter may be withdrawn until it lies proximal to the remaining thrombus.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. Syner-KINASE should be used with caution in elderly patients (see section 4.4).

Patients with renal or hepatic impairment

A dose reduction may be required in patients with impaired renal or hepatic impairment (see section 5.2). 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.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

Haemorrhage that occurs during treatment with Syner-KINASE may be controlled with local pressure and treatment continued. If severe bleeding occurs, treatment with Syner-KINASE must be stopped and inhibitors such as aprotinin, epsilon- amino caproic acid, p-aminoethylbenzoic acid or tranexamic acid can be given. In serious cases, human fibrinogen, Factor XII, packed red cells or whole blood should be given as appropriate. For correction of volume deficiency, dextrans should be avoided.

25,000IU, 100,000IU strengths: 4 years.

10,000IU, 250,000IU and 500,000IU strengths: 3 Years.

Do not store above 25°C.

Keep the vial in the outer container to protect from light.

All single pack presentations are contained in borosilicate clear type 1 (8 ml) glass vials closed with chlorobutyl rubber stoppers and sealed with an aluminium flip-off cap.

Each vial size is colour coded:

10,000 IU – Grey
25,000 IU – Orange
100,000 IU – Green
250,000 IU – Red
500,000 IU – Purple

Syner-KINASE must be reconstituted before use with the correct volume of 9 mg/ml (0.9%) sodium chloride solution for injection (not provided). This produces a colourless solution.

There are no special requirements for the handling of this product. Instructions on administration are provided in Section 4.2.