Urokinase for Injection 500,000 IU

  1. Name of the medicinal product

Urokinase 500,000 IU Powder for solution for injection or  infusion Taj Pharma

  1. Qualitative and quantitative composition

Each vial contains 500,000 IU of urokinase produced from human urine.

For a full list of excipients, see section 6.1.

  1. Pharmaceutical form

White powder for solution for injection or infusion.

  1. Clinical particulars

4.1 Therapeutic indications

Urokinase is indicated for the lysis of blood clots in the following conditions:

  • thrombosed intravascular catheters and cannulae
  • extensive acute proximal deep vein thrombosis
  • acute massive pulmonary embolism
  • acute occlusive peripheral arterial disease with limb threatening ischemia

4.2 Posology and method of administration

Urokinase should be restricted to hospital use only. Adequate diagnostic and monitoring techniques should be available.

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.

Instructions on reconstitution with the recommended solvent are provided in section 6.6.

Thrombosed intravascular catheters and cannula

5,000 to 25,000 IU Urokinase 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 Urokinase 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 3 times in 24 hours 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 Urokinase 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 Urokinase 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

The initial dosage as in adults should be used but the dosage may be adjusted depending on response. Urokinase 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).

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.

Urokinase may be used in children of all ages for the treatment of thrombosed central venous catheters using the same lock procedure as in adults.

4.3 Contraindications

  • Hypersensitivity to urokinase or to any of the excipients
  • Active clinically relevant bleeding
  • Recent major surgery
  • Recent cerebrovascular accident (e.g. within 2 months)
  • Recent trauma including cardiopulmonary resuscitation, thoracic or neurosurgery (e.g. within 2 months)
  • Severe hypertension
  • Severe hepatic or renal insufficiency unless the patient is receiving renal replacement therapy
  • Blood coagulation defects
  • Aneurysm
  • Intracranial neoplasm
  • Acute pancreatitis or pericarditis or bacterial endocarditis

4.4 Special warnings and precautions for use

In the following conditions the risk of bleeding may be increased and should be weighed against the anticipated benefits of treatment with urokinase:

  • Recent severe gastrointestinal bleeding
  • Recent surgery
  • Recent obstetric delivery
  • Severe cerebrovascular disease
  • Moderate coagulation defects including those due to severe renal or hepatic disease
  • High likelihood of a left heart thrombus
  • Known septic thrombotic disease
  • Elderly patients, especially those over 75 years of age

If severe bleeding occurs during systemic treatment with Urokinase, treatment should be stopped immediately (see section 4.9). Bleeding from puncture sites may be controlled with local pressure.

Concomitant administration of urokinase with other thrombolytics, anticoagulants or anti-platelet agents may increase the risk of bleeding (see section 4.5).

Urokinase 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.

4.5 Interaction with other medicinal products and other forms of interaction

Loss of activity of urokinase has been noted when dissolved in 5% glucose at a concentration of 1,500 IU/ml and stored in PVC containers (see section 6.2). No information is available regarding other dilutions of urokinase.

Anticoagulants

Concurrent administration of oral anticoagulants or heparin may increase the risk of haemorrhage.

Medicinal products affecting platelet function

Concurrent administration of substances that affect platelet function (e.g. acetylsalicylic acid, other non-steroidal anti-inflammatory agents, dipyridamole, and dextrans) may increase the risk of haemorrhage.

4.6 Fertility, pregnancy and lactation

There is a limited amount of data from the use of urokinase in pregnant women. Urokinase should not be given during pregnancy or in the immediate post-partum period unless clearly necessary.

It is unknown whether urokinase is excreted into human breast milk. Breast-feeding should be avoided during treatment with Urokinase.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

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.

The most frequent and severe adverse effect of urokinase therapy is haemorrhage, with puncture site being the most common location. Intracranial (including fatal cases), hepatic and gingival haemorrhages have also been reported.

Embolic episodes may occur after fragments of clot have been released. Cholesterol embolisms have also been reported.

Urokinase is reportedly non-antigenic but hypersensitivity reactions including urticaria and very rare cases of fatal anaphylaxis have been reported. Infusion reactions including fever and shaking chills (rigors) have also been reported.

The following frequency convention was used as a basis for the evaluation of undesirable effects:

Very common

Common:

Uncommon:

Rare:

Very rare

≥ 1/10

≥ 1/100 to < 1/10

≥ 1/1,000 to < 1/100

≥ 1/10,000 to < 1/1,000

< 1/10,000

Immune system disorders
Rare Hypersensitivity reactions, including urticaria

Anaphylaxis

Nervous system disorders
Common Stroke
Vascular disorders
Very Common Haemorrhage, including from puncture site and wound

Epistaxis

Thromboembolism

Embolism, including pulmonary embolism

Haematuria (microscopic)

Common Haematoma, including intracranial, retroperitoneal and at puncture site

Gastrointestinal haemorrhage, intracranial haemorrhage

Artery dissection

Cholesterol embolism

Rare Vascular pseudoaneurysm

Hematuria (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

4.9 Overdose

Haemorrhage that occurs during treatment with Urokinase may be controlled with local pressure and treatment continued. If severe bleeding occurs, treatment with Urokinase 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.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

ATC code: B01A D04, antithrombotic agent.

Urokinase is a highly purified form of naturally occurring human urokinase extracted from urine. It is a thrombolytic agent which converts plasminogen into plasmin (fibrinolysin) a proteolytic enzyme that breaks down fibrin.

5.2 Pharmacokinetic properties

Urokinase is eliminated rapidly from the circulation by the liver with a half-life of up to 20 minutes. The inactive degradation products are excreted primarily by the kidneys and in bile. Elimination is delayed in patients with liver disease and impaired kidney function.

5.3 Preclinical safety data

There are no pre-clinical safety data of additional value to the prescribing physician.

  1. Pharmaceutical particulars

6.1 List of excipients

Mannitol

Disodium edetate

Disodium phosphate dodecahydrate

Sodium hydroxide

6.2 Incompatibilities

Urokinase should be reconstituted before use only with the solvent described in Section 6.6. It has been reported to lose 15-20% of its activity in solutions of 5% glucose containing 1,500 units/ml in PVC containers. No information is available regarding other dilutions of urokinase.

Urokinase must not be mixed with other medicinal products.

6.3 Shelf life

  • 10,000IU, 250,000IU and 500,000IU strengths – 3 Years

Use reconstituted material immediately

6.4 Special precautions for storage

Do not store above 25°C.

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

6.5 Nature and contents of container

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.

6.6 Special precautions for disposal and other handling

Urokinase 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.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

 

Urokinase for Injection 500,000 IU

PACKAGE LEAFLET INFORMATION FOR THE USER

Urokinase 500,000 IU Powder for solution for injection or infusion

Read all of this leaflet carefully before you start taking/using this medicine. It contains a summary of the information available on Urokinase. The information in this leaflet applies only to your medicine.

  • keep this You may need to read it again
  • if you have further questions, please ask your doctor or your pharmacist
  • this medicine has been prescribed for Do not pass it on to others. It may harm them, even if their symptoms are the same as yours
  • if any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor

This leaflet answers the following questions:

  1. What Urokinase is and what it is used for
  2. Before you are given Urokinase
  3. How Urokinase is given
  4. Possible side-effects
  5. How to store Urokinase
  6. Further information
  1. What Urokinase is and what it is used for:

The name of your medicine is Urokinase. The active ingredient is urokinase, a thrombolytic that can help to dissolve blood clots that may form in:

  • intravenous catheters or cannulae (surgical tubes used to withdraw fluids from, or introduce fluids into the body)
  • lungs
  • deep veins
  • peripheral arteries (blood vessels away from the heart, such as in the leg)

2.  Before you are given Urokinase:

Urokinase will not be given to you if you:

  • are allergic (hypersensitive) to urokinase or any of the other ingredients of Urokinase (See Section 6)
  • are currently bleeding
  • had a major surgical operation or a stroke recently (in the past 2 months)
  • have severe high blood pressure
  • have abnormal blood clotting
  • have abnormal blood vessels
  • have cancer of the brain
  • have infection of the pancreas or heart
  • have severe liver or kidney disease

Special care will be taken with Urokinase if you:

  • have been recently bleeding from the stomach or intestines
  • had surgery or have given birth recently
  • have severe blood vessel disease in your brain
  • have problems with your heart
  • are elderly, particularly if you are aged over 75 years

In all these circumstances your doctor will decide whether or not you should be given Syner- KINASE.

Taking or using other medicines:

Please inform your doctor if you are taking, or have recently taken any of the following medicines, or any other medicines, including medicines obtained without a prescription:

  • heparin or other anticoagulants
  • acetylsalicylic acid (aspirin)
  • non-steroidal anti-inflammatory agents
  • dipyridamole
  • dextrans

Pregnancy and breast-feeding:

Ask your doctor or pharmacist for advice before taking any medicine.

Urokinase must not be used in pregnancy or immediately after delivery unless otherwise recommended by your doctor.

Do not breast-feed during treatment with Urokinase.

3.  How Urokinase is given:

Urokinase will be given to you by a doctor or nurse. You will not be asked to administer Syner- KINASE to yourself.

Before you are given Urokinase it will be dissolved in saline (solution of salt and water). It should never be injected into a muscle or under the skin. The amount and duration of Syner- KINASE treatment will be decided by your doctor.

  • if you are being treated for a blocked intravascular catheter or cannulae, Urokinase may be injected directly into the catheter or cannulae and left for a while before removing the fluid. This may be repeated several Urokinase may also be injected into the blocked tube over a period of time.
  • if you are being treated for blood clots in your lungs, deep veins or peripheral arteries, Syner- KINASE may be injected into a vein (usually in the arm) or directly into the blocked Progress of the treatment may be checked by special X-rays. After the clot has been dissolved, you may be put on anticoagulant therapy (blood thinning) to prevent a recurrence.

 

Use in children

Urokinase can be used in children to dissolve blood clots in intravenous catheters or cannulae.

4.  Possible side-effects:

Like all medicines, Urokinase can have side-effects but not everybody will get them.

Tell your doctor immediately if you notice:

  • any bleeding
  • any sign of an allergic reaction, such as difficulty with breathing, swelling of face, lips or throat, skin rash or hives

Other side effects include

Very common side effects (affects more than 1 user in 10)

  • unusual bleeding, particularly from puncture wounds or nose bleeds
  • blood detected in the urine after a urine test
  • blood clots: small fragments of a blood clot may be released and pass along the blood vessel and cause blockage elsewhere, such as in the lungs, heart or limbs
  • a decrease in haematocrit (a red blood cell test) and a temporary increase in certain liver enzymes

 

Common side effects (affects 1 to 10 users in 100)

  • bleeding in the stomach or into/around the brain or at puncture sites
  • stroke
  • tearing of an artery wall
  • blockage of blood vessels due to cholesterol (fat)
  • fever, chills and/or shivering

Uncommon side effects (affects 1 to 10 users in 1000)

  • kidney failure

Rare side effects (affects 1 to 10 users in 10,000)

  • visible blood in the urine
  • injury and swelling in an artery wall

If you experience any of the above side effects, or if you notice anything else which is unusual, and not mentioned in this leaflet, please inform your doctor or pharmacist immediately.

5.  How to store Urokinase:

  • keep out of the reach and sight of children
  • do not store above 25˚C
  • do not keep reconstituted material for later use
  • store in the original container and package in order to protect from light
  • do not use after the expiry date stated on the label. The expiry date refers to the last day of the month
  • do not use if the contents of the vial are discoloured
  • medicines should not be disposed of via waste water or household waste

6.  Further information:

The active ingredient is urokinase.

The other ingredients are: Mannitol, Disodium Edetate, Disodium Phosphate Dodecahydrate, Sodium Hydroxide.

What Urokinase looks like and contents of the pack:

 Each pack contains one vial (small bottle). The white powder contents are Urokinase.

There are different strengths available:

Urokinase 500,000 IU

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com