Abbokinase Open-Cath (Urokinase)

ABBOKINASE® OPEN-CATH®

Abbott

Urokinase

Fibrinolytic

Action And Clinical Pharmacology: Urokinase acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen.

When used as directed for i.v. catheter clearance only small amounts of urokinase may reach the circulation; therefore, therapeutic serum levels are not expected to be achieved. Nevertheless, one should be aware of the clinical pharmacology of urokinase.

I.V. infusion of urokinase in doses recommended for lysis of pulmonary embolism is followed by increased fibrinolytic activity. This effect disappears within a few hours after discontinuation, but a decrease in plasma levels of fibrinogen and plasminogen and an increase in the amount of circulating fibrin (ogen) degradation products may persist for 12 to 24 hours. There is a lack of correlation between clot embolysis and changes in coagulation and fibrinolytic assay results.

Information is incomplete about the pharmacokinetic properties in man. Urokinase administered by i.v. infusion is cleared rapidly by the liver. The serum half-life in man is 20 minutes or less. Patients with impaired liver function (e.g., cirrhosis) would be expected to show a prolongation in half-life. Small fractions of an administered dose are excreted in bile and urine.

Indications And Clinical Uses: For the restoration of patency to i.v. catheters, including central venous catheters, obstructed by clotted blood or fibrin.

Contra-Indications: This drug is contraindicated in individuals with a history of hypersensitivity to urokinase.

Because thrombolytic therapy increases the risk of bleeding, urokinase is contraindicated in the following situations: active internal bleeding, history of cerebrovascular accident, recent (within 2 months), intracranial or intraspinal surgery, recent trauma including cardiopulmonary resuscitation, intracranial neoplasm, arteriovenous malformation, or aneurysm, known bleeding diathesis, severe uncontrolled arterial hypertension and aortic dissection.

There have been no reports however, which would suggest a contraindication for the use of urokinase for i.v. catheter clearance.

Manufacturers’ Warnings In Clinical States: Excessive pressure should be avoided when urokinase is injected into the catheter. Such force could cause rupture of the catheter or expulsion of the clot into the circulation. During attempts to determine catheter occlusion, vigorous suction should not be applied due to possible damage to the vascular wall or collapse of soft-wall catheters.

Catheters may be occluded by substances other than fibrin clots, such as precipitates. Urokinase is not effective in such cases and there is the possibility that the substances may be forced into the vascular system.

Precautions: Pregnancy: Reproduction studies have been performed in mice and rats at doses up to 1 000 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to urokinase.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactation: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when urokinase is administered to a nursing woman.

Children: Safety and effectiveness in children have been established.

Adverse Reactions: The potential exists for adverse reactions to occur as a result of using urokinase for the removal of clot obstruction for i.v. catheters.

The following adverse reactions have been associated with i.v. therapy: Bleeding: The type of bleeding associated with thrombolytic therapy can be placed into 2 broad categories: a) superficial or surface bleeding, observed mainly at invaded or disturbed sites (e.g., venous cutdowns, arterial punctures, sites of recent surgical intervention, etc.), and b) internal bleeding, involving e.g., the gastrointestinal tract, genitourinary tract, vagina, or i.m. retroperitoneal, or intracerebral sites. Bleeding through Gore-Tex grafts has been reported.

Several fatalities due to intracranial or retroperitoneal hemorrhage have occurred during thrombolytic therapy.

Should serious bleeding occur, urokinase infusion should be discontinued and, if necessary, blood loss and reversal of the bleeding tendency can be effectively managed with whole blood (fresh blood preferable), packed red blood cells and cryoprecipitate or fresh frozen plasma.

Dextran should not be used. Although the use of epsilon aminocaproic acid in humans as an antidote for urokinase has not been documented, it may be considered in an emergency situation.

Allergic Reactions: In vitro tests with urokinase, as well as intradermal tests in humans, gave no evidence of induced antibody formation. Relatively mild allergic type reactions, e.g., bronchospasm and skin rash, have been reported rarely. When such reactions occur, they usually respond to conventional therapy. In addition, rare cases of anaphylaxis have been reported.

Miscellaneous: Fever and chills, including shaking chills (rigors), nausea and/or vomiting, transient hypotension or hypertension, dyspnea, tachycardia, cyanosis, back pain, hypoxemia, and acidosis have been reported together and separately. Rare cases of myocardial infarction have also been reported. A cause and effect relationship has not been established.

Febrile episodes have occurred in approximately 2 to 3% of treated patients. Symptomatic treatment of fever with acetaminophen is usually sufficient to alleviate discomfort. The use of acetaminophen rather than ASA is recommended.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Urokinase therapy should be discontinued if there is bleeding and fresh whole blood or fresh-frozen plasma should be administered; if these fail to control bleeding, the use of epsilon aminocaproic acid (EACA) is suggested although there is not documented evidence for this use in humans.

Mild external bleeding is usually controlled by the application of local pressure.

Dosage And Administration: Reconstitute according to the recommendations described under Preparation of Solution. One mL or 1.8 mL of this preparation is to be utilized for each catheter clearing procedure. Because Abbokinase contains no preservatives, any unused portion should be discarded.

Administration: When the following procedure is used to clear a central venous catheter, the patient should be instructed to exhale and hold his breath any time the catheter is not connected to i.v. tubing or a syringe. This is to prevent air from entering the open catheter. As an added precaution, any central venous catheter not connected to i.v. tubing or a syringe should be clamped or connected to a closed stopcock.

Aseptically disconnect the i.v. tubing connection at the catheter hub and attach an empty 10 mL syringe. Determine occlusion of the catheter by gently attempting to aspirate blood from the catheter with the 10 mL syringe.

If aspiration is not possible, remove the 10 mL syringe and attach a tuberculin syringe filled with prepared urokinase equal to the internal volume of the catheter. Slowly and gently inject the solution into the catheter. Care must be taken to avoid rupture of the catheter or expulsion of the intact clot into the circulation. Aseptically remove the tuberculin syringe and connect an empty syringe (e.g., 5 mL) to the catheter. Wait at least 5 minutes before attempting to aspirate the solution and residual clot with the empty syringe. Repeat aspiration attempts every 5 minutes. If the catheter is not open within 30 minutes, the catheter may be capped allowing urokinase to remain in the catheter for 30 to 60 minutes before again attempting to aspirate. A second injection of urokinase into the catheter may be necessary in resistant cases.

When patency is restored, aspirate 4 to 5 mL of blood to assure removal of all urokinase solution and clot residue. Remove the blood-filled syringe and replace it with a 10 mL syringe filled with 0.9% Sodium Chloride Injection USP. The catheter should then be gently irrigated with this solution to assure patency of the catheter. After the catheter has been irrigated, remove the 10 mL syringe and aseptically reconnect sterile i.v. tubing to the catheter hub.

Preparation of Solution: Dil-U-Vial:

1. Remove protective cap. Turn plunger-stopper a quarter turn and press to force diluent into lower chamber.

2. Roll and tilt to effect solution. Do not shake. Use only a clear, colorless solution.

3. Sterilize top of stopper with a suitable germicide.

4. Insert needle through the centre of stopper until tip is barely visible. Withdraw dose. No further dilution is required.

It is recommended that vigorous shaking be avoided during reconstitution; roll and tilt to enhance reconstitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Availability And Storage: Each vial of sterile lyophilized powder contains: urokinase activity 5 000 IU/mL. Nonmedicinal ingredients: gelatin, mannitol, monobasic sodium phosphate anhydrous and sodium chloride. Sodium hydroxide and/or hydrochloric acid have been added prior to lyophilization for pH adjustment. Vials of 1 mL. Store powder below 25°C. Avoid freezing.

Reviewed 1998

ABBOKINASE® OPEN-CATH® Abbott Urokinase Fibrinolytic

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