Kinlytic

Urokinase is a thrombolytic (THROM-bo-LIT-ik) drug, sometimes called a "clot-busting" drug. It helps your body produce a substance that dissolves unwanted blood clots.

Urokinase is used to treat blood clots in the lungs.

Urokinase may also be used for purposes not listed in this medication guide.

If possible before you receive urokinase, tell your doctor if you have a brain tumor or aneurysm, hemophilia or other bleeding disorder, high blood pressure, or if you have recently had a stroke, brain or spinal surgery, or medical emergency requiring CPR (cardiopulmonary resuscitation).

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

Ask your doctor before taking aspirin or ibuprofen (Motrin, Advil) shortly after you have received urokinase. These medications can increase your risk of bleeding.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Urokinase increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have bleeding that will not stop. Bleeding may occur from a surgical incision, or from the skin where a needle was inserted during a blood test or while receiving injectable medication. You may also have bleeding on the inside of your body, such as in your stomach or intestines, kidneys or bladder, brain, or within the muscles.

Call your doctor at once if you have signs of bleeding inside your body, such as:

• easy bruising or bleeding (nosebleeds, bleeding gums, bleeding from a wound, incision, catheter, or needle injection);

• bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• red or pink urine; or

• sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.

Some side effects may occur during or within 1 hour after the injection. Tell your caregiver right away if you feel chilled or feverish, nauseated, light-headed, or have chest tightness, back pain, trouble breathing, or fast heartbeats.

Also call your doctor at once if you have:

• chest pain or heavy feeling, pain spreading to the jaw or shoulder, nausea, sweating, general ill feeling;

• swelling, rapid weight gain, little or no urinating;

• severe stomach pain, nausea, and vomiting;

• darkening or purple discoloration of your fingers or toes;

• very slow heartbeats, shortness of breath, feeling light-headed;

• sudden severe back pain, muscle weakness, numbness or loss of feeling in your arms or legs;

• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety, confusion, severe chest pain, shortness of breath, irregular heartbeats; or

• pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• a blood thinner (heparin, warfarin, Coumadin, Jantoven);

• NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or

• medication used to prevent blood clots--abciximab, eptifibatide, tirofiban, vorapaxar.

This list is not complete. Other drugs may interact with urokinase, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Kinlytic™ is indicated in adults:

• For the lysis of acute massive pulmonary emboli, defined as obstruction of blood flow to a lobe or multiple segments.
• For the lysis of pulmonary emboli accompanied by unstable hemodynamics, i.e., failure to maintain blood pressure without supportive measures.

The diagnosis should be confirmed by objective means, such as pulmonary angiography or non-invasive procedures such as lung scanning.

The use of Kinlytic™ is contraindicated in patients with a history of hypersensitivity to the product (see WARNINGS and ADVERSE REACTIONS).

Because thrombolytic therapy increases the risk of bleeding, Kinlytic™ is contraindicated in the situations listed below (see WARNINGS).

• Active internal bleeding
• Recent (e.g., within two months) cerebrovascular accident
• Recent (e.g., within two months) intracranial or intraspinal surgery
• Recent trauma including cardiopulmonary resuscitation
• Intracranial neoplasm, arteriovenous malformation, or aneurysm
• Known bleeding diatheses
• Severe uncontrolled arterial hypertension

Kinlytic™ IS INTENDED FOR INTRAVENOUS INFUSION ONLY.

Kinlytic™ treatment should be instituted soon after onset of pulmonary embolism. Delay in instituting therapy may decrease the potential for optimal efficacy (see CLINICAL PHARMACOLOGY).

Dosing

• A loading dose of 4,400 international units per kilogram of Kinlytic™ is given at a rate of 90 mL per hour over a period of 10 minutes. This is followed by a continuous infusion of 4,400 international units per kilogram per hour at a rate of 15 mL for 12 hours.  
• Administration of Kinlytic™ may be repeated as necessary. 
• A dosing and preparation chart for patients who weigh 37 to 114 kilograms (81 to 250 pounds) is provided as a guide in the Preparation Section that follows below. If the patient is outside of these weights, calculate with dosing information provided above.

Preparation

• The Dose Preparation-Pulmonary Embolism chart is a guidance tool/aid provided for the convenience of the practitioner and may not be complete for every patient.
• Kinlytic™ contains no preservatives. Do not reconstitute until immediately before use. Any unused portion of the reconstituted material should be discarded.
• Reconstitute Kinlytic™ by aseptically adding 5 mL of Sterile Water for Injection, USP, without preservatives, to the vial. DO NOT USE Bacteriostatic Water for Injection, USP.
• After reconstitution, the drug product will contain 50,000 international units per milliliter.
• After reconstituting, visually inspect each vial of Kinlytic™ for discoloration and for the presence of particulate material. The solution should be pale and straw-colored; highly colored solutions should not be used. Thin translucent filaments may occasionally occur in reconstituted Kinlytic™ vials, but do not indicate any decrease in potency of this product. To minimize formation of filaments, avoid shaking the vial during reconstitution. Roll and tilt the vial to enhance reconstitution. The solution may be terminally filtered, for example, through a 0.45 micron or smaller cellulose membrane filter.
• No other medication should be added to this solution.
• Prior to infusing, dilute the reconstituted Kinlytic™ with 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP.

The following Dose Preparation-Pulmonary Embolism chart may be used as an aid in the preparation of Kinlytic™ for administration. For administration directions, see next section.

Administration

• Kinlytic™ is administered using a constant infusion pump that is capable of delivering a total volume of 195 mL.
• The loading dose of Kinlytic™ admixture (4,400 international units per kilogram) should be delivered at a rate of 90 mL per hour over a period of 10 minutes.
• This is followed by a continuous infusion of 4,400 international units per kilogram per hour of Kinlytic™ at a rate of 15 mL per hour for 12 hours.
• Since some of the Kinlytic™ admixture will remain in the tubing at the end of an infusion pump delivery cycle, the following flush procedure should be performed to insure that the total dose of Kinlytic™ is administered. A solution of 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP, approximately equal in amount to the volume of the tubing in the infusion set should be administered via the pump to flush the Kinlytic™ admixture from the entire length of the infusion set. The pump should be set to administer the flush solution at the continuous rate of 15 mL per hour.
• No other drug products/solutions may be administered in the same line with Kinlytic™.

Anticoagulation After Terminating Kinlytic™ Treatment

After infusing Kinlytic™, anticoagulation treatment is recommended to prevent recurrent thrombosis. Do not begin anticoagulation until the aPTT has decreased to less than twice the normal control value. If heparin is used, do not administer a loading dose of heparin. Treatment should be followed by oral anticoagulants.

Kinlytic™ is supplied as a sterile lyophilized preparation (NDC 24430-1003-1). Each vial contains 250,000 international units urokinase activity, 25 mg mannitol, 250 mg Albumin (Human), and 50 mg sodium chloride. Refrigerate Kinlytic™ powder at 2° to 8°C (36° to 46°F) (See USP).

1. Sato S. et al. Elevated Urokinase-Type Plasminogen Activator Plasma Levels Are Associated With Deterioration of Liver Function But Not With Hepatocellular Carcinoma. J Gastroenterology, 1994; 29:745-750.
2. Bell WR. Thrombolytic Therapy: A Comparison Between Urokinase and Streptokinase. Sem Thromb Hemost. 1975; 2:1-13.
3. Sasahara AA, Hyers TM, Cole CM, et al. The Urokinase Pulmonary Embolism Trial. Circulation. 1973; 47 (suppl. 2):1-108.
4. Daniels LB, Parker JA, Patel SR, Grodstein F, Goldhaber SZ. Relation of Duration of Symptoms With Response to Thrombolytic Therapy in Pulmonary Embolism. Am J Cardiol. 1997; 80:184-188.
5. Urokinase Pulmonary Embolism Trial Study Group: Urokinase-Streptokinase Embolism Trial. JAMA. 1974; 229:1606-1613.
6. Sasahara AA, Bell WR, Simon TL, et al. The Phase II Urokinase-Streptokinase Pulmonary Embolism Trial. Thrombos Diathes Haemorrh (Stuttg). 1975; 33:464-476.

Rx

©ImaRx Therapeutics, Inc. 2007

Printed in USA

ImaRx Therapeutics, Inc. Tucson Arizona, 85719, USA

Ref: 80003 V:01 June 2007