Actosolv™ (urokinase injection) is indicated in adults:
The diagnosis should be confirmed by objective means, such as pulmonary angiography or noninvasive procedures such as lung scanning.
Actosolv™ (urokinase injection) IS INTENDED FOR INTRAVENOUS INFUSION ONLY.
Actosolv™ (urokinase injection) treatment should be instituted soon after onset of pulmonary embolism. Delay in instituting therapy may decrease the potential for optimal efficacy (see CLINICAL PHARMACOLOGY).
Administer Actosolv™ (urokinase injection) with a programmable infusion pump only.
Change the infusion rate immediately after completion of the loading dose.
The following Dose Preparation-Pulmonary Embolism chart may be used as an aid in the preparation of Actosolv™ (urokinase injection) for administration. For administration directions, see next section.
Dose Preparation-Pulmonary Embolism
For administration, use a programmable infusion pump only.
After ten minutes, change the initial loading dose rate to the maintenance dose rate.
|Patient Weight [kilograms (pounds)]||Total Dosea (Loading and Continuous Infusion)||Number of Actosolv™ Vials Needed for Total Dose||Total Volume of Sterile Water for Injection needed for Reconstitution of Actosolv™ (urokinase injection) Vialsb||+||Volume of 0.9% Sodium Chloride or 5% Dextrose Injection, USP for Infusion (mL)||=||Final Volume (mL) for Loading and Continuous Infusion|
| aLoading Dose + dose administered during 12-hour period. |
bEach vial is reconstituted with 5 mL of Sterile Water for Injection, USP, without preservatives. (See Preparation.)
After infusing Actosolv™ (urokinase injection) , 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.
The use of Actosolv™ (urokinase injection) 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, Actosolv™ (urokinase injection) is contraindicated in the situations listed below (see WARNINGS).
The risk of serious bleeding is increased with use of Actosolv™ (urokinase injection). Fatalities due to hemorrhage, including intracranial and retroperitoneal, have been reported in association with urokinase therapy.
Concurrent administration of Actosolv™ (urokinase injection) with other thrombolytic agents, anticoagulants, or agents inhibiting platelet function may further increase the risk of serious bleeding.
Actosolv™ (urokinase injection) therapy requires careful attention to all potential bleeding sites (including catheter insertion sites, arterial and venous puncture sites, cutdown sites, and other needle puncture sites).
Intramuscular injections and nonessential handling of the patient must be avoided during treatment with Actosolv™ (urokinase injection). Venipunctures should be performed as infrequently as possible and with care to minimize bleeding.
Should an arterial puncture be necessary, upper extremity vessels are preferable. Direct pressure should be applied for at least 30 minutes, a pressure dressing applied, and the puncture site checked frequently for evidence of bleeding.
In the following conditions, the risk of bleeding may be increased and should be weighed against the anticipated benefits:
When internal bleeding occurs, it may be more difficult to manage than that which occurs with conventional anticoagulant therapy. Should potentially serious spontaneous bleeding (not controllable by direct pressure) occur, the infusion of Actosolv™ (urokinase injection) should be terminated immediately, and measures to manage the bleeding implemented. Serious blood loss may be managed with volume replacement, including packed red blood cells. Dextran should not be used. When appropriate, fresh frozen plasma and/or cryoprecipitate may be considered to reverse the bleeding tendency.
Post-marketing reports of hypersensitivity reactions have included anaphylaxis (with rare reports of fatal anaphylaxis), bronchospasm, orolingual edema and urticaria (see ADVERSE REACTIONS: Allergic Reactions). There have also been reports of other infusion reactions which have included one or more of the following: fever and/or chills/rigors, hypoxia, cyanosis, dyspnea, tachycardia, hypotension, hypertension, acidosis, back pain, vomiting, and nausea. Reactions generally occurred within one hour of beginning Actosolv™ (urokinase injection) infusion. Patients who exhibit reactions should be closely monitored and appropriate therapy instituted.
Infusion reactions generally respond to discontinuation of the infusion and/or administration of intravenous antihistamines, corticosteroids, or adrenergic agents.
Antipyretics which inhibit platelet function (aspirin and other non-steroidal anti-inflammatory agents) may increase the risk of bleeding and should not be used for treatment of fever.
Cholesterol embolism has been reported rarely in patients treated with all types of thrombolytic agents; the true incidence is unknown. This serious condition, which can be lethal, is also associated with invasive vascular procedures (e.g., cardiac catheterization, angiography, vascular surgery) and/or anticoagulant therapy. Clinical features of cholesterol embolism may include livedo reticularis, “purple toe” syndrome, acute renal failure, gangrenous digits, hypertension, pancreatitis, myocardial infarction, cerebral infarction, spinal cord infarction, retinal artery occlusion, bowel infarction and rhabdomyolysis.
Actosolv™ (urokinase injection) is made from human neonatal kidney cells grown in tissue culture. Products made from human source material may contain infectious agents, such as viruses, that can cause disease. The risk that Actosolv™ (urokinase injection) will transmit an infectious agent has been reduced by screening donors for prior exposure to certain viruses, by testing donors for the presence of certain current virus infections, by testing for certain viruses during manufacturing, and by inactivating and/or removing certain viruses during manufacturing (see DESCRIPTION). Despite these measures, Actosolv™ (urokinase injection) may carry a risk of transmitting infectious agents, including those that cause Creutzfeldt-Jakob disease (CJD) or other diseases not yet known or identified; thus, the risk of transmission of infectious agents cannot be totally eliminated. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) is considered extremely remote.
This product is formulated in 5% albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, albumin carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of Creutzfeldt-Jakob disease (CJD) also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.
All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to ImaRx Therapeutics, Inc. [1-866-634-6279].
Actosolv™ (urokinase injection) should be used in hospitals where the recommended diagnostic and monitoring techniques are available.
The clinical response and vital signs should be observed frequently during and following Actosolv™ (urokinase injection) infusion. Blood pressure should not be taken in the lower extremities to avoid dislodgement of possible deep vein thrombi.
Before beginning thrombolytic therapy, obtain a hematocrit, platelet count, and an activated partial thromboplastin time (aPTT). If heparin has been given, it should be discontinued and the aPTT should be less than twice the normal control value before thrombolytic therapy is started.
Following intravenous infusion of Actosolv™ (urokinase injection) , before (re)instituting anticoagulants, the aPTT should be less than twice the normal control value.
Results of coagulation tests and measures of fibrinolytic activity do not reliably predict either efficacy or risk of bleeding for patients receiving Actosolv™ (urokinase injection).
Adequate data are not available on the long-term potential for carcinogenicity in animals or humans.
Pregnancy Category B: 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 Actosolv™ (urokinase injection). 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.
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 Actosolv™ (urokinase injection) is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Actosolv™ (urokinase injection) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Actosolv™ (urokinase injection) should be used with caution in elderly patients.
The most serious adverse reactions reported with Actosolv™ (urokinase injection) administration include fatal hemorrhage and anaphylaxis (see WARNINGS).
Bleeding is the most frequent adverse reaction associated with Actosolv™ and can be fatal (see WARNINGS).
In controlled clinical studies using a 12-hour infusion of urokinase for the treatment of pulmonary embolism (UPET and USPET),3,5,6 bleeding resulting in at least a 5% decrease in hematocrit was reported in 52 of 141 urokinase-treated patients. Significant bleeding events requiring transfusion of greater than 2 units of blood were observed during the 14-day study period in 3 of 141 urokinasetreated patients in these studies. Multiple bleeding events may have occurred in an individual patient. Most bleeding occurred at sites of external incisions and vascular puncture, with lesser frequency in gastrointestinal, genitourinary, intracranial, retroperitoneal, and intramuscular sites.
There are limited well-controlled clinical studies performed using urokinase. The adverse reactions described in the following sections reflect both the clinical use of Actosolv™ (urokinase injection) in the general population and limited controlled study data. Because post-marketing reports of adverse reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.
Rare cases of fatal anaphylaxis have been reported (see WARNINGS). In controlled clinical trials, allergic reaction was reported in 1 of 141 patients ( < 1%).
The following allergic-type reactions have been observed in clinical trials and/or post-marketing experience: bronchospasm, orolingual edema, urticaria, skin rash, and pruritus (see WARNINGS).
Infusion reaction symptoms include hypoxia, cyanosis, dyspnea, tachycardia, hypotension, hypertension, acidosis, fever and/or chills/rigors, back pain, vomiting, and nausea (see WARNINGS).
Other adverse events occurring in patients receiving Actosolv™ (urokinase injection) therapy in clinical studies, regardless of causality, include myocardial infarction, recurrent pulmonary embolism, hemiplegia, stroke, decreased hematocrit, substernal pain, thrombocytopenia, and diaphoresis.
Additional adverse reactions reported from post-marketing experience include cardiac arrest, vascular embolization (cerebral and distal) including cholesterol emboli (see WARNINGS), cerebral vascular accident, pulmonary edema, reperfusion ventricular arrhythmias and chest pain. A cause and effect relationship has not been established.
The immunogenicity of Actosolv™ (urokinase injection) has not been studied.
No information provided.