The risk of serious bleeding is increased with use of Abbokinase®. Fatalities due to hemorrhage, including intracranial and retroperitoneal, have been reported in association with urokinase therapy.
Concurrent administration of Abbokinase® with other thrombolytic agents, anticoagulants, or agents inhibiting platelet function may further increase the risk of serious bleeding.
Abbokinase® 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 Abbokinase®. 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:
Recent (within 10 days) major surgery, obstetrical delivery, organ biopsy, previous puncture of non-compressible vessels
Recent (within 10 days) serious gastrointestinal bleeding
High likelihood of a left heart thrombus, for example, mitral stenosis with atrial fibrillation
Subacute bacterial endocarditis
Hemostatic defects including those secondary to severe hepatic or renal disease
Diabetic hemorrhagic retinopathy
Any other condition in which bleeding might constitute a significant hazard or be particularly difficult to manage because of its location
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 Abbokinase® 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.
ANAPHYLAXIS AND OTHER INFUSION REACTIONS
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 Abbokinase® 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.
PRODUCT SOURCE AND FORMULATION WITH ALBUMIN
Abbokinase® 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 Abbokinase® 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, Abbokinase® may carry a risk of transmitting infectious agents, including those that cause the 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 Abbott Laboratories
Abbokinase® 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 Abbokinase® 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 the intravenous infusion of Abbokinase®, 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 Abbokinase®.
Anticoagulants and agents that alter platelet function (such as aspirin, other non-steroidal anti-inflammatory agents, dipyridamole, and GP IIb/IIIa inhibitors) may increase the risk of serious bleeding.
Administration of Abbokinase® prior to, during, or after other thrombolytic agents may increase the risk of serious bleeding.
Because concomitant use of Abbokinase® with agents that alter coagulation, inhibit platelet function, or are thrombolytic may further increase the potential for bleeding complications, careful monitoring for bleeding is recommended.
The interaction of Abbokinase® with other drugs has not been studied and is not known.
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 Abbokinase®. 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 Abbokinase® is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Abbokinase® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Abbokinase® should be used with caution in elderly patients.