Kinlytic Side Effects

Please note - some side effects for Kinlytic may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Kinlytic Side Effects - for the Professional

Kinlytic

The most serious adverse reactions reported with Kinlytic™ administration include fatal hemorrhage and anaphylaxis.

Bleeding

Bleeding is the most frequent adverse reaction associated with Kinlytic™ and can be fatal.

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 urokinase-treated 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.

Sources of Information on Adverse Reactions

There are limited well-controlled clinical studies performed using urokinase. The adverse reactions described in the following sections reflect both the clinical use of Kinlytic™ 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.

Allergic Reactions

Rare cases of fatal anaphylaxis have been reported. 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.

Infusion reaction symptoms include hypoxia, cyanosis, dyspnea, tachycardia, hypotension, hypertension, acidosis, fever and/or chills/rigors, back pain, vomiting, and nausea. 

Other Adverse Reactions

Other adverse events occurring in patients receiving Kinlytic™ 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, cerebral vascular accident, pulmonary edema, reperfusion ventricular arrhythmias and chest pain. A cause and effect relationship has not been established.

Immunogenicity

The immunogenicity of Kinlytic™ has not been studied.

Side Effects by Body System - for Healthcare Professionals

Hematologic

Hematologic side effects of urokinase are unusual, but can be serious. Hemorrhage requiring blood transfusion is rare. Minor bleeding at venipuncture or arterial cutdown sites, macroscopic hematuria, or epistaxis is observed in 9% of patients. Serious hemorrhage occurs in 5% to 7% of patients. Intracranial hemorrhage in up to 1% of patients and rare cases of intramyocardial hemorrhage have been reported. Patients with uncontrolled hypertension or a history of stroke appear to be at a significantly higher risk for intracranial hemorrhagic complications. Several fatalities due to intracranial or retroperitoneal hemorrhage have occurred during thrombolytic therapy.

Rare cases of embolization during or after urokinase therapy have been reported. There is speculation that fibrinolysis could increase pericatheter thrombosis, which can result in local or distal thromboembolism.

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

In a study (PROACT II trial) involving patients with acute ischemic stroke, symptomatic intracerebral hemorrhage (ICH) occurred in 10.9% of patients receiving intra-arterial urokinase at a mean 10.2 hours after the start of therapy. Mortality associated with urokinase-induced ICH was 83%. Patients with a blood glucose of greater than 200 mg/dL at stroke onset may be at an increased risk of developing symptomatic ICH.

Cardiovascular

A 67-year-old man with severe coronary artery disease, post-coronary artery bypass grafting presented with unstable angina, and was found to have a completely occluded saphenous vein graft to the right coronary artery (RCA). The patient's history, electrocardiogram, and creatine kinase CK isoenzymes were diagnostic of infarction. During catheterization, fresh thrombus was observed in the RCA. Because the patient was a suboptimal surgical candidate, intracoronary urokinase 50,000 intl units/hr was initiated. The dosage was titrated upward to 300,000 intl units/hr because of new angina that began one hour after the urokinase infusion was started. New myocardial infarction (MI) was diagnosed, with CK enzymes peaking at 2,060 intl units/L (positive MB isoenzymes) 13 hours after urokinase therapy was started. Repeat arteriography revealed significant resolution of thrombus in the graft, but residual intraluminal filling defects. No distal embolization was seen.

The authors of this report reviewed 72 reported cases of urokinase infusions for chronic total saphenous vein graft occlusions, and found a 17% incidence of thromboembolic or MI events associated with urokinase therapy.

Since cardiovascular side effects may be more likely among the population of patients in whom urokinase is indicated, their relationship to the drug is not always clear. Transient hyper- or hypotension, dyspnea, tachycardia, and cyanosis, and rare cases of myocardial infarction have been associated with urokinase. Serious ventricular arrhythmias, including ventricular fibrillation, hemopericardium, and death from cardiogenic shock have been associated with thrombolytic therapy, in general.

Hypersensitivity

Hypersensitivity reactions are unusual because, unlike some thrombolytic agents, urokinase does not appear to induce the formation of antibodies. Infusions may be associated with fevers, chills, or rigors. Relative mild rashes or cases of bronchospasm and rare cases of anaphylaxis have been reported.

Gastrointestinal

Gastrointestinal side effects include hemorrhagic gastritis associated with the thrombolytic state. Nausea and vomiting have been reported during urokinase infusions.

Respiratory

The authors of this case report speculated that thrombolytic therapy may have caused local pulmonary parenchymal hemorrhage or encapsulated blood. The nodular lesion spontaneously resolved after one month.

Pulmonary embolism occurred in a patient with a Hickman catheter following local instillation of urokinase to restore permeability of the catheter.

Respiratory complications associated with urokinase, such as dyspnea, may be representative of the underlying disease rather than drug therapy. A single case of a nodular density on tomography has been associated with urokinase in a young male who had been treated for massive pulmonary embolism.

Hepatic

Rare cases of jaundice, hyperbilirubinemia, and elevated hepatic transaminases have been associated with infusions of urokinase or streptokinase. It has been suggested that hepatic dysfunction may not be caused by the toxic or allergic effects of the drugs themselves, but by the high activities of the proteolytic enzymes, plasminogen activator, and plasmin which are generated by the action of these drugs.

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