The following adverse reactions have been associated with intravenous therapy and may also occur with intracoronary artery infusion:
Bleeding: The reported incidence of bleeding (major or minor) has varied widely depending on the indication, dose, route and duration of administration, and concomitant therapy.
Minor bleeding can be anticipated mainly at invaded or disturbed sites. If such bleeding occurs, local measures should be taken to control the bleeding.
Severe internal bleeding involving gastrointestinal (including hepatic bleeding), genitourinary, retroperitoneal, or intracerebral sites has occurred and has resulted in fatalities. In the treatment of acute myocardial infarction with intravenous Streptokinase, the GISSI and ISIS-2 studies reported a rate of major bleeding (requiring transfusion) of 0.3-0.5%. However, rates as high as 16% have been reported in studies which required administration of anticoagulants and invasive procedures.
Major bleed rates are difficult to determine for other dosages and patient populations because of the different dosing and intervals of infusions. The rates reported appear to be within the ranges reported for intravenous administration in acute myocardial infarction.
Should uncontrollable bleeding occur, Streptokinase infusion should be terminated immediately, rather than slowing the rate of administration of or reducing the dose of Streptokinase. If necessary, bleeding can be reversed and blood loss effectively managed with appropriate replacement therapy. Although the use of aminocaproic acid in humans as an antidote for Streptokinase has not been documented, it may be considered in an emergency situation.
Allergic Reactions: Fever and shivering, occurring in 1-4% of patients (1,2) , are the most commonly reported allergic reactions with intravenous use of Streptase, Streptokinase, in acute myocardial infarction. Anaphylactic and anaphylactoid reactions ranging in severity from minor breathing difficulty to bronchospasm, periorbital swelling or angioneurotic edema have been observed rarely. Other milder allergic effects such as urticaria, itching, flushing, nausea, headache and musculoskeletal pain have also been observed, as have delayed hypersensitivity reactions such as vasculitis and interstitial nephritis. Anaphylactic shock is very rare, having been reported in 0-0.1% of patients (1,2,4) .
Mild or moderate allergic reactions may be managed with concomitant antihistamine and/or corticosteroid therapy. Severe allergic reactions require immediate discontinuation of Streptase, Streptokinase, with adrenergic, antihistamine, and/or corticosteroid agents administered intravenously as required.
Respiratory: There have been reports of respiratory depression in patients receiving Streptokinase. In some cases, it was not possible to determine whether the respiratory depression was associated with Streptokinase or was a symptom of the underlying process. If respiratory depression is associated with Streptokinase, the occurrence is believed to be rare.
Other Adverse Reactions: Transient elevations of serum transaminases have been observed. The source of these enzyme rises and their clinical significance is not fully understood.
There have been reports in the literature of cases of back pain associated with the use of Streptokinase. In most cases the pain developed during Streptokinase intravenous infusion and ceased within minutes of discontinuation of the infusion.
The following adverse reactions have been associated with intravenous therapy and may also occur with intracoronary artery infusion:
Bleeding: The reported incidence of bleeding (major or minor) has varied widely depending on the indication, dose, route and duration of administration, and concomitant therapy.
Minor bleeding can be anticipated mainly at invaded or disturbed sites. If such bleeding occurs, local measures should be taken to control the bleeding.
Severe internal bleeding involving gastrointestinal (including hepatic bleeding), genitourinary, retroperitoneal, or intracerebral sites has occurred and has resulted in fatalities. In the treatment of acute myocardial infarction with intravenous Streptokinase, the GISSI and ISIS-2 studies reported a rate of major bleeding (requiring transfusion) of 0.3-0.5%. However, rates as high as 16% have been reported in studies which required administration of anticoagulants and invasive procedures.
Major bleed rates are difficult to determine for other dosages and patient populations because of the different dosing and intervals of infusions. The rates reported appear to be within the ranges reported for intravenous administration in acute myocardial infarction.
Should uncontrollable bleeding occur, Streptokinase infusion should be terminated immediately, rather than slowing the rate of administration of or reducing the dose of Streptokinase. If necessary, bleeding can be reversed and blood loss effectively managed with appropriate replacement therapy. Although the use of aminocaproic acid in humans as an antidote for Streptokinase has not been documented, it may be considered in an emergency situation.
Allergic Reactions: Fever and shivering, occurring in 1-4% of patients (1,2) , are the most commonly reported allergic reactions with intravenous use of Streptase, Streptokinase, in acute myocardial infarction. Anaphylactic and anaphylactoid reactions ranging in severity from minor breathing difficulty to bronchospasm, periorbital swelling or angioneurotic edema have been observed rarely. Other milder allergic effects such as urticaria, itching, flushing, nausea, headache and musculoskeletal pain have also been observed, as have delayed hypersensitivity reactions such as vasculitis and interstitial nephritis. Anaphylactic shock is very rare, having been reported in 0-0.1% of patients (1,2,4) .
Mild or moderate allergic reactions may be managed with concomitant antihistamine and/or corticosteroid therapy. Severe allergic reactions require immediate discontinuation of Streptase, Streptokinase, with adrenergic, antihistamine, and/or corticosteroid agents administered intravenously as required.
Respiratory: There have been reports of respiratory depression in patients receiving Streptokinase. In some cases, it was not possible to determine whether the respiratory depression was associated with Streptokinase or was a symptom of the underlying process. If respiratory depression is associated with Streptokinase, the occurrence is believed to be rare.
Other Adverse Reactions: Transient elevations of serum transaminases have been observed. The source of these enzyme rises and their clinical significance is not fully understood.
There have been reports in the literature of cases of back pain associated with the use of Streptokinase. In most cases the pain developed during Streptokinase intravenous infusion and ceased within minutes of discontinuation of the infusion.
DRUG INTERACTIONSThe interaction of Streptase, Streptokinase, with other drugs has not been well studied.
Use of Anticoagulants and Antiplatelet Agents -- Streptase, Streptokinase, alone or in combination with antiplatelet agents and anticoagulants, may cause bleeding complications. Therefore, careful monitoring is advised. In the treatment of acute MI, aspirin, when not otherwise contraindicated, should be administered with Streptokinase ( see below ).
Anticoagulation and Antiplatelets After Treatment for Myocardial Infarction -- In the treatment of acute myocardial infarction, the use of aspirin has been shown to reduce the incidence of reinfarction and stroke. The addition of aspirin to Streptokinase causes a minimal increase in the risk of minor bleeding (3.9% vs. 3.1%), but does not appear to increase the incidence of major bleeding (see SIDE EFFECTS ) (2) . The use of anticoagulants following administration of Streptokinase increases the risk of bleeding, but has not yet been shown to be of unequivocal clinical benefit. Therefore, whereas the use of aspirin is recommended unless otherwise contraindicated, the use of anticoagulants should be decided by the treating physician.
Anticoagulation After IV Treatment for Other Indications -- Continuous intravenous infusion of heparin, without a loading dose, has been recommended following termination of Streptase, Streptokinase, infusion for treatment of pulmonary embolism or deep vein thrombosis to prevent rethrombosis. The effect of Streptokinase on thrombin time (TT) and activated partial thromboplastin time (APTT) will usually diminish within 3 to 4 hours after Streptokinase therapy, and heparin therapy without a loading dose can be initiated when the TT or the APTT is less than twice the normal control value.
