anistreplase (anisoylated plasminogen-streptokinase activator complex, APSAC)
Eminase

Available forms
Available by prescription only
Injection: 30 units/single-dose vial

Indications and dosages
 Acute coronary arterial thrombosis during an acute MI. Adults: 30 units by direct I.V. injection over 2 to 5 minutes.

Pharmacodynamics
Enzymatic action: Anistreplase is derived from Lys-plasminogen and streptokinase. It activates the endogenous fibrinolytic system to produce plasmin, which degrades fibrin clots, fibrinogen, and other plasma proteins, including procoagulant factors V and VIII.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Information not available.
Metabolism: Immediately after injection, anistreplase is deacylated by a nonenzymatic process to form the active streptokinase-plasminogen complex.
Excretion: Unknown. The half-life of acylated and deacylated anistreplase is 88 to 112 minutes.

Contraindications and precautions
Contraindicated in patients with history of severe allergic reaction to anistreplase or streptokinase and in those with active internal bleeding, CVA, recent (within the past 2 months) intraspinal or intracranial surgery or trauma, aneurysm, arteriovenous malformation, intracranial neoplasm, uncontrolled hypertension, or known bleeding diathesis.
  Use cautiously in patients with recent (within 10 days) major surgery, trauma (including cardiopulmonary resuscitation), GI or GU bleeding, cerebrovascular disease, hypertension, mitral stenosis, atrial fibrillation, acute pericarditis, subacute bacterial endocarditis, septic thrombophlebitis, and diabetic hemorrhagic retinopathy. Also use cautiously in women who are pregnant or within the first 10 days postpartum; in patients receiving anticoagulants; and in those older than age 75.

Interactions
Drug-drug. Adrenocorticoids, cefamandole, cefoperazone, cefotetan, corticotropin (long-term therapy), ethacrynic acid, glucocorticoids, plicamycin, valproic acid: May increase risk of severe hemorrhage. Use with extreme caution and monitor patient closely.
Drugs that alter platelet function (including aspirin, dipyridamole, and NSAIDs), heparin, oral anticoagulants: May increase risk of bleeding. Monitor patient closely.

Adverse reactions
CNS: intracranial hemorrhage.
CV: flushing, ARRHYTHMIAS,conduction disorders, hypotension.
GI: hemorrhage, gum or mouth hemorrhage.
GU: hematuria.
Hematologic: bleeding tendency, bleeding at puncture sites, eosinophilia.
Musculoskeletal: arthralgia.
Respiratory: hemoptysis.
Skin: hematoma, urticaria, pruritus, delayed purpuric rash (2 weeks after therapy).
Other: anaphylaxis.

Effects on lab test results
• May decrease plasminogen and fibrogen levels.
• May increase eosinophil count, thrombin time, PTT, and PT.

Overdose and treatment
Indications of overdose include signs of potentially serious bleeding: bleeding gums, epistaxis, hematoma, spontaneous ecchymoses, oozing at catheter site, increased pulse, and pain from internal bleeding.
 Discontinue drug and restart when bleeding stops.

Special considerations
• The following tests may be needed before and after drug administration: PTT, PT, thrombin time, hemoglobin, hematocrit, fibrinogen determination, platelet count, and fibrin-fibrinogen degradation products.
• Anistreplase remains active in vitro and can cause degradation of fibrinogen in blood samples drawn for analysis.
• Start therapy as soon as possible after onset of clinical symptoms of acute MI.
• Anistreplase is derived from human plasma. No cases of hepatitis or HIV infection have been reported to date.
• Reconstitute by slowly adding 5 ml sterile water for injection. Direct the stream against the side of the vial, not at the drug itself. Gently roll the vial to mix the dry powder and water. To avoid excessive foaming, don’t shake vial. Solution should be colorless to pale yellow.
• Don’t mix with other medications or further dilute after reconstitution.
• Store lyophilized powder in the refrigerator.
• Discard drug that isn’t administered within 30 minutes of reconstituting.
• Coronary angiography may be useful to monitor effectiveness.
• ECG monitoring is recommended to detect arrhythmias linked to acute MI or reperfusion and may help determine effectiveness of treatment.
• Monitor vital signs, mental status, and neurologic status.
• To decrease risk of rethrombosis, heparin therapy may be started after administration.
• Addition of fibrinolysis inhibitor (for example, aprotinin) or aminocaproic acid to blood samples drawn to obtain specific measurement of fibrinogen will attenuate the degradation of fibrinogen in thrombolytic-treated patients.
• Keep patient on strict bed rest and apply pressure dressings to recently invaded sites. To minimize risk of bleeding, avoid nonessential handling or moving of patient, invasive procedures such as biopsies, and I.M. injections.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• No age-specific problems have been reported to date. Risk-benefit must be assessed in patients age 75 and older because preexisting conditions increase the risk of hemorrhagic complications.

Patient education
• Instruct patient and caregiver to recognize and report signs and symptoms of internal bleeding.
• Inform patient about importance of strict bed rest.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use