ZIKINAZ®
 

Streptokinase

Dosage Form

Injection, Powder for reconstitution:     Streptokinase 1500000 IU

Pharmacologic Category

Fibrinolytic

Indications

Treatment of acute evolving myocardial infarction, acute pulmonary embolism, deep vein thrombosis, arterial thrombosis or embolism, occlusion of arterio-venus cannula

Pregnancy Risk Factor

Category C

Lactation

It is not known whether streptokinase is excreted in the breast milk, nor has it harmful effects on the newborn. In the absence of further information, it is recommended that breast-feeding be discontinued in women who are to receive ZIKINAZ.

Pediatric Use

Safety and effectiveness in children have not been established.

Mechanism of Action

Streptokinase acts with plasminogen to produce an 'activator complex' that converts plasminogen to the proteolytic enzyme, plasmin. Experimental studies have shown that streptokinase induces lysis of the thrombus both superficially and also from within the thrombus.

Contraindications

Because thrombolytic therapy increases the risk of bleeding, ZIKINAZ, administered either systemically or locally, is contraindicated in the following situations:

Existing or recent hemorrhage and hemorrhagic diathesis, potential for internal bleeding, all forms of reduced blood coagulability, in particular spontaneous fibrinolysis and extensive clotting disorders, recent (within 2 months) cerebrovascular accident, recent (within 10 days) facial or head trauma, intracranial or intraspinal surgery, known intracranial neoplasm and all known neoplasms with risk of hemorrhage, invasive operations, e.g. recent organ biopsy, invasive diagnostic procedure, recent implantation of a vessel prosthesis, long-term traumatic closed-chest massage or other recent surgery, arteriovenous malformation or aneurysm, hemorrhagic diathesis including thrombocytopenia or pronounced hepatic or renal dysfunction, severe uncontrolled hypertension, hypertonic fundus, severe liver or kidney damage, acute pancreatitis, simultaneous treatment with oral anticoagulants (INR >1.3), endocarditis or pericarditis.

Because of the danger of allergic anaphylactic reactions, ZIKINAZ is also contraindicated:

Immediately after streptococcal infections which have produced a high

antistreptokinase titer (acute rheumatic fever, acute glomerulo-nephritis, etc.), more than 5 days and less than 12 months since previous streptokinase therapy.

Precautions

It is recommended that IM Injection be avoided for the first 24 hours.

Streptokinase Infusion may cause hypotension as a result of rapid rate of infusion.

On termination of streptokinase treatment, the patient should be given anticoagulants in an attempt to prevent re-thrombosis. Preferably heparin should be given, starting four hours after the end of thrombolysis and then an oral anticoagulant may be introduced after 24 hours of streptokinase discontinuation.

Following 7 to 10 days of treatment with streptokinase, the patient’s anti-streptokinase antibodies titer Increases considerably and returns to normal only after up to 12 months. Normally a second treatment with streptokinase should not be considered within 12 months of the first. If a second treatment is considered necessary within 12 months the loading dose should be individually determined. The titrated Initial dose should be calculated determining the smallest quantity of streptokinase required.

If heparin or oral anticoagulants have been given before commencing streptokinase therapy, further administration should be topped. The streptokinase infusion can then be started after 4 hours.

Geriatric patients 75 years of age and older may be at increased risk of cerebral hemorrhage during streptokinase therapy.

Adverse Reactions

Hemorrhage and bleeding: Hemorrhages at invaded or disturbed sites, including the injection site, and ecchymoses; gastrointestinal or genitourinary bleedings, epistaxis.

Immune system disorders: Development of antistreptokinase, allergic-anaphylactic reactions such as rash, flushing, itching, urticaria, angioneurotic edema, minor breathing difficulty, periorbital swelling, bronchospasm or hypotension.

Cardiac complication and vascular disorders: Hypotension, heart rate and rhythm disorders, angina pectoris, recurrent ischemia, heart failure, reinfarction, cardiogenic shock, pericarditis, pulmonary edema.

Gastrointestinal disorders: Nausea, diarrhea, epigastric pain and vomiting.

General disorders: Headache and back pain, muscle pain, chills and/or fever as well as asthenia/malaise.

Laboratory investigations: Transient elevations of serum transaminase as well as of bilirubin.

Drug Interactions

There is an increased risk of hemorrhage in patients simultaneously or previously receiving anticoagulants (such as heparin or coumarin derivatives) or drugs which inhibit platelet formation or function (e.g. platelet aggregation inhibitors, dextrans, phenylbutazone, dipyridamole, non-steroidal anti-inflammatory drugs). However, the effect of heparin can be neutralized rapidly by administration of protamine sulphate. The aPTT should not be more than twice the normal control value before thrombolytic therapy is started. In the case of prior treatment with coumarin derivatives, the INR must be less than 1.3 before starting streptokinase infusion.

Dosage and Administration

·         Method for Reconstitution:

Sodium chloride 0.9% is the preferred diluent for ZIKINAZ, although Dextrose 5% in water may be used.

1- Add 5 ml of the diluents slowly to the vial of ZIKINAZ, directing the needle point to the wall of the vial. Abolish residual vacuum by briefly loosening the needle from the syringe.

2- Tilt and roll the vial gently. Swirl the contents gently to affect dissolution. Do not shake to avoid foaming.

3- Once the powder is completely dissolved, transfer the content of the vial into 45 ml of the physiological saline.

Do not add any other medication to ZIKINAZ vials.

·         Acute evolving transmural myocardial infarction:

 

1,500,000 IU ZIKINAZ is made up in 100 ml of physiological saline or Dextrose solution and administered over 30 to 60 minutes.

 

Alternatively intracoronary bolus doses of 10000 to 30000 IU have been administered in up to 20 ml infusion solution over 15 seconds to 2 minutes. Maintenance doses of 2000 to 4000 IU/min for 60 minutes by intracoronary infusion have been given.

 

·         Deep vein thrombosis, pulmonary embolism arterial thrombosis or embolism:

A loading dose of 250,000 IU of ZIKINAZ in 100ml to 300 ml of physiological saline or Dextrose solution infused into a peripheral vein over 30 minutes has been found appropriate as standard dose. Following the loading dose, a maintenance infusion of ZIKINAZ 100000 IU/h is given for 24 to 72 hours.

·         Occlusion of arterio-venous cannula:

ZIKINAZ equivalent to 250,000 IU may be administered over 25-35 minutes in 2 ml of solution to clear an occluded arterio-venous cannula. The drug is infused directly into the cannula which is then clamped for 2 hours, aspirated and flushed with physiological saline.

Storage and Preservation

Store at 2°C to 8°C.

Protect from light.