streptokinase
Streptase

Available forms
Available by prescription only
Injection: 250,000 IU, 750,000 IU, 1,500,000 IU in vials for reconstitution

Indications and dosages
 Lysis of coronary artery thrombi after acute MI. Adults: 1,500,000 IU by I.V. infusion over 60 minutes or an intracoronary loading dose of 20,000 IU via coronary catheter, followed by a maintenance dosage of 2,000 IU/minute for 60 minutes as an infusion.
 Venous thrombosis, pulmonary embolism, and arterial thrombosis and embolism. Adults: Loading dose of 250,000 IU I.V. infusion over 30 minutes. Sustaining dose: 100,000 IU/hour I.V. infusion for 72 hours for deep vein thrombosis, 100,000 IU/hour over 24 hours by I.V. infusion pump for pulmonary embolism, 100,000 IU/hour by I.V. infusion for 24 to 72 hours for arterial thrombosis or embolism.
 Arteriovenous cannula occlusion. Adults: 250,000 IU in 2-ml solution by I.V. infusion pump into each occluded limb of the cannula over 25 to 35 minutes. Clamp off cannula for 2 hours, then aspirate contents of cannula, flush with saline solution, and reconnect.

Pharmacodynamics
Thrombolytic action: Streptokinase promotes thrombolysis by activating plasminogen in two steps. First, plasminogen and streptokinase form a complex, exposing plasminogen-activating site, and second, cleavage of peptide bond converts plasminogen to plasmin.
In treatment of acute MI, streptokinase prevents primary or secondary thrombus formation in microcirculation surrounding the necrotic area.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Doesn’t cross the placental barrier but antibodies do.
Metabolism: Insignificant.
Excretion: Removed from circulation by antibodies and reticuloendothelial system. Half-life is biphasic; initially it’s 18 minutes (from antibody action) and then extends up to 83 minutes. Anticoagulant effect may persist for 12 to 24 hours after infusion is discontinued.

Contraindications and precautions
Contraindicated in patients with ulcerative wounds, active internal bleeding, and recent CVA; recent trauma with possible internal injuries; visceral or intracranial malignant neoplasms; ulcerative colitis; diverticulitis; severe hypertension; acute or chronic hepatic or renal insufficiency; uncontrolled hypocoagulation; chronic pulmonary disease with cavitation; subacute bacterial endocarditis or rheumatic valvular disease; or recent cerebral embolism, thrombosis, or hemorrhage.
  Also contraindicated within 10 days after intra-arterial diagnostic procedure or any surgery, including liver or kidney biopsy, lumbar puncture, thoracentesis, paracentesis, or extensive or several cutdowns. I.M. injections and other invasive procedures are contraindicated during streptokinase therapy.
 Use cautiously in patients with arterial embolism that originates from the left side of the heart.
 Not recommended by manufacturer to restore patency of occluded I.V. catheters because of the risk of life-threatening reactions.

Interactions
Drug-drug. Aminocaproic acid: Inhibits streptokinase effects on plasminogen activation. Don’t use together.
Anticoagulants: May cause hemorrhage. It may also be necessary to reverse effects of oral anticoagulants before beginning therapy. Monitor patient closely.
Aspirin, indomethacin, phenylbutazone, or other drugs that affect platelet activity: Increases risk of bleeding. Monitor patient closely.
Drug-herb. Dong quai, feverfew, garlic, ginger, horse chestnut, red clover: Increases risk of bleeding. Discourage use together.

Adverse reactions
CNS: polyradiculoneuropathy, headache, fever.
CV: reperfusion arrhythmias, hypotension, vasculitis.
EENT: periorbital edema.
GI: nausea.
Hematologic: bleeding.
Musculoskeletal: musculoskeletal pain.
Respiratory: minor breathing difficulty, bronchospasm, apnea.
Skin: urticaria, pruritus, flushing, phlebitis at injection site.
Other: hypersensitivity reactions (anaphylaxis), delayed hypersensitivity reactions (interstitial nephritis, serum sickness-like reactions), angioedema.

Effects on lab test results
• May increase PT, PTT, and INR. May decrease hematocrit.

Overdose and treatment
Overdose may cause serious bleeding, which may result in bleeding gums, epistaxis, hematoma, spontaneous ecchymoses, oozing at catheter site, increased pulse, and pain from internal bleeding.
 Discontinue drug, and restart therapy when bleeding stops.

Special considerations
 ALERT Prescribing, dispensing, and dosing errors have been reported using the abbreviation IU. Take care to write clearly or spell out if possible.
• Reconstitute vial with 5 ml normal saline solution injection or D₅W according to manufacturer’s instructions; roll gently to mix. Don’t shake. Use immediately; refrigerate remainder and discard after 8 hours. Store powder at room temperature.
• Rate of I.V. infusion depends on thrombin time and streptokinase resistance; higher loading dose may be needed in patients with recent streptococcal infection or recent treatment with streptokinase, to compensate for antibody drug neutralization.
• Don’t discontinue therapy for minor allergic reactions that can be treated with antihistamines or corticosteroids; about one-third of patients experience a slight temperature elevation, and some have chills. Symptomatic treatment with acetaminophen (but not aspirin or other salicylates) is indicated if temperature reaches 104° F (40° C). Patients may be pretreated with corticosteroids, repeating doses during therapy, to minimize pyrogenic or allergic reactions.
• If minor bleeding can be controlled by local pressure, don’t decrease dose so more plasminogen is available for conversion to plasmin.
• Antibodies to streptokinase can persist for 3 to 6 months or longer after the initial dose; if further thrombolytic therapy is needed, consider urokinase.
• Monitor pulse, color, and sensation of limbs every hour.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Patients age 75 and older have a greater risk of cerebral hemorrhage because they’re likely to have preexisting cerebrovascular disease.

Patient education
• Explain use and administration to patient and family.

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