Streptase


streptokinase

Streptase

Pharmacologic class: Group C beta-hemolytic streptococcal nonenzymatic protein

Therapeutic class: Thrombolytic

Pregnancy risk category C

Action

Converts plasminogen to plasmin, an enzyme that degrades fibrin clots and lyses thrombi and emboli

Availability

Powder for injection: 250,000, 750,000, and 1.5 million international units/vial

Indications and dosages

➣ Acute evolving transmural myocardial infarction

Adults: 1.5 million international units by I.V. infusion over 1 hour as soon as possible after symptom onset. For intracoronary infusion, 20,000 international units by I.V. bolus via coronary catheter, followed by infusion of 2,000 international units/minute over 1 hour (total of 140,000 international units).

➣ Deep-vein thrombosis (DVT)

Adults: Loading dose of 250,000 international units by I.V. infusion over 30 minutes, followed by 100,000 international units/hour I.V. for 72 hours. Begin therapy as soon as possible after thrombotic symptoms begin (preferably within 7 days).

➣ Pulmonary emboli

Adults: Loading dose of 250,000 international units by I.V. infusion over 30 minutes, then 100,000 international units/hour I.V. for 24 hours (or 72 hours if concurrent DVT is suspected). Begin therapy as soon as possible after thrombotic symptoms begin (preferably within 7 days).

➣ Arterial thrombosis or emboli

Adults: Loading dose of 250,000 international units by I.V. infusion over 30 minutes, then 100,000 international units/hour I.V. for 24 to 72 hours. Begin therapy as soon as possible after thrombotic symptoms begin (preferably within 7 days).

Contraindications

• Hypersensitivity to drug or anistreplase

• Cerebrovascular accident, intracranial or intraspinal surgery within past 2 months

• Active internal bleeding

• Intracranial neoplasm

• Severe, uncontrolled hypertension

Precautions

Use cautiously in:

• severe hepatic or renal disease, recent major surgery or trauma, obstetric delivery, acute pericarditis, infectious endocarditis, atrioventricular malformation or aneurysm, suspected thrombus in left side of heart, septic thrombophlebitis or occluded arteriovenous cannula at seriously infected site

• conditions in which bleeding may be hard to manage (such as organ biopsy, peptic ulcer, previous puncture of noncompressible blood vessel)

• history of cerebrovascular disease

• use of drug within past 2 years

• concurrent anticoagulant use

• elderly patients

• pregnant or breastfeeding patients.

Administration

See Before giving, make sure hydrocortisone is available to treat allergic reaction and aminocaproic acid is available to treat excessive bleeding.

See As ordered, give test dose of 100 international units intradermally to check for hypersensitivity. Wheal-and-flare response within 20 minutes indicates probable allergy.

• To reconstitute, add 5 ml of normal saline solution or dextrose 5% in water to each vial, then dilute again to 45 ml. Roll vial gently between hands; don't shake.

• If necessary, dilute further to 50 ml in plastic container or to 500 ml in glass bottle.

• Don't mix with other drugs or give other drugs through same I.V. line.

Adverse reactions

CNS: headache, intracranial hemorrhage

CV: hypotension, arrhythmias

EENT: periorbital swelling

GI: nausea, vomiting, GI hemorrhage

GU: hematuria

Hematologic: anemia, bleeding tendency

Musculoskeletal: musculoskeletal pain

Respiratory: minor breathing difficulties, bronchospasm, apnea

Skin: urticaria, itching, flushing

Other: bleeding at puncture sites, delayed hypersensitivity reaction

Interactions

Drug-drug. Anticoagulants, aspirin, dipyridamole, indomethacin, phenylbutazone: increased risk of bleeding

Drug-diagnostic tests. Hemoglobin: decreased value

International Normalized Ratio, transaminases: increased values

Partial thromboplastin time (PTT), prothrombin time (PT): prolonged

Patient monitoring

• Monitor vital signs and neurologic status carefully after giving test dose and throughout therapy.

See Watch for signs and symptoms of hypersensitivity reaction. Stop drug if these occur.

• Check for bleeding every 15 minutes for first hour, every 30 minutes for next 7 hours, then every 4 hours.

See Stop therapy and contact prescriber immediately if excessive bleeding occurs.

• Assess neurologic status closely. Watch for indications of intracranial bleeding.

• Handle patient gently and sparingly. If necessary, pad bed rails to prevent injury.

• Monitor pulse rate every hour. Also monitor distal circulation.

• Monitor PTT, PT, plasma thrombin time, hemoglobin, hematocrit, and platelet count.

• Avoid giving I.M. injections during therapy.

Patient teaching

• Tell patient why he's receiving drug.

See Teach patient to recognize and immediately report signs or symptoms of hypersensitivity reaction or excessive bleeding.

• Instruct patient to report unusual bruising or bleeding. Teach him safety measures to avoid bruising and bleeding.

• Advise patient that he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

streptokinase

(strep-toe-kye-nase) streptokinase,

Kabbikinase

(trade name),

Streptase

(trade name)

Classification

Therapeutic: thrombolytics
Pharmacologic: plasminogen activators
Pregnancy Category: C

Indications

Acute myocardial infarction (MI).Pulmonary embolism (PE).Deep vein thrombosis (DVT).Acute peripheral arterial thrombosis.Occluded arteriovenus cannulae.

Action

Combines with plasminogen to form activator complexes, then converts plasminogen to plasmin, which is then able to degrade clot-bound fibrin.

Therapeutic effects

Lysis of thrombi in coronary arteries, with preservation of ventricular function.Lysis of pulmonary emboli and subsequent restoration of blood flow.Restoration of cannula patency and function.

Pharmacokinetics

Absorption: Complete after IV administration. Administration into occluded cannulae has a more localized effect.Distribution: Streptokinase appears to cross the placenta minimally, if at all. Remainder of distribution for streptokinase is not known.Metabolism and Excretion: Rapidly cleared from circulation by antibodies and other unknown mechanisms.Half-life: Initial half–life (due to clearance by antibodies)–18 min, then 83 minutes.

Time/action profile (fibrinolysis)

ROUTEONSETPEAKDURATION
IVimmediaterapid4 hr (up to 12 hr)

Contraindications/Precautions

Contraindicated in: Active internal bleeding; History of cerebrovascular accident; Recent (within 2 mo) intracranial or intraspinal injury or trauma; Intracranial neoplasm, arteriovenous malformation, or aneurysm; Severe uncontrolled hypertension; Known bleeding tendencies; Hypersensitivity; cross-sensitivity with anistreplase and streptokinase may occur.Use Cautiously in: Recent (within 10 days) major surgery, trauma, GI or GU bleeding; Left heart thrombus; Severe hepatic or renal disease; Hemorrhagic ophthalmic conditions; Septic phlebitis; Previous puncture of a noncompressible vessel; Subacute bacterial endocarditis or acute pericarditis; Recent streptococcal infection or previous therapy with anistreplase or streptokinase (within 5 days–6 mo); may produce resistance because of antibody formation; increased dosage requirements may be encountered (anistreplase and streptokinase only); Previous therapy with streptokinase or anistreplase (within 12 mo); may produce resistance because of antibody formation; Geriatric patients (>75 yr; increased risk of intracranial bleeding); Pregnancy, lactation, or children (safety not established).Exercise Extreme Caution in: Patients receiving warfarin therapy; Early postpartum period (10 days).

Adverse Reactions/Side Effects

Central nervous system

  • intracranial hemorrhage (life-threatening)

Ear, Eye, Nose, Throat

  • epistaxis
  • gingival bleeding

Respiratory

  • bronchospasm
  • hemoptysis

Cardiovascular

  • reperfusion arrhythmias
  • hypotension
  • recurrent ischemia/thromboembolism (life-threatening)

Gastrointestinal

  • GI bleeding (life-threatening)
  • hepatotoxicity
  • nausea
  • retroperitoneal bleeding (life-threatening)
  • vomiting

Genitourinary

  • GU tract bleeding (life-threatening)

Dermatologic

  • ecchymoses
  • flushing
  • urticaria

Hematologic

  • bleeding (life-threatening)

Local

  • hemorrhage at injection site
  • phlebitis at injection site

Musculoskeletal

  • musculoskeletal pain

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever

Interactions

Drug-Drug interaction

Aspirin, other NSAIDs, warfarin, heparin and heparin-like agents, abciximab, eptifibatide, tirofiban, clopidogrel, ticlopidine, or dipyridamole —concurrent use ↑ risk of bleeding, although these agents are frequently used together or in sequence.Effects may be ↓ by antifibrinolytic agents, including aminocaproic acid or tranexamic acid.↑ anticoagulant effect and bleeding risk with anise, arnica, chamomile, clove, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng, licorice, and others.

Route/Dosage

Myocardial Infarction

Intravenous (Adults) 1.5 million IU given as a continuous infusion over up to 60 minutes.Intracoronary: (Adults) 20,000 IU bolus followed by 2000 IU/min infusion for 60 min.

Deep Venous Thrombosis, Pulmonary Emboli, Arterial Emboli, or Other Thromboses

Intravenous (Adults) 250,000 IU loading dose, followed by 100,000 IU/hr for 24 hr for pulmonary emboli, 72 hr for recurrent pulmonary emboli or deep vein thrombosis.

Occluded Arteriovenous Cannulae

Intravenous (Adults) 250,000 IU/2 mL instilled into occluded catheter.

Availability

Powder for injection: 250,000 IU/vial, 600,000 IU/vial, 750,000 IU/vial, 1,500,000 IU/vial

Nursing implications

Nursing assessment

  • Begin therapy as soon as possible after the onset of symptoms.
    • Monitor vital signs, including temperature, continuously for myocardial infarction. Do not use lower extremities to monitor BP. Notify health care professional if systolic BP >180 mm Hg or diastolic BP >110 mm Hg. Thrombolytic therapy should not be given if hypertension is uncontrolled. Inform health care professional if hypotension occurs. Hypotension may result from the drug, hemorrhage, or cardiogenic shock.
    • Assess patient carefully for bleeding every 15 min during the 1st hr of therapy, every 15–30 min during the next 8 hr, and at least every 4 hr for the duration of therapy. Frank bleeding may occur from sites of invasive procedures or from body orifices. Internal bleeding may also occur (decreased neurologic status; abdominal pain with coffee-grounds emesis or black, tarry stools; hematuria; joint pain). If uncontrolled bleeding occurs, stop medication and notify health care professional immediately.
    • Inquire about previous reaction to streptokinase therapy. Assess patient for hypersensitivity reaction (rash, dyspnea, fever, changes in facial color, swelling around the eyes, wheezing). If these occur, inform health care professional promptly. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
    • Inquire about recent streptococcal infection. Streptokinase may be less effective if administered between 5 days and 12 mo of a streptococcal infection.
    • Assess neurologic status throughout therapy. Altered sensorium or neurologic changes may be indicative of intracranial bleeding.
  • Myocardial Infarction: Monitor ECG continuously. Notify health care professional if significant arrhythmias occur. IV lidocaine or procainamide (Pronestyl) may be ordered prophylactically. Monitor cardiac enzymes. Radionuclide myocardial scanning and/or coronary angiography may be ordered 7–10 days after therapy to monitor effectiveness of therapy.
    • Assess intensity, character, location, and radiation of chest pain. Note presence of associated symptoms (nausea, vomiting, diaphoresis). Administer analgesics as directed. Notify health care professional if chest pain is unrelieved or recurs.
    • Monitor heart sounds and breath sounds frequently. Inform health care professional if signs of HF occur (rales/crackles, dyspnea, S3 heart sound, jugular venous distention, relieved CVP).
  • Pulmonary Embolism: Monitor pulse, BP, hemodynamics, and respiratory status (rate, degree of dyspnea, ABGs).
  • Deep Vein Thrombosis/Acute Arterial Occlusion: Observe extremities and palpate pulses of affected extremities every hour. Notify health care professional immediately if circulatory impairment occurs. Computerized tomography, impedance plethysmography, quantitative Doppler effect determination, and/or angiography or venography may be used to determine restoration of blood flow and duration of therapy; however, repeated venograms are not recommended.
  • Cannula Occlusion: Monitor ability to aspirate blood as indicator of patency. Ensure that patient exhales and holds breath when connecting and disconnecting IV syringe to prevent air embolism.
  • Lab Test Considerations: Hematocrit, hemoglobin, platelet count, fibrin/fibrin degradation product (FDP/fdp) titer, fibrinogen concentration, prothrombin time, thrombin time, and activated partial thromboplastin time may be evaluated before and frequently during therapy. Bleeding time may be assessed before therapy if patient has received platelet aggregation inhibitors.
    • Obtain type and crossmatch and have blood available at all times in case of hemorrhage.
    • Stools should be tested for occult blood loss and urine for hematuria periodically during therapy.
    • high alert: If local bleeding occurs, apply pressure to site. If severe or internal bleeding occurs, discontinue infusion. Clotting factors and/or blood volume may be restored through infusions of whole blood, packed RBCs, fresh frozen plasma, or cryoprecipitate. Do not administer dextran; it has antiplatelet activity. Aminocaproic acid (Amicar) may be used as an antidote.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)
Risk for injury (Side Effects)

Implementation

  • high alert: Overdosage and under-dosage of thrombolytic medications have resulted in patient harm or death. Have second practitioner independently check original order, dosage calculations, and infusion pump settings.
  • Thrombolytic agents should be used only in settings in which hematologic function and clinical response can be adequately monitored.
    • Starting two IV lines before therapy is recommended: one for the thrombolytic agent, the other for any additional infusions.
    • Avoid invasive procedures, such as IM injections or arterial punctures, with this therapy. If such procedures must be performed, apply pressure to all arterial and venous puncture sites for at least 30 min. Avoid venipunctures at noncompressible sites (jugular vein, subclavian site).
    • Acetaminophen may be ordered to control fever.
  • Intracoronary: Dilute 250,000 IU vial to a total volume of 125 mL with 0.9% NaCl or D5W. Administer 20,000 IU (10 mL) via bolus injection.
  • Rate: Intracoronary bolus is administered over 15 sec–2 min.
  • Intravenous Administration
  • pH: 6.5.
  • pH: .
  • Intermittent Infusion: Diluent: Reconstitute with 5 mL of 0.9% NaCl or D5W (direct to sides of vial) and swirl gently; do not shake. Dilute further with 0.9% NaCl for a total volume of 45–500 mL (45 mL for MI, 90 mL for deep vein thrombosis or pulmonary embolism). Solution is slightly yellow in color. Administer through 0.8-micron pore–size filter. Use reconstituted solution within 24 hr.
  • Rate: Administer dose for MI within 60 min.
    • Intracoronary bolus should be followed by an intracoronary maintenance infusion of 2000 IU/min for 60 min.
    • Loading dose for deep vein thrombosis or pulmonary embolismis administered over 30 min, followed by an infusion of 100,000 IU/hr.
    • Use infusion pump to ensure accurate dose.
  • Y-Site Compatibility: alfentanil, amikacin, aminophylline, ascorbic acid, atracurium, atropine, aztreonam, benztropine, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, cefazolin, cefonocid, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, cimetidine, clindamycin, cyanocobalamin, cyclosporine, dexamethasone, digoxin, diphenhydramine, dobutamine, dopamine, doxycycline, enalaprilat, ephedrine, epinephrine, epoetin alfa, erythromycin, esmolol, famotidine, fentanyl, fluconazole, folic acid, furosemide, gentamicin, glycopyrrolate, heparin, hydrocortisone, imipenem/cilastatin, indomethacin, insulin, 'isoproterenol, ketorolac, labetalol, lidocaine, magnesium sulfate, mannitol, meperidine, methoxamine, methyldopate, methylprednisolone, metoclopramide, metoprolol, midazolam, morphine, multivitamins, nafcillin, naloxone, nitroglycerin, nitroprusside, norepinephrine, ondansetron, oxacillin, oxytocin, penicillin G, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, phytonadione, potassium chloride, procainamide, propranolol, pyridoxime, ranitidine, sodium bicarbonate, succinylcholine, sufentanil, theophylline, thiamine, ticarcillin/clavulanate, tobramycin, trimetaphan, verapamil
  • Y-Site Incompatibility: azathioprine, bivalirudin, chlorpromazine, dantrolene, diazepam, diazoxide, ganciclovir, hydroxyzine, nalbuphine, pentamidine, phenytoin, prochlorperazine, promethazine, trimethoprim/sulfamethoxazole, vancomycin
  • Additive Incompatibility: Do not admix with any other medication.
  • Cannula/Catheter Clearance: Dilute 250,000 IU in 2 mL of 0.9% NaCl or D5W.
  • Rate: Administer slowly, over 25–35 min, into each occluded limb of cannula, and then clamp for at least 2 hr. Aspirate contents carefully and flush lines with 0.9% NaCl.

Patient/Family Teaching

  • Explain purpose of medication and the need for close monitoring to patient and family. Instruct patient to report hypersensitivity reactions (rash, dyspnea) and bleeding or bruising.
  • Explain need for bedrest and minimal handling during therapy to avoid injury. Avoid all unnecessary procedures such as shaving and vigorous tooth brushing.

Evaluation/Desired Outcomes

  • Lysis of thrombi and restoration of blood flow.
  • Cannula patency.

Streptase

A brand name for the blood clot dissolving enzyme drug STREPTOKINASE.