thrombolytic agents

alteplase: AL-te-plase

tenecteplase: te-NEK-te-plase

Therapeutic Classification: thrombolytics

Pharmacologic Classification: plasminogen activators

High Alert

Alteplase, tenecteplase

Acute MI. Acute ischemic stroke.

Alteplase

Acute massive pulmonary emboli (PE).

Alteplase

Occluded central venous access devices.

Directly activate plasminogen, converting it to plasmin, which is then able to degrade fibrin present in clots.

Therapeutic effects:

Lysis of thrombi in coronary arteries, with preservation of ventricular function or improvement of ventricular function (and ↓ risk of HF or death).
Lysis of PE.
Lysis of thrombi causing ischemic stroke, reducing risk of neurologic sequelae.
Restoration of cannula or catheter patency and function.

Absorption: IV administration results in complete bioavailability. Intracoronary administration or administration into occluded catheters or cannulae has a more localized effect.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Alteplase, tenecteplase: Rapidly metabolized by the liver.

Half-Life: Alteplase: 35 min; tenecteplase: 20–24 min (initial phase), 90–130 min (terminal phase).

( fibrinolysis)

ROUTE		ONSET		PEAK		DURATION
Alteplase IV		30 min		60 min		unknown
Tenecteplase IV		rapid		unknown		unknown

Contraindicated in:

Active internal bleeding;
History of cerebrovascular accident;
Recent (within 2 mo) intracranial or intraspinal injury or trauma;
Intracranial neoplasm, AV malformation, or aneurysm;
Severe uncontrolled hypertension;
Known bleeding tendencies;
Hypersensitivity; cross-sensitivity with other thrombolytics may occur.

Use Cautiously in:

Recent (within 10 days) major surgery, trauma, GI, or GU bleeding;
Left heart thrombus;
Severe renal impairment;
Severe hepatic impairment;
Hemorrhagic ophthalmic conditions;
Septic phlebitis;
Previous puncture of a noncompressible vessel;
Subacute bacterial endocarditis or acute pericarditis;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety not established in children;
Geri: ↑risk of intracranial bleeding in patients >75 yr.

Exercise Extreme Caution in:

Concurrent use of anticoagulant therapy (↑ risk of intracranial bleeding).

CV: hypotension, reperfusion arrhythmias

Derm: ecchymoses, flushing, urticaria

EENT: epistaxis, gingival bleeding

GI: nausea, vomiting

Hemat: BLEEDING

Local: hemorrhage at injection site, phlebitis

MS: musculoskeletal pain

Neuro: INTRACRANIAL HEMORRHAGE

Resp: bronchospasm, hemoptysis

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Drug-drug:

Aspirin, other NSAIDs, warfarin, heparin, low molecular weight heparins, direct thrombin inhibitors, eptifibatide, tirofiban, clopidogrel, ticagrelor, prasugrel, or dipyridamole may ↑ risk of bleeding, although these agents are frequently used together or in sequence.
Antifibrinolytic agents, including aminocaproic acid or tranexamic acid, may ↓ effectiveness.

Drug-Natural Products:

Anise, arnica, chamomile, clove, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, Panax ginseng, or licorice may ↑ risk of bleeding.

Alteplase

Myocardial Infarction (Accelerated or Front-Loading Infusion)
IV (Adults ): 15 mg bolus, then 0.75 mg/kg (up to 50 mg) over 30 min, then 0.5 mg/kg (up to 35 mg) over next 60 min; usually accompanied by heparin therapy.
Myocardial Infarction (3-Hr Infusion)
IV (Adults >65 kg): 60 mg over 1st hr (6–10 mg given as a bolus over first 1–2 min), 20 mg over the 2nd hr, and 20 mg over the 3rd hr for a total dose of 100 mg.
IV (Adults <65 kg): 0.75 mg/kg over 1st hr (0.075–0.125 mg/kg given as a bolus over first 1–2 min), 0.25 mg/kg over the 2nd hr, and 0.25 mg/kg over the 3rd hr for a total dose of 1.25 mg/kg (not to exceed 100 mg total).
Pulmonary Embolism
IV (Adults ): 100 mg over 2 hr; follow with heparin.
Acute Ischemic Stroke
IV (Adults ): 0.9 mg/kg (not to exceed 90 mg), given as an infusion over 1 hr, with 10% of the dose given as a bolus over the 1st min.
Occluded Venous Access Devices
IV (Adults and Children >30 kg): 2 mg/2 mL instilled into occluded catheter; if unsuccessful, may repeat once after 2 hr.
IV (Adults and Children <30 kg): 110% of the lumen volume (not to exceed 2 mg in 2 mL) instilled into occluded catheter; if unsuccessful, may repeat once after 2 hr.

Tenecteplase

Myocardial Infarction
IV (Adults <60 kg): 30 mg as a single dose.
IV (Adults ≥60 kg and <70 kg): 35 mg as a single dose.
IV (Adults ≥70 kg and <80 kg): 40 mg as a single dose.
IV (Adults ≥80 kg and <90 kg): 45 mg as a single dose.
IV (Adults ≥90 kg): 50 mg as a single dose.
Acute Ischemic Stroke
IV (Adults ≥90 kg): 25 mg as a single dose.
IV (Adults ≥80 kg and <90 kg): 22.5 mg as a single dose.
IV (Adults ≥70 kg and <80 kg): 20 mg as a single dose.
IV (Adults ≥60 kg and <70 kg): 17.5 mg as a single dose.
IV (Adults <60 kg): 15 mg as a single dose.

Alteplase

Powder for injection: 2 mg/vial; 50 mg/vial; 100 mg/vial

Tenecteplase

Powder for injection: 25 mg/vial; 50 mg/vial

Begin therapy as soon as possible after the onset of symptoms.
- Monitor vital signs, including temperature, continuously for coronary thrombosis and at least every 4 hr during therapy for other indications. Do not use lower extremities to monitor BP. Notify health care provider if systolic BP >180 mm Hg or diastolic BP >110 mm Hg. Should not be given if hypertension is uncontrolled. Inform health care provider if hypotension occurs. Hypotension may result from the drug, hemorrhage, or cardiogenic shock.
- Assess 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 (↓ 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 provider immediately.
- Assess neurologic status during therapy. Altered sensorium or neurologic changes may be indicative of intracranial bleeding.
- Assess for hypersensitivity reactions (anaphylaxis). If hypersensitivity reaction occurs, discontinue therapy and implement supportive measures (epinephrine) as indicated.
MI: Monitor ECG continuously. Notify health care provider if significant arrhythmias occur. 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). Notify health care provider if chest pain is unrelieved or recurs.
- Monitor heart sounds and breath sounds frequently. Inform health care provider if signs/symptoms of HF occur (rales/crackles, dyspnea, S₃ heart sound, jugular venous distention).
Acute Ischemic Stroke: Assess neurologic status. Determine time of onset of stroke symptoms. Alteplase must be administered within 3–4.5 hr of onset (within 3 hr in patients >80 yr, those taking oral anticoagulants, those with a baseline National Institutes of Health Stroke Scale score of 25, or those with both a history of stroke and diabetes).
PE: Monitor HR, BP, hemodynamics, and respiratory status (rate, degree of dyspnea, arterial blood gases).
Cannula/Catheter 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 titer, fibrinogen concentration, PT, thrombin time, and aPTT may be evaluated before and frequently during therapy. Bleeding time may be assessed before therapy if patient has received platelet 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.

Toxicity and Overdose:

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 may be used as an antidote.

High Alert: Overdose and underdose of thrombolytic medications have resulted in patient harm or death. Have second practitioner independently check original order, dose calculations, and infusion pump settings.
Do not confuse Activase with Cathflo Activase or TNKase. Do not confuse TNKase with t-PA.
Thrombolytic agents should be used only in settings in which hematologic function and clinical response can be adequately monitored.
- Insert 2 IV lines before therapy; 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 ≥30 min. Avoid venipunctures at noncompressible sites (jugular vein, subclavian site).
- Acetaminophen may be ordered to control fever.

Alteplase

IV Administration:

Intermittent Infusion: Activase: Reconstitution: Use sterile water for injection as diluent (do not use bacteriostatic water). Reconstitute 20-mg vials with 20 mL and 50-mg vials with 50 mL using an 18-gauge needle. Avoid excess agitation during dilution; swirl or invert gently to mix. Solution may foam upon reconstitution. Bubbles will resolve upon standing a few minutes. Solution will be clear to pale yellow. Stable for 8 hr at room temperature. Diluent: May be further diluted immediately before use in an equal amount of 0.9% NaCl or D5W. Concentration: 1 mg/mL. Rate:
Y-Site Compatibility:
- eptifibatide
- lidocaine
- metoprolol
- propranolol
- tobramycin
- vancomycin
Y-Site Incompatibility:
- bivalirudin
- cangrelor
- dobutamine
- dopamine
- heparin
- nitroglycerin

Tenecteplase

IV Administration:

Y-Site Incompatibility: Do not administer other drugs through same IV line.

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise 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.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Lysis of thrombi in coronary arteries, with preservation of ventricular function or improvement of ventricular function (and ↓ risk of HF or death).
Lysis of PE.
Lysis of thrombi causing ischemic stroke, reducing risk of neurologic sequelae.
Restoration of cannula or catheter patency and function.

alteplase: Activase, Cathflo Activase,

tenecteplase: TNKase

alteplase: Activase rt-PA

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Canadian Brand Names ⬆