thrombolytic agents

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).

Adv. Reactions/Side Effects ⬆ ⬇

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)

Interactions ⬆ ⬇

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.

Availability ⬆ ⬇

Alteplase

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

Tenecteplase

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

Route/Dosage ⬆ ⬇

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.

US Brand Names ⬆ ⬇

alteplase: Activase, Cathflo Activase,

tenecteplase: TNKase

Action ⬆ ⬇

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.

Classifications ⬆ ⬇

Therapeutic Classification: thrombolytics

Pharmacologic Classification: plasminogen activators

Pharmacokinetics ⬆ ⬇

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).

Canadian Brand Names ⬆ ⬇

alteplase: Activase rt-PA

Time/Action Profile ⬆ ⬇

( fibrinolysis)

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

Patient/Family Teaching ⬆ ⬇

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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇