Tissue Plasminogen Activator Alteplase

Tissue Plasminogen Activator Alteplase Uses, Dosage, Side Effects, Food Interaction and all others data.

Tissue Plasminogen Activator Alteplase is a serine protease responsible for fibrin-enhanced conversion of plasminogen to plasmin. It produces limited conversion of plasminogen in the absence of fibrin. When introduced into the systemic circulation at pharmacologic concentration, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This initiates local fibrinolysis with limited systemic proteolysis.

Pharmacodynamics: Following administration of 100 mg Tissue Plasminogen Activator Alteplase, there is a decrease (16%-36%) in circulating fibrinogen. In a controlled trial, 8 of 73 patients (11%) receiving Tissue Plasminogen Activator Alteplase (1.25 mg/kg body weight over 3 hours) experienced a decrease in fibrinogen to below 100 mg/dL.

Pharmacokinetics: Tissue Plasminogen Activator Alteplase in acute myocardial infarction (AMI) patients is rapidly cleared from the plasma with an initial half-life of less than 5 minutes. There is no difference in the dominant initial plasma half-life between the 3-hour and accelerated regimens for AMI. The plasma clearance of alteplase is 380-570 mL/min, primarily mediated by the liver. The initial volume of distribution approximates plasma volume.

Tissue Plasminogen Activator Alteplase
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Tissue Plasminogen Activator Alteplase
Availability	Prescription only
Generic	Alteplase
Alteplase Other Names	Alteplasa, Alteplase, Alteplase (genetical recombination), Alteplase, recombinant, Alteplase,recombinant, Plasminogen activator (human tissue-type protein moiety), rt-PA, t-PA, t-plasminogen activator, Tissue plasminogen activator, Tissue plasminogen activator alteplase, Tissue plasminogen activator, recombinant, tPA
Related Drugs	aspirin, lisinopril, metoprolol, propranolol, Xarelto, clopidogrel, Eliquis, warfarin, Plavix, Brilinta
Type
Formula	C₂₅₆₉H₃₉₂₈N₇₄₆O₇₈₁S₄₀
Weight	59042.3 Da
Groups	Approved
Therapeutic Class	Anti-platelet drugs, Fibrinolytics (Thrombolytics)
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

Acute Ischemic Stroke: Tissue Plasminogen Activator Alteplase is used for the treatment of acute ischemic stroke. Exclude intracranial hemorrhage as the primary cause of stroke signs and symptoms prior to initiation of treatment. Initiate treatment as soon as possible but within 3 hours after symptom onset.

Acute Myocardial Infarction: Tissue Plasminogen Activator Alteplase is used for use in acute myocardial infarction (AMI) for the reduction of mortality and the reduction of the incidence of heart failure.

Pulmonary Embolism: Tissue Plasminogen Activator Alteplase is used for the lysis of acute massive pulmonary embolism, defined as:

Acute pulmonary emboli obstructing blood flow to a lobe or multiple lung segments.
Acute pulmonary emboli accompanied by unstable hemodynamics, e.g., failure to maintain blood pressure without supportive measures.

Tissue Plasminogen Activator Alteplase is also used to associated treatment for these conditions: Acute Ischemic Stroke (AIS), Acute Myocardial Infarction (AMI), Acute massive pulmonary embolism, Central venous access device thrombosis

How Tissue Plasminogen Activator Alteplase works

Tissue Plasminogen Activator Alteplase binds to fibrin rich clots via the fibronectin finger-like domain and the Kringle 2 domain. The protease domain then cleaves the Arg/Val bond in plasminogen to form plasmin. Plasmin in turn degrades the fibrin matrix of the thrombus, thereby exerting its thrombolytic action.

Dosage

Tissue Plasminogen Activator Alteplase dosage

Acute Ischemic Stroke: Administer Tissue Plasminogen Activator Alteplase as soon as possible but within 3 hours after onset of symptoms. The recommended dose is 0.9 mg/kg (not to exceed 90 mg total dose), with 10% of the total dose administered as an initial intravenous bolus over 1 minute and the remainder infused over 60 minutes. During and following Tissue Plasminogen Activator Alteplase administration for the treatment of acute ischemic stroke, frequently monitor and control blood pressure. In patients without recent use of oral anticoagulants or heparin, Tissue Plasminogen Activator Alteplase treatment can be initiated prior to the availability of coagulation study results. Discontinue Tissue Plasminogen Activator Alteplase if the pretreatment International Normalized Ratio (INR) is greater than 1.7 or the activated partial thromboplastin time (aPTT) is elevated.

Acute Myocardial Infarction: Administer Tissue Plasminogen Activator Alteplase as soon as possible after the onset of symptoms. The recommended total doses for acute myocardial infarction (AMI) is based on patient weight, not to exceed 100 mg, regardless of the selected administration regimen (accelerated or 3 hour). There are two Tissue Plasminogen Activator Alteplase dose regimens (accelerated and 3-hour) for use in the management of AMI; there are no controlled studies to compare clinical outcomes with these regimens

Pulmonary Embolism (PE): The recommended dose is 100 mg administered by IV infusion over 2 hours. Institute parenteral anticoagulation near the end of or immediately following the Tissue Plasminogen Activator Alteplase infusion when the partial thromboplastin time or thrombin time returns to twice normal or less.

Following bolus dose, if indicated:

50 mg vials: administer using either a polyvinyl chloride bag or glass vial and infusion set.
100 mg vials: remove from the vial any quantity of drug in excess of that specified for patient treatment. Insert the spike end of an infusion set through the same puncture site created by the transfer device in the stopper of the vial of reconstituted Tissue Plasminogen Activator Alteplase. Peel the clear plastic hanger from the vial label. Hang the Tissue Plasminogen Activator Alteplase vial from the resulting loop.

Tissue Plasminogen Activator Alteplase is for intravenous administration only. Extravasation of Tissue Plasminogen Activator Alteplase infusion can cause ecchymosis or inflammation. If extravasation occurs, terminate the infusion at that IV site and apply local therapy. Do not add any other medication to infusion solutions containing Tissue Plasminogen Activator Alteplase.

Pediatric Use: Safety and effectiveness of Tissue Plasminogen Activator Alteplase in pediatric patients have not been established.

Geriatric Use:

Acute Ischemic Stroke: In exploratory, multivariate analyses of Studies 1 and 2, age greater than 77 years was one of several interrelated baseline characteristics associated with an increased risk of intracranial hemorrhage. Efficacy results suggest a reduced but still favorable clinical outcome for Tissue Plasminogen Activator Alteplase-treated elderly.
Acute Myocardial Infarction: In a large trial of accelerated-infusion Tissue Plasminogen Activator Alteplase that enrolled 41,021 patients with AMI to one of four thrombolytic regimens [see Clinical Studies (14.2)], patients over 75 years of age, a predefined subgroup, comprised 12% of enrolment. In these patients, the incidence of stroke was 4.0% for the Tissue Plasminogen Activator Alteplase accelerated infusion group, 2.8% for streptokinase IV [SK (IV)], and 3.2% for streptokinase SQ [SK (SQ)]. The incidence of combined 30-day mortality or nonfatal stroke was 20.6% for accelerated infusion of Tissue Plasminogen Activator Alteplase, 21.5% for SK (IV), and 22.0% for SK (SQ).

Side Effects

The following adverse reactions are:

Bleeding
Orolingual Angioedema
Cholesterol Embolization
Reembolization of Deep Venous Thrombi during Treatment for Acute Massive Pulmonary
Embolism.

Precaution

Increases the risk of bleeding. Avoid intramuscular injections. Monitor for bleeding. If serious bleeding occurs, discontinue Tissue Plasminogen Activator Alteplase.
Monitor patients during and for several hours after infusion for orolingual angioedema. If angioedema develops, discontinue Tissue Plasminogen Activator Alteplase.
Cholesterol embolism has been reported rarely in patients treated with thrombolytic agents.
Consider the risk of reembolization from the lysis of underlying deep venous thrombi in patients with pulmonary embolism.

Food Interaction

Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Tissue Plasminogen Activator Alteplase Hypertension interaction

[Major] The use of thrombolytics is contraindicated in patients with an active bleed (internal), trauma

Risk versus benefit should be carefully considered in the following conditions and thrombolytic therapy administered with caution in patients with recent (10 days) serious GI bleed or recent (10 days) surgical procedure (coronary bypass graft, obstetrical delivery, organ biopsy, puncture of noncompressible vessel), left heart thrombus, subacute bacterial endocarditis, hemostatic defect, CV disease, diabetic hemorrhagic retinopathy, or pregnancy.

Clinical monitoring of hematopoietic, bleeding and coagulation functions is recommended prior to initiation of thrombolytic therapy.

Measures of fibrinolytic activity and

Tissue Plasminogen Activator Alteplase Drug Interaction

Major: heparin, heparinModerate: aspirin, aspirin, clopidogrel, clopidogrelUnknown: charcoal, charcoal, epinephrine, epinephrine, amoxicillin, amoxicillin, lorazepam, lorazepam, acetaminophen, acetaminophen, acetaminophen, acetaminophen, ondansetron, ondansetron

Tissue Plasminogen Activator Alteplase Disease Interaction

Major: bleeding risks

Pregnancy & Breastfeeding use

Pregnancy Category C. Tissue Plasminogen Activator Alteplase is embryocidal in rabbits when intravenously administered in doses of approximately two times (3 mg/kg) the human dose for AMI. No maternal or fetal toxicity was evident at 0.65 times (1 mg/kg) the human dose in pregnant rats and rabbits dosed during the period of organogenesis. There are no adequate and well-controlled studies in pregnant women. It is not known whether Tissue Plasminogen Activator Alteplase is excreted in human milk. Many drugs are excreted in human milk.

Storage Condition

Store lyophilized Tissue Plasminogen Activator Alteplase at controlled room temperature not to exceed 30°C, or under refrigeration (2-8°C). Protect the lyophilized material during extended storage from excessive exposure to light. If stored between 2-30°C, Tissue Plasminogen Activator Alteplase may be used within 8 hours following reconstitution. Discard any unused solution after administration is complete. Do not use beyond the expiration date stamped on the vial.