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  • CLASSES

    Fibrinolytics

    DEA CLASS

    Rx

    DESCRIPTION

    Recombinant thrombolytic agent given as single IV bolus for AMI
    Longer half-life, increased fibrin specificity, and increased resistance to PAI-1 compared to alteplase with similar clinical outcomes of 30-day mortality, intracranial bleeding, and minor bleeding
    Major (non-cerebral) bleeding and blood transfusions were lower with tenecteplase (ASSENT 2 trial) compared to alteplase

    COMMON BRAND NAMES

    TNKase

    HOW SUPPLIED

    TNKase Intravenous Inj Pwd F/Sol: 50mg

    DOSAGE & INDICATIONS

    For the treatment of acute myocardial infarction with ST-elevation (STEMI) due to coronary artery thrombosis.
    NOTE: Standard management of myocardial infarction should be implemented concomitantly with tenecteplase treatment.
    NOTE: Randomized controlled trials have demonstrated beneficial outcomes when fibrinolytic therapy is administered as early as possible after onset of STEMI symptoms (e.g., prehospital fibrinolysis or within 30 minutes of hospital arrival). When indicated for patients with acute myocardial infarction and ST-elevation (STEMI), fibrinolytic therapy may be administered within 12 hours following the onset of symptoms. It is reasonable to administer fibrinolytic therapy within 24 hours of the onset of STEMI symptoms in patients who have continuing ischemic symptoms and ST elevation greater than 0.1 mV in at least 2 contiguous precordial leads or at least 2 adjacent limb leads.
    NOTE: During pre-marketing trials, the safety and efficacy of tenecteplase was primarily studied in AMI patients receiving aspirin and heparin. In the primary efficacy and safety trial, ASSENT 2, the use of glycoprotein IIb/IIIa inhibitors was discouraged for the first 24 hours following randomization. Tenecteplase has also been used to treat myocardial infarction in combination with enoxaparin as an alternative to unfractionated heparin.
    Intravenous dosage
    Adults

    A single bolus dose of 30 to 50 mg is administered IV over 5 seconds based on patient weight (30 mg for less than 60 kg, 35 mg for 60 to 69 kg, 40 mg for 70 to 79 kg, 45 mg for 80 to 89 kg, or 50 mg for 90 kg or greater patient). The maximum total IV dose is 50 mg. If serious bleeding (not controlled by local pressure) occurs, concomitant anticoagulant therapy should be immediately discontinued.

    For re-establishing patency of an occluded IV catheter or occluded arteriovenous (AV) cannula.
    Intracatheter instillation dosage
    Adults

    Up to 4 mg (2 mg in each lumen) has been studied in clinical trials. Dwell time has ranged from 1 to 72 hours. Repeat doses may be necessary.

    Children and Adolescents weighing 30 kg or more

    2 mg instilled in a single lumen with a dwell time of 15 to 120 minutes has been studied for dysfunctional central venous catheters (CVC). If CVC function was not restored within 120 minutes, the first dose was withdrawn and a second dose administered.

    Infants and Children weighing less than 30 kg

    Instillations equal to 110% of the internal lumen volume of the dysfunctional central venous catheter (CVC), not to exceed 2 mg, has been studied; dwell time ranged from 15 to 120 minutes. If CVC function was not restored within 120 minutes, the first dose was withdrawn and a second dose administered.

    For the treatment of acute ischemic stroke†.
    Intravenous dosage
    Adults

    0.25 mg/kg (Max: 25 mg) IV or 0.4 mg/kg (Max: 40 mg) IV as a single dose.[64716] [64755] Guidelines suggest tenecteplase 0.25 mg/kg within 4.5 hours of symptom onset as reasonable over alteplase in patients without contraindications for IV fibrinolysis who are also eligible to undergo mechanical thrombectomy and 0.4 mg/kg within 6 hours of symptom onset as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion.[64716]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    50 mg/total dose IV.

    Geriatric

    50 mg/total dose IV.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is needed. Use caution in patients with hemostatic defects due to hepatic disease; the bleeding risk of tenecteplase may be increased and should be weighed against the anticipated benefits.

    Renal Impairment

    No dosage adjustment is needed. Use caution in patients with hemostatic defects due to renal disease; the bleeding risk of tenecteplase may be increased and should be weighed against the anticipated benefits.
     
    Intermittent hemodialysis
    No dosage adjustment is needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Tenecteplase should be reconstituted before IV administration; for IV use only.
    After reconstitution, visually inspect parenteral products for particulate matter and discoloration before administration.
     
    Reconstitution:
    Reconstitution of tenecteplase should be carried out using the diluent, syringe, needle and dispensing system provided by the manufacturer. Reconstitute only with Sterile Water for Injection without preservatives. Do not reconstitute with Bacteriostatic Water for Injection.
    Reconstitute one vial of tenecteplase (50 mg) with 10mL Sterile Water for Injection. Remove the protective flip-cap from one vial of Sterile Water for Injection. Remove the shield assembly from the supplied syringe device (B-D TwinPak Dual Cannula Device) and aseptically withdraw 10 mL of Sterile Water for Injection from the supplied diluent vial. Do not discard the shield assembly.
    Inject the entire contents of the syringe (10 mL) into the tenecteplase vial directing the diluent stream into the powder. Slight foaming upon reconstitution is not unusual; allow the vial to stand undisturbed for several minutes to dissipate any large bubbles.
    Gently swirl the vial until contents are completely dissolved. DO NOT SHAKE. The reconstituted vial results in a colorless to pale yellow transparent solution containing tenecteplase at 5 mg/mL.
    The tenecteplase vial contains no antibacterial preservatives. Therefore, it should be reconstituted just before use. If the reconstituted drug is not used immediately, the vial should be refrigerated between 2 and 8 degrees C (36 and 46 degrees F) and used within 8 hours.
    Determine the appropriate dose of tenecteplase (see Dosage) and withdraw the appropriate volume from the reconstituted vial with the supplied syringe. Discard any unused portions.
    Although the administration syringe supplied by the manufacturer is compatible with a conventional needle, this syringe is designed to be used with needleless IV access systems (see product information for Luer-Lok or split septum IV access). Once the appropriate dose of tenecteplase is drawn into the syringe, stand the shield vertically on a flat surface (with green side down) and passively recap the red hub cannula. Remove the entire shield assembly, including the red hub cannula, by twisting counter-clockwise.
     
    Intravenous injection:
    Administer via a dedicated IV line in which no other medications are being simultaneously injected or infused. Reconstituted tenecteplase should be administered as a single IV bolus over 5 seconds.
    Precipitation may occur when tenecteplase is administered in an IV line containing dextrose. Dextrose-containing lines should be flushed with a saline-containing solution before and following single bolus administration of tenecteplase.

    STORAGE

    TNKase:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze reconstituted product
    - Reconstituted unused product should be stored at 36-46 degrees F and used within 8 hours
    - Store in refrigerator (36 to 46 degrees F) or at room temperature, not to exceed 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Tenecteplase is contraindicated in patients with a prior hypersensitivity to tenecteplase and should be used with caution in patients with a known hypersensitivity to alteplase, reteplase, or other alteplase variants.
     
    During tenecteplase therapy, results of coagulation tests or measures of fibrinolytic activity may be unreliable, unless specific precautions are taken to prevent in vitro artifacts. Tenecteplase is an enzyme that remains active in a patient's blood sample during in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis.

    Cardiac arrhythmias, hypertension

    Tenecteplase is contraindicated in patients with severe uncontrolled hypertension. In patients with systolic blood pressure of 180 mmHg or more and/or diastolic blood pressure of 110 mmHg or more, the risks of bleeding with tenecteplase therapy are increased and should be weighed against the potential benefits. In addition, cardiac arrhythmias, including sinus bradycardia, premature ventricular depolarizations, and ventricular tachycardia can develop as a result of reperfusion following coronary thrombolysis. Have anti-arrhythmic therapy for bradycardia and/or ventricular irritability available when tenecteplase is administered.

    Aneurysm, arteriovenous malformation, bleeding, brain tumor, coagulopathy, diabetic retinopathy, endocarditis, head trauma, hepatic disease, intracranial mass, organ biopsy, peptic ulcer disease, pericarditis, renal disease, renal failure, spinal anesthesia, stroke, surgery, venipuncture

    Due to an increased risk for bleeding, tenecteplase is contraindicated in patients with the following conditions: aneurysm or arteriovenous malformation; known coagulopathy or bleeding diathesis; active internal bleeding; brain tumor or intracranial mass; spinal anesthesia; intracranial surgery or intraspinal surgery within the last 2 months; history of head trauma, or history of cerebrovascular accident (stroke). In the following populations or conditions, the risks of bleeding with tenecteplase therapy are increased and should be weighed against the potential benefits: recent GI bleeding (e.g., peptic ulcer disease) or genitourinary bleeding, major surgery (e.g., CABG), organ biopsy, trauma (including cardiopulmonary resuscitation), venipuncture of a noncompressible vessel, acute pericarditis, diabetic retinopathy (or other hemorrhagic ophthalmic conditions), cerebrovascular disease, infectious endocarditis, and hemostatic defects due to severe hepatic disease or renal disease associated with renal failure. Use tenecteplase with extreme caution in other conditions that can be exacerbated as a result of bleeding or in which bleeding could be hazardous or difficult to control due to its location.

    Geriatric

    In general, the use of thrombolysis in geriatric patients is controversial due to the uncertain benefits of therapy, relative to the increased risk of bleeding events. Tenecteplase should be used with extreme caution in the very elderly population (older than 75 years of age) due to the substantial increase in bleeding risk and potential increase in 30-day mortality with advancing age which was documented in the ASSENT 2 study. The 30-day mortality rates, as well as the incidence of intracranial hemorrhage, total stroke, and major bleeding, increased with advancing age in the ASSENT 2 study.[26284]

    Intramuscular injections

    Intramuscular injections and any nonessential handling of the patient should be avoided for the first few hours following treatment with tenecteplase. Intramuscular injections may cause bleeding, bruising, or hematomas due to anticoagulant effects secondary to tenecteplase therapy. Venipunctures should be performed only when required; monitor venipuncture sites carefully.

    Infection, thrombophlebitis

    Systemic infection can occur if thrombolytics (such as tenecteplase) are administered into an occluded IV or AV cannula that is proximal to an infection site or in the presence of septic thrombophlebitis.

    Anticoagulant therapy

    Thrombolytics should be used with caution in patients who have recently received glycoprotein IIb/IIIa inhibitors or anticoagulant therapy (e.g., warfarin) due to the potential for enhanced risk of bleeding. Although sustained antibody formation in patients who received tenecteplase has not been clearly documented, readministration of tenecteplase should be undertaken with caution. If an anaphylactic reaction occurs, appropriate therapy should be administered.

    Atrial fibrillation, mitral stenosis

    Tenecteplase may increase the risk of thromboembolic events in conditions where there is a high likelihood of left heart thrombus, such as patients with mitral stenosis or atrial fibrillation.

    Labor, obstetric delivery, pregnancy

    There are no adequate and well-controlled studies of tenecteplase use in pregnant women. Use tenecteplase during pregnancy only if the potential benefits justify the potential fetal risks. Tenecteplase did not elicit maternal and embryo toxicity in rabbits following a single IV administration of 5 mg/kg (approximately 7 times the human exposure at the dose for acute myocardial infarction), but maternal and embryo toxicity occurred in rabbits given multiple IV administrations. In pregnancy, labor, and obstetric delivery, the risks of bleeding with tenecteplase therapy are increased and should be weighed against the potential benefits.

    Breast-feeding

    It is not known if tenecteplase is excreted into human breast milk. Because many drugs are excreted in human milk, use caution when administering tenecteplase to a breast-feeding woman.

    ADVERSE REACTIONS

    Severe

    GI bleeding / Delayed / 1.0-1.9
    stroke / Early / 1.8-1.8
    retroperitoneal bleeding / Delayed / 0-1.0
    angioedema / Rapid / 0-1.0
    laryngeal edema / Rapid / 0-1.0
    intracranial bleeding / Delayed / 0.9-0.9
    anaphylactoid reactions / Rapid / 0-0.1
    renal failure (unspecified) / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    cholesterol microembolization / Early / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    bradycardia / Rapid / Incidence not known

    Moderate

    bleeding / Early / 0-21.8
    hematoma / Early / 1.7-12.3
    hematuria / Delayed / Incidence not known
    hemoptysis / Delayed / Incidence not known
    antibody formation / Delayed / Incidence not known
    livedo reticularis / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known

    Mild

    epistaxis / Delayed / 1.5-1.5
    rash / Early / 0-1.0
    urticaria / Rapid / 0-1.0
    ecchymosis / Delayed / Incidence not known
    purpura / Delayed / Incidence not known
    nausea / Early / Incidence not known
    fever / Early / Incidence not known
    vomiting / Early / Incidence not known

    DRUG INTERACTIONS

    Abciximab: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Alpha interferons: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Altretamine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Aminocaproic Acid: (Severe) The actions of aminocaproic acid can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Anagrelide: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Antimetabolites: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Antithrombin III: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Antithymocyte Globulin: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antithymocyte globulin.
    Apixaban: (Severe) Due to the increased bleeding risk, avoid concurrent use of apixaban with thrombolytic agents.
    Aprotinin: (Severe) Aprotinin interferes with fibrinolysis by inhibiting the actions of kallikrein and plasmin, and it could inhibit fibrinolysis by thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Argatroban: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
    Arsenic Trioxide: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Aspirin, ASA: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Carisoprodol: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Dipyridamole: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Omeprazole: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Oxycodone: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Aspirin, ASA; Pravastatin: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Betrixaban: (Major) Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and thrombolytic agents are used concomitantly. Coadministration of betrixaban and thrombolytic agents may increase the risk of bleeding.
    Bexarotene: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Bismuth Subsalicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Bivalirudin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
    Chlorambucil: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Cilostazol: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Clofarabine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Clopidogrel: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Dabigatran: (Major) Based on the pharmacology of dabigatran, other oral anticoagulants and thrombolytic agents could cause additive risk of bleeding when given concurrently with dabigatran.
    Dalteparin: (Moderate) An additive risk of bleeding may be seen in patients receiving dalteparin in combination with other agents known to increase the risk of bleeding such thrombolytic agents. Monitor clinical and laboratory response closely during concurrent use.
    Danaparoid: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
    Defibrotide: (Severe) Coadministration of defibrotide with fibrinolytics (thrombolytic agents) is contraindicated. The pharmacodynamic activity and risk of hemorrhage with fibrinolytics are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic fibrinolytic therapy (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the fibrinolytic have abated.
    Denileukin Diftitox: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Desirudin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
    Desvenlafaxine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
    Dipyridamole: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Drotrecogin Alfa: (Major) Patients receiving thrombolytic agents are at increased risk of bleeding during drotrecogin alfa therapy.
    Duloxetine: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SNRI with medications which impair platelet function and to promptly report any bleeding events to the practitioner.
    Edoxaban: (Major) Coadministration of edoxaban and thrombolytic agents should be avoided due to an increased risk of bleeding during concurrent use. Occasionally, short-term coadministration may be necessary in patients transitioning to and from edoxaban. Long-term coadminstration is not recommended. Promptly evaluate any signs or symptoms of blood loss in patients on concomitant therapy.
    Enoxaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving enoxaparin in combination with other agents known to increase the risk of bleeding such as thrombolytic agents (e.g. alteplase, reteplase, streptokinase). Monitor clinical and laboratory response closely during concurrent use.
    Eptifibatide: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Estramustine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
    Folate analogs: (Moderate) Due to the thrombocytopenic effects of folate analogs, when used as antineoplastic agents, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytics.
    Fondaparinux: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Garlic, Allium sativum: (Moderate) Since garlic produces clinically-significant antiplatelet effects, it should be used cautiously in patients receiving thrombolytic agents. Avoid concurrent use of herbs which interact with thrombolytic agents when possible. If Garlic supplements are taken, monitor appropriate parameters to attain proper clinical endpoints.
    Ginger, Zingiber officinale: (Moderate) Since ginger inhibits thromboxane synthetase, a platelet aggregation inducer, and is a prostacyclin agonist, use with caution during times when bleeding is a concern. This includes patients receiving thrombolytic agents, however, no clinical data are available.
    Ginkgo, Ginkgo biloba: (Major) Ginkgo biloba should be used cautiously in patients taking thrombolytic agents. Ginkgo can produce clinically-significant antiplatelet effects; a compound found in Ginkgo biloba, ginkgolide-B, may act as a selective antagonist of platelet activating factor (PAF). Although a review of Ginkgo biloba in 1992 stated that no known drug interactions exist, spontaneous hyphema has been reported in an elderly male who began taking ginkgo while stabilized on daily aspirin. After ginkgo was stopped, no further bleeding was noted despite continuing the aspirin therapy. Other clinical data exist that describe spontaneous subdural hematomas associated with chronic Ginkgo biloba ingestion.
    Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if coadministered with thrombolytic agents. Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea and thrombolytics are coadministered.
    Heparin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with coagulation such as thrombolytic agents; the risk of bleeding may be increased. If coadministration with thrombolytic agents is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
    Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
    Intravenous Lipid Emulsions: (Moderate) Fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
    Lepirudin: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
    Levomilnacipran: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SNRI.
    Lomustine, CCNU: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Magnesium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Methoxsalen: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs including increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking thrombolytic agents until data confirming the safety of this drug combination are available.
    Milnacipran: (Moderate) Platelet aggregation may be impaired by serotonin norepinephrine reuptake inhibitors (SNRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SNRI.
    Nonsteroidal antiinflammatory drugs: (Moderate) NSAIDs can cause GI bleeding, inhibit platelet aggregation, prolong bleeding time; these pharmacodynamic effects may be increased when administered to patients receiving thrombolytic agents. Patients receiving these drugs concurrently should be monitored closely for bleeding.
    Pegaspargase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Pentosan: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Photosensitizing agents (topical): (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Photosensitizing agents: (Moderate) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
    Platelet Inhibitors: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Prasugrel: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Rivaroxaban: (Major) Due to the increased bleeding risk, avoid concurrent use of rivaroxaban with thrombolytic agents; the safety of concomitant use has not been studied.
    Salicylates: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Salsalate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
    Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with an SSRI.
    Sodium Hyaluronate, Hyaluronic Acid: (Moderate) Increased bruising or bleeding at the injection site may occur when using hyaluronate sodium with thrombolytic agents, especially if used within the 3 weeks prior to the procedure.
    Sulfinpyrazone: (Moderate) Agents that may effect hemostasis including sulfinpyrazone, can increase the likelihood of hemorrhage if administered during or immediately before therapy with thrombolytic agents.
    Thrombin Inhibitors: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents with thrombin inhibitors.
    Ticagrelor: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Ticlopidine: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Tinzaparin: (Moderate) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
    Tirofiban: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Tranexamic Acid: (Severe) Antifibrinolytic agents, including tranexamic acid, can antagonize the actions of thrombolytic agents. Although antifibrinolytic agents can be beneficial in the treatment of thrombolytic-induced hemorrhage, the safety of concomitant administration of these agents has not been confirmed.
    Trazodone: (Moderate) Platelet aggregation may be impaired by trazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with trazodone.
    Tretinoin, ATRA: (Moderate) Patients with thrombocytopenia are at increased risk of bleeding complications. An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
    Venlafaxine: (Moderate) Platelet aggregation may be impaired by venlafaxine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered concurrently with venlafaxine.
    Vilazodone: (Moderate) Platelet aggregation may be impaired by vilazodone due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with vilazodone.
    Vorapaxar: (Major) Concomitant administration of platelet inhibitors and thrombolytic agents could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution.
    Vorinostat: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
    Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving thrombolytic agents. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be closely monitored for signs and symptoms of bleeding when a thrombolytic agent is administered with vortioxetine and instructed to promptly report any bleeding events to the practitioner.
    Warfarin: (Severe) Based on the pharmacology of warfarin, other thrombolytic agents could cause additive risk of bleeding when given concurrently with warfarin. Pre-treatment with oral anticoagulants is reported to be an independent risk factor for intracranial hemorrhage in thrombolytic-treated patients. Prothrombin times stabilized during administration of both agents will change slightly when heparin is discontinued.

    PREGNANCY AND LACTATION

    Pregnancy

    It is not known if tenecteplase is excreted into human breast milk. Because many drugs are excreted in human milk, use caution when administering tenecteplase to a breast-feeding woman.

    MECHANISM OF ACTION

    Tenecteplase is a fibrin-specific, recombinant TNK-tissue type plasminogen activator, which exerts its thrombolytic action on the endogenous fibrinolytic system to convert plasminogen to plasmin. Unlike streptokinase or urokinase, most of the activity of alteplase or tenecteplase is dependent on the presence of fibrin. Minimal amounts of plasminogen are converted to plasmin in the absence of fibrin. In experimental models, tenecteplase has a slower plasma clearance and greater fibrin specificity and is 80-fold more resistant to plasminogen activator inhibitor-1 than alteplase.[26283] This fibrin specificity decreases the potential for systemic activation of plasminogen and the resulting degradation of circulating fibrinogen. After administration of 30, 40, or 50 mg of tenecteplase, there are decreases in circulating fibrinogen (4% to 15%) and plasminogen (11% to 24%). In contrast, alteplase appears to be less fibrin-specific, reportedly decreasing circulating fibrinogen and plasminogen by 40% and 50%, respectively. The clinical significance of fibrin-specificity on safety (e.g., bleeding) or efficacy has not been established. Biological potency is determined by an in vitro clot lysis assay and is expressed in tenecteplase-specific units. The specific activity of tenecteplase has been defined as 200 units/mg.

    PHARMACOKINETICS

    Tenecteplase is administered intravenously. Human pharmacokinetic studies of tenecteplase are limited. Tenecteplase is primarily eliminated by hepatic metabolism. After IV bolus administration to acute myocardial infarction patients, tenecteplase exhibits a biphasic disposition from the plasma. The initial half-life is about 20 to 24 minutes, followed by a terminal half-life ranging from 90 to 130 minutes. The mean plasma clearance is 151 mL/minute. The tenecteplase plasma clearance was increased with higher tenecteplase dosage. Compared to alteplase, tenecteplase has a lower plasma clearance, longer elimination half-life, and may be more resistant to inactivation to plasminogen activator inhibitor-1 (PAI-1).[26283] [26286]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none