Tenecteplase is a thrombolytic agent which may be administered as a single, rapid IV bolus for the treatment of acute myocardial infarction. Tenecteplase is a modified form of human tissue plasminogen activator that binds to fibrin and converts plasminogen to plasmin. Tenecteplase is produced by recombinant DNA technology from genetically modified Chinese hamster ovary cells. Compared to alteplase, tenecteplase has a prolonged half-life, increased specificity for fibrin, and increased resistance to plasminogen activator inhibitor-1 (PAI-1). In a comparative trial with accelerated alteplase dosing (ASSENT-2), tenecteplase is associated with similar rates for 30-day mortality, combined death and non-fatal stroke, intracranial bleeding, hemorrhagic stroke, total stroke, and minor bleeding; however, the incidence of major (non-cerebral) bleeding and need for blood transfusions are lower with tenecteplase. The greater fibrin-specificity of tenecteplase may account for the lower rate of non-cerebral bleeding compared with alteplase; however, the clinical significance of fibrin-specificity has not been determined. The major advantage of tenecteplase is its simple and rapid bolus administration, which may increase the potential for early treatment of acute myocardial infarction. Early (less than 70 minutes of symptoms), pre-hospital administration of thrombolytics has been associated with improved mortality and infarct size versus later administration (MITI trial). Tenecteplase has been used to treat myocardial infarction in combination with enoxaparin or unfractionated heparin.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution
-Aseptically withdraw 10 mL of Sterile Water for Injection from the supplied diluent vial using a sterile syringe. Only use with the Sterile Water for Injection supplied by the manufacturer for reconstitution.
-Reconstitute the tenecteplase vial by 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 preparation results in a colorless to pale yellow transparent solution yielding a final concentration of tenecteplase 5 mg/mL.
-Determine the appropriate dose of tenecteplase and withdraw the appropriate volume from the reconstituted vial with the syringe. Discard any unused solution.
-Storage: The tenecteplase vial contains no antibacterial preservatives; therefore, reconstitute immediately before use. If the reconstituted solution is not used immediately, refrigerate the vial at 2 to 8 degrees C (36 to 46 degrees F) and use within 8 hours.
Intravenous injection
-Using sterile technique, connect the tenecteplase syringe directly to the IV port.
-Flush dextrose-containing lines with 0.9% Sodium Chloride Injection before and after single bolus administration of tenecteplase. Precipitation may occur when tenecteplase is administered in an IV line containing dextrose.
-Administer by IV bolus over 5 seconds.
Tenecteplase can cause bleeding, including intracranial bleeding and fatal bleeding. In a comparative trial of accelerated alteplase dosing vs. rapid push tenecteplase, the 30-day mortality rate was equivalent for both groups (6.1%). In addition, the incidence of intracranial bleeding was similar in persons treated with tenecteplase (0.93%) compared to persons who received front-loaded alteplase (0.94%); the total incidence of stroke was also similar (1.78% for tenecteplase vs. 1.66% for alteplase). The incidence of non-intracranial major bleeding (26.43% for tenecteplase vs. 28.95% for alteplase) and the need for blood transfusions (4.25% vs. 5.49%) were lower in persons treated with tenecteplase as compared to alteplase.
In tenecteplase clinical trials, 0.64% (4 of 625 persons) tested for antibody formation to tenecteplase had a positive antibody titer at 30 days. The observed incidence of antibody positivity in an assay may be caused by several factors including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to tenecteplase with the incidence of antibodies to other products may be misleading.
Cholesterol microembolization has been reported in persons treated with thrombolytic agents. Investigate the cause of any new embolic event and treat appropriately.
Hypersensitivity, including urticarial and anaphylactoid reactions, have been reported after administration of tenecteplase (e.g., anaphylaxis, angioedema, laryngeal edema, rash, and urticaria). Monitor persons treated with tenecteplase during and for several hours after infusion. If symptoms of hypersensitivity occur, initiate appropriate therapy (e.g., antihistamines, corticosteroids).
Rapid coronary lysis can result in cardiac arrhythmia exacerbation, but these are generally transient. Arrhythmias that have been observed include sinus bradycardia, accelerated idioventricular rhythm, premature ventricular contractions (PVCs), and ventricular tachycardia. Arrhythmias may be managed with standard anti-arrhythmic measures. In general, these adverse reactions are secondary to clot lysis and subsequent reperfusion of ischemic areas and not directly attributable to thrombolytic therapy. Other serious reactions reported specifically with tenecteplase which may be sequelae of myocardial infarction include: cardiogenic shock, atrioventricular block, pulmonary edema, heart failure, cardiac arrest, recurrent myocardial ischemia, myocardial reinfarction, myocardial rupture, cardiac tamponade, pericarditis, pericardial effusion, mitral regurgitation, thrombosis, embolism, and electromechanical dissociation. The true incidence and causality of these events relative to tenecteplase are unknown.
In a clinical trial in persons with ST-elevation myocardial infarction (STEMI) in whom primary percutaneous coronary intervention (PCI) was planned, there were trends towards worse outcomes in the individual components of the primary endpoint between tenecteplase plus PCI compared to PCI alone. Mortality occurred in 6.7% of persons receiving tenecteplase plus PCI vs. 4.9% of persons receiving PCI alone; cardiogenic shock occurred in 6.3% of persons receiving tenecteplase plus PCI vs. 4.8% of persons receiving PCI alone, and heart failure occurred in 12% of persons receiving tenecteplase plus PCI vs. 9.2% of persons receiving PCI alone. In addition, there were trends towards worse outcomes in recurrent myocardial infarction (6.1% vs. 3.7%, respectively; p = 0.03) and repeat target vessel revascularization (6.6% vs. 3.4%, respectively; p = 0.0045) in persons receiving tenecteplase plus PCI vs. PCI alone.
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.
Tenecteplase is contraindicated in persons with aneurysm or arteriovenous malformation; known coagulopathy or bleeding diathesis; active internal bleeding; brain tumor; intracranial or intraspinal surgery or trauma (e.g., head trauma) within 2 months; or history of cerebrovascular accident (stroke).
In the ASSENT-2 study, rates of 30-day mortality, stroke, intracranial hemorrhage and major bleeds requiring blood transfusion or leading to hemodynamic complications were higher in geriatric persons (65 years and older) than in those younger than 65 years.
Avoid intramuscular injections and nonessential handling of the patient for the first few hours after treatment with tenecteplase. Perform arterial and venous punctures carefully and only as required. To minimize bleeding from noncompressible sites, avoid internal jugular and subclavian venous punctures. If an arterial puncture is necessary during tenecteplase infusion, use an upper extremity vessel that is accessible to manual compression. Apply pressure for at least 30 minutes.
Concomitant use of other drugs that impair hemostasis, such as anticoagulant therapy, with tenecteplase increases the risk of bleeding. If serious bleeding that is not controlled by local pressure occurs, discontinue any concomitant heparin or antiplatelet agents immediately and treat appropriately.
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.
In persons with large acute myocardial infarction, STEMI, providers should choose either thrombolysis or percutaneous coronary intervention (PCI) as the primary treatment strategy for reperfusion. Rescue PCI or subsequent elective PCI may be performed after administration of thrombolytic therapies if medically appropriate; however, the optimal use of adjunctive antithrombotic and antiplatelet therapies in this setting is unknown. In a clinical trial in persons with STEMI in whom primary PCI was planned, there were trends toward worse outcomes in the individual components (i.e., mortality, cardiogenic shock, heart failure) of the primary endpoint between tenecteplase plus PCI compared to PCI alone.
Tenecteplase is associated with laboratory test interference. 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 blood under in vitro conditions, which can lead to degradation of fibrinogen in blood samples removed for analysis.
There are no data on the use of tenecteplase during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Published data consisting of a few case reports with the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects. Myocardial infarction is a medical emergency that can be fatal if left untreated. Life-sustaining therapy during pregnancy should not be withheld because of the potential concerns regarding the effects of tenecteplase on the fetus. Tenecteplase did not elicit maternal and embryo toxicity in rabbits after a single IV administration of tenecteplase 5 mg/kg (approximately 7 times the human exposure based on AUC at the dose for ST-elevation myocardial infarction).
There are no data on the presence of tenecteplase in either human or animal milk, the effects on the breast-fed infant, or the effect on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tenecteplase and any potential adverse effects on the breast-fed infant from tenecteplase or the underlying maternal condition.
For the treatment of acute myocardial infarction, STEMI for reduction of cardiovascular mortality:
Intravenous dosage:
Adults weighing 90 kg or more: 50 mg IV as a single dose as soon as possible after the onset of symptoms.
Adults weighing 80 to 89 kg: 45 mg IV as a single dose as soon as possible after the onset of symptoms.
Adults weighing 70 to 79 kg: 40 mg IV as a single dose as soon as possible after the onset of symptoms.
Adults weighing 60 to 69 kg: 35 mg IV as a single dose as soon as possible after the onset of symptoms.
Adults weighing less than 60 kg: 30 mg IV as a single dose as soon as possible after the onset of symptoms.
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 as a single dose within 4.5 hours of stroke symptom onset.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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; Aspirin: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Acetaminophen; Ibuprofen: (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.
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.
Aminocaproic Acid: (Contraindicated) 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.
Aminolevulinic Acid: (Minor) Agents that decrease clotting, such as thrombolytic agents, could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Amlodipine; Celecoxib: (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.
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.
Antithrombin III: (Major) An additive risk of bleeding may be seen in patients receiving thrombolytic agents and anticoagulants.
Apixaban: (Contraindicated) Due to the increased bleeding risk, avoid concurrent use of apixaban with thrombolytic agents.
Aprotinin: (Contraindicated) 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; Caffeine: (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; 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.
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.
Bupivacaine; Meloxicam: (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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Celecoxib: (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.
Celecoxib; Tramadol: (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.
Chlorambucil: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (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.
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.
Citalopram: (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.
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.
Danazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Defibrotide: (Contraindicated) 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.
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.
Diclofenac: (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.
Diclofenac; Misoprostol: (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.
Diflunisal: (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.
Diphenhydramine; Ibuprofen: (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.
Diphenhydramine; Naproxen: (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.
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.
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: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
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.
Escitalopram: (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.
Estramustine: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Etodolac: (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.
Fenoprofen: (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.
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.
Fluoxetine: (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.
Flurbiprofen: (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.
Fluvoxamine: (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.
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: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and thrombolytic agents as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
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.
Hydrocodone; Ibuprofen: (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.
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.
Ibuprofen: (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.
Ibuprofen; Famotidine: (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.
Ibuprofen; Oxycodone: (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.
Ibuprofen; Pseudoephedrine: (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.
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.
Indomethacin: (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.
Interferon Alfa-2b: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Interferon Alfa-n3: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
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.
Ketoprofen: (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.
Ketorolac: (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.
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.
Meclofenamate Sodium: (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.
Mefenamic Acid: (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.
Meloxicam: (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.
Methenamine; Sodium Salicylate: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of bleeding.
Methotrexate: (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.
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.
Nabumetone: (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.
Naproxen: (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.
Naproxen; Esomeprazole: (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.
Naproxen; Pseudoephedrine: (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.
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.
Olanzapine; Fluoxetine: (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.
Oxaprozin: (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.
Paroxetine: (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.
Peginterferon Alfa-2a: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Peginterferon Alfa-2b: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Pemetrexed: (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.
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.
Piroxicam: (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.
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.
Pralatrexate: (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.
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.
Ropeginterferon alfa-2b: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
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.
Sertraline: (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.
Sulindac: (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.
Sumatriptan; Naproxen: (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.
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.
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.
Tolmetin: (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.
Tranexamic Acid: (Contraindicated) 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.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with thrombolytic agents is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease clotting like thrombolytic agents could decrease the efficacy of verteporfin therapy.
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: (Contraindicated) 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.
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. 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.
Tenecteplase is administered intravenously. After IV bolus administration in persons with ST-elevation myocardial infarction, tenecteplase exhibits a biphasic disposition from the plasma. Vd at central compartment is 4.2 to 5.4 L (approximating plasma volume). Steady-state Vd is approximately 50% higher (6.12 to 8.01 L), suggesting some extravascular distribution. Tenecteplase is primarily eliminated by hepatic metabolism. It displays linear pharmacokinetics with mean maximum concentrations increased in a dose-proportional manner, and mean plasma clearance is similar for 30, 40, and 50 mg doses ranging from 99 to 119 mL/minute. The terminal half-life of tenecteplase is 90 to 130 minutes. After administration of 30, 40, or 50 mg doses of tenecteplase, circulating fibrinogen is decreased 4% to 15% and plasminogen is decreased 11% to 24%.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Special Populations
Geriatric
Persons of older age have a slower plasma clearance of tenecteplase.
Gender Differences
Women have a slower plasma clearance of tenecteplase.
Other
Body Weight
A stepwise linear regression analysis indicated that total body weight accounted for 19% of the variability in plasma clearance and 11% of the variability in volume of distribution.