TNKase

Vascular Occlusion Management Fibrinolytics

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

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.
Reconstitute 1 vial of tenecteplase 50 mg with 10mL of Sterile Water for Injection. Remove the protective flip-cap from 1 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.
Determine the appropriate dose of tenecteplase and withdraw the appropriate volume from the reconstituted vial with the supplied syringe. Discard any unused solution.
Stand the shield vertically on a flat service (with green side down) and passively recap the red hub cannula. Remove the entire shield assembly, including the red hub cannula, by twisting counterclockwise. The shield assembly also contains the clear-ended blunt plastic cannula; retain for split septum IV access.
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:
Although the administration syringe supplied by the manufacturer is compatible with a conventional needle, the syringe is designed to be used with needleless IV access systems. Follow the instructions applicable to the IV system in use.
Spilt septum system: Remove the green cap and attach the clear-ended blunt plastic cannula to the syringe. Remove the shield and use the blunt plastic cannula to access the split septum injection port. The blunt plastic cannula has 2 side ports and air or fluid expelled through the cannula will exit in 2 sideways directions; direct away from face or mucous membranes.
Luer-Lok system: Connect syringe directly to IV port.
Conventional needle (not supplied in the kit): Attach a large bore needle (e.g., 18 gauge) to the syringe's universal Luer-Lok.
Flush dextrose-containing lines with a saline-containing solution 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.

heart failure / Delayed / 12.0-12.0
cardiogenic shock / Early / 6.3-6.3
myocardial infarction / Delayed / 6.1-6.1
stroke / Early / 1.8-1.8
intracranial bleeding / Delayed / 0.9-0.9
cholesterol microembolization / Early / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
arrhythmia exacerbation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
bradycardia / Rapid / Incidence not known

antibody formation / Delayed / 0.6-0.6
bleeding / Early / Incidence not known
premature ventricular contractions (PVCs) / Early / Incidence not known

rash / Early / Incidence not known
urticaria / Rapid / Incidence not known

TNKase

Rx

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

50 mg IV as a single dose as soon as possible after the onset of symptoms.

45 mg IV as a single dose as soon as possible after the onset of symptoms.

40 mg IV as a single dose as soon as possible after the onset of symptoms.

35 mg IV as a single dose as soon as possible after the onset of symptoms.

30 mg IV as a single dose as soon as possible after the onset of symptoms.

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.

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.

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.

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

†Indicates off-label use

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.

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.

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.
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: (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.
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.
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: (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.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent administration of thrombolytic agents and salicylates may further increase the serious risk of 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.
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.
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.
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.
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.
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: (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.
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.
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.
Methenamine; Sodium 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.
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.
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.
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.
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: (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/TNKase Intravenous Inj Pwd F/Sol: 50mg

50 mg/total dose IV.

50 mg/total dose IV.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

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.

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

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.