Tenecteplase

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Many drugs can increase the risk of bleeding if you taken them before, during, or after treatment with tenecteplase. Not all possible drug interactions are listed in this medication guide. It is very important to ask your doctor before you start or stop using any other medicine, especially:

• aspirin or heparin;
• a blood thinner (warfarin, Coumadin, Jantoven);
• dipyridamole; or
• other medicines to treat or prevent blood clot--abciximab, dabigatran, dalteparin, desirudin, enoxaparin, eptifibatide, fondaparinux, omacetaxine, tinzaparin, or tirofiban.

This list is not complete and many other drugs can interact with tenecteplase. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

You should not receive this medication if you have internal bleeding, brain cancer or aneurysm, a history of stroke, a bleeding or blood clotting disorder, or if you have had brain or spinal cord injury or surgery within the past 2 months.

Before you are treated with tenecteplase, tell your doctor if you have a blood vessel disorder of the eye, severe liver or kidney disease, high blood pressure, an infection of the lining of your heart (also called bacterial endocarditis), a recent history of stomach or urinary bleeding, if you have recently had a baby, or if you have recently had a serious injury or major surgery.

Also tell your doctor if you take a blood thinner such as warfarin (Coumadin), or other medications to treat or prevent blood clots.

Tell your caregivers at once if you have a serious side effect such as blood in your urine or stools, nosebleed, coughing up blood, bleeding from a skin wound or the IV needle, fast or slow heart rate, or feeling like you might pass out.

Tenecteplase may cause rare but serious side effects such as: purple discoloration of your legs or toes, sudden numbness or weakness, problems with vision or speech, chest pain or heavy feeling, urinating less than usual or not at all, muscle pain or tenderness, dark colored urine, unusual sensations in your back, numbness or tingling in your legs or feet, muscle weakness or loss of use, or loss of bowel or bladder control.

Tenecteplase can cause you to have unusual results with blood tests. Tell any doctor who treats you that you have recently received tenecteplase.

Bleeding

The most frequent adverse reaction associated with TNKase is bleeding (see WARNINGS).

Should serious bleeding occur, concomitant heparin and antiplatelet therapy should be discontinued. Death or permanent disability can occur in patients who experience stroke or serious bleeding episodes.

For TNKase (tenecteplase) -treated patients in ASSENT-2, the incidence of intracranial hemorrhage was 0.9% and any stroke was 1.8%. The incidence of all strokes, including intracranial bleeding, increases with increasing age (see PRECAUTIONS: Geriatric Use).

In the ASSENT-2 study, the following bleeding events were reported (see Table 3).

Table 3: ASSENT-2
Non-ICH Bleeding Events

Non-intracranial major bleeding and the need for blood transfusions were lower in patients treated with TNKase (tenecteplase) .

Types of major bleeding reported in 1% or more of the patients were hematoma (1.7%) and gastrointestinal tract (1%). Types of major bleeding reported in less than 1% of the patients were urinary tract, puncture site (including cardiac catheterization site), retroperitoneal, respiratory tract,and unspecified. Types of minor bleeding reported in 1% or more of the patients were hematoma (12.3%), urinary tract (3.7%), puncture site (including cardiac catheterization site) (3.6%), pharyngeal (3.1%), gastrointestinal tract (1.9%), epistaxis (1.5%),and unspecified (1.3%).

Allergic Reactions

Allergic-type reactions (e.g., anaphylaxis, angioedema, laryngeal edema,rash, and urticaria) have rarely ( < 1%) been reported in patients treated with TNKase (tenecteplase) .Anaphylaxis was reported in < 0.1% of patients treated with TNKase (tenecteplase) ; however, causality was not established. When such reactions occur, they usually respond to conventional therapy.

Other Adverse Reactions

The following adverse reactions have been reported among patients receiving TNKase (tenecteplase) in clinical trials. These reactions are frequent sequelae of the underlying disease, and the effect of TNKase (tenecteplase) on the incidence of these events is unknown.

These events include cardiogenic shock, arrhythmias, 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. These events can be life-threatening and may lead to death. Nausea and/or vomiting, hypotension,and fever have also been reported.

Read the entire FDA prescribing information for Tnkase (Tenecteplase)

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if tenecteplase crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using tenecteplase. 

If possible before you receive tenecteplase, tell your doctor if you have a brain tumor or aneurysm, high blood pressure, hemophilia or other bleeding disorder, a history of stroke, or if you have recently had a head injury or surgery on your brain or spinal cord.

In an emergency situation it may not be possible to tell your caregivers about your health conditions. Make sure any doctor caring for you afterward knows you have received this medicine.

You should not be treated with tenecteplase if you are allergic to it, or if you have:

• active bleeding inside your body;

• a recent history of medical trauma or injury;

• severe or uncontrolled high blood pressure;

• a genetic disorder affecting the blood vessels in your brain;

• a brain tumor, blood vessel disorder, or aneurysm (dilated blood vessel);

• a bleeding or blood clotting disorder (such as hemophilia);

• a history of stroke; or

• if you have had brain or spinal cord injury or surgery within the past 2 months.

If possible before you receive tenecteplase, tell your doctor if you have:

• a past history of strokes;

• a recent history of bleeding in your brain, stomach, intestines, or urinary tract;

• high blood pressure;

• heart problems;

• an infection of the lining of your heart (also called bacterial endocarditis);

• liver or kidney disease;

• eye problems caused by diabetes;

• severe bruising or infection around a vein where an IV was placed;

• if you are pregnant or have recently had a baby;

• if you have recently had an organ biopsy; or

• if you have recently had a serious injury or major surgery.

In an emergency situation it may not be possible to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medicine.

Thrombolytic agent; biosynthetic (recombinant DNA origin) form of human tissue-type plasminogen activator (t-PA).1 2 3 4 5 6 7

General

• Initiate therapy as soon as possible after acute MI.1 10 (See Acute Myocardial Infarction under Uses.)

Administration

IV Administration

For solution compatibility information, see Solution Compatibility under Stability.

Administer IV.1

Consult the manufacturer's labeling for instructions for using the B-D 10-mL Syringe with TwinPak Dual Cannula Device for reconstitution and administration.1

Reconstitute with 10 mL of sterile water for injection without preservatives to provide a solution containing 5 mg/mL.1

If foaming (usually slight) occurs, leave vial undisturbed for several minutes to allow dissipation of any large bubbles.1 Gently swirl until contents are completely dissolved; avoid shaking.1

Administer over 5 seconds.1

Dosage

Expressed in mg.1

Biologic potency is determined using an in vitro clot lysis assay and is expressed in tenecteplase-specific units.1 Each mg is equivalent to 200 tenecteplase-specific units.1

Dose based on patient weight.1

Adults

Prescribing Limits

Adults

Total dose should not exceed 50 mg.1

• Binds to fibrin and converts plasminogen to plasmin.1

• A relatively fibrin-selective plasminogen activator.1 Exhibits higher fibrin selectivity and greater resistance to plasminogen-activator inhibitors (e.g., PAI-1) than alteplase.2 3 4 5 6 7

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Signs of a pancreas problem (pancreatitis) like very bad stomach pain, very bad back pain, or very bad upset stomach or throwing up.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Chest pain or pressure.
• Very bad headache.
• Very bad belly pain.
• Change in color of skin.
• Change in eyesight.
• Muscle pain.
• Dark urine.
• A heartbeat that does not feel normal.
• Slow heartbeat.

Promotes initiation of fibrinolysis by binding to fibrin and converting plasminogen to plasmin. Tenecteplase is essentially alteplase with the exception of 3 point mutations and is more fibrin specific, more resistant to plasminogen activator inhibitor -1 (PAI-1), with a longer duration of action compared to alteplase. Produced by recombinant DNA technology using a mammalian cell line (Chinese hamster ovary cells).

Distribution

Vd is weight related and approximates plasma volume

Metabolism

Primarily hepatic

Excretion

Clearance: Plasma: 99-119 mL/minute

Half-Life Elimination

Biphasic: Initial: 20-24 minutes; Terminal: 90-130 minutes

Management of ST-elevation myocardial infarction (STEMI) for the lysis of thrombi in the coronary vasculature to restore perfusion and reduce mortality.

Recommended criteria for treatment of STEMI (ACCF/AHA; O’Gara, 2013): Ischemic symptoms within 12 hours of treatment or evidence of ongoing ischemia 12-24 hours after symptom onset with a large area of myocardium at risk or hemodynamic instability.

STEMI ECG definition: New ST-segment elevation at the J point in at least 2 contiguous leads of ≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous precordial leads or limb leads on ECG. New or presumably new left bundle branch block (LBBB) may interfere with ST-elevation analysis and should not be considered diagnostic in isolation.

At non-PCI-capable hospitals, the ACCF/AHA recommends thrombolytic therapy administration when the anticipated first medical contact (FMC)-to-device time at a PCI-capable hospital is >120 minutes due to unavoidable delays.

Mild to moderate impairment: No dosage adjustment provided in manufacturer’s labeling.

Severe impairment: No dosage adjustment provided in manufacturer’s labeling; weigh the risk of bleeding against the benefits with tenecteplase especially in those with a coagulopathy.

Store under refrigeration of 2°C to 8°C (36°F to 46°F) or at room temperature; do not exceed 30°C (86°F). If reconstituted and not used immediately, store in refrigerator and use within 8 hours.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Anticoagulants: Thrombolytic Agents may enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Aprotinin: May diminish the therapeutic effect of Thrombolytic Agents. Consider therapy modification

Dabigatran Etexilate: Thrombolytic Agents may enhance the anticoagulant effect of Dabigatran Etexilate. Management: Carefully monitor for bleeding. Dabigatran Canadian labeling recommends avoiding use with thrombolytic agents. Consider avoiding alteplase treatment of acute ischemic stroke in patients receiving dabigatran (see full drug monograph for details). Monitor therapy

Desirudin: Thrombolytic Agents may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with thrombolytic agents prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Thrombolytic Agents. Bleeding may occur. Consider therapy modification

Limaprost: May enhance the adverse/toxic effect of Thrombolytic Agents. The risk for bleeding may be increased. Monitor therapy

Prostacyclin Analogues: Thrombolytic Agents may enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Monitor therapy

Salicylates: May enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Monitor therapy

>10%:

Hematologic & oncologic: Hemorrhage (ASSENT-2 trial: minor: 22%; major: 5%), hematoma (local: minor: 12%; major: 2%)

1% to 10%:

Cardiovascular: Cerebrovascular accident (2%)

Gastrointestinal: Gastrointestinal hemorrhage (minor: 2%; major: 1%)

Genitourinary: Genitourinary tract hemorrhage (minor: 4%; major: <1%)

Hematologic & oncologic: Local hemorrhage (catheter puncture site: minor: 4%; major: <1%)

Respiratory: Pharyngeal bleeding (minor: 3%), epistaxis (minor: 2%)

Frequency not defined:

Cardiovascular: Atrioventricular block, cardiac arrhythmia, cardiac failure, cardiac tamponade, cardiogenic shock, embolism, hypotension, ischemic heart disease (recurrent), mitral valve insufficiency (regurgitation), myocardial reinfarction, myocardial rupture, pericardial effusion, pericarditis, pulmonary edema, thrombosis

Gastrointestinal: Nausea, vomiting

Miscellaneous: Fever

<1% (Limited to important or life-threatening): Anaphylaxis, angioedema, intracranial hemorrhage, laryngeal edema, respiratory tract hemorrhage, retroperitoneal hemorrhage, skin rash, thrombolytic drug-induced cholesterol embolism (clinical features may include acute renal failure, bowel infarction, cerebral infarction, gangrenous digits, hypertension, livedo reticularis, myocardial infarction, pancreatitis, “purple toe” syndrome, retinal artery occlusion, rhabdomyolysis, spinal cord infarction), urticaria

Data not available