TNKase

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tenecteplase may cause you to bleed more easily, which can be severe or life-threatening. Tell your caregivers if you have any unusual bleeding, or bleeding that will not stop. You may also have bleeding on the inside of your body, such as in your stomach or intestines. Tell your caregivers if you have blood in your urine or stools, or if you cough up blood or vomit that looks like coffee grounds. These could be signs of bleeding in your digestive tract.

Tell your caregivers at once if you have:

• easy bruising or bleeding (nosebleeds, bleeding gums);
• bleeding from a recent injury or surgery incision;
• bleeding around the IV needle; or
• a light-headed feeling, like you might pass out.

Also tell your caregivers if you have rare but serious side effects such as:

• chest pain, slow or uneven heartbeats;
• pain, swelling, hot or cold feeling, skin changes, or discoloration anywhere on your body;
• sudden leg or foot pain, foot ulcer, purple toes or fingers;
• swelling or severe pain or signs of infection in your fingers or toes;
• numbness, weakness, or tingly feeling in your legs or feet;
• sudden numbness or weakness, problems with speech or balance, vision problems;
• little or no urinating;
• unexplained muscle pain, tenderness, or weakness especially if you also have fever, unusual tiredness, and dark colored urine;
• muscle weakness or loss of function, loss of bowel or bladder control; or
• severe pain in your upper stomach spreading to your back.

Common side effects may include:

• nausea, vomiting; or
• fever.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tenecteplase is in a group of drugs called tissue plasminogen activators (TPAs). It works by causing the body to over-produce a substance called plasmin to dissolve unwanted blood clots.

Tenecteplase is used to prevent death from a heart attack (acute myocardial infarction).

Tenecteplase may also be used for other purposes not listed in this medication guide.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tenecteplase increases your risk of bleeding, which can be severe or life-threatening. Call your doctor or seek emergency medical attention if you have bleeding that will not stop. Bleeding may occur from a surgical incision, or from the skin where a needle was inserted during a blood test or while receiving injectable medication. You may also have bleeding on the inside of your body, such as in your stomach or intestines, kidneys or bladder, brain, or within the muscles.

Call your doctor at once if you have signs of bleeding inside your body, such as:

• easy bruising or bleeding (nosebleeds, bleeding gums, bleeding from a wound, incision, catheter, or needle injection);

• bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• red or pink urine; or

• sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance.

Also call your doctor at once if you have:

• chest pain or heavy feeling, pain spreading to the jaw or shoulder, nausea, sweating, general ill feeling;

• swelling, rapid weight gain, little or no urinating;

• severe stomach pain, nausea, and vomiting

• darkening or purple discoloration of your fingers or toes;

• very slow heartbeats, shortness of breath, feeling light-headed;

• sudden severe back pain, muscle weakness, numbness or loss of feeling in your arms or legs,

• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety, confusion, severe chest pain, shortness of breath, irregular heartbeats; or

• pancreatitis--severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate.

Common side effects may include:

• nausea, vomiting; or

• fever.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Acute Myocardial Infarction

Management of acute MI in conjunction with anticoagulants (e.g., heparin) and/or platelet-aggregation inhibitors (e.g., aspirin); used to reduce post-MI mortality.1 5 7 10

30-day and 1-year mortality rates similar after tenecteplase 30–50 mg or an accelerated infusion of alteplase.1 5

Clinical benefit diminishes as the time period from symptom onset to initiation of therapy increases.10 Administer as soon as possible after onset of acute MI symptoms.1 AHA and ACC recommend administration within 30 minutes of hospital admission or first contact with the health-care system.10

AHA and ACC recommend use of any marketed thrombolytic agent (e.g., tenecteplase, alteplase, reteplase) in patients having ischemic symptoms characteristic of MI for ≤12 hours and ST-segment elevation or new or presumed new left bundle-branch block.10

ACC and AHA state that thrombolytic therapy is reasonable within 12–24 hours of symptom onset in patients with persistent ischemic symptoms accompanied by ST-segment elevation, provided no contraindications exist.10

Thrombolytic therapy may be reasonable in patients with true posterior MI presenting within 12 hours after onset of symptoms, provided no contraindications exist.10

Pulmonary Embolism

Has been used for the treatment of acute PE†.16 17 20 1005

The American College of Chest Physicians (ACCP) generally recommends against the use of systemic thrombolytic therapy in most patients with acute PE; however, in patients with acute PE associated with hypotension (e.g., systolic BP <90 mm Hg), thrombolytic therapy may provide some benefit in terms of mortality reduction and is suggested as a possible treatment in patients without a high risk of bleeding.1005

In the U.S.

• Tnkase

Available Dosage Forms:

• Kit
• Powder for Solution

Therapeutic Class: Thrombolytic

Pharmacologic Class: Tissue Plasminogen Activator

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Children—Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of tenecteplase in children with use in other age groups.

Geriatric

The need for treatment with tenecteplase may be increased in elderly patients with blood clots. However, the chance of bleeding may also be increased. It is especially important that you discuss the use of this medicine with your doctor.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Defibrotide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Alteplase, Recombinant
• Anistreplase
• Apixaban
• Ardeparin
• Argatroban
• Bemiparin
• Bivalirudin
• Certoparin
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Desirudin
• Edoxaban
• Enoxaparin
• Fondaparinux
• Heparin
• Lepirudin
• Nadroparin
• Parnaparin
• Pentosan Polysulfate Sodium
• Phenindione
• Phenprocoumon
• Protein C
• Reteplase, Recombinant
• Reviparin
• Rivaroxaban
• Streptokinase
• Tenecteplase
• Tinzaparin
• Urokinase
• Warfarin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aspirin
• Dipyridamole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood disease, bleeding problems, or a history of bleeding in any part of the body or
• Brain disease or tumor or
• Heart or blood vessel disease, including irregular heartbeat or
• High blood pressure or
• Liver disease or
• Stroke—The chance of bleeding may be increased

• Infection—Chance of spreading the infection into the blood stream

Also, tell your doctor if you have recently had any of the following conditions:

• Falls or blow to the body or head or any other injury or
• Injections into a blood vessel or
• Placement of any tube into the body or
• Surgery of any kind, including dental surgery—The chance of serious bleeding may be increased

If you have recently had a baby, use of this medicine may cause serious bleeding.

Use TNKase as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

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.

General

Tenecteplase is a modified form of human tissue plasminogen activator (tPA) that binds to fibrin and converts plasminogen to plasmin. In the presence of fibrin, in vitro studies demonstrate that Tenecteplase conversion of plasminogen to plasmin is increased relative to its conversion in the absence of fibrin. This fibrin specificity decreases systemic activation of plasminogen and the resulting degradation of circulating fibrinogen as compared to a molecule lacking this property. Following administration of 30, 40, or 50 mg of TNKase, there are decreases in circulating fibrinogen (4%–15%) and plasminogen (11%–24%). The clinical significance of fibrin-specificity on safety (e.g., bleeding) or efficacy has not been established. Biological potency is determined by an in vitro clot lysis assay and is expressed in Tenecteplase-specific units. The specific activity of Tenecteplase has been defined as 200 units/mg.

Pharmacokinetics

In patients with acute myocardial infarction (AMI), TNKase administered as a single bolus exhibits a biphasic disposition from the plasma. Tenecteplase was cleared from the plasma with an initial half-life of 20 to 24 minutes. The terminal phase half-life of Tenecteplase was 90 to 130 minutes. In 99 of 104 patients treated with Tenecteplase, mean plasma clearance ranged from 99 to 119 mL/min.

The initial volume of distribution is weight related and approximates plasma volume. Liver metabolism is the major clearance mechanism for Tenecteplase.

General

Standard management of myocardial infarction should be implemented concomitantly with TNKase treatment. Arterial and venous punctures should be minimized. Noncompressible arterial puncture must be avoided and internal jugular and subclavian venous punctures should be avoided to minimize bleeding from the noncompressible sites. In the event of serious bleeding, heparin and antiplatelet agents should be discontinued immediately. Heparin effects can be reversed by protamine.

Readministration

Readministration of plasminogen activators, including TNKase, to patients who have received prior plasminogen activator therapy has not been systematically studied. Three of 487 patients tested for antibody formation to TNKase had a positive antibody titer at 30 days. The data reflect the percentage of patients whose test results were considered positive for antibodies to TNKase in a radioimmunoprecipitation assay, and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to TNKase with the incidence of antibodies to other products may be misleading. Although sustained antibody formation in patients receiving one dose of TNKase has not been documented, readministration should be undertaken with caution. If an anaphylactic reaction occurs, appropriate therapy should be administered.

Drug Interactions

Formal interaction studies of TNKase with other drugs have not been performed. Patients studied in clinical trials of TNKase were routinely treated with heparin and aspirin. Anticoagulants (such as heparin and vitamin K antagonists) and drugs that alter platelet function (such as acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors) may increase the risk of bleeding if administered prior to, during, or after TNKase therapy.

Drug/Laboratory Test Interactions

During TNKase therapy, results of coagulation tests and/or measures of fibrinolytic activity may be unreliable unless specific precautions are taken to prevent in vitro artifacts. Tenecteplase is an enzyme that, when present in blood in pharmacologic concentrations, remains active under in vitro conditions. This can lead to degradation of fibrinogen in blood samples removed for analysis.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals have not been performed to evaluate the carcinogenic potential, mutagenicity, or the effect on fertility.

Pregnancy (Category C)

TNKase has been shown to elicit maternal and embryo toxicity in rabbits given multiple IV administrations. In rabbits administered 0.5, 1.5, and 5.0 mg/kg/day, vaginal hemorrhage resulted in maternal deaths. Subsequent embryonic deaths were secondary to maternal hemorrhage and no fetal anomalies were observed. TNKase does not elicit maternal and embryo toxicity in rabbits following a single IV administration. Thus, in developmental toxicity studies conducted in rabbits, the no observable effect level (NOEL) of a single IV administration of TNKase on maternal or developmental toxicity was 5 mg/kg (approximately 8–10 times the human dose). There are no adequate and well‑controlled studies in pregnant women. TNKase should be given to pregnant women only if the potential benefits justify the potential risk to the fetus.

Nursing Mothers

It is not known if TNKase is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TNKase is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of TNKase in pediatric patients have not been established.

Geriatric Use

Of the patients in ASSENT-2 who received TNKase, 4,958 (59%) were under the age of 65; 2,256 (27%) were between the ages of 65 and 74; and 1,244 (15%) were 75 and over. The 30-day mortality rates by age were 2.5% in patients under the age of 65, 8.5% in patients between the ages of 65 and 74, and 16.2% in patients age 75 and over. The ICH rates were 0.4% in patients under the age of 65, 1.6% in patients between the ages of 65 and 74, and 1.7% in patients age 75 and over. The rates of any stroke were 1.0% in patients under the age of 65, 2.9% in patients between the ages of 65 and 74, and 3.0% in patients age 75 and over. Major bleeding rates, defined as bleeding requiring blood transfusion or leading to hemodynamic compromise, were 3.1% in patients under the age of 65, 6.4% in patients between the ages of 65 and 74, and 7.7% in patients age 75 and over. In elderly patients, the benefits of TNKase on mortality should be carefully weighed against the risk of increased adverse events, including bleeding.