Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1626
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rdfs:label |
TNKase (Injection, Powder, Lyophilized, For Solution)
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dailymed-instance:dosage |
Dosage: TNKase (Tenecteplase) is for
intravenous administration only. The recommended total dose
should not exceed 50 mg and is based upon patient weight. A single bolus dose should be administered over 5 seconds
based on patient weight. Treatment should be initiated as soon
as possible after the onset of AMI symptoms . The safety and efficacy of TNKase have only been
investigated with concomitant administration of heparin and
aspirin as described in CLINICAL STUDIES. THE10 mL SYRINGE WITH
TWINPAKDUAL CANNULA DEVICE<br/>Reconstitution: NOTE: Read all
instructions completely before beginning reconstitution and
administration.<br/>Administration:
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dailymed-instance:descripti... |
TNKase (Tenecteplase) is a tissue
plasminogen activator (tPA) produced by recombinant DNA technology using
an established mammalian cell line (Chinese Hamster Ovary cells).
Tenecteplase is a 527 amino acid glycoprotein developed by introducing
the following modifications to the complementary DNA (cDNA) for natural
human tPA: a substitution of threonine 103 with asparagine, and a
substitution of asparagine 117 with glutamine, both within the kringle 1
domain, and a tetra-alanine substitution at amino acids
296���299 in the protease domain. Cell culture is carried out in
nutrient medium containing the antibiotic gentamicin (65 mg/L). However,
the presence of the antibiotic is not detectable in the final product
(limit of detection is 0.67��g/vial). TNKase is a sterile,
white to off-white, lyophilized powder for single intravenous (IV) bolus
administration after reconstitution with Sterile Water for Injection
(SWFI), USP. Each vial of TNKase nominally contains 52.5 mg
Tenecteplase, 0.55 g L-arginine, 0.17 g phosphoric acid, and 4.3 mg
polysorbate 20, which includes a 5% overfill. Each vial will
deliver 50 mg of Tenecteplase.
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dailymed-instance:clinicalP... |
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 anin vitro clot lysis
assay and is expressed in Tenecteplase-specific units. The
specific activity of Tenecteplase has been defined as 200
units/mg.<br/>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.
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
TNKase therapy in patients with acute
myocardial infarction is contraindicated in the following situations
because of an increased risk of bleeding :
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dailymed-instance:supply |
TNKase (Tenecteplase) is supplied as a
sterile, lyophilized powder in a 50 mg vial under partial vacuum. Each
50 mg vial of TNKase is packaged with one 10 mL vial of Sterile Water
for Injection, USP for reconstitution, the B-D 10
mL syringe with TwinPakDual Cannula Device, and
three alcohol prep pads. NDC 50242-038-61.<br/>Stability and Storage: Store lyophilized TNKase at controlled room temperature
not to exceed 30��C (86��F) or under
refrigeration 2���8��C
(36���46��F). Do not use beyond the expiration date stamped on the vial.
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dailymed-instance:genericDr... | |
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:possibleD... |
diseasome-diseases:1358,
diseasome-diseases:1427,
diseasome-diseases:1890,
diseasome-diseases:1892,
diseasome-diseases:2202,
diseasome-diseases:2203,
diseasome-diseases:2280,
diseasome-diseases:2285,
diseasome-diseases:2364,
diseasome-diseases:242,
diseasome-diseases:2835,
diseasome-diseases:2869,
diseasome-diseases:342,
diseasome-diseases:370,
diseasome-diseases:392,
diseasome-diseases:46,
diseasome-diseases:631,
diseasome-diseases:657,
diseasome-diseases:79
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dailymed-instance:precautio... |
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.<br/>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 radioimmunoprecipitationassay, 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.<br/>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.<br/>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.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies in animals have not been performed to evaluate
the carcinogenic potential, mutagenicity, or the effect on
fertility.<br/>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.<br/>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.<br/>Pediatric Use: The safety and effectiveness of TNKase in pediatric
patients have not been established.<br/>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 transfusionor 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.
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dailymed-instance:genericMe... |
Tenecteplase
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dailymed-instance:fullName |
TNKase (Injection, Powder, Lyophilized, For Solution)
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dailymed-instance:adverseRe... |
Bleeding: The most frequent adverse reaction associated with TNKase
is bleeding . 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-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 (seePRECAUTIONS: Geriatric
Use). In the ASSENT-2 study, the following bleeding events were
reported (see Table 3). Non-intracranial major bleeding and the need for blood
transfusions were lower in patients treated with TNKase. 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%).<br/>Allergic Reactions: Allergic-type reactions (e.g., anaphylaxis, angioedema,
laryngeal edema, rash, and urticaria) have rarely (<1%) been reported in patients treated with TNKase.
Anaphylaxis was reported in<0.1% of patients
treated with TNKase; however, causality was not established.
When such reactions occur, they usually respond to conventional
therapy.<br/>Other Adverse Reactions: The following adverse reactions have been reported among
patients receiving TNKase in clinical trials. These reactions
are frequent sequelae of the underlying disease, and the effect
of TNKase 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.
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dailymed-instance:indicatio... |
TNKase (Tenecteplase) is indicated for use
in the reduction of mortality associated with acute myocardial
infarction (AMI). Treatment should be initiated as soon as possible
after the onset of AMI symptoms .
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dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
TNKase
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