Clinical medicine profile
Tenecteplase
Therapeutic agent (verify pharmacological class)
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- 4 CONTRAINDICATIONS TNKase is contraindicated in patients with [see Warnings and Precautions (5.1) ] : Active internal bleeding History of cerebrovascular accident Intracranial or intraspinal surgery or trauma within 2 months Intracranial neoplasm, arteriovenous malformation, or aneurysm Known bleeding diathesis Severe uncontrolled hypertension Active internal bleeding ( 4 ) History of cerebrovascular accident ( 4 ) Intracranial or intraspinal surgery or trauma within 2 months ( 4 ) Intracranial neoplasm, arteriovenous malformation, or aneurysm ( 4 ) Known bleeding diathesis ( 4 ) Severe uncontrolled hypertension ( 4 )
Precautions
- 5 WARNINGS AND PRECAUTIONS Bleeding: Increases the risk of bleeding.
- Avoid intramuscular injections.
- Monitor for bleeding.
- ( 5.1 ) Thromboembolism: The use of thrombolytics can increase the risk of thrombo-embolic events in patients with high likelihood of left heart thrombus.
- ( 5.2 ) Cholesterol Embolization: Has been reported in patients treated with thrombolytic agents.
- ( 5.3 ) Arrhythmias: It is recommended that anti-arrhythmic therapy for bradycardia and/or ventricular irritability be available when TNKase is administered.
- ( 5.4 ) Increased Risk of Heart Failure and Recurrent Ischemia when used with Planned Percutaneous Coronary Intervention (PCI) in STEMI: In patients with a large ST segment elevation myocardial infarction, physicians should choose either thrombolysis or 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.
- ( 5.5 ) Hypersensitivity: Monitor patients treated with TNKase during and for several hours after infusion.
- If symptoms of hypersensitivity occur, initiate appropriate therapy (e.g., antihistamines, corticosteroids).
- ( 5.6 ) 5.1 Bleeding TNKase can cause bleeding, including intracranial hemorrhage and fatal bleeding.
- Concomitant use of other drugs that impair hemostasis increases the risk of bleeding.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
symptoms. ( 2.1 ) TNKase is for intravenous administration only, administered as a single bolus over 5 seconds. Individualize dosage based on patient's weight. ( 2.1 ) 2.1 Recommended Dosage Initiate treatment as soon as possible after the onset of STEMI symptoms. TNKase is for intravenous (IV) administration only, administered as a single bolus over 5 seconds. Individualize dosage based on the patient's weight (see Table 1 ). Table 1: Recommended Dosage Patient Weight (kg) TNKase (mg) Volume TNKase From one vial of TNKase reconstituted with 10 mL Sterile Water for Injection. to be administered (mL) < 60 30 6 ≥ 60 to < 70 35 7 ≥ 70 to < 80 40 8 ≥ 80 to < 90 45 9 ≥ 90 50 10 2.2 Preparation Follow the below steps to prepare TNKase for administration: Remove the shield assembly from the supplied B-D ® 10 mL syringe with TwinPak™ Dual Cannula Device (see Figure 1 ) and aseptically withdraw 10 mL of Sterile Water for Injection, USP, from the supplied diluent vial using the red hub cannula syringe filling device. Only use the supplied Sterile Water for Injection, USP for reconstitution. Note: Do not discard the shield assembly. Aseptically reconstitute the vial with 10 mL Sterile Water for Injection, USP by directing the stream into the lyophilized powder to obtain a final concentration of 5 mg/mL. Slight foaming upon reconstitution is not unusual; any large bubbles will dissipate if the product is allowed to stand undisturbed for several minutes. Gently swirl until contents are completely dissolved. DO NOT SHAKE. The reconstituted preparation results in a colorless to pale yellow transparent solution. Determine the appropriate dose of TNKase [see Dosage and Administration (2.1) ] and withdraw this volume (in milliliters) from the reconstituted vial with the syringe. Discard any unused solution. Stand the shield vertically on a flat surface (with green side down) and passively recap the red hub cannula. Remove the entire shield assembly, including the red hub cannula, by twisting counterclockwise. Note: The shield assembly also contains the clear-ended blunt plastic cannula; retain for split septum intravenous access. Figure 1 Figure 1 2.3 Administration Follow the below steps for administration of TNKase; Inspect the product prior to administration for particulate matter and discoloration. Administer TNKase as reconstituted at 5 mg/mL. Precipitation may occur when TNKase is administered in an intravenous line containing dextrose. Flush dextrose-containing lines with a saline-containing solution prior to and following single bolus administration of TNKase. Administer reconstituted TNKase as a single intravenous bolus over 5 seconds. Because TNKase contains no antibacterial preservatives, reconstitute immediately before use. If the reconstituted TNKase is not used immediately, refrigerate the TNKase vial at 2°C to 8°C (36°F to 46°F) and use within 8 hours. Although the supplied syringe is compatible with a conventional needle, this syringe is designed to be used with needleless intravenous systems. From the information below, follow the instructions applicable to the intravenous system in use. Split septum intravenous system : Remove the green cap. 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. Because the blunt plastic cannula has two side ports, air or fluid expelled through the cannula will exit in two sideways directions; direct away from face or mucous membranes. Luer-Lok ® system: Connect syringe directly to intravenous port. Conventional needle (not supplied in this kit): Attach a large bore needle, e.g., 18 gauge, to the syringe's universal Luer-Lok ® . Dispose of the syringe, cannula and shield per established procedures. 2.4 Chemical Incompatibilities TNKase is incompatible with dextrose containing solutions. When used together, precipitation may occur. Flush dextrose containing lines with saline-containing solution before using TNKase.
8.4 Pediatric Use The safety and effectiveness of TNKase in pediatric patients have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- 1 INDICATIONS AND USAGE TNKase ® is indicated to reduce the risk of death associated with acute ST elevation myocardial infarction (STEMI).
- TNKase is a tissue plasminogen activator, indicated to reduce the risk of death associated with acute ST elevation myocardial infarction (STEMI).
Adverse effects
- label: Bleeding [see Contraindications (4) , Warnings and Precautions (5.1) ] Hypersensitivity [see Warnings and Precautions (5.6) ] The most common adverse reactions are bleeding and hypersensitivity.
- ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Roche at 1-800-526-6367 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Immunogenicity Four of 625 (0.64%) patients tested for antibody formation to TNKase had a positive antibody titer at 30 days in studies with TNKase.
- 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.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
(tPA) that binds to fibrin and converts plasminogen to plasmin.
Read complete mechanism
(tPA) that binds to fibrin and converts plasminogen to plasmin. In the presence of fibrin, in vitro studies demonstrate that tenecteplase-mediated 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. The clinical significance of fibrin-specificity on safety (e.g., bleeding) or efficacy has not been established.
Product-specific
Product-specific
See product SmPC
In patients with STEMI, TNKase administered as a single IV bolus exhibits a biphasic disposition from the plasma. Volume of distribution at central compartment ranges from 4.22 to 5.43 L, approximating plasma volume. Steady-state volume of distribution was approximately 50% great...
Liver metabolism is the major clearance mechanism for tenecteplase. Body weight A stepwise linear regression analysis indicated that total body weight explained 19% of the variability in plasma clearance and 11% of the variability in volume of
After IV bolus administration, the terminal phase
of tenecteplase was 90 to 130 minutes. In 99 of 104 patients treated with TNKase, TNKase has linear PK with mean maximum concentrations increased in a dose-proportional manner and mean plasma clearance was similar for the 30, 40, and 50 mg doses ranging from 99 to 119 mL/min.
Pregnancy, lactation & diet
8.1 Pregnancy Risk Summary There are risks to the mother and fetus from acute ST elevation myocardial infarction, which is a medical emergency in pregnancy and can be fatal if left untreated (see Clinical Considerations ). Published data consisting of a small number of case reports involving the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects. 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. TNKase does not elicit maternal and direct embryo toxicity in rabbits following a single IV administration. 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 (5 mg/kg) was approximately 7 times human exposure (based on AUC) at the dose for STEMI. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Myocardial infarction is a medical emergency which can be fatal if left untreated. Life-sustaining therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of tenecteplase on the fetus.
8.1 Pregnancy Risk Summary There are risks to the mother and fetus from acute ST elevation myocardial infarction, which is a medical emergency in pregnancy and can be fatal if left untreated (see Clinical Considerations ). Published data consisting of a small number of case reports involving the use of related thrombolytic agents in pregnant women have not identified an increased risk of major birth defects. 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. TNKase does not elicit maternal and direct embryo toxicity in rabbits following a single IV administration. 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 (5 mg/kg) was approximately 7 times human exposure (based on AUC) at the dose for STEMI. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Myocardial infarction is a medical emergency which can be fatal if left untreated. Life-sustaining therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of tenecteplase on the fetus. 8.2 Lactation Risk Summary There are no data on the presence of tenecteplase in either human or animal milk, the effects on the breastfed infant, or the effect on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TNKase and any potential adverse effects on the breastfed infant from the TNKase or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of TNKase in pediatric patients have not been established. 8.5 Geriatric Use In the ASSENT-2 study, 41% (3500/8458) of patients who were treated with TNKase were aged 65 years or older. In this population, rates of 30-day mortality, stroke, intracranial hemorrhage and major bleeds requiring blood transfusion or leading to hemodynamic complications were higher than in those aged less than 65 years.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| METALYSE 8 000 U and Solvent | Ingelheim Pharmaceuticals (Pty) Ltd | 15128 Tenecteplase 8 000 units. The reconstituted… | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.