Tenekteplaza

When ATH:
B01AD11

Pharmacological action

The recombinant fibrin-specific plasminogen activator. It binds to the fibrin component of the thrombus and selectively catalyzes the conversion of bound thrombus plasminogen to plasmin, which breaks down fibrin clot foundation. In comparison with a natural tissue plasminogen activator, tenecteplase has a higher affinity for fibrin and resistance to inactivate endogenous plasminogen activator inhibitor I. After administration of tenecteplase dose dependent consumption observed alpha 2-antiplasmin (plasmin inhibitor in the liquid phase,) followed by increasing concentrations of systemic plasmin, which corresponds to the intended effect of plasminogen activation. Comparative studies in patients, received the maximum dose of tenecteplase (10 tys.ED, equivalently 50 mg), decreased fibrinogen concentrations less than 15%, and the concentration of plasminogen less, than 25%, and the use of alteplase reduces the concentration of fibrinogen and plasminogen approximately 50%. Through 30 days after start of the drug to the antibody were identified tenecteplase. A single in / introduction of tenecteplase promotes artery recanalization, due to thrombosis which developed acute myocardial infarction. This effect is dose-dependent. The use of tenecteplase reduces mortality from myocardial infarction (on 6,2% through 30 days). When using the frequency of bleeding tenecteplase (excluding intracranial) is 26,4% (below, than with alteplase - 28,9%,). Therefore, the need for transfusion therapy using significantly lower tenecteplase (4,3% group and tenecteplase 5,5% group alteplase). The frequency of intracranial hemorrhage was 0,93% group and tenecteplase 0,94% group alteplase. In cases, when the treatment was started later, than 6 h after the onset of symptoms of myocardial infarction, the use of tenecteplase (compared with alteplase) It had the advantage in terms of 30-day mortality (4,3% group and tenecteplase 9,6% group alteplase), the incidence of stroke (0,4% and 3,3%, respectively) and the frequency of intracranial hemorrhage (0% and 1,7% respectively).

Pharmacokinetics

Tenecteplase output from the bloodstream by binding to receptors in liver and degraded to form smaller peptides. After a single injection of tenecteplase in patients with acute myocardial infarction observed biphasic elimination of tenecteplase antigen from blood plasma. When using the drug at therapeutic doses, depending on the nature of excretion of the administered dose tenecteplase not observed. The initial T1 / 2 - 24 ± 5,5 min, what in 5 times greater than T1 / 2 of natural tissue plasminogen activator. The final T1 / 2 is 129 ± 87 minutes; plasma clearance - 119 ± 49 mL / min. With increased body mass index observed a moderate increase in plasma clearance, with increasing age marked decrease in this indicator. In women, plasma clearance figures are usually lower, than men, that can be attributed to lower body weight in females. Tenecteplase is excreted in the bile, so it is assumed, that renal dysfunction does not alter the pharmacokinetics of. Pharmacokinetic studies with abnormal liver function have not been conducted.

Testimony.

Acute myocardial infarction (tromboliticheskaya therapy).

Contraindications

Hypersensitivity, disease, accompanied by significant bleeding within the last 6 Months, gyemorragichyeskii diatyez, concomitant use of oral anticoagulants (International standardized index more 1,3), CNS disease history (neoplasms, aneurysm, surgery on the brain and spinal cord), severe uncontrolled hypertension, major surgery, biopsy of parenchymal organ, or significant trauma within the past 2 Months (incl. injury in conjunction with acute myocardial infarction currently), recently transferred TBI, prolonged or traumatic cardiopulmonary resuscitation (more 2 m) during the last 2 Sun, severe liver dysfunction, incl. hepatic failure, cirrhosis, portal hypertension (incl. with esophageal varices) and active hepatitis, diabeticheskaya gemorragicheskaya retinopathy, etc.. hemorrhagic diseases of the eye, stomach ulcer or duodenum 12 in Art. exacerbation, artery aneurysm or having blood / venous malformation of blood vessels, neoplasm with increased risk of bleeding, Acute pericarditis and / or subacute bacterial endocarditis, acute pancreatitis.

Carefully. Systolic blood pressure more 160 mmHg., stroke or transient ischemic attack in history, recently transferred bleeding from the gastrointestinal tract or urogenital system (during the last 10 days), recently made the / m injection (during the last 2 days), advanced age (senior 75 years), weight less 60 kg, cerebrovascular diseases, pregnancy, lactation.

Dosage regimen

Batching. B /, single, for 5-10 s.

The dose depends on the body weight. The maximum dose does not exceed 10 tys.ED (50 mg tenecteplase).

The volume of solution required dose for administration: 6 ml (6 tys.ED or 30 mg tenecteplase) - Body weight of less than 60 kg, 7 ml - with a body weight of 60-70 kg (7 tys.ED or 35 mg), 8 ml (8 tys.ED or 40 mg) - Body weight 70-80 kg, 9 ml (9 thousand units, or 45 mg) - Body weight 80-90 kg, 1 ml (10 tys.ED or 50 mg) - Body weight more 90 kg.

Previously installed catheter / in the only 0,9% NaCl solution, It can be used for administration of tenecteplase. After injection catheter must be flushed before the further use for administration, etc.. PM. For the administration of the drug should not be used catheter, through which carried out the introduction of dextrose. Unused solution should be discarded.

To be effective, treatment with tenecteplase is necessary to use ASA and heparin, which should be administered immediately after the diagnosis of acute myocardial infarction to prevent thrombotic events.

The use of ASA should begin immediately after the detection of symptoms of acute myocardial infarction and to continue, at least, until the patient is discharged from hospital. The recommended starting dose for oral administration is 150-325 mg / day. If the patient can not swallow tablets, an initial dose of 150-250 mg may be administered ACK / in. The dose of ASA in the next few days is determined by the attending physician.

Heparin should start immediately after confirmation of the diagnosis of acute myocardial infarction and to continue, at least, during 24 no. The dose of heparin is calculated based on body weight. When body weight 67 kg or less, the initial single dose of heparin for in / bolus not exceed 4 tys.ED, followed by an infusion at a rate heparin 800 U / h, more 67 kg - 5 and tys.ED 1 tys.ED / h respectively. There should be appointed for the initial dose of heparin in / bolus patients, already receiving heparin. Heparin infusion rate should be adjusted to maintain the index at 50-75 APTT with (1.5-2.5 times higher than the reference time or the concentration of heparin in a plasma 0,2-0,5 U / ml).

Side effect

The most frequently - bleeding: outdoor (usually from the puncture site of the blood vessels); internal (gastrointestinal, pulmonary, of the urinary tract, gemoperikard, bleeding in the retroperitoneal space and the brain with the development of relevant neurological symptoms, such as sedation, afazija, convulsions). Patients with stroke and intracranial hemorrhage are described cases of death and permanent disability.

Often (more 1/10), often (more 1/100 less 1/10), infrequently (more 1/1000 less 1/100), rarely (more 1/10 000 less 1/1000).

From the nervous system: rare - intracranial hemorrhage.

From the CCC: very often - reperfusion arrhythmias, bleeding from vessels, often - ecchymosis, rarely - thromboembolism, rarely - hemopericardium.

The respiratory system: often - nosebleeds, infrequently - pulmonary hemorrhage.

From the digestive system: frequently - gastrointestinal bleeding, nausea, vomiting, rarely - bleeding in the retroperitoneal space.

On the part of the part of the genitourinary system: often - bleeding from the urinary tract.

Other: very often - external bleeding, usually from the puncture site or damaged blood vessels.

Reaction, identified in special studies: very often - lowering blood pressure, often - fever.

Injury, toxic effects and complications of the procedures, associated with drug: infrequently - anaphylactoid reactions (incl. rash, hives, bronchospasm, laryngeal edema), very rarely - embolism of cholesterol crystals.

Surgical and therapeutic procedures: often - the need for blood transfusion.

Overdose. Symptoms: bleeding.

Treatment: in the case of prolonged significant bleeding may require blood transfusions.

Cautions

The introduction of the drug should carry a doctor, having experience of thrombolytic therapy and the ability to control its effectiveness. This does not exclude the possibility of tenecteplase prehospital. The introduction of the drug is recommended in conditions, When available standard resuscitation equipment and drugs.

Bleeding - the most common complication in the use of the drug. Simultaneous use of heparin may contribute to bleeding. After the dissolution of fibrin resulting from the application of tenecteplase, bleeding may occur in areas recently performed punctures and injections. Therefore, thrombolytic therapy requires careful monitoring of possible areas of bleeding (including the location of the catheter, arterial and venous puncture, cuts and injections). Avoid the use of rigid catheters, in / m injections and unjustified manipulation during treatment.

In the event of serious bleeding, especially, intracranial hemorrhage, simultaneous administration of heparin should be stopped immediately. Keep in mind the possibility of the appointment of protamine, if heparin has been appointed for 4 hours before the bleeding. In rare cases,, When these measures are ineffective conservative treatment, It can be shown to the rational administration of transfusion products. Introduction of cryoprecipitate transfusion, fresh frozen plasma and platelets may be appointed in accordance with the clinical and laboratory parameters, re-determined after each administration. Infusion of cryoprecipitate desirable to carry out to achieve a concentration of fibrinogen about 1 g / l. It is also possible the use of antifibrinolytic agents.

Coronary thrombolysis may be associated with the occurrence of arrhythmia, associated with reperfusion.

Experience of using antagonists of glycoprotein llb / llla during the first 24 hours after the start of treatment offline.

The use of tenecteplase may be accompanied by an increased risk of thromboembolic complications in patients with thrombosis of the left heart, incl. mitral stenosis or atrial fibrillation.

Antibody molecule tenecteplase were found after treatment, but the experience of re-use of tenecteplase is absent.

The experience of the drug in pregnant women is not. No data on the excretion of tenecteplase in breast milk. It is possible to correlate the degree of risk and the expected benefits in the appointment of the drug in case of acute myocardial infarction during pregnancy and lactation.

Physical and chemical properties of the prepared solution is stable for 24 h at a temperature of 2-8 ° C and for the 8 hours at a temperature 30 °C. From the microbiological point of view,, the solution should be used immediately after preparation. If the solution was not immediately used, terms and conditions of storage prior to use coming under the responsibility of a doctor, prescribers.

Drug Interactions

There is no evidence of clinically significant interactions with other tenecteplase. preparations, commonly used in patients with acute myocardial infarction.

PM, changing the properties of blood coagulation, and also affect the function of platelets, may increase the risk of bleeding, when you used to, simultaneously, or after administration of tenecteplase.

Incompatible with dextrose solutions. Do not mix with others. PM.