METALIZE

Active material: Tenekteplaza
When ATH: B01AD11
CCF: Fibrinolitik – recombinant plasminogen activator, genetically modified
ICD-10 codes (testimony): I21
When CSF: 01.12.11.07
Manufacturer: BOEHRINGER INGELHEIM PHARMA GmbH & Co. KG (Germany)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for / in as a white or pale yellow mass, almost odorless.

Excipients: arginine, phosphoric acid 85%, polysorbate 20.

Solvent: water d / and – 6 ml.

Colourless glass bottles type I (1) with plastic protective cover grey, together with the solvent in a plastic syringe, disposable needle and adapter – packs cardboard.

Valium for drug of a solution for / in as a white or pale yellow mass, almost odorless.

Excipients: arginine, phosphoric acid 85%, polysorbate 20.

Solvent: water d / and – 8 ml.

Colourless glass bottles type I (1) with plastic protective cap yellow-green, together with the solvent in a plastic syringe, disposable needle and adapter – packs cardboard.

Valium for drug of a solution for / in as a white or pale yellow mass, almost odorless.

Excipients: arginine, phosphoric acid 85%, polysorbate 20.

Solvent: water d / and – 10 ml.

Colourless glass bottles type I (1) with plastic protective cap Red, together with the solvent in a plastic syringe, disposable needle and adapter – packs cardboard.

* activity is measured in units tenekteplazy actions (ED), calculated using the special standard and tenekteplazy activity incompatible with units of other thrombolytic funds.

Pharmacological action

Fibrinolytic medication, recombinant plasminogen activator, genetically modified.

Tenekteplaza – recombinant fibrin-specific plasminogen activator, is a derivative of natural Tissue plasminogen activator, modified in three sites.

Tenecteplase is associated with fibrin blood component blood clot and selectively catalyzes conversion associated with thrombus plazminoguena in plazmin, which breaks down fibrin clot foundation. In comparison with natural Tissue plasminogen activator tenecteplase has a higher affinity to solubility coefficient and resistance to the action of endogenous inaktiviruûŝemu plasminogen activator inhibitor I.

After the introduction of the tenekteplazy observed dose-dependent consumption of α₂-antiplazmina (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 (10 000 ED, equivalently 50 mg), decreased fibrinogen concentrations less than 15%, and concentration plazminoguena – less than 25%, application of al′teplazy led to a decrease in Fibrinogen concentration plazminoguena and approximately 50%. Through 30 days after the beginning of Metalize^® tenekteplaze antibodies have been identified.

Angiographic data show, that a single on/in the introduction tenekteplazy contributes to 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 using al′teplazy – 28.9%). Therefore, the need for transfusion therapy using significantly lower tenecteplase (4.3% group and tenecteplase 5.5% al′teplazy group). The frequency of intracranial hemorrhage was 0.93% group and tenecteplase 0.94% al′teplazy group. In cases, When the treatment was started later than in 6 h after the onset of symptoms of myocardial infarction, the use of tenecteplase (compared to al′teplazoj) It had the advantage in terms of 30-day mortality (4.3% group and tenecteplase 9.6% al′teplazy group), the incidence of stroke (0.4% and 3.3% respectively) and the frequency of intracranial hemorrhage (0% and 1.7% respectively).

Pharmacokinetics

Metabolism and excretion

Tenecteplase output from the bloodstream by binding to receptors in liver and degraded to form smaller peptides.

After a single injection of tenekteplazy in patients with acute myocardial infarction observed two-phase tenekteplazy Antigen excretion from blood plasma. If you are using the drug in therapeutic doses, depending on the nature of tenekteplazy inference from the imposed dose not observed.

Initial T_1/2 makes 24 ± 5.5 m (mean value ± standard deviation), what in 5 times more T_1/2 natural woven Activator plazminoguena. The final T_1/2 is 129 ± 87 m; plasma clearance – 119± 49 mL/min.

Pharmacokinetics in special clinical situations

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 in the human kidney, no changes in pharmacokinetics.

Study of pharmacokinetics in human liver was not conducted.

Testimony

is thrombolytic therapy of acute myocardial infarction.

Dosage regimen

Dose is calculated depending on the body weight, the maximum dose should not exceed 10 000 ED (50 mg tenecteplase). Volume solution for introducing the necessary dose is calculated according to the table:

The required dose is introduced by a quick single on/in the injections for 5-10 sec. Previously installed catheter / in the only 0.9% solution of sodium chloride can be used to introduce Metalize^®.

After the introduction of Metalize^® the catheter must be washed before further using it to introduce other medicines.

For the effectiveness of therapy Metalize^® You must use of acetylsalicylic acid and heparin. These drugs should be imposed immediately after the diagnosis of acute myocardial infarction to prevent thrombus formation.

Use of acetylsalicylic acid You must start immediately after identifying symptoms 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, the initial dose 150-250 mg acetylsalicylic acid can be administered in / in. The dose of acetylsalicylic acid in the coming days is determined by the attending physician.

Heparin must begin immediately after the confirmation of the diagnosis Acute myocardial infarction and to continue, at least, during 24 no. The dose of heparin is calculated based on body weight. To patients with a body weight 67 kg or less the initial single dose of heparin for in / bolus not exceed 4000 IU followed by heparin infusion at a rate 800 U / h. To patients weighing more 67 kg the initial single dose of heparin for in / bolus not exceed 5000 IU followed by heparin infusion at a rate 1000 U / h. There should be appointed for the initial dose of heparin in / bolus patients, already receiving heparin. Heparin infusion rate should be adjusted to maintain a level indicator APTT 50-75 sec (in 1.5-2.5 times higher than the reference time or the content of heparin in plasma 0.2-0.5 U / ml).

Preparation of the solution for the on / in the

To dissolve Metalize^® you must add the total volume of water for injection, contained in the attached syringe, vial with powder.

1. Check, that the bottle has a volume of, sufficient for solution preparation according to the body weight of the patient.

2. Check the integrity of the bottle cap.

3. Open the protective cover of the vial.

4. Remove the cap from the syringe. Then immediately screw the enclosed syringe on the vial adapter and the adapter tip pierce the vial stopper in the middle.

5. Slowly pushing the plunger of the syringe, add water to a vial for injection, avoid the appearance of foam.

6. Solutions poroshok, gently rotating the bottle.

7. The prepared solution should be clear, a colorless or pale yellow. For administration it can only be used a transparent solution, does not contain visible particles.

8. Immediately prior to use turn the bottle with a syringe attached to it in such a way, to the syringe at the bottom.

9. Fill the syringe with the correct amount of the prepared solution, calculated depending on the body weight of the patient.

10. Disconnect the syringe from the vial adapter.

11. Metalize^® should be entered in/for a period of 5-10 sec. To introduce Metalize^® do not use the catheter, through which carried out the introduction of dextrose (Glucose).

12. Unused solution should be discarded.

Cultivation of the drug can also be implemented using an attached needle.

Side effect

Most often occurring side effect, involving Metalize^®, is bleeding. Types of bleeding, associated with thrombolytic therapy, can be divided into two large groups:

— External bleeding (usually, from places of vascular punctures);

-internal bleeding: gastrointestinal, Lung and bleeding from the urinary tract, gemoperikard, bleeding in the retroperitoneal space and the brain (with the development of appropriate neurological symptoms, such as sedation, afazija, convulsions). In patients with stroke and intracranial hemorrhage are the cases of death and disability.

CNS: infrequently (>1/1000, but <1/100) – intracranial hemorrhage.

Cardio-vascular system: Often (>1/10) – reperfusion arrhythmias, decrease in blood pressure; rarely (>1/10 000, but <1/1000) – gemoperikard.

From the blood coagulation system: Often (>1/10) – bleeding; often (>1/100, but <1/10) – ecchymosis; infrequently (>1/1000, but <1/100) – thromboembolism.

The respiratory system: often (>1/100, but <1/10) – nose bleed; infrequently (>1/1000, but <1/100) – pneumorrhagia.

From the digestive system: often (>1/100, but <1/10) – gastrointestinal bleeding, nausea, vomiting; infrequently (>1/1000, but <1/100) – bleeding in the retroperitoneal space.

From the urinary system: often (>1/100, but <1/10) – bleeding from the urinary tract.

Local reactions: Often (>1/10) – External bleeding (usually from the puncture site or damaged blood vessels).

Allergic reactions: infrequently (>1/1000, but <1/100) – anaphylactoid reactions (rash, hives, bronchospasm, laryngeal edema).

Other: often (>1/100, but <1/10) – fever, the need for blood transfusion; rarely (<1/10 000) – cholesterol Crystal embolization.

Contraindications

- Diseases, accompanied by significant bleeding within the last 6 Months;

- Gyemorragichyeskii diatyez;

-admission oral anticoagulants (INR > 1.3);

-central nervous system diseases in history (neoplasms, aneurysm, surgery on the brain and spinal cord);

— severe uncontrolled hypertension;

-major surgical interventions, biopsy of parenchymal organ, or significant trauma within the past 2 Months (incl. injury in conjunction with acute myocardial infarction currently), recently migrated cranio-cerebral injury;

-prolonged or traumatic cardiopulmonary resuscitation (>2 m) during the last 2 weeks;

-severe liver, incl. hepatic failure, cirrhosis, portal hypertension (incl. with esophageal varices) and active hepatitis;

-haemorrhagic diabetic retinopathy, or other hemorrhagic diseases of the eye;

- A stomach ulcer or duodenal ulcer in the acute phase;

-aneurysm of an artery or the presence of arterial/venous vascular developmental;

— tumor with a high risk of bleeding;

-acute pericarditis and/or subacute bacterial endocarditis;

- Acute pancreatitis;

-hypersensitivity to tenekteplaze or other component of the drug.

In the following cases when assigning Metalize^® You should carefully assess the degree of perceived usefulness and possible risk of bleeding:

-sistolicescoe ad>160 mm Hg. Art.;

-stroke or transient cerebral circulation disorder;

— recently transferred from the gastrointestinal bleeding or urinary tract (during the last 10 days);

-cerebrovascular disease;

— recently made in the/m injection (during the last 2 days);

- Old age (senior 75 years);

-low weight (< 60 kg).

Pregnancy and lactation

Experience of applying Metalize^® during pregnancy is not. No data on the excretion of tenecteplase in breast milk.

If necessary, the appointment of the drug in the case of acute myocardial infarction during pregnancy or lactation (breast-feeding) should match the expected benefit to the mother and the degree of risk to the fetus or child.

Cautions

Appointment Metalize^® must be treated by a doctor, having experience of thrombolytic therapy and the ability to control its effectiveness. This does not exclude the possibility of applying Metalize^® at the pre-hospital stage. Like the other trombolitičeskie tools, Introduction to Metalize^® It is recommended that in the context, When the available standard resuscitation equipment and medicines.

The most frequent complication, involving Metalize^®, is bleeding. Simultaneous use of heparin may contribute to bleeding. After the dissolution of fibrin as a result of the application of Metalize^®, 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 injection and unreasonable manipulation during treatment Metalize^®. 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, can be viewed introduction transfusion medications. Introduction of cryoprecipitate transfusion, fresh frozen plasma and platelets may be assigned in accordance with the clinical and laboratory indicators, 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 application of glycoprotein IIb/IIIa antagonists during the first 24 hours after the start of treatment offline.

Use Metalize^® may be accompanied by an increased risk of thromboembolic complications in patients with thrombosis of left heart, incl. mitral stenosis or atrial fibrillation.

Antibody molecule tenecteplase were found after treatment. However, the experience of reapplying Metalize^® missing.

Overdose

Symptoms: overdose of the drug may increase the risk of bleeding.

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

Drug Interactions

No data on the presence of clinically significant interactions Metalize^® with other drugs, commonly used in patients with acute myocardial infarction.

Medications, changing the properties of blood coagulation, and preparations, affect platelet function, may increase the risk of bleeding, when you used to, at the same time as or after the appointment of Metalize^®.

Pharmaceutical interaction

The drug is not compatible with the solution of dextrose.

Injectable Metalize^® not to be confused with other drugs.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature no higher than 30 ° C. Shelf life of lyophilisate – 2 year. Shelf life of the solvent – 3 year.

Physical and chemical properties of the prepared solution is stable for 24 h at a temperature from 2° to 8° c and for 8 h at 30° c. From a microbiological standpoint, the solution should be used immediately after cooking. If the solution was not immediately used, terms and conditions of storage prior to use coming under the responsibility of a doctor, prescribers. Usually do not exceed term of storage 24 h at a temperature from 2° to 8° c and 8 h at 30° c.