Actylysis - instructions for use, dose, side effects, contraindications

Active substanceAlteplaseAlteplase

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Actylase®

lyophilizate d / infusion

Boehringer Ingelheim International GmbH Germany

Dosage form: & nbsplyophilizate for solution for infusion

Composition:

Each vial with lyophilizate contains:

Active substance:

Alteplase 50.0 mg

Excipients:

L-arginine 1742.0 mg,

Phosphoric acid, 85%¹: to pH 7.2 ± 0.2

Polysorbate 80: 3.5 - 5.0 mg

Note:

Excess is 3.5% of the nominal amount of the active ingredient and excipients in the vial.

To fill the free space until the bottle is finally capped, nitrogen, which is not part of the drug, is used.

Residual traces: gentamicin (used in the manufacturing process).

Each vial with a solvent contains:

Water for Injection: 50 ml

1 ml of the solution after dilution contains 1 mg of alteplase.

¹To determine the pH

Description:Lyophilizate: Lyophilized mass of white or light yellow color. Solvent: Colorless transparent liquid.

Pharmacotherapeutic group:Fibrinolytic agent - plasminogen activator

ATX: & nbsp

B.01.A.D.02 Alteplase

Pharmacodynamics:Active component AKTILIZE - alteplase, is a recombinant human tissue activator of plasminogen, a glycoprotein that directly activates the transformation of plasminogen into plasmin. After intravenous administration alteplase remains relatively inactive in the circulation system. It is activated by binding to fibrin, which causes the transformation of plasminogen into plasmin and leads to the dissolution of a fibrin clot. Due to the relative specificity for fibrin, the use of alteplase at a dose of 100 mg leads to a moderate decrease in circulating fibrinogen (up to about 60% in 4 hours), which by 24 hours usually increases to more than 80%. The concentrations of plasminogen and alpha-2-antiplasmin in the blood decrease after 4 hours, respectively, to 20% and 35% of the baseline values, and after 24 hours again increase to more than 80%. A significant and prolonged decrease in the level of circulating fibrinogen was observed in only a few patients.

Patients with acute myocardial infarction (AMI)

In patients with acute myocardial infarction, two dosing regimens AKTILIZE were studied. Comparative effectiveness of these two regimes was not carried out.

Accelerated drug infusion in patients with AMI

Four regimens of thrombolytic therapy were studied. The use of ACTILISE at a dose of 100 mg for 90 minutes, together with intravenous infusion of heparin, was characterized by low mortality after 30 days (6.3%) compared with streptokinase therapy (1.5 million ME - 60 min) with subcutaneous or intravenous administration of heparin (7.3%) (p = 0.001).

3-hour infusion in patients with AMI

When ACTHYLISE was compared with placebo for 5 hours after the onset of symptoms, an increase in 30-day survival was established in patients receiving ACTYLIZE, an improvement in left ventricular function was assessed in assessing the ejection fraction with contrast ventriculography, a decrease in infarct size was observed, less episodes of cardiogenic shock, ventricular fibrillation, pericarditis, compared with patients receiving placebo.

Patients with pulmonary embolism

In a study conducted in patients with angiographically documented acute massive pulmonary embolism, treatment was found to lead to a significant reduction in the incidence of pulmonary hypertension caused by pulmonary artery embolism.

Patients with ischemic stroke (acute period)

Clinically expressed intracranial hemorrhage was observed in 5.9% of patients receiving ACTILIZE and 1.1% of patients receiving placebo, which depended on the age of the patients, but not on the time that elapsed from the onset of symptoms before treatment.This analysis also confirmed that the rapid onset of AKTILIZE results in better treatment outcomes after 3 months. There was also evidence of the possibility of extending the "window" of the therapeutic effect to 4.5 hours.

In the usual clinical setting, the safety and efficacy of ACTYLIZE in acute stroke were evaluated in the case of treatment initiation within 3 hours of the onset of symptoms. It was found that the frequency of clinically expressed intracranial bleeding (within 24 hours) in these studies was comparable, it was 7.3% and 8.6%, mortality (after 3 months) was 11.3% and 17%.

Patients with acute stroke 3-4.5 hours after the onset of symptoms (patients with a neurological deficit that could be quantified). A favorable result of treatment was found in a larger number of patients receiving alteplase (52.4%), compared with patients receiving placebo (45.2%). Patients treated with alteplase also experienced a "global outcome," but the incidence of clinically expressed intracranial bleeding was higher in the case of alteplase compared with placebo.Systematic intracranial hemorrhages (ECASS III) were 2.4% compared with 0.2% placebo (p = 0.008). Mortality was low, significant differences between patients receiving alteplase (7.7%) or placebo (8.4%), not established. Thus, AKTILIZE, applied 3-4.5 hours after the onset of symptoms, significantly improves clinical outcomes in patients with acute ischemic stroke. The safety and effectiveness of the use of AKTILIZE in the treatment of acute ischemic stroke, which occurs within up to 4.5 hours after the onset of symptoms, continues to be evaluated in the registry (SITS-ISTR: The Safe Implementation of Thrombolysis in Stroke Registry). At present, it has been established that by 3 months the incidence of clinically expressed intracranial bleeding was slightly higher in the case of treatment initiation after 3-4.5 hours (9.13%) compared with the beginning of treatment during the first 3 hours (7.49%). The mortality rate in the case of starting treatment in 3-4.5 hours (12.4%) and for 0-3 hours (12.3%) was similar.

Pharmacokinetics:ACTYLIZE is quickly excreted from the bloodstream and metabolized mainly in the liver (plasma clearance is 550-680 ml / min). The half-life of plasma (T_1/2_α) is 4-5 minutes, which means that after 20 minutes, less than 10% of the initial alteplase concentration remains in the plasma. It is shown that for the remaining dose of alteplase.retained deep in tissues, half-life (T₁_/2β) is about 40 minutes. When AKTILIZE is used to restore the patency of non-functioning catheters installed in the central veins, it is not expected to achieve pharmacological concentrations in the plasma.

Indications:

1. Thrombolytic therapy of acute myocardial infarction

- 90-minute (accelerated) dosing regimen (see "Dosage and Administration"): for patients in whom treatment can be started within 6 hours after the onset of symptoms;

- 3-hour dosing regimen (see "Dosage and Administration"): for patients in whom treatment can be initiated between 6 and 12 hours after the onset of symptoms.

It is proved that in acute myocardial infarction, ACTILISE reduces mortality in the first 30 days after the onset of an infarction.

2. Thrombolytic therapy of massive pulmonary thromboembolism accompanied by unstable hemodynamics

This diagnosis should be, if possible, confirmed objectively, for example, angiography of the pulmonary artery, or non-invasive methods, for example, lung tomography. Clinical studies on mortality and long-term results of pulmonary embolism treatment have not been conducted.

3. Thrombolytic therapy of ischemic stroke in acute period

Treatment should begin as soon as possible, within 4.5 hours after the onset of stroke symptoms and after the elimination of intracranial bleeding with an adequate imaging technique (using appropriate imaging techniques, for example, a computed tomography (CT) method of the brain or another diagnostic method sensitive to bleeding detection (eg, MRI) .The effect of treatment depends on the time of its onset, that is, earlier treatment increases the likelihood of a favorable outcome.

Contraindications:

The drug AKTILIZE should not be used in patients with known hypersensitivity to the active substance (alteplase), gentamicin (residual traces from the manufacturing process) or to any auxiliary substance.

The drug AKTILIZE should not be used in those cases when there is an increased risk of bleeding:

- extensive bleeding now or within the previous 6 months, hemorrhagic diathesis;

- simultaneous effective treatment with oral anticoagulants, for example, warfarin (international standardized ratio> 1.3) (see section "Special instructions", subsection Bleeding);

- diseases of the central nervous system in the history (including neoplasms, aneurysm, surgical intervention on the brain or spinal cord);

- intracranial (including subarachnoidal) hemorrhage at present or in anamnesis, suspected hemorrhagic stroke;

- severe uncontrolled arterial hypertension;

- extensive surgical intervention or extensive trauma during the previous 3 months, recent craniocerebral trauma;

- prolonged or traumatic cardiopulmonary resuscitation (> 2 min), labor for 10 previous days, a recent puncture of an uncompensated blood vessel (eg subclavian or jugular vein);

- severe liver disease, including liver failure, cirrhosis, portal hypertension (including varicose veins of the esophagus) and active hepatitis;

- bacterial endocarditis, pericarditis;

acute pancreatitis;

- confirmed peptic ulcer of the stomach or duodenum during the last three months;

- arterial aneurysms, defects in the development of arteries / veins;

- a neoplasm with an increased risk of bleeding;

- Hypersensitivity to the components of the drug.

In the case of using the drug for the treatment of acute myocardial infarction and pulmonary embolism, in addition to the above, there are the following contraindications:

- hemorrhagic stroke or stroke of unknown etiology in history

- ischemic stroke or transient ischemic attack during the last 6 months with the exception of the current acute ischemic stroke for 4.5 hours.

In the case of a drug for the treatment of acute ischemic stroke. in addition to the above, there are the following contraindications:

- signs of intracranial hemorrhage according to CT of the brain and clinical symptoms of intracranial hemorrhage with normal CT of the brain;

- the onset of symptoms of ischemic stroke more than 4.5 hours before the start of the infusion or the lack of accurate information about the time of onset of symptoms;

- rapid improvement of the condition in acute ischemic stroke or mild symptoms at the time of infusion;

- a severe stroke, based on clinical data (for example, if the indicator NIHSS > 25 (National Institutes of Health Stroke Scale)) and / or according to the results of appropriate imaging techniques (computed tomography or magnetic resonance imaging);

- convulsions at the beginning of a stroke;

- information about a stroke or serious head injury last 3 months;

- the presence of a history of stroke of any etiology in patients with diabetes mellitus;

- the use of heparin within 48 hours before the onset of the stroke, if at this time the activated partial thromboplastin time (APTT) is increased;

- the number of platelets is less than 100,000 / μL;

- systolic blood pressure above 185 mm Hg. or diastolic blood pressure above 110 mm Hg. or the need for intensive care (intravenous administration of drugs) to reduce blood pressure to these boundaries;

- the concentration of glucose in the blood <2.77 or> 22.20 mmol / l

The drug AKTILIZE is not indicated for the treatment of acute stroke in children and adolescents under 18 years.

Use of the drug in patients older than 80 years (see the section "With caution").

Carefully:

In the following cases, when prescribing AKTILISE, the extent of the intended benefit and the possible risk of bleeding should be carefully assessed:

- Recently performed intramuscular injection or small recent interventions such as biopsy (needle), puncture (needle) of large vessels, cardiac massage during resuscitation.

- Diseases (not mentioned in the list of contraindications) at which the risk of bleeding is increased.

- Simultaneous reception of oral anticoagulants: treatment with AKTILIZE can be considered only when laboratory indicators of anticoagulant activity are not clinically significant.

In the treatment of acute myocardial infarction and acute pulmonary embolism, the following special caveats and measures precautions:

- Systolic blood pressure> 160 mm Hg. Art.

- An elderly age at which the risk of intracranial hemorrhage may increase. Since in elderly patients the likelihood of a positive outcome of this treatment also increases, a thorough evaluation of the benefit-risk ratio is necessary.

In the treatment of acute ischemic stroke, the following special warnings and precautions should be borne in mind:

The use of ACTYLIZE in patients with acute ischemic stroke, in comparison with the use of this drug for other indications, is accompanied by an increased risk of intracranial hemorrhage, since bleeding occurs predominantly in the necrotic area. This should especially be taken into account in the following cases:

- all conditions characterized by a high risk of bleeding;

- presence of small asymptomatic aneurysms of cerebral vessels;

delay in initiating treatment;

- in patients who were previously treated with acetylsalicylic acid or other antiplatelet agents, an increased risk of intracerebral hemorrhage is possible, especially if the use of AKTILIZE is started at a later date. Given the increased risk of cerebral hemorrhage, the applied dose of alteplase should not exceed 0.9 mg / kg (the maximum dose is 90 mg);

- in patients older than 80 years, in comparison with younger patients, the risk of cerebral hemorrhage may increase and the overall benefit of treatment may decrease. Therefore, the question of the use of AKTILIZE should be carefully considered and addressed individually, taking into account the assumed risk.

Treatment should not begin later than 4.5 hours after the onset of symptoms, due to an unfavorable benefit / risk ratio, due to the following circumstances:

- The positive effect of treatment is reduced with late initiation of therapy;

- mortality increases mainly in patients who have previously received acetylsalicylic acid;

- the risk of bleeding increases.

Pregnancy and lactation:

Pregnancy

The experience of using AKTILIZE during pregnancy and lactation is very limited. In preclinical studies conducted with the use of alteplase in doses exceeding the doses used in humans, there were signs of immaturity of the fetus and / or embryotoxicity, which were considered a consequence of the pharmacological activity of the drug. Alteplase does not have a teratogenic effect.

In diseases that directly threaten life, it is necessary to weigh the relationship between use and potential risk.

In this regard, the use of AKTILIZE during pregnancy and lactation is not recommended.

Breastfeeding period

The question of the penetration of alteplase into breast milk of a woman has not been studied.

Fertility

There are no clinical data on the effect of ACTILISE on fertility. In preclinical studies, the negative effect of alteplase on fertility is not established.

Dosing and Administration:

ACTYLIZE should be used as soon as possible after the onset of symptoms.

1. Myocardial infarction

a) 90-minute (accelerated) dosing regimen for patients with myocardial infarction, in whom treatment can be initiated within 6 hours after the onset of symptoms:

15 mg - intravenously (intravenously)

50 mg - IV infusion for the first 30 minutes, followed by an infusion of 35 mg for 60 minutes before reaching the maximum dose of 100 mg.

In patients with body weight less than 65 kg, the total dose is adjusted taking into account the body weight:

15 mg - in / in the stream,

0.75 mg / kg (maximum 50 mg) for 30 minutes in / drip, followed by infusion of 0.5 mg / kg (maximum 35 mg) for 60 minutes.

b) A 3-hour dosing regimen for patients in whom treatment can be initiated between 6 and 12 hours after the onset of symptoms:

10 mg - in / in the stream,

50 mg - IV infusion during the first hour, followed by iv infusion at a rate of 10 mg for 30 minutes, until the maximum dose of 100 mg is reached within 3 hours.

In patients with a body weight of less than 65 kg, the total dose should not exceed 1.5 mg / kg. The recommended maximum dose of alteplase for acute myocardial infarction is 100 mg.

Auxiliary therapy:

Auxiliary antithrombotic therapy is indicated in patients with myocardial infarction with segment elevation ST according to current international recommendations.

2. Embolism of the pulmonary artery

The total dose of 100 mg should be administered within 2 hours. The greatest experience was obtained with the use of the following dosing regimen:

10 mg IV in struino for 1 to 2 minutes,

90 mg IV drip for 2 hours.

In patients with a body weight of less than 65 kg, the total dose should not exceed 1.5 mg / kg. Auxiliary therapy:

After applying AKTILIZE, in the event that the APTT values are less than twice the upper limit of the norm, the infusion application of heparin should be initiated (or continued). The dose of heparin should be adjusted to maintain the AF HB between 50-70 seconds (values should exceed the original in 1.5 - 2.5 times).

3. Ischemic stroke (acute period)

The recommended dose of 0.9 mg / kg (maximum 90 mg) is administered infuzionalno within 60 minutes after the initial iv dose of the drug,which is 10% of the total dose.

Therapy should be started as soon as possible, within 4.5 hours, after the onset of symptoms. The therapeutic effect depends on the time of the beginning of therapy, that is, the earlier the treatment is started, the greater the probability of a favorable outcome.

Auxiliary therapy:

The safety and efficacy of the above treatment regimen used in combination with heparin and acetylsalicylic acid within the first 24 hours after the onset of symptoms have not been adequately studied. In this regard, in the first 24 hours after the initiation of therapy, ACTYLIZE of acetylsalicylic acid or intravenous administration of heparin should be avoided. If the use of heparin is required for other indications (for example, for prevention of deep vein thrombosis), its dose should not exceed 10,000 ME per day, while the drug is administered subcutaneously.

Instructions for use

The dry substance contained in the ACTILIZE Injection Vial (50 mg) is dissolved under aseptic conditions with sterile water for injection so that the final alteplase concentration is I mg / ml (according to the table below).

VACCINE VACCINE	50 mg
The volume of sterile water for adding to the dry matter	injection, 50 ml
The final concentration	1 mg / ml alteplase

Thus, in order to obtain a final alteplase concentration of 1 mg / ml, an entire volume of the applied solvent should be added to the ACTILIZE vial containing the dry matter.

When preparing the preparation from an appropriate amount of powder and solvent, the resulting mixture should be gently mixed until completely dissolved. Strong agitation should be avoided (foam may form).

The preparation after dilution is a clear, colorless or pale yellow solution. Before use, it is necessary to visually check the color of the solution and the presence of particles in it. The solution obtained initially can be further diluted with a sterile solution (9 mg / ml, 0.9%) of sodium chloride for injection, with a minimum alteplase concentration of 0.2 mg / ml.

The solution obtained initially can not be further diluted with water for injection or solutions for infusions based on carbohydrates, for example, dextrose. The drug AKTILIZE should not be mixed with other drugs (even with heparin), neither in the infusion bottle nor in the common system for intravenous administration.

Side effects:

The frequency of adverse reactions that may occur during therapy is given in the following gradation: very often (≥1 / 10); often (≥1 / 100. <1/10); infrequently (≥1 / 1,000, <1/100); rarely (≥1 / 10,000, <1/1 000); very rarely (<1/10 000); frequency (frequency can not be estimated from available data).

Application for myocardial infarction, Embolism of the pulmonary artery and ischemic stroke in an acute period

The most common undesirable reaction associated with the use of AKTILIZE. is bleeding (≥1 / 100, <1/10: massive bleeding:> 1:10: any bleeding) leading to a decrease in hematocrit and / or hemoglobin.

There may be a hemorrhage in any part or cavity of the body and lead to a life-threatening situation, temporary disability or death.

Bleeding associated with thrombolytic therapy can be divided into two main categories:

- external bleeding (usually from the sites of puncture or damage to blood vessels);

- internal bleeding in any part or body cavity.

With intracranial hemorrhages, the following neurologic symptoms may be associated: drowsiness, aphasia, hemiparesis, convulsions.

The indication of fat embolism, not observed in the population of patients participating in clinical trials, is based on spontaneous reporting.

Compared with studies with myocardial infarction, the number of patients with pulmonary embolism and stroke who participated in clinical trials (within 0 - 4.5 hours from the onset of symptoms of these diseases) was very small. Therefore, small numerical differences noted when compared with data obtained from myocardial infarction were most likely due to a small sample size. In addition to intracranial hemorrhage (as an adverse event) in stroke and reperfusion arrhythmias (as a side effect of myocardial infarction), there are no clinical grounds for suggesting qualitative and quantitative differences in the spectrum of side effects of AKTILIZE in case of pulmonary embolism and acute ischemic stroke or myocardial infarction.

Immune system disorders:

Rarely: anaphylactoid reactions, they are usually weakly expressed, but in some cases can be life threatening; rashes, urticaria, bronchospasm, angioedema, a decrease in blood pressure, shock, or any other hypersensitivity reactions.

If these reactions develop, conventional antiallergic therapy should be used. It was found that a relatively large proportion of patients with similar reactions had angiotensin-converting enzyme inhibitors at the same time. Anaphylactic reactions (in the strict sense of this concept, that is, conditioned IgE) on AKTILIZE are not known. In rare cases (less than 0.1%) transient formation of antibodies to AKTILIZE (in low titres) was observed, but the clinical significance of this phenomenon has not been established.

Disorders from the side of the organ of vision:

Rarely: hemorrhage in the eyes.

Disorders from the cardiovascular system:

Often: bleeding (such as hematoma)

Rarely: pericardial bleeding, embolism, which may be accompanied by the corresponding consequences from the affected internal organs, bleeding to the parenchymal organs (such as hepatic bleeding, pulmonary hemorrhage).

Disturbances from the respiratory organs. organs of the thoracic cavity and mediastinum:

Infrequently: bleeding from the respiratory tract (such as bleeding from the pharynx, hemoptysis, nosebleeds).

Disorders from the gastrointestinal tract:

Often: gastrointestinal bleeding (such as gastric bleeding, bleeding from a stomach ulcer, bleeding from the rectum, bloody vomiting, melena, bleeding from the oral cavity).

Infrequently: bleeding from the gums.

Rarely: retroperitoneal bleeding (eg, retroperitoneal hematoma), nausea.

Unknown: vomiting.

Nausea and vomiting can also be symptoms of myocardial infarction.

Disturbances from the skin and subcutaneous fat:

Often: ecchymosis.

Disorders from the kidneys and urinary tract:

Often: urogenital bleeding (such as hematuria, bleeding from the urinary tract).

General disorders and reactions at the injection site:

Often: bleeding at the puncture site, bleeding at the injection site (eg, bruising at the site of the catheter, bleeding at the site of the catheter).

Reactions, identified by special studies:

Infrequently: lowering of blood pressure.

Unknown: fever.

Damage, toxic effects and complications due to procedures associated with the use of the drug:

Unknown: fat embolism.

The need for surgical and therapeutic procedures:

Unknown: need for transfusions.

Application for myocardial infarction

Heart Disease:

Infrequently: reperfusion arrhythmias (arrhythmia, extrasystole, atrial fibrillation, atrioventricular block from I degree to complete blockade, bradycardia, tachycardia, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia). Reperfusion arrhythmias can lead to cardiac arrest, endanger life and require the use of conventional antiarrhythmic therapy.

The use of myocardial infarction and pulmonary embolism

Impaired nervous system:

Often: intracranial hemorrhage (such as, a hemorrhage in a brain, cerebral hematoma, hemorrhagic stroke, hemorrhagic stroke transformation, intracranial hematoma, subarachnoid hemorrhage).

Application in ischemic stroke (acute period)

Impaired nervous system:

Often: intracranial hemorrhage (such as, cerebral hemorrhage, cerebral hematoma, hemorrhagic stroke, hemorrhagic stroke transformation, intracranial hematoma, subarachnoid hemorrhage).

The main undesirable phenomenon was symptomatic intracranial hemorrhage (their frequency reached 10%). However, there was no increase in the incidence of complications or overall mortality.

Overdose:

Despite the relative specificity of the effect of the drug on fibrin, overdose can lead to a clinically significant decrease in the level of fibrinogen and other factors of blood coagulation.

In most cases, it is sufficient to stop the introduction of AKTILISE and expect a physiological recovery of these factors. However, if serious bleeding develops, infusion of freshly frozen plasma or fresh blood is recommended; if necessary, synthetic antifibrinolytic agents can be prescribed.

Interaction:

Special studies of the interaction of AKTILIZE with other medications commonly used in acute myocardial infarction have not been carried out.

The use of drugs that affect blood clotting or altering the function of platelets before, during or after the initiation of therapy ACTUELISE may increase the risk of bleeding.

Simultaneous use of ACE inhibitors may increase the risk of anaphylactoid reactions. These reactions were observed in a relatively large proportion of patients receiving ACE inhibitors.

Special instructions:

Treatment AKTILIZE should be performed by a doctor who has experience of thrombolytic therapy and the ability to monitor its effectiveness. When using ACTYLIZE, as well as other thrombolytic drugs, it is recommended to have standard resuscitation equipment and appropriate medications.

General Precautions

Hypersensitivity

After the end of the treatment, stable formation of antibodies to the recombinant human tissue plasminogen activator was not observed. Systematized experience of re-use of ACTYLIZE is not available.

Anaphylactoid reactions associated with the use of AKTILIZE are rare and can be caused by hypersensitivity to the active substance (alteplase), gentamicin (residual traces from the production process) or to any auxiliary substance. The cork of a glass vial with lyophilisate AKTILIZE contains natural rubber (latex derivative), which can cause allergic reactions.

If an anaphylactoid reaction develops, the infusion should be stopped and appropriate treatment prescribed. It is recommended to regularly monitor the tolerability of treatment, especially in patients who are simultaneously receiving ACE inhibitors (see "Side Effects" section).

Bleeding

The most frequent complication of ACTYLIZE therapy is bleeding. The simultaneous use of heparin may contribute to the occurrence of bleeding. Since AKTILIZE dissolves fibrin, bleeding can occur from the sites of recent punctures. Therefore, thrombolytic therapy requires careful monitoring of possible bleeding zones (including places of catheter insertion, arterial and venous punctures, incisions and injections). Avoid using rigid catheters, intramuscular injections, and unreasonable manipulations during treatment with AKTILIZE.

In the event of severe bleeding, especially cerebral, fibrinolytic therapy, as well as the use of heparin should be immediately discontinued. In the event that heparin was used within 4 hours before the onset of bleeding, consideration should be given to the advisability of administering protamine.In rare cases, when the above conservative measures are ineffective, bleeding continues, and the use of blood products may be indicated. Transfusion administration of cryoprecipitate, freshly frozen plasma and platelets can be prescribed in accordance with clinical and laboratory parameters, determined repeatedly after each administration. Cryoprecipitate infusion should preferably be performed until a fibrinogen concentration of 1 g / l is achieved. You can consider the use of antifibrinolytic drugs (for example, tranexamic acid), but no special studies have been conducted.

In acute myocardial infarction and pulmonary embolism, AKTILIZE should not be used in a dose exceeding 100 mg, and for acute ischemic stroke, a dose of more than 90 mg, the risk of intracranial hemorrhage increases.

In the treatment of acute myocardial infarction, the following special warnings and precautions

Arrhythmias

Coronary thrombolysis can lead to arrhythmia associated with reperfusion. Reperfusion arrhythmias can lead to cardiac arrest, pose a threat to life and require the use of conventional antiarrhythmic therapy.

Glycoprotein antagonists Iib/IIIa

Concomitant use of glycoprotein antagonists Iib/IIIa increases the risk of bleeding.

Thromboembolism

The use of thrombolytic agents may increase the risk of thromboembolism in patients with thrombosis of the left heart, for example, with mitral stenosis or with atrial fibrillation.

In the treatment of acute ischemic stroke, the following special warnings and precautions

Treatment should be conducted under the guidance of an experienced physician who has the skills and experience of providing intensive neurological care. To control the appointment of treatment, the results of diagnostic tests performed earlier (see the section "Indications", 3. Thrombolytic therapy of ischemic instulitis in an acute period) can be appropriately taken into account.

It is necessary to monitor blood pressure (BP) during treatment and within 24 hours after its termination. With an increase in systolic blood pressure> 180 mm Hg. Art. or diastolic blood pressure> 105 mm Hg. Art. recommended intravenous use of antihypertensive drugs.

The therapeutic effect is reduced in patients who have suffered a stroke before, or in the presence of uncontrolled diabetes mellitus.In such patients, the benefit-risk ratio is considered less favorable, although it remains positive.

In patients with mild stroke, the risk is greater than the expected benefit, therefore, the use of AKTILIZE is not recommended.

In patients with severe stroke, the risk of intracranial bleeding and death is increased, in these cases, AKTILIZE should not be used.

Patients with extensive cerebral infarction have an increased risk of adverse outcome, including severe intracerebral hemorrhage and death. In such cases, the risk and benefit of therapy should be carefully weighed. In stroke, the likelihood of a favorable outcome of treatment decreases with age, and with increasing severity of stroke and increased blood glucose. At the same time, the likelihood of serious disability and death or serious intracranial hemorrhage increases regardless of treatment. ACTYLIZE should not be used in patients with severe stroke (according to clinical and / or visualization data)when the initial values of blood glucose are <2.77 mmol / l or> 22.20 mmol / l.

Reperfusion of the ishimized area can lead to brain edema in the infarction zone. Because of the increased risk of hemorrhages, the use of antiplatelet agents should not be initiated within the first 24 hours after thrombolysis with alteplase.

To date, the experience of using AKTILIZE in children is limited.

Effect on the ability to drive transp. cf. and fur:Not applicable. The drug is intended for the treatment of urgent conditions.

Form release / dosage:

Liofilizate for the preparation of a solution for infusions complete with a solvent.

Packaging:

1 bottle of colorless glass type 1, containing 50 mg of lyophilizate for the preparation of a solution for infusions, sealed with chlorobutyl stopper, rolled up with an aluminum cap and protective plastic cover "Flip off" green and 1 bottle with solvent 50 ml of colorless glass type 1. ukuporenny chlorobutyl stopper, rolled aluminum cap and protective plastic cover "Flip off" blue color together with instructions for use are enclosed in a cardboard box.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

The prepared solution can be stored in the refrigerator for 24 hours, and at a temperature of no higher than 25 ° C - up to 8 hours (on a cardboard box and on the label of the vial with lyophilizate).

At a temperature of no higher than 25 ° C (on the label of the vial with a solvent).

Keep out of the reach of children.

Shelf life:

3 years

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014214 / 01

Date of registration:31.07.2008 / 16.05.2017

Expiration Date:Unlimited

The owner of the registration certificate:Boehringer Ingelheim International GmbHBoehringer Ingelheim International GmbH Germany

Manufacturer: & nbsp

BOEHRINGER INGELHEIM PHARMA, GmbH & Co.KG Germany

Representation: & nbspBehringer Ingelheim, LLCBehringer Ingelheim, LLC

Information update date: & nbsp04.12.2017

Illustrated instructions

Instructions

Actylase® (Actilyse®)