Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions in the form of a white or pale yellow mass.
1 f. 1 ml of finished r-ra
alteplase 50 mg 1 mg
Excipients: L-arginine - 1742 mg, phosphoric acid - 536 mg, polysorbate 80 - 5 mg, gentamicin - residual traces (used in the manufacturing process).
Solvent: water d / and (50 ml).
Vials of colorless glass with lyophilizate (1) complete with a solvent (1 pc.) - cardboard boxes.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Thrombolytic. Recombinant human tissue plasminogen activator, glycoprotein, which directly activates the transformation of plasminogen into plasmin.
After intravenous administration, alteplase remains relatively inactive in the systemic circulation. It is activated by binding to fibrin, which causes the conversion of plasminogen to plasmin and leads to dissolution of the 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 the circulating fibrinogen content (up to about 60% after 4 hours), which generally rises to more than 80% by 24 hours. Concentrations of plasminogen and? 2- antiplasmin in the blood after 4 hours decrease, respectively, to 20% and 35% of the initial 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
In patients with acute myocardial infarction, two regimens of dosing of Actylize В® were studied. Comparative effectiveness of these two regimes was not carried out.
Accelerated infusion of the drug in patients with acute myocardial infarction
Four regimens of thrombolytic therapy were studied. The use of actilize В® at a dose of 100 mg for 90 min, 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 SC or IV heparin (7.3%) (p = 0.001).
3-hour infusion in patients with acute myocardial infarction
When comparing actiliside with placebo for 5 hours after the onset of symptoms, the patients receiving Actylize В® showed an increase in the 30-day survival rate, an improvement in left ventricular function in the evaluation of the ejection fraction with contrast ventriculography, a reduction in infarct size, fewer episodes of cardiogenic shock, ventricular fibrillation, pericarditis were observed, compared to 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 hemorrhages were observed in 5.9% of patients receiving Actilease В® and 1.1% of patients who received placebo, which depended on the age of the patients, but not on the time elapsed from the onset of symptoms before treatment. This analysis also confirmed that the rapid onset of the use of Actilease В® leads to better results of treatment after 3 months. There was also evidence of the possibility of expanding the "window" of the therapeutic effect to 4.5 h.
In normal clinical settings, the safety and efficacy of Actileze В® 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) was comparable in these studies, it was 7.3% and 8.6%, mortality (after 3 months) was 11.3% and 17%.
Patients with acute stroke 3-4.5 h after the onset of symptoms (patients with a neurologic 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 bleeding (ECASS III) was 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, Actylise В® , used 3-4.5 h after the onset of symptoms, significantly improves clinical outcomes in patients with acute ischemic stroke.
The safety and effectiveness of the use of actilize В® in the treatment of acute ischemic stroke, which occurs within up to 4.5 hours after the onset of symptoms, continues to be assessed in the register (SITS-ISTR: The Safe Implementation of Thrombolysis in the Stroke registry). At present, it has been established that by the age of 3 months the incidence of clinically expressed intracranial bleeding was slightly higher in the case of treatment start in 3-4.5 hours (9.13%) compared with the start of treatment during the first 3 hours (7.49%). Mortality in the case of treatment beginning 3-4.5 hours (12.4%) and for 0-3 hours (12.3%) was similar.
Actylase В® is rapidly excreted from the bloodstream and metabolized, mainly in the liver. Plasma clearance of the drug is 550-680 ml / min.
T 1/2 in the? -phase 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, which remains deep in the tissues of T 1/2 in the? -phase is about 40 minutes.
When Aktilize В® 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.
- Thrombolytic therapy of acute myocardial infarction in the first 6 hours after the development of symptoms (90-minute / fast / dosing regimen) or in the period from 6 to 12 hours after the development of symptoms (3-hour dosing regimen). It is proved that in case of acute myocardial infarction Actylise В® reduces mortality in the first 30 days after the onset of the infarction;
- Thrombolytic therapy of massive pulmonary thromboembolism accompanied by unstable hemodynamics. The 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 outcomes of pulmonary embolism have not been conducted;
- Thrombolytic therapy of ischemic stroke in an acute period. Treatment should begin as early as possible, within 4.5 hours after the onset of stroke symptoms and after the elimination of intracranial bleeding by an adequate imaging technique (using appropriate imaging techniques such as a CT scan or other diagnostic method sensitive to bleeding detection , MRI) .The effect of treatment depends on the time of its onset, that is, earlier treatment increases the likelihood of a favorable outcome.
Actylase В® should be used as soon as possible after the onset of symptoms.
With myocardial infarction with a 90-minute (accelerated) dosing regimen for patients in whom treatment can be initiated within 6 hours after the onset of symptoms, the drug is administered at a dose of 15 mg IV, then 50 mg in the form of an IV infusion for the first 30 minutes, followed by an infusion of 35 mg for 60 minutes until the maximum dose of 100 mg is reached.
In patients with a body weight of less than 65 kg, the dose of the drug should be calculated depending on the body weight. Initially, the drug is administered at a dose of 15 mg IV, then 0.75 mg / kg body weight (max. 50 mg) for 30 minutes in / drip, followed by an infusion of 0.5 mg / kg (maximum 35 mg) for 60 min .
With a 3-hour dosing regimen for patients in whom treatment can be initiated between 6 hours and 12 hours after the onset of symptoms, the drug is given at a dose of 10 mg IV in struino, then 50 mg in the form of an IV infusion over a the first hour, followed by iv infusion of 10 mg for 30 minutes until the maximum dose of 100 mg was 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 Actileze В® for acute myocardial infarction is 100 mg.
Auxiliary antithrombotic therapy is indicated in patients with myocardial infarction with ST-segment elevation according to current international recommendations.
With thromboembolism of the pulmonary artery, Actylise В® is administered in a total dose of 100 mg for 2 hours. The greatest experience was obtained using the following dosing regimen: first the drug is administered at a dose of 10 mg IV for 1 to 2 minutes, then 90 mg / in a 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 body weight.
Auxiliary therapy: after the application of Actilease В® , if the APTT is less than twice the IGNT, the infusion application of heparin should be prescribed (or continued). The dose of heparin should be adjusted to maintain the APTT between 50-70 seconds (values вЂ‹вЂ‹should exceed the baseline by 1.5-2.5 times).
In ischemic stroke (acute period), the recommended dose is 0.9 mg / kg (maximum 90 mg), as an IV infusion 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. Therefore, in the first 24 hours after the initiation of therapy with Actylise В®, the use of acetylsalicylic acid or IV injection of heparin should be avoided. If the use of heparin is required for other indications (for example, for prophylaxis of deep vein thrombosis), its dose should not exceed 10,000 IU per day, with the drug being injected w / c.
Rules for the preparation of a solution for infusions
To obtain a final alteplase concentration of 1 mg / ml, the entire volume of the supplied solvent (sterile water for injection) (50 ml) should be added under aseptic conditions to the Aktilis Lot В® containing the lyophilizate (50 mg).
Aquilize Bottle В® 50 mg
The volume of sterile water for injection, added to a dry substance of 50 ml
Final concentration 1 mg / ml
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 Actylise В® should not be mixed with other drugs (even with heparin), neither in the vial for infusions, nor in the general system for intravenous administration.
The use of myocardial infarction, pulmonary embolism and ischemic stroke in an acute period
The most common adverse reaction associated with the use of Actilease В® 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 places 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.
In comparison 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 adverse effects of the drug Actilease В® in case of pulmonary embolism and acute ischemic stroke, or with myocardial infarction.
On the part of the immune system: 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 simultaneously used ACE inhibitors. Anaphylactic reactions (in the strict sense of this concept, that is, caused by IgE) are not known on Actilez В® . In rare cases (less than 0.1%) transient formation of antibodies to Actylase В® (in low titers) was observed, but the clinical significance of this phenomenon has not been established.
From the side of the organ of vision: hemorrhage into the retina of the eye.
From the cardiovascular system: pericardial bleeding, bleeding (such as hematoma); Embolisms, which can be accompanied by corresponding consequences from affected internal organs; bleeding to the parenchymal organs (such as intrahepatic bleeding, pulmonary hemorrhage).
On the part of the respiratory system: bleeding from the respiratory tract (such as bleeding from the pharynx, hemoptysis, nosebleed).
From the digestive system: gastrointestinal bleeding (such as gastric bleeding, bleeding from stomach ulcers, rectal bleeding, bloody vomiting, melena, bleeding from the oral cavity, bleeding from the gums, retroperitoneal bleeding (eg, retroperitoneal hematoma), nausea, Vomiting Nausea and vomiting can also be symptoms of myocardial infarction.
From the skin: ecchymosis.
From the urinary system: urogenital bleeding (such as hematuria, bleeding from the urinary tract).
General disorders and reactions at the injection site: 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 in special studies: lowering blood pressure, increasing body temperature.
Complications due to procedures associated with the use of the drug: fat embolism.
The need for surgical and therapeutic procedures: the need for transfusions.
Application for myocardial infarction
From the side of the cardiovascular system: reperfusion arrhythmia (arrhythmia, extrasystole, atrial fibrillation, AV 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
From the side of the nervous system: intracranial hemorrhage (such as cerebral hemorrhage, cerebral hematoma, hemorrhagic stroke, hemorrhagic stroke transformation, intracranial hematoma, subarachnoid hemorrhage).
Application in ischemic stroke (acute period)
From the side of the nervous system: 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, the increase was not established morbidity or total mortality.
- increased sensitivity to the active ingredient (alteplase), gentamicin (residual traces of the manufacturing process) or any excipient.
The drug should not be used if at increased risk of bleeding:
- extensive bleeding now or within the previous 6 months;
- hemorrhagic diathesis;
- simultaneous effective treatment with oral anticoagulants, such as warfarin (INR> 1.3);
- CNS disease history (including neoplasm, aneurysm, surgery on the brain or spinal cord);
- intracranial (including subarachnoid) hemorrhage now or in the anamnesis;
- suspicion of hemorrhagic stroke;
- severe uncontrolled hypertension;
- major surgery or severe trauma within the previous 10 days (including any injury received on the background of developing myocardial infarction);
- recently transferred traumatic brain injury;
- long or traumatic cardiopulmonary resuscitation (over 2 min);
- birth within the previous 10 days;
- newly manufactured needling incompressible blood vessels (e.g., subclavian or jugular Vienna);
- severe liver disease including liver failure, cirrhosis, portal hypertension (including with esophageal varices), active hepatitis;
- bacterial endocarditis, pericarditis;
- confirmed gastric ulcer and duodenal ulcer in the past 3 months;
- arterial aneurysms, malformations of the arteries and veins;
- neoplasm with increased bleeding risk;
- Hypersensitivity to the components of the drug.
In the case of a drug for the treatment of acute myocardial infarction and pulmonary embolism , besides the above mentioned contraindications, there are the following contraindications:
- stroke, hemorrhagic stroke or a history of unknown etiology;
- an ischemic stroke or transient ischemic attack within the past 6 months (excluding the current acute ischemic stroke within 4.5 hours).
In the case of treatment for acute ischemic stroke , besides the above mentioned contraindications, there are the following contraindications:
- the beginning of ischemic stroke symptoms for more than 4.5 hours before the start of the infusion, or the absence of accurate information about the time of onset of the disease;
- a rapid improvement in acute ischemic stroke or mild symptoms at time of the start of infusion;
- heavily flowing stroke, based on the clinical data (e.g., if the exponent NIHSS (National Institutes of Health Stroke Scale ))> 25) and / or from appropriate imaging techniques (computed tomography or nuclear magnetic resonance);
- cramps in the beginning of stroke;
- information about a stroke or serious head injury during the previous 3 months;
- the occurrence of previous stroke and diabetes mellitus;
- the use of heparin within 48 hours prior to stroke if APTT increased at a given time;
- platelet count <100,000 / mm;
- systolic blood pressure above 185 mmHg or diastolic blood pressure above 110 mmHg or the need for intensive care (w / w administering medications) to reduce blood pressure to such limits;
- the concentration of blood glucose <3 or> 20 mmol / l.
The drug Micardis В® is not indicated for the treatment of acute stroke in children and adolescents under the age of 18 years.
Use of the drug in patients older than 80 years (see. Section "Precautions").
With care, pre-assessing the degree of the intended use and the possible risk of bleeding, use in patients with:
- newly formed / m or smaller injection recent interventions such as biopsy (needle), needling (needle) of large vessels, cardiac massage resuscitation;
- diseases (not mentioned in the list of contraindications), with increased risk of bleeding;
- simultaneous reception of oral anticoagulation treatment with Actilyse В® can only be considered when laboratory parameters anticoagulant activity are not clinically significant.
When the treatment of acute myocardial infarction and acute pulmonary embolism should further bear in mind the following special warnings and precautions:
- Systolic blood pressure> 160 mm Hg .;
- old age, at which may increase the risk of intracranial hemorrhage. Because elderly patients the likelihood of a positive outcome of the treatment is also increased, requires careful assessment of benefit / risk ratio.
In the treatment of acute ischemic stroke should be further borne in mind the following special warnings and precautions:
Application Actilyse В® in patients with acute ischemic stroke, compared with the use of this drug in other indications, accompanied by an increased risk of intracranial hemorrhage, since bleeding occurs predominantly in necrotic area . This is especially to be taken into account in the following cases:
- all conditions characterized by a high risk of bleeding;
- The presence of small asymptomatic aneurysms of cerebral blood vessels;
- Delay the start of treatment;
- patients who have previously been treated with acetylsalicylic acid or other antiplatelet agents, possible increased risk of intracerebral hemorrhage, especially if the application of Actilyse В® initiated at a later time. Given the increased risk of cerebral hemorrhage, alteplase applied dose should not exceed 0.9 mg / kg (maximum dose of 90 mg);
- in patients older than 80 years, compared with younger patients, may increase the risk of brain hemorrhage and decrease the overall benefits of treatment. Therefore, the application of Actilyse В®must be carefully considered and dealt with individually according to the perceived risk.
Treatment should not start later than 4.5 h after the onset of symptoms, due to the unfavorable benefit / risk ratio, which is caused by the following circumstances:
- a positive treatment effect decreases during the late start of therapy;
- increased mortality mainly in patients previously treated with acetylsalicylic acid;
- increases the risk of bleeding.
PREGNANCY AND LACTATION
Experience of using Actilyse В® during pregnancy and lactation is very limited. In preclinical studies conducted with alteplase in doses exceeding the doses used in humans, showed signs of immaturity of the fetus and / or embryotoxicity, considered a consequence of the pharmacological activity of the drug. Alteplase is not teratogenic.
In diseases directly life threatening, it is necessary to weigh the relationship between the benefits and potential risks. In connection with this application Actilyse В®during pregnancy and lactation is not recommended.
Question about the penetration of alteplase in the breast milk of women has not been studied.
Clinical data on the effect of Micardis В®on fertility are not available.
In preclinical studies, the negative effect of alteplase on fertility has been established.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe liver disease including liver failure, cirrhosis, portal hypertension (esophageal varicose veins), active hepatitis.
APPLICATION FOR CHILDREN
To date, experience with Actilyse В® in children is limited.
APPLICATION IN ELDERLY PATIENTS
In patients older than 80 years, compared with younger patients, may increase the risk of brain hemorrhage and decrease the overall benefits of treatment. Therefore, the application of Actilyse В® should be carefully considered and dealt with individually according to the perceived risk.
Treatment Actilyse В® should hold a doctor who has experience of thrombolytic therapy and the ability to monitor its effectiveness. When using Actilyse В® , as well as other thrombolytic agents, it is advisable to have available standard resuscitation equipment and related drugs.
After treatment sustained production of antibodies against recombinant human tissue plasminogen activator were not observed. Systematic reuse experience ActilyseВ® not available. Anaphylactoid reactions associated with the use of Actilyse В®Are rare and may be caused by hypersensitivity to the active substance (Alteplase), gentamicin (residual traces of the manufacturing process) or any excipient. Stopper glass vial with lyophilized Actilyse В® contains natural rubber (latex derivative thereof) which may cause allergic reactions. In the case of anaphylactoid reaction, the infusion should be discontinued and appropriate treatment. It recommended regular monitoring of the tolerability of treatment, especially in patients concomitantly receiving ACE inhibitors.
The most common complication of therapy Actilyse В® is bleeding.
The simultaneous use of heparin may contribute to bleeding. Since Actilyse В® dissolves fibrin may occur bleeding of the locations recent puncture. Therefore, thrombolytic therapy requires careful monitoring for possible bleeding zones (including the insertion site of the catheter, arterial and venous punctures, cuts and injections). Avoid using rigid catheters, v / m and unwarranted manipulation injection during treatment Micardis В® .
In case of severe bleeding (especially cerebral), fibrinolytic therapy, as well as the use of heparin should be stopped immediately. If, within 4 hours before the onset of bleeding, heparin was used, should consider the appropriateness of the use of protamine.
In rare cases, when the above conservative measures are ineffective, bleeding continues, it shows the use of blood products. Transfusion administering cryoprecipitate, fresh frozen plasma and platelets should be used in accordance with clinical and laboratory parameters determined again after each administration. Infusion of cryoprecipitate preferably carried out until a fibrinogen concentration of 1 g / l. It is possible to consider the use of antifibrinolytic agents (e.g., tranexamic acid), however, special studies have been conducted.
In acute myocardial infarction and pulmonary embolism should not be used Actilyse В®at a dose exceeding 100 mg, and in acute ischemic stroke - in a dose of 90 mg, as increased risk of intracranial hemorrhage.
In the treatment of acute myocardial infarction should further bear in mind the following special warnings and precautions:
Coronary thrombolysis may result in arrhythmias associated with reperfusion.
Reperfusion arrhythmias may lead to cardiac arrest, life-threatening and require the use of conventional antiarrhythmic therapies.
The antagonists of the glycoprotein IIb / IIIa
Concomitant use of antagonists of the glycoprotein IIb / IIIa increases the risk of bleeding.
The use of thrombolytic agents may increase the risk of venous thromboembolism in patients with thrombosis of the left heart, such as mitral stenosis or atrial fibrillation.
In the treatment of acute stroke should further bear in mind the following special warnings and precautions:
Treatment should be carried out exclusively by an experienced doctor who have skills and experience in providing intensive neurological care. To control the appointment of treatment can be appropriately taken into account the results of diagnostic surveys conducted previously.
It is necessary to monitor blood pressure during treatment and for 24 hours after its closure. With an increase in systolic blood pressure> 180 mm Hg or diastolic BP> 105 mmHg recommended I / use of antihypertensive drugs.
The therapeutic effect is reduced in patients undergoing earlier stroke, or in the presence of uncontrolled diabetes. In these patients, the ratio of benefit-risk is considered less favorable, but still remained positive.
In patients with mild stroke risk is greater than the expected benefits, so the use of Actilyse В® is not recommended.
In patients with severe stroke are at increased risk of intracranial hemorrhage and death in these cases, Micardis В® should not be used.
In patients with large cerebral infarction there is an increased risk of adverse outcomes, including expressed intracerebral hemorrhage and death. In such cases, you should carefully weigh the risks and benefits of therapy.
Stroke probability of a favorable outcome of treatment is reduced with increasing age, as well as increase the degree of severity of stroke and at an elevated blood glucose concentration. At the same time, the probability of a serious breach of legal capacity, and death or serious intracranial hemorrhage is increased regardless of treatment. Actilyse В®should not be used in patients with a severe form of stroke (clinical data and / or data imaging studies) and in those cases where the initial blood glucose value was <50 mg / dL or> 400 mg / dl.
Reperfusion of the ischemic area can lead to brain edema in the infarcted area. Because of the increased risk of hemorrhages use of antiplatelet agents should not be initiated within the first 24 hours after thrombolysis via alteplase.
Use in Pediatrics
To date, experience with Actilyse В® in children is limited.
Symptoms: in spite of the relative specificity to fibrin, an overdose may experience clinically significant reduction in fibrinogen and clotting factors.
Treatment: in most cases sufficient watchful waiting with the expectation of physiological regeneration of these factors after cessation of Micardis В® . In the event of severe bleeding recommended transfusion of fresh frozen plasma or whole blood and may have a synthetic Antifibrinolytics if necessary.
Specific interaction studies Actilyse В® with other drugs normally used in acute myocardial infarction, was conducted.
Application of medicaments influencing blood coagulation or platelet function altering, before, during or after the initiation of therapy Actilyse В® may increase the risk of bleeding.
The simultaneous use of ACE inhibitors may increase the risk of anaphylactoid reactions. These reactions are observed in a relatively large proportion of patients treated with ACE inhibitors.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored protected from light at a temperature not higher than 25 В° C. Shelf life - 3 years.
The prepared solution can be refrigerated for 24 hours; at a temperature not exceeding 25 В° C - to 8 hours.