Actilyse [Alteplase]

Actilyse should be applied as early as possible from the onset of symptoms.
Withmyocardial infarction with a 90-minute (accelerated) dosing regimen for patients in whom treatment can be initiated within 6 h after the development of symptoms,the drug is administered at a dose of 15 mg i.v. in a jet, then 50 mg as an intravenous 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 prescribed in a dose of 15 mg IV bolus, then 750 μg / kg body weight (maximum 50 mg) for 30 minutes IV a drip, followed by infusion of 500 μg / kg (maximum 35 mg) for 60 minutes .
Withmyocardial infarction with a 3-hour dosing regimen for patients in whom treatment can be initiated between 6 h and 12 h after the development of symptoms, the drug is prescribed at a dose of 10 mg IV bolus, then 50 mg as an intravenous infusion for the first hour, followed by an IV infusion 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 Actilyse in acute myocardial infarction is 100 mg.
Auxiliary therapy: Acetylsalicylic acid should be prescribed as soon as possible after the onset of thrombosis and continue to be taken during the first months after a myocardial infarction. The recommended dose is 100-300 mg / day. At the same time, heparin should be used for a period of 24 hours or more (with an accelerated dosing regimen of at least 48 hours). It is recommended to start with iv injection of heparin at a dose of 5000 U / h before starting thrombolytic therapy. Subsequently, heparin is administered infusionally at a rate of 1000 U / h. The dose of heparin should be adjusted depending on the results of repeated determination of the APTT (values ​​should be 1.5-2.5 times the initial level).
Withpulmonary embolism Actilyse 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 in a jet for 1-2 minutes, then 90 mg IV drip for 2 h. In patients with a body weight less than 65 kg, the total dose should not exceed 1.5 mg / kg body weight.
Auxiliary therapy: after the use of Actilyse, if the APTT is less than 2 times the initial level, heparin should be prescribed (or continued). Further infusion is also carried out under the control of APTT, which should not exceed the baseline level more than 1.5-2.5 times.
Withischemic stroke The recommended dose is 900 mcg / kg (maximum 90 mg), as an intravenous infusion for 60 minutes after the initial intravenous injection dose of 10% of the total dose. Therapy should be started as soon as possible after the onset of symptoms (preferably within 3 hours).
Auxiliary therapy: The safety and efficacy of the above treatment regimen, used in combination with heparin and acetylsalicylic acid in the first 24 hours after the onset of symptoms, are not well understood. In this regard, in the first 24 hours after the start of therapy, the use of acetylsalicylic acid or iv heparin should be avoided. If the use of heparin is required for other indications (for example, for the prevention of deep vein thrombosis), its dose should not exceed 10,000 IU per day, while the drug is injected s / c.

The clinical experience of using Actilyse during pregnancy and lactation is limited. The issue of isolating alteplazy with breast milk has not been studied.
If necessary, the use of the drug (diseases that directly threaten life) during pregnancy and lactation should assess the expected benefits of therapy for the mother and the potential risk to the fetus or infant.

In the following cases, when Actilyse is prescribed, the degree of perceived benefit and possible risk of bleeding should be carefully evaluated:
- a recent intramuscular injection or minor recent interventions, such as a biopsy, puncture of large vessels, heart massage during resuscitation;
- diseases (not mentioned in the list of contraindications) for which the risk of bleeding is increased.
In the treatment of acute myocardial infarction and acute pulmonary embolism, the drug should be used with caution:
- with systolic blood pressure above 160 mm Hg. v .;
- in old age, when the risk of intracranial hemorrhage may increase. Since in elderly patients the probability of a positive outcome of this treatment also increases, a careful evaluation of the benefit / risk ratio is necessary.
In the treatment of acute ischemic stroke, the drug should be used with caution, because the use of Actilyse in this category of patients (compared to the use of this drug for other indications) is accompanied by a markedly increased risk of intracranial hemorrhage, since the bleeding occurs mainly in the necrotic area.
This should especially be taken into account in the following cases:
- all conditions listed in the section "Contraindications", and in general, all conditions characterized by a high risk of bleeding;
- the presence of small asymptomatic cerebral vascular aneurysms;
- in patients who have previously been treated with acetylsalicylic acid or other antiplatelet agents, an increased risk of intracerebral hemorrhage is possible, especially if the use of Actilyse was started at a later date. Given the increased risk of cerebral hemorrhage, the dose of alteplase used should not exceed 900 mcg / kg (the maximum dose is 90 mg).
Treatment should not begin later than 3 hours after the onset of symptoms, due to an unfavorable benefit / risk ratio, due to the following circumstances:
- The positive effect of treatment decreases with late initiation of therapy;
- mortality increases mainly in patients who previously received acetylsalicylic acid;
- the risk of bleeding increases.
Treatment Actilyse should be carried out by a physician with experience in thrombolytic therapy and the ability to control its effectiveness. When using Actilyse, it is recommended to have available standard resuscitation equipment and appropriate medicines.
Bleeding is the most common complication of Actilyse therapy. The simultaneous use of heparin may contribute to the occurrence of bleeding. As Actilyse dissolves fibrin, bleeding from recent puncture sites may occur. Therefore, thrombolytic therapy requires careful monitoring of areas of possible bleeding (including the insertion of a catheter, arterial and venous punctures, incisions and injections). The use of hard catheters, intramuscular injections and unreasonable manipulations during the treatment of Actilyse should be avoided.
In the event of severe bleeding, especially cerebral, fibrinolytic therapy, as well as the use of heparin should be immediately discontinued. If heparin was used for 4 hours prior to the onset of bleeding, consideration should be given to the advisability of using protamine. In rare cases where the above conservative measures are ineffective, the use of blood products may be indicated. Transfusion administration of cryoprecipitate, fresh frozen plasma and platelets can be prescribed in accordance with clinical and laboratory parameters, which are determined again after each injection. Infusion of cryoprecipitate is preferably carried out to achieve a fibrinogen concentration of 1 g / l. You can consider the use of antifibrinolytic agents (for example, tranexamic acid), but no special studies have been conducted.
In acute myocardial infarction and pulmonary embolism, Actilise should not be used in a dose exceeding 100 mg, and in acute ischemic stroke in a dose of more than 90 mg, since increases the risk of intracranial hemorrhage.
After the end of treatment, stable formation of antibodies to the recombinant human tissue tissue activator plasminogen was not observed. Systematic experience re-use of Actilyse is not available. In case of anaphylactoid reaction, the infusion should be stopped and appropriate treatment should be prescribed. Regular monitoring of treatment tolerability is recommended, especially for patients who simultaneously receive ACE inhibitors.
In the treatment of acute myocardial infarction, the following precautions should also be kept in mind:
- coronary thrombolysis may lead to arrhythmias associated with reperfusion;
- Experience with the use of glycoprotein IIb / IIIa antagonists during the first 24 hours after the start of treatment is absent;
- 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 stroke, the following precautions should be kept in mind.
Treatment should be carried out exclusively by an experienced doctor with skills and experience in providing intensive neurological care, in a specialized department, with the ability to conduct the full range of neuroimaging studies.
It is necessary to monitor blood pressure during treatment and within 24 hours after its completion. With an increase in systolic blood pressure above 180 mm Hg. Art. or diastolic blood pressure below 105 mm Hg. Art. recommended IV the use of antihypertensive drugs.
The therapeutic effect is reduced in patients who have had a previous stroke, or in the presence of uncontrolled diabetes. In such patients, the benefit / risk ratio is considered less favorable, although it still remains positive. In patients with a very small stroke, the risk exceeds the expected benefit, so the use of Actilyse is not recommended.
Patients with very severe stroke have an increased risk of intracranial bleeding and death. In these cases, Actilyse should not be used.
In patients with extensive cerebral infarctions, there is an increased risk of adverse outcome, including pronounced 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 increasing age, as well as with increasing severity of stroke and with elevated levels of glucose in the blood. At the same time, the likelihood of a serious disability and death or serious intracranial hemorrhage increases, regardless of treatment. Actilyse should not be used in patients over 80 years of age, in the case of severe stroke (according to clinical data and / or according to imaging studies), and in cases where the initial blood glucose values ​​are less than 50 mg / dL or more than 400 mg / dL.
Reperfusion of the ischemic region can lead to swelling of the brain in the infarction area. Because of the increased risk of hemorrhage, the use of platelet aggregation inhibitors should not be started during the first 24 hours after thrombolysis with alteplase.
Use in Pediatrics
Currently, the experience of using Actilyse in children is limited.

Symptoms: despite the relative specificity for fibrin, overdose may have a clinically significant decrease in fibrinogen levels and blood coagulation factors.
Treatment: in most cases, a wait-and-see tactic is sufficient with a view to the physiological regeneration of these factors after the termination of the administration of Actilize.If severe bleeding occurs, transfusion of fresh frozen plasma or fresh whole blood is recommended, if necessary, synthetic antifibrinolytics can be prescribed.