Purolase, lyophilizate. 2 mln.me 50 ml

Pharmacological action

Thrombolytic. Recombinant fibrin-specific plasminogen activator of urokinase type.

It is a single chain molecule with molecular weight 46000 Da consisting of two polypeptide chains-domains with molecular weight 17000 and 29000 Da, which contain regulatory part and catalytic enzyme domain, respectively, and are connected by disulfide bridge. Due to its regulatory part, it specifically interacts with fibrin-linked plasminogen and catalyzes the conversion of plasminogen to plasmin, a protease capable of lysing fibrin clots (thrombi).

Pharmacokinetics

Data on the pharmacokinetics of the drug Purolase have not been provided.

Indications

Active ingredient

Composition

How to take, the dosage

Intravenous administration only

The drug should be administered as soon as possible within the first 6 hours of the onset of clinical symptoms. It is permissible to administer the drug within 6 to 12 hours of the onset of the disease if appropriate indications for thrombolytic therapy exist. It should be taken into account that the effectiveness of thrombolytic therapy during this period may decrease.

The recommended total dose of the drug should not exceed 100,000 IU/kg body weight.

The drug may be given as a “double bolus” or “bolus plus infusion” regimen.

Dual bolus administration.

The drug is administered intravenously in a “double bolus” regimen: first bolus 4,000,000 ME + second bolus (0 ¸ 4,000,000) ME, at a dose of 4,000,000 ¸ 8,000,000 ME, depending on the patient’s body weight according to Table 1.

The dose of the first bolus must not exceed 4,000,000 ME.

The route of administration:

The contents of two vials of the drug (4,000,000 ME) are carefully dissolved in 40 ml of 0.9% sodium chloride solution (20 ml for each vial) and the entire volume (40 ml) is given intravenously as a first bolus by trickling. If the patient weighs more than 60 kg, a second additional bolus is administered at a dose according to Table 1. For this purpose, the contents of the additional vial(s) of drug are dissolved in 20 ml of 0.9% sodium chloride solution and 10-40 ml (1,000,000-4,000,000 ME) of the total volume is given 25 min after the first bolus intravenously as a second bolus by jetting.

To ensure reliable solubility of the drug, dissolve each vial in 20 mL of 0.9% sodium chloride solution, not less. The concentration of the drug solution in 0.9% sodium chloride solution should not exceed 100,000 IU/ml. The drug solution is prepared immediately before use and should not be stored.

Injection of the drug by bolus + infusion.

In patients weighing 60 to 85 kg, the drug is given intravenously in a total dose of 6 000 000 ME (2 000 000 ME bolus followed by 4 000 000 ME as an infusion for 60 minutes).

In patients weighing more than 85 kg, the drug is administered intravenously in a total dose of 8,000,000 ME (2,000,000 ME bolus followed by 6,000,000 ME as an infusion for 60 minutes).

In patients weighing less than 60 kg, the drug is administered intravenously according to the regimen: 2,000,000 ME bolus followed by an infusion for 60 minutes, the dose of which is calculated according to the formula:

100,000 IU/kg × [body weight in kg] minus 2,000,000 ME.

The scheme of administration of the drug:

The contents of one vial (2,000,000 ME) are dissolved in 20 ml of 0.9% sodium chloride solution and administered bolus. For preparation of infusion solution the contents of two (4 000 000 ME) or three (6 000 000 ME) vials are dissolved in 0.9% sodium chloride solution (20 ml per vial), then the total volume of solution is adjusted to 100 ml and given intravenously for 60 min.

To ensure reliable solubility of the drug, dissolve each vial in 20 ml of 0.9% sodium chloride solution, not less. The concentration of the drug solution in 0.9% sodium chloride solution should not exceed 100,000 IU/ml. The drug solution is prepared immediately before use and should not be stored.

Interaction

Special Instructions

Treatment of myocardial infarction should be performed by qualified specialists according to the standards of medical care for patients with acute myocardial infarction with the mandatory use of anticoagulant and antiplatelet therapy.

Particular recommendations for the use of anticoagulant and antiplatelet therapy to increase the effectiveness of Purolaza® therapy.

The simultaneous use of acetylsalicylic acid, clopidogrel and heparin is recommended and should be administered immediately after the diagnosis of acute myocardial infarction is established. The recommended initial dose of acetylsalicylic acid is 160-250 mg. In this case, for a rapid onset of action of the drug, it is necessary to use a tablet of acetylsalicylic acid not coated with an enteric coating.

The first dose should always be chewed and wait until it is absorbed from the mouth. Subsequently, it is recommended that acetylsalicylic acid be taken at a dose of 75-100 mg per day indefinitely after a heart attack.

Clopidogrel is used at a loading dose of 300 mg with transition to a maintenance dose of 75 mg per day for the first 12 months after a myocardial infarction. Heparin dose is calculated depending on body weight. Heparin infusion is recommended to start with intravenous bolus of 60 IU/kg, but not more than 4000 IU, with subsequent infusion of heparin during 24-48 hours at a rate of 1000 IU/h, under control of AHTV every 3 hours until increase of AHTV by 2-2.5 times higher than initial values.

Synopsis

Contraindications

– Illnesses manifested by increased bleeding (hemorrhagic diathesis – hemophilia, thrombocytopenia, etc.) or conditions of high risk of bleeding.

– Hypersensitivity to the drug;

– Extensive surgery or major trauma up to 4 weeks old;

– Resuscitative measures requiring intensive indirect cardiac massage, including cardiopulmonary resuscitation for more than 10 minutes;

– Cardiogenic shock (Killip class IV);

– Liver disease with significant hemostasis disorders;

– Puncture of compression vessels (v. subclavia);

– Diabetic hemorrhagic retinopathy;

– Prior hemorrhagic stroke;

– Systolic blood pressure (BP) ³ 180 mm. Hg or diastolic BP ³ 110 mmHg, Refractory to treatment;

– Suspected aortic dissection;

– Septic endocarditis;

– Pregnancy, lactation;

– Children under 18 years of age, because the effectiveness and safety of the drug in this group has not been studied.

Side effects

Bleeding of varying severity. If local bleeding develops (e.g., from puncture sites, gums, etc.), which are the most common side effects of the drug, usually no additional interventions are required. If serious complications develop – internal bleeding (decrease in hemoglobin by more than 3 g/dL), immediate stopping of the drug and, if necessary, blood transfusion is required.

If hemorrhagic stroke is suspected, an urgent consultation with a neurologist and appropriate examination (CT scan, etc.) and treatment is required.

Effective coronary thrombolysis may be accompanied by the occurrence of reperfusion arrhythmias, which may require conventional antiarrhythmic therapy.

The administration of the drug in therapeutic doses generally does not result in a decrease of BP.

Allergic reactions when administering the drug are usually not observed or expressed very mildly. If allergic reactions develop, generally accepted antiallergic therapy is used. Anaphylactic reactions (i.e., caused by IgE) have not been observed even with repeated administration of the drug.

Overdose

Symptoms: hemorrhagic complications.

Treatment: Minor bleeding can be stopped without stopping the drug by temporarily stopping the heparin infusion with additional monitoring of the activated partial thromboplastin time (APT).

In the event of life-threatening bleeding, the drug administration should be stopped and fresh frozen plasma or whole blood should be administered. If necessary, an antifibrinolytic agent, such as aminocapro or tranexamic acid, may be given to neutralize the effects of the drug.

Similarities