Enixum Injection solution 8000 anti-Ha IU/0.8 ml (10000 anti-Ha IU/1.0 ml) 0.8 ml ampoule, 10 pcs.

Composition

Active ingredient: enoxaparin sodium 8000 anti-Xa IU (80 mg); excipients: water for injection-up to 0.8 ml

. Pharmacological action

Pharmacotherapeutic group: direct-acting anticoagulant.

ATX code: B 01 AB 05

Pharmacological properties

Characteristic Enoxaparin sodium is a low molecular weight heparin. Average molecular weight about 4500 daltons: less than 2000 daltons – < 20%,2000 to 8000 daltons – > 68%, more than 8000 daltons – < 20%,2000 to 8000 daltons – > Enoxaparin sodium is obtained by alkaline hydrolysis of benzyl ether of heparin isolated from the mucosa of the small intestine of pigs. Its structure is characterized by a non-reducing fragment of 2-O-sulfo-4-enpyrazinosuronic acid and a reducing fragment of 2-N,6-O-disulfo-D-glucopyranoside. The structure of enoxaparin sodium contains about 20% (ranging from 15% to 25%) of the 1,6-anhydro derivative in the reducing fragment of the polysaccharide chain. Pharmacodynamics In vitro enoxaparin sodium has high activity against coagulation factor Xa (anti-Xa activity is approximately 100 IU / ml) and low activity against coagulation factor IIa (anti-IIa or antithrombin activity is approximately 28 IU / ml). This anticoagulant activity is mediated by antithrombin III (AT-III). In addition to anti-Xa/IIa activity, additional anticoagulant and anti-inflammatory properties of enoxaparin sodium have also been identified in both human and animal models, which include AT-III dependent inhibition of other clotting factors such as Factor VIIa, activation of the release of the tissue factor pathway inhibitor, and decreased release of von Willebrand factor from the vascular endothelium into the bloodstream. These factors contribute to the overall anticoagulant effect of enoxaparin sodium. When used in prophylactic doses, enoxaparin sodium slightly changes the activated partial thromboplastin time( APTT), practically does not affect platelet aggregation and the degree of binding of fibrinogen to platelet receptors. Anti-IIa activity in plasma is approximately 10 times lower than anti-Xa activity. The average maximum anti-IIa activity is observed approximately 3-4 hours after subcutaneous administration and reaches 0.13 IU / ml and 0.19 IU / ml after repeated administration of 1 mg/kg of body weight-with a double administration and 1.5 mg/kg of body weight – with a single administration, respectively. The average maximum anti-Xa plasma activity is observed 3-5 hours after subcutaneous administration of the drug and is approximately 0.2; 0.4; 1.0 and 1.3 anti-Xa IU / ml after subcutaneous administration of 20 mg,40 mg and 1 mg / kg and 1.5 mg/kg, respectively.

Pharmacokinetics

The pharmacokinetics of enoxaparin sodium in therapeutic doses are linear. Variability within and between patient groups is low. After a single subcutaneous administration of Enixum® at a dose of 1 mg/kg, Cmax is 0.49±0.07 IU / ml, Tmax is 3.19+1.08 hours, and AUC0–24 = 4.44+0.91 IU×ml/hour. According to the literature, after repeated subcutaneous administration of enoxaparin sodium at a dose of 40 mg once a dayand subcutaneous administration of enoxaparin sodium at a dose of 1.5 mg/kg once a day, the equilibrium concentration is reached by day 2, and the area under the pharmacokinetic curve is on average 15% higher than after a single administration. After repeated subcutaneous administration of enoxaparin sodium at a daily dose of 1 mg/kg twice a day, the equilibrium concentration is reached in 3-4 days, and the area under the pharmacokinetic curve is on average 65% higher than after a single administration. The bioavailability of enoxaparin sodium with subcutaneous administration, estimated on the basis of anti-Xa activity, is close to 100%.

The volume of distribution of anti-Xa activity of enoxaparin sodium is approximately 5 liters and approaches the volume of blood. Enoxaparin sodium is a low-clearance drug. After intravenous administration for 6 hours at a dose of 1.5 mg/kg of body weight, the average plasma clearance of anti-Xa was 0.74 l / h.

Enoxaparin sodium is mainly metabolized in the liver by desulfation and / or depolymerization to form low-molecular-weight substances with very low biological activity.

Elimination of the drug is monophasic with a half-life (T 1/2) of 4 hours (after a single subcutaneous injection) and 7 hours (after repeated administration of the drug). Renal excretion of active fragments of the drug is approximately 10% of the administered dose and the total excretion of active and inactive fragments is approximately 40% of the administered dose.

Elderly patients: Elimination is delayed due to a physiological decrease in renal function. This change does not affect the dosage and mode of administration during preventive therapy, if the function of the ventricles of such patients remains within acceptable limits, that is, it is slightly reduced.

Patients with impaired renal function The clearance of enoxaparin sodium decreases in patients with reduced renal function. There was a decrease in the clearance of enoxaparin sodium in renal failure. After repeated subcutaneous administration of 40 mg enoxaparin sodium once a day, anti-Xa activity increases, represented by the area under the pharmacokinetic curve, with mild (creatinine clearance (CC) 50-80 ml/min) and moderate (CC 30-50 ml/min) renal insufficiency. In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), the area under the pharmacokinetic curve at steady state is on average 65% higher with repeated subcutaneous administration of 40 mg of the drug once a day.

Overweight patients and overweight people with subcutaneous administration of the drug have a slightly lower clearance. If no dose adjustment is made for the patient’s body weight, then after a single subcutaneous injection of 40 mg of enoxaparin sodium, anti-Xa activity will be 50% higher in women with a body weight of less than 45 kg and 27% higher in men with a body weight of less than 57 kg compared to patients with a normal average body weight.

Indications

− prevention of venous thrombosis and embolism in surgical interventions, especially in orthopedic and General surgical operations;− prevention of venous thrombosis and embolism in patients who are on bedrest in connection with acute terapevticheskie (including congestive heart failure and decompensation of chronic heart failure (III or class IV NYHA), acute infectious diseases; acute stage of remotedesktopclient in combination with one of the risk factors of venous thrombosis(see “Special instructions”));− treatment of deep vein thrombosis, accompanied or not accompanied by pulmonary thromboembolism;− treatment of unstable angina and non-Q wave myocardial infarction in combination with acetylsalicylic acid; – prevention of thrombosis in the extracorporeal circulatory system during hemodialysis (usually with a session duration of no more than 4 hours);− treatment of acute ST-segment elevation myocardial infarction in patients undergoing medication or subsequent percutaneous coronary intervention.

Use during pregnancy and lactation

Pregnancy

Currently, the available clinical data are insufficient to determine the possible teratogenic or fetotoxic effects of enoxaparin sodium when prescribed for preventive purposes during pregnancy. Enixum® should not be used during pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus.

During treatment with the drug, spinal or epidural anesthesia should not be performed. If an epidural is planned, preventive treatment with enoxaparin sodium should be discontinued, if possible, at least 12 hours before anesthesia. Enoxaparin sodium is not recommended for use in pregnant women with prosthetic heart valves.

Breast-feeding Periodit is not known whether unchanged enoxaparin sodium is excreted in human breast milk. Absorption of enoxaparin sodium in the gastrointestinal tract in a newborn is unlikely. However, as a precautionary measure, breastfeeding women treated with enoxaparin sodium should be advised to discontinue breastfeeding.

Contraindications

-hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low-molecular-weight heparins;− active major bleeding, as well as conditions and diseases that have a high risk of bleeding: threatened abortion, cerebral vascular aneurysm or dissecting aortic aneurysm (except in cases of surgical intervention for this reason), recent hemorrhagic stroke, uncontrolled bleeding, thrombocytopenia in combination with a positive in vitro test for antiplatelet antibodies in the presence of enoxaparin sodium;− children under 18 years of age, since the effectiveness and safety of this category of patients have not been established (see the section “Special instructions”).

With caution

Conditions where there is a potential risk of bleeding:- hemostatic disorders (including hemophilia, thrombocytopenia, hypocoagulation, Willebrand’s disease, etc.), severe vasculitis;− peptic ulcer of the stomach or duodenum or other erosive and ulcerative lesions of the gastrointestinal tract in the anamnesis;− a recent ischemic stroke. − uncontrolled severe arterial hypertension;− diabetic or hemorrhagic retinopathy;− severe diabetes mellitus− – recently undergone or anticipated neurological or ophthalmic surgery;− spinal or epidural anesthesia (potential risk of developing a hematoma), spinal puncture (recently transferred);− recent delivery. − bacterial endocarditis (acute or subacute);− pericarditis or pericardial effusion;− renal and / or hepatic insufficiency;− intrauterine contraception (IUD); – severe trauma (especially of the central nervous system (CNS)), open wounds on large surfaces− – simultaneous administration of drugs that affect the hemostatic system;− heparin-induced thrombocytopenia (in the anamnesis) in combination with or without thrombosis. There are no data on the clinical use of enoxaparin sodium in the following diseases: active tuberculosis, radiation therapy (recently transferred).

Side effects

Side effects were classified by frequency as follows: very frequent(≥ 1/10), frequent (≥1/100 – <1/10), infrequent (≥1/1000 – <1/100), rare (≥1/10000 – <1/1000), very rare (

Bleeding may occur, especially in the presence of concomitant risk factors: organic changes with a tendency to bleed, age, renal failure, low body weight, and certain drug combinations (see “Interactions with other drugs”). If bleeding develops, it is necessary to cancel the drug administration, determine the cause of bleeding and start appropriate therapy. Very frequent — bleeding in the prevention of venous thrombosis, in surgical patients and in the treatment of deep vein thrombosis with or without thromboembolism. Frequent-bleeding in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina, non-Q-wave myocardial infarction and ST-segment elevation myocardial infarction. Infrequent-retroperitoneal bleeding and intracranial bleeding in patients treated for deep vein thrombosis with or without thromboembolism, as well as with ST-segment elevation myocardial infarction. Rare-retroperitoneal bleeding in the prevention of venous thrombosis in surgical patients and in the treatment of angina pectoris, myocardial infarction without Q wave. When using enoxaparin sodium on the background of spinal/epidural anesthesia and postoperative use of penetrating catheters, rare cases of formation of neuroaxial hematomas have been described, leading to neurological disorders of varying severity, including long-term or irreversible paralysis (see “Special Instructions”).

Thrombocytopenia and thrombocytosis are very common-thrombocytosis in the prevention of venous thrombosis in surgical patients and in the treatment of deep vein thrombosis with or without thromboembolism. Frequent-thrombocytopenia. In the prevention of venous thrombosis in surgical patients and in the treatment of deep vein thrombosis with or without thromboembolism, as well as in ST-segment elevation myocardial infarction. Infrequent-thrombocytopenia in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina pectoris, myocardial infarction without Q wave. Very rare — autoimmune thrombocytopenia in ST-segment elevation myocardial infarction. In rare cases, the development of autoimmune thrombocytopenia in combination with thrombosis has been reported. In some cases, thrombosis was complicated by an organ infarction or limb ischemia (see the section “Special instructions”).

Prochieochen often-increased activity of “hepatic” transaminases. Often — allergic reactions, hives, itching, redness of the skin, hematoma and pain at the injection site. Infrequently-skin (bullous rashes), inflammatory reaction at the injection site, skin necrosis at the injection site. Rarely — anaphylactic and anaphylactoid reactions, hyperkalemia. Skin necrosis may develop at the injection site, which is preceded by the appearance of purpura or erythematous painful papules. In these cases, therapy with the drug should be discontinued. It is possible to form solid inflammatory nodules-infiltrates at the injection site of the drug, which disappear after a few days and are not a reason for discontinuing the drug.

Interaction

Do not mix Enixum® with other medications in the same syringe. When used concomitantly with other drugs that affect hemostasis (salicylates, including acetylsalicylic acid, nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, dextran with a molecular weight of 40 kDa, ticlopidine, clopidogrel, systemic glucocorticosteroids (corticosteroids), thrombolytics or anticoagulants, other antiplatelet drugs, including antagonists of glycoprotein IIb/IIIa receptors), increases the risk of bleeding (see “Special instructions”).

How to take, course of administration and dosage

Except in special cases (see below “Treatment of ST-segment elevation myocardial infarction, medication or percutaneous coronary intervention” and “Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis”), enoxaparin sodium is administered deep subcutaneously. Injections should preferably be performed in the patient’s “lying down” position. Injections should be performed alternately in the left or right anterolateral or posterolateral surface of the abdomen. The needle should be inserted vertically (not laterally) into the skin fold for the entire length, collected and held until the injection is completed between the thumb and index finger. The skin fold is released only after the injection is completed. Do not massage the injection site after administration of the drug. The pre-filled disposable syringe is ready for use.

The drug should not be administered intramuscularly!

Prevention of venous thrombosis and embolism in surgical procedures, especially in orthopedic and general surgical operations. In patients with a moderate risk of developing thrombosis and embolism (for example, abdominal surgery), the recommended dose of the drug is 20 mg once a day subcutaneously. The first injection should be given 2 hours before surgery.

Patients with a high risk of developing thrombosis and embolism (for example, during orthopedic operations, surgical operations in oncology, patients with additional risk factors not related to surgery, such as congenital or acquired thrombophilia, malignancy, bed rest for more than three days, obesity, a history of venous thrombosis, varicose veins of the lower extremities, pregnancy), the drug is recommended at a dose of 40 mg once a day subcutaneously, with the introduction of the first dose for 12 hours before surgery, or at a dose of 30 mg twice a day with the start of administration 12-24 hours after surgery. The average duration of treatment with the drug is 7-10 days. If necessary, therapy can be continued as long as there is still a risk of developing thrombosis and embolism, and until the patient switches to outpatient mode. In orthopedic operations, it may be advisable to continue treatment after the initial therapy by injecting the drug at a dose of 40 mg once a day for 3 weeks. Features of using the drug during spinal / epidural anesthesia, as well as during coronary revascularization procedures, are described in the section “Special instructions”. Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases.

The recommended dose of enoxaparin sodium is 40 mg once daily subcutaneously for at least 6 days. Therapy should be continued until the patient fully switches to outpatient mode (for a maximum of 14 days). Treatment of deep vein thrombosis that is or is not accompanied by pulmonary embolism. Enixum® is administered subcutaneously at the rate of 1.5 mg / kg of body weight once a day or at a dose of 1 mg / kg of body weight twice a day. In patients with complicated thromboembolic disorders, the drug is recommended to be used at a dose of 1 mg/kg twice a day.

The average duration of treatment is 10 days. Indirect anticoagulant therapy should be initiated immediately, and enoxaparin sodium therapy should be continued until the therapeutic anticoagulant effect is achieved (INR values should be 2.0–3.0). If necessary, control of the anticoagulant effect should be evaluated by anti-Xa activity. Treatment of unstable angina and non-Q-wave myocardial infarction in combination with acetylsalicylic acid Enixum® is administered at the rate of 1 mg/kg of body weight every 12 hours, subcutaneously, with simultaneous administration of acetylsalicylic acid orally at a dose of 100-325 mg once a day. The average duration of treatment is at least 2 days and continues until the patient’s clinical condition stabilizes. Usually, the drug administration lasts from 2 to 8 days. Treatment of ST-segment elevation myocardial infarction, by medication or by percutaneous coronary intervention. Treatment begins with intravenous bolus administration of enoxaparin sodium at a dose of 30 mg and immediately after it (within 15 minutes) is administered subcutaneously at a dose of 1 mg/kg of body weight(and during the first two subcutaneous injections, a maximum of 100 mg of enoxaparin sodium can be administered). Then, all subsequent subcutaneous doses are administered every 12 hours at the rate of 1 mg/kg of body weight (i. e., if the body weight is more than 100 kg, the dose may exceed 100 mg). In patients 75 years and older, the initial intravenous bolus is not used.Enoxaparin sodium is administered subcutaneously at a dose of 0.75 mg / kg every 12 hours (moreover, during the first two subcutaneous injections, a maximum of 75 mg of enoxaparin sodium can be administered). Then, all subsequent subcutaneous doses are administered every 12 hours at the rate of 0.75 mg/kg of body weight (i. e., if the body weight is more than 100 kg, the dose may exceed 75 mg). When combined with thrombolytics (fibrin-specific and fibrin-non-specific), enoxaparin sodium should be administered in the interval from 15 minutes before the start of thrombolytic therapy to 30 minutes after it. After detection of acute ST-segment elevation myocardial infarction, acetylsalicylic acid should be administered simultaneously as soon as possible, which, in the absence of contraindications, should continue for at least 30 days in doses from 75 to 325 mg daily. The recommended duration of treatment with the drug is 8 days or until the patient is discharged from the hospital, if the period of hospitalization is less than 8 days. Intravenous bolus administration of enoxaparin sodium should be carried out through a venous catheter and enoxaparin sodium should not be mixed or administered together with other medicinal products. In order to avoid the presence of traces of other drugs in the system and their interaction with enoxaparin sodium, the venous catheter should be flushed with a sufficient amount of 0.9% sodium chloride solution or 5% dextrose solution before and after intravenous bolus administration of enoxaparin sodium. Enoxaparin sodium is compatible with 0.9% sodium chloride solution and 5% dextrose solution. For bolus administration of 30 mg of enoxaparin sodium in the treatment of acute ST-segment elevation myocardial infarction, an excessive amount of the drug is removed from glass syringes of 60 mg,80 mg and 100 mg so that only 30 mg (0.3 ml) remains in them. A dose of 30 mg can be directly administered intravenously. For intravenous bolus administration of enoxaparin sodium through a venous catheter, pre-filled syringes for subcutaneous administration of the drug 60 mg,80 mg and 100 mg can be used. It is recommended to use syringes of 60 mg, as this reduces the amount of drug removed from the syringe.20 mg syringes are not used, as they do not contain enough preparation for bolus administration of 30 mg of enoxaparin sodium. Syringes of 40 mg are not used, as they do not have divisions and therefore it is impossible to accurately measure the amount of 30 mg. In patients undergoing percutaneous coronary intervention, if the last subcutaneous injection of enoxaparin sodium was performed less than 8 hours before the balloon catheter was inserted into the site of narrowing of the coronary artery, additional administration of enoxaparin sodium is not required. If the last subcutaneous injection of enoxaparin sodium was administered more than 8 hours before inflating the balloon catheter, an intravenous additional bolus injection of enoxaparin sodium at a dose of 0.3 mg/kg should be performed. To increase the accuracy of additional intravenous bolus administration of small volumes into a venous catheter during percutaneous coronary interventions, it is recommended to dilute the drug to a concentration of 3 mg / ml. Dilution of the solution is recommended immediately before administration. To obtain a solution of enoxaparin sodium with a concentration of 3 mg / ml using a pre-filled syringe, it is recommended to use a container with an infusion solution, from which part of the solution is extracted to the required volume using a conventional syringe. Enoxaparin sodium (the contents of the hypodermic syringe) is injected into the remaining infusion solution in the container.

Volume of the pre-filled syringe

The amount of infusion solution left in

the tank 0.3 ml 10 ml 0.6 ml 20 ml

The contents of the container with a diluted solution of enoxaparin sodium are carefully mixed. For administration with a syringe, the required volume of diluted enoxaparin sodium solution is extracted, which is calculated by the formula: Volume of diluted solution = Patient’s body weight (kg) x 0.1 or using the table below. Volumes that should be administered intravenously after dilution.

Patient’s body weight [kg] Required dose (0.3 mg / kg) [mg]The volume of solution required for administration, diluted to a concentration of 3 mg / ml 45 13,5 4,550 15 555 16,5 5,560 18 665 19,5 6,570 21 775 22,5 7,580 24 885 25,5 8,590 27 995 28,5 9,5100 30 10

Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis (usually with a session duration of no more than 4 hours)The average dose of enoxaparin sodium is 1 mg / kg of body weight. For patients with a high risk of bleeding, the dose should be reduced to 0.5 mg / kg of body weight with double vascular access or to 0.75 mg with single vascular access. During hemodialysis, Enixum® should be injected into the arterial section of the shunt at the beginning of the hemodialysis session. One dose is usually sufficient for a four-hour session, but if fibrin rings are detected during longer hemodialysis, the drug can be additionally administered at the rate of 0.5-1 mg/kg of body weight.

Overdose

Symptoms: hemorrhagic complications in case of accidental overdose with subcutaneous administration of enoxaparin sodium. With accidental ingestion of even large doses, absorption of the drug is unlikely. Treatment: neutralize the effect of enoxaparin sodium by slow intravenous (iv) administration of protamine sulfate.1 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of enoxaparin sodium, if the drug was administered no more than 8 hours before the administration of protamine sulfate.0.5 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of enoxaparin sodium, if it was administered more than 8 hours ago or if a second dose of protamine sulfate is necessary. If 12 or more hours have elapsed since the introduction of enoxaparin sodium, the introduction of protamine sulfate is not required. However, even with high doses of protamine sulfate, the anti-Xa activity of enoxaparin sodium is not completely neutralized (by a maximum of 60%).

Description

colorless or yellowish, or brownish-yellowish transparent liquid.

Special instructions

General information

Low-molecular-weight heparins are not interchangeable, as they differ in the production process, molecular weight, specific anti-Xa activity, dosage units and dosage regimen, which are associated with differences in their pharmacokinetics and biological activity (antithrombin activity and platelet interaction). Therefore, it is necessary to strictly follow the recommendations for the use of each drug belonging to the class of low-molecular-weight heparins.

Bleedingas with other anticoagulants, Enixum® may cause bleeding of any location (see “Side effects”). If bleeding develops, it is necessary to find its source and prescribe appropriate treatment.

Bleeding in elderly patients When enoxaparin sodium was used in prophylactic doses, there was no increase in the risk of bleeding in elderly patients. When using enoxaparin sodium in therapeutic doses in elderly patients (especially at the age of 80 years and older), there is an increased risk of bleeding. Careful monitoring of these patients is recommended (see section “Pharmacokinetics” and section “Dosage and administration”, subsection “Elderly patients”).

Concomitant use of other drugs that affect hemostasis It is recommended that the use of drugs that affect hemostasis (salicylates, including acetylsalicylic acid, NSAIDs, including ketorolac, dextran with a molecular weight of 40 kDa, ticlopidine, clopidogrel, corticosteroids, thrombolytics, anticoagulants, antiplatelet agents, including glycoprotein IIb/IIIa receptor antagonists) be discontinued before the start of treatment. treatment with enoxaparin sodium, except in cases where their use is necessary. If combinations of enoxaparin sodium with these drugs are indicated, careful clinical monitoring and monitoring of appropriate laboratory parameters should be carried out.

Renal insufficiency In patients with impaired renal function, there is a risk of bleeding as a result of increased systemic exposure to enoxaparin sodium. In patients with severe renal impairment (creatinine clearance less than 30 ml / min), there is a significant increase in exposure to enoxaparin sodium, so it is recommended to adjust the dose, both with preventive and therapeutic use of the drug. Although no dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance 30-50 ml / min or 50-80 ml / min), careful monitoring of these patients is recommended (see sections “Pharmacokinetics” and “Dosage and administration”, subsection “Patients with renal insufficiency”).

Low body weight There has been an increase in exposure to enoxaparin sodium when used prophylactically in women weighing less than 45 kg and in men weighing less than 57 kg, which may lead to an increased risk of bleeding. Careful monitoring of these patients is recommended.

Obese patients Obese patients have an increased risk of developing thrombosis and embolism. The safety and efficacy of enoxaparin sodium in prophylactic doses in obese patients (body mass index greater than 30 kg / m2) is not fully defined, and there is no consensus on dose adjustment. These patients should be closely monitored for signs and symptoms of thrombosis and embolism.

The risk of developing antibody-mediated heparin-induced thrombocytopenia also exists when using low-molecular-weight heparins to control the number of platelets in the peripheral blood.If thrombocytopenia develops, it is usually detected between 5 and 21 days after the start of enoxaparin sodium therapy. In this regard, it is recommended to regularly monitor the number of platelets in the peripheral blood before starting treatment with Enixum® and during its use. If there is a confirmed significant decrease in the number of platelets (by 30-50% compared to baseline), it is necessary to immediately cancel enoxaparin sodium and transfer the patient to another therapy.

Spinal / epidural anaesthetism Cases of neuroaxial hematomas have been described when enoxaparin sodium is used while undergoing spinal / epidural anaesthesia with the development of long-term or irreversible paralysis. The risk of these events is reduced when enoxaparin sodium is administered at a dose of 40 mg or lower. The risk increases with higher doses of enoxaparin sodium, as well as with the use of permanent catheters after surgery or with the simultaneous use of additional drugs that affect hemostasis, such as NSAIDs (see “Interaction with other drugs”). The risk is also increased with traumatic or repeated spinal puncture, or in patients who have a history of spinal surgery or spinal deformity. To reduce the possible risk of bleeding associated with the use of enoxaparin sodium and epidural or spinal anesthesia/analgesia, the pharmacokinetic profile of the drug should be taken into account (see “Pharmacokinetics”). Catheter insertion or removal is best performed when the anticoagulant effect of enoxaparin sodium is low, but the exact time to achieve a sufficient reduction in the anticoagulant effect in different patients is unknown. Catheter insertion or removal should be performed at least 12 hours after administration of lower doses of Enixum® (20 mg once a day,30 mg once or twice a day,40 mg once a day) and at least 24 hours after administration of higher doses of Enixum® (0.75 mg/kg of body weight twice a day,1 mg/kg of body weight twice a day,1.5 mg/kg of body weight once a day). At these time points, the anti-Xa activity of enoxaparin sodium still continues to be detected, and time delays do not guarantee that the development of a neuroaxial hematoma can be avoided. Patients receiving enoxaparin sodium at doses of 0.75 mg / kg body weight twice a day or 1 mg / kg body weight twice a day, with this (twice a day) dosage regimen, should not enter a second dose in order to increase the interval before installing or replacing the catheter. Similarly, consideration should be given to delaying the next dose of enoxaparin sodium for at least 4 hours, based on an assessment of the benefit/risk ratio (risk of thrombosis and bleeding during the procedure, taking into account the presence of risk factors in patients). However, it is possible to give clear recommendations on the time of administration of the next dose of enoxaparin sodium after removal of the catheter. It should be noted that in patients with a creatinine clearance of less than 30 ml/min, the elimination of enoxaparin sodium slows down. Therefore, in this category of patients, doubling the time from catheter removal should be considered: at least 24 hours for lower doses of enoxaparin sodium (30 mg once daily) and at least 48 hours for higher doses (1 mg/kg body weight per day). If the doctor prescribes anticoagulant therapy during epidural / spinal anesthesia or lumbar puncture, the patient should be constantly monitored for any neurological symptoms, such as back pain, impaired sensory and motor functions (numbness or weakness in the lower extremities), impaired bowel and/or bladder function. The patient should be instructed to inform the doctor immediately if the symptoms described above occur. If symptoms that are characteristic of a spinal cord hematoma are suspected, urgent diagnosis and treatment are required, including, if necessary, spinal cord decompression.

Heparin-induced thrombocytopenia With extreme caution, Enixum® should be used in patients who have a history of heparin-induced thrombocytopenia with or without strombosis. The risk of developing heparin-induced thrombocytopenia may persist for several years. If a history of heparin-induced thrombocytopenia is suspected, then in vitro platelet aggregation tests are of limited importance in predicting the risk of its development. The decision to use Enixum® in this case can only be made after consultation with the appropriate specialist.

Percutaneous coronary angioplasty In order to minimize the risk of bleeding associated with invasive vascular instrumental manipulation in the treatment of unstable angina and non-Q-wave myocardial infarction and acute ST-segment elevation myocardial infarction, these procedures should be performed at intervals between administration of Enixum®. This is necessary in order to achieve hemostasis after percutaneous coronary intervention. If a closure device is used, the femoral artery introducer can be removed immediately. When applying manual compression, the introduction of the femoral artery should be removed 6 hours after the last intravenous or subcutaneous injection of enoxaparin sodium. If treatment with enoxaparin sodium continues, the next dose should be administered no earlier than 6-8 hours after removal of the femoral artery introducer. It is necessary to monitor the site of introduction of the introducer in order to detect signs of bleeding and hematoma formation in a timely manner. Patients with mechanical artificial heart valves

The use of enoxaparin sodium for the prevention of thrombosis in patients with mechanical artificial heart valves has not been sufficiently studied. There have been isolated reports of cardiac valve thrombosis in patients with mechanical artificial heart valves treated with enoxaparin sodium to prevent thrombosis. Evaluation of these reports is limited due to the presence of competing factors contributing to the development of artificial heart valve thrombosis, including the underlying disease, and due to insufficient clinical data.

Pregnant women with mechanical artificial heart valves

The use of enoxaparin sodium for the prevention of thrombosis in pregnant women with mechanical artificial heart valves has not been sufficiently studied. In a clinical study of pregnant women with mechanical artificial heart valves using enoxaparin sodium at a dose of 1 mg / kg body weight twice a day to reduce the risk of thrombosis and embolism,2 out of 8 women developed blood clots, which led to blockage of the heart valves and death of the mother and fetus. There are isolated post-marketing reports of heart valve thrombosis in pregnant women with mechanical artificial heart valves treated with enoxaparin sodium to prevent thrombosis. Pregnant women with mechanical artificial heart valves have a high risk of developing thrombosis and embolism.

Laboratory tests At doses used to prevent thromboembolic complications, enoxaparinnatria does not significantly affect the bleeding time and blood clotting parameters, as well as platelet aggregation or their binding to fibrinogen. When the dose is increased, the APTT and activated blood clotting time may be prolonged. The increase in APTT and activated clotting time are not directly linearly related to the increase in anticoagulant activity of the drug, so there is no need to monitor them.

Prevention of venous thrombosis and embolism in patients with acute therapeutic diseases who are on bed rest in case of acute infection, acute rheumatic conditions prophylactic use of enoxaparin sodium is justified only if the above conditions are combined with one of the following risk factors for venous thrombosis:− age over 75 years; – malignant neoplasms;− a history of thrombosis and embolism. − obesity. − hormone therapy;− heart failure;− chronic respiratory failure.

The safety and efficacy of enoxaparin sodium in children under 18 years of age have not been established.

Effects on the performance of potentially dangerous activities that require special attention and responsiveness There are no data indicating a negative effect of enoxaparin sodium on the ability to drive vehicles and engage in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Solution for injection 10000 anti-Xa IU (100 mg)/ml.0.2 ml; 0.3 ml; 0.4 ml; 0.5 ml; 0.6 ml; 0.7 ml; 0.8 ml or 1.0 ml in ampoules of colorless glass with a colored break ring or with a colored dot and notch. The ampoules are additionally marked with one, two or three colored rings and/or a two-dimensional barcode, and/or alphanumeric encoding, or without additional colored rings, a two-dimensional barcode, or alphanumeric encoding.1,2 or 5 ampoules in a contour cell package made of polyvinyl chloride film and aluminum foil or polymer film or without foil and film.1 contour cell pack of 1,2 or 5 ampoules; 2 contour cell packs of%^%1 or 5 ampoules together with instructions for use in a cardboard pack. The pack is covered on both sides with stickers made of self-adhesive material for control of opening or without stickers.0,2 ml; 0,3 ml; 0,4 ml; 0,5 ml; 0,6 ml; 0,7 ml; 0,8 ml or 1,0 ml in glass sterile syringes, graduated or not graduated; with a needle, a protective cap, with or without an additional automatic or non-automatic device for protecting the needle after using the syringe.1 or 2 syringes each in a contour cell package made of polyvinyl chloride or polyethylene terephthalate film and polymer film or polypropylene film, or polyethylene film, or polymer-coated packaging paper, or paper for packaging medical devices, or aluminum foil.1 or 5 contour cell packages together with instructions for use in a pack of cardboard. The pack is covered on both sides with stickers made of self-adhesive material for control of opening or without stickers.

Storage conditions

At a temperature not exceeding 25 °C. Do not freeze it. Keep out of reach of children

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Enoxaparin sodium

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Weight

Weight: 181 g.