Clexane solution for injection 6000 anti-Ha IU/0.6 ml 0.6 ml syringes, 10 pcs.

Composition

Composition per syringe:

Active ingredient: enoxaparin sodium 60 mg*;

solvent: water for injection up to 0.6 ml;

* – weight is calculated based on the content of enoxaparin sodium used (theoretical activity is 100 anti-Xa IU / mg).

Pharmacological action

Enoxaparin sodium is a low molecular weight heparin with an average molecular weight of about 4500 daltons (Da): less than 2000 Da – < 20%, from 2000 to 8000 Da – > 68%, more than 8000 Da – < 20%, from 2000 to 8000 Da – > Enoxaparin sodium is obtained by alkaline depolymerization 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-No,6-O-disulfo-O-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 a purified in vitro system, enoxaparin sodium has high anti-Xa activity (approximately 100 IU / ml) and low anti-IIa or antithrombin activity (approximately 28 IU/ml). This anticoagulant activity acts through antithrombin III (AT-Sh), providing anticoagulant activity in humans. Except for anti-Ha/Pa activity also revealed additional anticoagulant and anti-inflammatory properties of enoxaparin sodium both in healthy people and patients, and in animal models. This includes AT-W-dependent inhibition of other clotting factors, such as factor Y 11a, activation of the release of the tissue factor pathway inhibitor (PTF), and reduction of the 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, it slightly changes the activated partial thromboplastin time (APTT), has virtually no effect on platelet aggregation and on the degree of binding of fibrinogen to platelet receptors.

Pharmacokinetics

Bioavailability and absorption

The absolute bioavailability of enoxaparin sodium with subcutaneous (subcutaneous) administration, estimated on the basis of anti-Xa activity, is close to 100%. The average maximum anti-Xa activity in blood plasma is observed 3-5 hours after subcutaneous administration and reaches approximately 0.2,0.4,1.0 and 1.3 anti-Xa IU / ml after a single subcutaneous administration of the drug at a dosage of 20 mg,40 mg,1 mg / kg and 1.5 mg/kg. Intravenous bolus administration of the drug at a dosage of 30 mg, accompanied by immediate subcutaneous administration of the drug at a dosage of 1 mg / kg every 12 hours, provides the initial maximum anti-Xa activity at the level of 1.16 IU / ml (n=16), the average exposure of the drug in the blood is approximately 88% of the equilibrium state, which is reached on the second day of therapy.

The pharmacokinetics of enoxaparin sodium in these dosage regimens are linear. Variability within and between patient groups is low. After repeated subcutaneous administration of 40 mg of enoxaparin sodium once a day and subcutaneous administration of enoxaparin sodium at a dose of 1.5 mg/kg of body weight once a day in healthy volunteers, the equilibrium concentration is reached by day 2, and the area under the pharmacokinetic curve is on average 15% higher than after a single dose of 2 of 30 administration. After repeated subcutaneous administration of enoxaparin sodium at a daily dose of 1 mg/kg body weight twice a day, the equilibrium concentration is reached in 3-4 days, and the area under the pharmacokinetic curve (AUC) is on average 65% higher than after a single administration, and the average values of maximum concentrations are 1.2 IU/ml and 0.52 IU/ml, respectively.

Anti-IIa activity in blood plasma is approximately 10 times lower than anti-Xa activity. The average maximum anti-Pa 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.

Distribution

The volume of distribution of anti-Xa activity of enoxaparin sodium is approximately 4.3 liters and is close to the volume of circulating blood.

Deduction

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 is 0.74 l / h.

Elimination of the drug is monophasic with half-lives (T 1/2) of about 5 hours (after a single subcutaneous injection) and about 7 hours (after repeated administration of the drug).

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

Special patient groups

Elderly patients (over 75 years of age): the pharmacokinetic profile of enoxaparin sodium does not differ in elderly patients and younger patients with normal renal function. However, as a result of decreased renal function with age, there may be a slowdown in the elimination of enoxaparin sodium in elderly patients.

Hepatic impairment: in a study involving patients with advanced cirrhosis treated with enoxaparin sodium at a dose of 4000 IU (40 mg) once a day, a decrease in maximum anti-Xa activity was associated with an increase in the severity of hepatic impairment (with a Child-Pugh score). This 3 out of 30 decrease was mainly due to a decrease in AT-III levels secondary to a decrease in AT-III synthesis in patients with impaired liver function.

Impaired renal function: decreased clearance of enoxaparin sodium was observed in patients with impaired renal function. After repeated subcutaneous administration of 40 mg enoxaparin sodium once a day, anti-Xa activity is increased, represented by the area under the pharmacokinetic curve (AUC) in patients with mild renal impairment (creatinine clearance >50 and >80 ml / min) and moderate (creatinine clearance >30 and <80 ml / min) and moderate (creatinine clearance > In patients with severe renal impairment (CC

Hemodialysis: The pharmacokinetics of enoxaparin sodium were comparable to those in the control population after a single intravenous dose of 25 IU,50 IU or 100 IU / kg (0.25,0.50 or 1.0 mg/kg), but the AUC was twice as high as in the control population.

Body weight: after repeated subcutaneous administration at a dose of 1.5 mg / kg once a day, the average AUC of anti-Xa activity at equilibrium is slightly higher in overweight patients (BMI 30-48 kg/m2) compared to patients with normal average body weight, while the maximum anti-Xa activity in blood plasma does not increase. In overweight patients, subcutaneous administration of the drug has 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 52% 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 during surgical interventions in moderate and high-risk patients, especially in orthopedic and general surgical interventions, including cancer.

Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases, including acute heart failure and decompensation of chronic heart failure (NYHA Class III or IV), respiratory failure, as well as in severe infections and rheumatic diseases with an increased risk of venous thrombosis.

Treatment of deep vein thrombosis with or without pulmonary embolism, except in cases of pulmonary embolism requiring thrombolytic therapy or surgery.

Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis.

Acute coronary syndrome:

– Treatment of unstable angina and non-ST-segment elevation myocardial infarction in combination with oral acetylsalicylic acid. – Treatment of acute ST – segment elevation myocardial infarction in patients undergoing medical treatment or subsequent percutaneous coronary intervention (PCI).

Use during pregnancy and lactation

There is no evidence that enoxaparin sodium penetrates the placental barrier during pregnancy. Since there are no adequate and well-controlled studies involving pregnant women, and animal studies do not always predict a response to the introduction of enoxaparin sodium during pregnancy in humans, it should be used during pregnancy only in exceptional cases, when there is an urgent need for its use, established by a doctor.

It is recommended to monitor the condition of patients for signs of bleeding or excessive anticoagulation, patients should be warned about the risk of bleeding.

There is no evidence of an increased risk of bleeding, thrombocytopenia, or osteoporosis in pregnant women, except in patients with artificial heart valves.

When planning epidural anesthesia, it is recommended to cancel enoxaparin sodium before it is performed.

Breast-feeding period

It is not known whether unchanged enoxaparin sodium is excreted in breast milk. Absorption of enoxaparin sodium in the gastrointestinal tract in a newborn is unlikely. Clexan® can be used during breastfeeding.

Recommendations for use

Features of drug administration:

The pre-filled disposable syringe is ready for use.

The drug should not be administered intramuscularly!

Subcutaneous administration:

Injections should preferably be performed in the patient’s “lying down” position. When using pre-filled 20 mg and 40 mg syringes, do not remove air bubbles from the syringe before injection to avoid drug loss. Injections should be performed alternately in the left or right anterolateral or posterolateral surface of the abdomen.

The needle should be inserted at full length, vertically (not laterally), into the skin fold, 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.

Intravenous bolus administration:

Intravenous bolus administration of enoxaparin sodium should be performed through a venous catheter. 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 infusion 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 can be safely administered 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 excess 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. 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 3 mg/ml enoxaparin sodium solution using a pre-filled 60 mg syringe, it is recommended to use a 50 ml infusion container (i. e. with 0.9% sodium chloride solution or 5% dextrose solution).30 ml of the solution is extracted and removed from the container with the infusion solution using a conventional syringe. Enoxaparin sodium (the contents of the hypodermic syringe 60 mg) is injected into the remaining 20 ml of the infusion solution in the container. 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

Contraindications

Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low-molecular-weight heparins.

Active clinically significant bleeding, as well as conditions and diseases that have a high risk of bleeding, including a recent hemorrhagic stroke, acute gastrointestinal (GI) ulcer, the presence of a malignant neoplasm with a high risk of bleeding, recent brain and spinal cord surgery, ophthalmic surgery, known or suspected presence of esophageal varicose veins, arteriovenous malformations, vascular aneurysms, vascular abnormalities of the spinal cord and brain the brain.

Spinal or epidural anesthesia or loco-regional anesthesia, when enoxaparin sodium was used for treatment in the previous 24 hours.

Immune-mediated heparin-induced thrombocytopenia (in the anamnesis) within the last 100 days or the presence of circulating antiplatelet antibodies in the blood.

Children under 18 years of age, as efficacy and safety in this category of patients have not been established.

Side effects

Disorders of the blood and lymphatic system:

common: bleeding, thrombocytopenia, thrombocytosis;

rare: cases of autoimmune thrombocytopenia with thrombosis; in some cases, thrombosis was complicated by the development of organ infarction or limb ischemia

Immune system disorders:

common: allergic reactions.

Liver and biliary tract disorders:

very often: increased activity of “liver” enzymes, mainly increased activity of transaminases, more than three times higher than the upper limit of normal.

Skin and subcutaneous tissue disorders:

common: urticaria, pruritus, erythema.

infrequently: bullous dermatitis.

General disorders and disorders at the injection site:

common: hematoma at the injection site, pain at the injection site, swelling at the injection site, bleeding, hypersensitivity reactions, inflammation, formation of seals at the injection site.

infrequently: irritation at the injection site, skin necrosis at the injection site.

Interaction

Clexan® should not be mixed with other medications!

Not recommended combinations:

Drugs that affect hemostasis (systemic salicylates, acetylsalicylic acid in doses that have an anti-inflammatory effect, nonsteroidal anti-inflammatory drugs (NSAIDs), including ketorolac, other thrombolytics (alteplase, reteplase, streptokinase, tenecteplase, urokinase)) are recommended to be discontinued before starting therapy with enoxaparin sodium. If concomitant use with enoxaparin sodium is necessary, caution should be exercised and careful clinical monitoring and monitoring of appropriate laboratory parameters should be carried out.

Combinations that require caution

Other medications that affect hemostasis, such as:

– inhibitors of platelet aggregation, including acetylsalicylic acid in doses that have an antiplatelet effect (cardioprotection), clopidogrel, ticlopidine and antagonists of glycoprotein IIb/IIIa receptors, indicated in acute coronary syndrome, due to an increased risk of bleeding;

– dextran with a molecular weight of 40 kDa;

– systemic glucocorticosteroids.

Medicinal products that increase the potassium content When used simultaneously with medicinal products that increase the potassium content in the blood serum, clinical and laboratory monitoring should be carried out.

How to take, course of administration and dosage

Subcutaneously, except in special cases.

Prevention of venous thrombosis and embolism during surgical interventions in moderate and high-risk patients.

In patients with a moderate risk of developing thrombosis and embolism (for example, abdominal surgery), the recommended dose of Klexan® 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 first dose administered 12 hours before surgery. If earlier preoperative prophylaxis is necessary (for example, in patients at high risk of developing thrombosis and thromboembolism awaiting delayed orthopedic surgery), the last injection should be made 12 hours before surgery and 12 hours after surgery.

The average duration of treatment with Klexan® 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.

For major orthopedic surgeries, it may be advisable to continue treatment after initial therapy by administering the drug at a dose of 40 mg once a day for five weeks.

For patients at high risk of venous thromboembolism who have undergone surgery, abdominal and pelvic surgery due to cancer, it may be advisable to increase the duration of administration of Klexan® at a dose of 40 mg once a day for four weeks.

Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases The recommended dose of Klexan® is 40 mg once a day, subcutaneously, for 6-14 days. Therapy should be continued until the patient is completely switched to outpatient mode (maximum for 14 days).

Treatment of deep vein thrombosis with or without pulmonary embolism

The drug is administered subcutaneously at the rate of 1.5 mg / kg of body weight once a day or 1 mg / kg of body weight twice a day. The dosage regimen should be selected by the doctor based on an assessment of the risk of thromboembolism and the risk of bleeding. In patients without thromboembolic complications and with a low risk of venous thromboembolism, the drug is recommended to be administered subcutaneously at the rate of 1.5 mg/kg of body weight once a day. In all other patients, including those with obesity, symptomatic pulmonary embolism, cancer, recurrent venous thromboembolism and proximal thrombosis (in the iliac vein), 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 treatment with Klexan® should be continued until the therapeutic anticoagulant effect is achieved (INR values should be 2.0-3.0).

Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis

The recommended dose of Klexan® is on average 1 mg / kg of body weight. If there is 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 / kg with single vascular access.

During hemodialysis, Clexan® should be inserted 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. There are no data available for patients using enoxaparin sodium for prevention or treatment and during hemodialysis sessions.

Treatment of unstable angina and non-ST-segment elevation myocardial infarction Clexan® is administered at the rate of 1 mg/kg of body weight every 12 hours, subcutaneously, with simultaneous use of antiplatelet therapy. The average duration of therapy is at least 2 days and continues until the patient’s clinical condition stabilizes. Usually, the drug administration lasts from 2 to 8 days. Acetylsalicylic acid is recommended for all patients who do not have contraindications, with an initial dose of 150-300 mg orally followed by a maintenance dose of 75-325 mg once a day.

Treatment of acute ST-segment elevation myocardial infarction, medication or percutaneous coronary intervention Treatment begins with a single intravenous bolus injection of enoxaparin sodium at a dose of 30 mg. Immediately after it, enoxaparin sodium is administered subcutaneously at a dose of 1 mg/kg of body weight. Next, the drug is administered subcutaneously at 1 mg / kg of body weight every 12 hours (maximum 100 mg of enoxaparin sodium for each of the first two subcutaneous injections, then-1 mg/kg of body weight for the remaining subcutaneous doses, that is, with a body weight of more than 100 kg, a single dose can not exceed 100 mg). As soon as possible after detection of acute ST-segment elevation myocardial infarction, patients should be prescribed acetylsalicylic acid simultaneously and, if there are no contraindications, acetylsalicylic acid (in doses of 75-325 mg) should be continued daily for at least 30 days.

The recommended duration of treatment with Klexan® is 8 days or until the patient is discharged from the hospital (if the period of hospitalization is less than 8 days).

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 and up to 30 minutes after it.

In patients aged 75 years and older, the initial intravenous bolus is not used. The drug is administered subcutaneously at a dose of 0.75 mg / kg every 12 hours (maximum 75 mg of enoxaparin sodium for each of the first two subcutaneous injections, then 0.75 mg/kg of body weight for the remaining subcutaneous doses, that is, with a body weight of more than 100 kg, a single dose can not exceed 75 mg).

In patients undergoing percutaneous coronary intervention, if the last subcutaneous injection of enoxaparin sodium was performed less than 8 hours before inflating the balloon catheter 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 performed more than 8 hours before inflating the balloon catheter, an additional intravenous bolus of enoxaparin sodium should be administered at a dose of 0.3 mg / kg.

Overdose

Accidental overdose of Clexan® with intravenous, extracorporeal or subcutaneous administration may lead to hemorrhagic complications. When taken orally, even large doses of the drug are unlikely to be absorbed.

Anticoagulant effects can mainly be neutralized by slow intravenous administration of protamine sulfate, the dose of which depends on the dose of the drug administered. One mg (1 mg) of protamine sulfate neutralizes the anticoagulant effect of one mg (1 mg) of Clexan® (see information on the use of protamine sulfate preparations), if enoxaparin sodium was administered no more than 8 hours before protamine administration.0.5 mg of protamine neutralizes the anticoagulant effect of 1 mg of the drug, if more than 8 hours have passed since the last dose was administered, or if a second dose of protamine is necessary. If 12 hours or more have passed since the introduction of enoxaparin sodium, the introduction of protamine is not required. However, even with high doses of protamine sulfate, the anti-Xa activity of Clexan® is not completely neutralized (by a maximum of 60%).

Description

clear, colorless to pale yellow solution.

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 use for each drug belonging to the class of low-molecular-weight heparins.

Bleeding

As with other anticoagulants, the administration of Clexan® may cause bleeding of any localization

If bleeding develops, it is necessary to find its source and prescribe appropriate treatment.

Enoxaparin sodium, like other anticoagulants, should be used with caution in conditions with an increased risk of bleeding, such as::

– hemostatic disorders;- a history of peptic ulcer disease; – a recent ischemic stroke;- severe arterial hypertension; – diabetic retinopathy; – neurosurgical or ophthalmic surgery;- simultaneous use of drugs that affect hemostasis

Bleeding in elderly patients

When using enoxaparin sodium in prophylactic doses in elderly patients, there was no increase in the risk of bleeding.

When using the drug 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

Simultaneous use of other drugs that affect hemostasis. The use of drugs that affect hemostasis (salicylates of systemic action, including acetylsalicylic acid in doses that have an anti-inflammatory effect, NSAIDs, including ketorolac, other thrombolytics (alteplase, reteplase, streptokinase, tenecteplase, urokinase)) is recommended to be discontinued before starting treatment with enoxaparin sodium, except in cases where their use is necessary. If their simultaneous use with enoxaparin sodium is indicated, then careful clinical monitoring and monitoring of appropriate laboratory parameters should be carried out.

Kidney failure

Patients with impaired renal function have an increased risk of bleeding as a result of increased systemic exposure to enoxaparin sodium. In patients with severe renal impairment (creatinine clearance >15 and > Although no dose adjustment is required in patients with mild (creatinine clearance >30 and ><50 ml/min) and moderate (creatinine clearance >50 and <50 ml/min) and moderate (creatinine clearance > Enoxaparin sodium is not recommended for patients with end-stage chronic kidney disease (CC).

Low body weight

There was an increase in exposure to enoxaparin sodium with its preventive use in women with a body weight of less than 45 kg and in men with a body weight of 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 (BMI greater than 30 kg / m2) is not fully defined and there is no consensus on dose adjustment.It is recommended to monitor patients for the development of symptoms and signs of thrombosis and embolism.

Control of the number of platelets in the peripheral blood.

The risk of developing antibody-mediated heparin-induced thrombocytopenia (GIT) also exists with the use of low-molecular-weight heparins, and this risk is higher in patients who have undergone heart surgery and patients with cancer. 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 enoxaparin sodium and during its use. The blood platelet count should be determined if there are symptoms that indicate GIT (a new episode of arterial and / or venous thromboembolic complications, painful skin damage at the injection site, allergic or anaphylactic reaction during treatment). If these symptoms occur, you should inform your doctor. If there is a confirmed significant decrease in platelet count (by 30-50% compared to baseline), enoxaparin sodium should be immediately discontinued and the patient should be transferred to another anticoagulant therapy without the use of heparins.

Spinal / epidural anesthesia

Cases of occurrence of neuroaxial hematomas with enoxaparin sodium and simultaneous spinal/epidural anesthesia with the development of long-term or irreversible paralysis are described. The risk of these events is reduced when the drug 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 the section “Interaction with other drugs”). The risk is also increased with traumatic or repeated spinal puncture, or in patients with 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 the section “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. It should also be taken into account that in patients with creatinine clearance of 15-30 ml/min, the elimination of enoxaparin sodium slows down.

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

The use of enoxaparin sodium in patients with a history of heparin-induced thrombocytopenia within the last 100 days or in the presence of circulating antibodies is contraindicated. Circulating antibodies can persist for several years. Enoxaparin sodium should be used with extreme caution in patients with a history (more than 100 days) of heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in this situation should be made only after evaluating the benefit/risk ratio and in the absence of heparin-free (non-heparin) therapy. alternative therapy.

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 drug administration. This is necessary to achieve hemostasis at the catheter insertion site after percutaneous coronary intervention. If a closure device is used, the femoral artery introducer can be removed immediately. When applying manual compression, the femoral artery introducer 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. Due to the lack of clinical data and the presence of ambiguous factors, including the underlying disease, it is difficult to assess such reports.

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 involving pregnant women with mechanical artificial heart valves, when enoxaparin sodium was administered at a dose of 1 mg/kg of body weight twice a day to reduce the risk of thrombosis and embolism,2 out of 8 women developed blood clots that 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 may have an increased risk of developing thrombosis and embolism.

Skin necrosis/cutaneous vasculitis

Skin necrosis and cutaneous vasculitis have been reported with low-molecular-weight heparins. If skin necrosis/cutaneous vasculitis develops, the drug should be discontinued.

Acute infectious endocarditis

The use of heparin is not recommended in patients with acute infectious endocarditis due to the risk of hemorrhagic stroke. If the use of the drug is considered absolutely necessary, the decision should be made only after a thorough individual assessment of the benefit-risk ratio.

Laboratory tests

In doses used for the prevention of thromboembolic complications, Klexan® 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.

Hyperkalemia

Heparins can inhibit the secretion of aldosterone by the adrenal glands, which leads to the development of hyperkalemia, especially in patients with diabetes mellitus, chronic renal failure, previous metabolic acidosis, taking medications that increase potassium content. Blood plasma potassium levels should be monitored regularly, especially in patients at risk.

Prevention of venous thrombosis and embolism in patients with acute therapeutic diseases who are on bed rest

In the 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;- history of thrombosis and embolism;- obesity; – hormone therapy; – heart failure;- chronic respiratory failure.

Impaired liver function

Enoxaparin sodium should be used with caution in patients with impaired liver function due to an increased risk of bleeding. Dose adjustment based on monitoring of anti-Xa activity in patients with cirrhosis of the liver is unreliable and is not recommended.

Form of production

Solution for injection,2000 anti-Xa IU/ 0.2 ml; 4000 anti-Xa IU/0.4 ml; 6000 anti-Xa IU/0.6 ml; 8000 anti-Xa IU/0.8 ml; 10000 anti-Xa IU/1 ml.

Storage conditions

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

Shelf

life is 3 years. Do not use the product 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: 191 g.