Clexane, 4000 anti-Xa IU/0.4 ml, solution for injection, 0.4 ml, 9 pcs.

Pharmacological properties of the drug Clexane

Low molecular weight heparin (average molecular weight about 4500 Da), in which the antithrombotic and anticoagulant activities of standard heparin are separated. Unlike standard unfractionated heparin, it is characterized by high anti-Xa activity (100 IU/ml) and weak anti-IIa or antithrombin activity (28 IU/ml). When used in recommended doses, enoxaparin sodium does not increase bleeding time. In prophylactic doses, enoxaparin sodium does not lead to significant changes in activated partial thromboplastin time (aPTT), and also does not affect platelet aggregation and fibrinogen binding to platelets. The pharmacokinetic parameters of the drug are assessed by changes in anti-Xa and anti-IIa activity in blood plasma over time in the recommended dose ranges. When administered subcutaneously, Clexane is quickly and almost completely absorbed. Absorption is directly proportional to the administered dose and is linear. The bioavailability of enoxaparin sodium when administered subcutaneously approaches 100%. Maximum anti-Xa activity in blood plasma is observed between the 3rd and 5th hour after subcutaneous administration and averages 0.18±0.04 IU/ml after administration of 2000 anti-Xa IU and 0. 43±0.11 IU/ml after administration of 4000 anti-Xa IU, and 1.01±0.14 IU/ml after administration of 10,000 anti-Xa IU. Maximum anti-IIa activity is observed on average 4 hours after subcutaneous administration at a dose of 4000 anti-Xa IU, while at the same time, when administered at a dose of 2000 anti-Xa IU, this activity cannot be determined by the traditional amidolytic method. The volume of distribution of enoxaparin sodium for anti-Xa activity almost corresponds to the volume of circulating blood. Metabolism of enoxaparin sodium occurs in the liver by desulfation and/or depolymerization to form low molecular weight heparin species with significantly lower biological potential. The half-life of anti-Xa activity corresponds to approximately 4 hours with a single dose and 7 hours with repeated administration. Anti-Xa activity is detectable up to approximately 24 hours after subcutaneous administration of 4000 anti-Xa IU enoxaparin sodium. Renal clearance of active metabolites is 10%, total renal excretion is 40% of the drug dose. Elimination of enoxaparin is longer in the elderly (half-life is 6–7 hours). In patients with renal failure (creatinine clearance ≤30 ml/min), AUC increases significantly (by 65%) with repeated administration of 4000 anti-Xa IU once daily. Pharmacokinetic parameters in patients with renal failure on hemodialysis do not change.

Where can I buy Clexane 4000

As a rule, Clexane 4000 became the most prescribed dose, so this particular dosage may not be found in city pharmacies. You can get out of the situation thanks to a two-time injection of Clexan 2000 or get by with half a syringe of Klesan 8000. But in this case, you will need to purchase separately sterile needles of the same type that are put on the syringes by the factory method.

The drug is sold by prescription. An analogue of Clexane, Eliquis, 2.5 mg of which is identical to 4000 units of Clexane, may be offered.

Indications for use of the drug Clexane

Prevention of venous thrombosis and embolism during orthopedic or general surgical operations, as well as in therapeutic patients on bed rest due to acute illnesses (heart failure of functional class III–IV according to the NYHA classification, respiratory failure, severe acute infectious process, rheumatic diseases) ; prevention of thrombus formation in the extracorporeal circuit during hemodialysis; treatment of deep vein thrombosis, including those accompanied by pulmonary embolism; treatment of unstable angina and acute myocardial infarction without a pathological Q (in combination with acetylsalicylic acid).

Nosological classification (ICD-10)

• I00 Rheumatic fever without mention of cardiac involvement
• I20.0 Unstable angina
• I21 Acute myocardial infarction
• I26 Pulmonary embolism
• I50 Heart failure
• I50.0 Congestive heart failure
• I74 Embolism and thrombosis of arteries
• I82 Embolism and thrombosis of other veins
• J96 Respiratory failure, not elsewhere classified
• Z100* CLASS XXII Surgical practice
• Z49.1 Care including extracorporeal dialysis

Use of the drug Clexane

The drug is used only in adults. For prophylactic and therapeutic use, enoxaparin is administered deeply subcutaneously. The drug is administered intravenously to achieve anticoagulation during hemodialysis. Enoxaparin cannot be administered intramuscularly! Clexane is injected into the antero- or posterolateral area of ​​the abdominal wall. The syringe needle is inserted over its entire length in a perpendicular direction to the surface of the skin fold, which is formed using the thumb and index finger and held throughout the entire injection. The patient should be in a supine position. 1 mg of enoxaparin sodium (0.01 ml solution) corresponds to approximately 100 anti-Xa IU activity. For the prevention of venous thrombosis and thromboembolism during operations with a moderate risk of thrombus formation (abdominal surgery) and in patients with a moderate risk of thromboembolism, the drug is recommended to be administered subcutaneously at a dose of 2000 anti-Xa IU once a day. For operations with a high risk of thromboembolism (surgeries on the hip or knee joint and oncological interventions), the drug is administered subcutaneously at a dose of 4000 anti-Xa IU once a day. In general surgical practice, the first dose of the drug is administered 2 hours before surgery. In orthopedic practice, the first dose of the drug is administered 12 hours before surgery. The duration of prophylactic use is on average 7–10 days. In orthopedics, it is used in a dose of 4000 anti-Xa once a day for up to 4 weeks. In immobilized medical patients at high risk of thromboembolism, the recommended dose is 4000 anti-Xa IU once daily for at least 6 days, but not more than 14 days. To prevent thrombus formation in the extracorporeal circuit during hemodialysis, the drug is used at a dose of 100 anti-Xa IU/kg of patient body weight. Enoxaparin is injected into the arterial line of the hemodialysis circuit before the start of the session. As a rule, the indicated dose is sufficient for dialysis for 4 hours; if fibrin rings appear, an additional dose of 50–100 anti-Xa IU/kg may be administered. For patients with a high risk of bleeding, the dose of the drug should be reduced to 50 anti-Xa IU/kg with dual vascular access and to anti-Xa IU/kg with single access. When fibrin rings appear, an additional dose of 50 to 100 anti-Xa IU/kg is administered. In the treatment of deep vein thrombosis, which is accompanied or not accompanied by pulmonary embolism, enoxaparin sodium is administered subcutaneously at a dose of 150 anti-Xa IU/kg once a day or at a dose of 100 anti-Xa IU/kg 2 times a day every 12 h. The duration of treatment should not exceed 10 days. If necessary, oral anticoagulants are simultaneously prescribed. Treatment is continued until the international normalization ratio (INR) reaches 2–3. Q wave in the acute phase, enoxaparin sodium is administered subcutaneously at a dose of 100 anti-Xa IU/kg every 12 hours (in combination with acetylsalicylic acid at a dose of 100–325 mg orally once a day) . The duration of treatment is 2–8 days until the patient’s condition is clinically stabilized. There is no need for dose adjustment in elderly patients with normal renal function. The use of enoxaparin sodium in children is not recommended. In patients with renal failure (creatinine clearance ≤30 ml/min), dose adjustment of the drug is required, since its effect in this category of patients is significantly enhanced. For prophylactic purposes, such patients are prescribed the drug in a dose of 20 mg (2000 anti-Xa IU) once a day, for therapeutic purposes - 1 mg/kg (100 anti-Xa IU/kg) once a day. Administration of the drug to patients with liver failure requires medical supervision.

Side effects of the drug Clexane

Hemorrhagic complications are possible (including isolated cases of massive bleeding, in particular retroperitoneal and intracranial; some of these cases were fatal); local or generalized allergic reactions; thrombocytopenia (mild, transient, asymptomatic thrombocytopenia in the first days of therapy; immunoallergic thrombocytopenia with thrombosis, which in some cases was complicated by organ infarction or limb ischemia); with prolonged treatment (more than 5 weeks) - early development of osteoporosis; increased activity of transaminases in blood serum; the development of neuraxial hematomas when using enoxaparin during epidural or spinal anesthesia in some cases can lead to neurological disorders of varying severity, including the formation of prolonged or permanent paralysis; reactions at the injection site (from mild irritation to pain, bruising and hematomas at the injection site, in exceptional cases - skin necrosis); skin bullous rashes or systemic allergic reactions, including anaphylactoid. If such side effects occur, treatment with the drug must be stopped. Isolated cases of hypersensitivity with cutaneous vasculitis have been reported; asymptomatic and reversible increase in platelet count and increase in liver enzyme activity.

Side effects

The side effects of enoxaparin sodium were studied in more than 15,000 patients participating in clinical trials, of which 1,776 patients were studied in the prevention of venous thrombosis and embolism during general surgery and orthopedic operations; in 1169 patients - for the prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases; in 559 patients - in the treatment of deep vein thrombosis with pulmonary embolism or without pulmonary embolism; in 1578 patients - in the treatment of unstable angina and myocardial infarction without a Q wave; in 10,176 patients - in the treatment of myocardial infarction with ST segment elevation.

The mode of administration of enoxaparin sodium differed depending on the indication. For the prevention of venous thrombosis and embolism during general surgical and orthopedic operations or in patients on bed rest, 40 mg subcutaneously was administered once a day. For the treatment of deep vein thrombosis with or without pulmonary embolism, patients received enoxaparin sodium at a dose of 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg subcutaneously once daily. In the treatment of unstable angina and myocardial infarction without a Q wave, the dose of enoxaparin sodium was 1 mg/kg subcutaneously every 12 hours, and in the case of myocardial infarction with ST segment elevation, an intravenous bolus of 30 mg was administered followed by 1 mg/kg subcutaneously. /k every 12 hours

Adverse reactions were classified by frequency of occurrence as follows: very common (≥1/10); frequent (≥1/100 - <1/10); uncommon (≥1/1000 - <1/100); rare (≥1/10000 - <1/1000); very rare (<1/10000), or the frequency is unknown (it is not possible to estimate the frequency of occurrence of an adverse reaction based on available data). Adverse reactions observed after the drug was marketed were classified as “frequency unknown.”

Vascular disorders

Bleeding

In clinical studies, bleeding was the most common adverse reaction. These included major bleeding, observed in 4.2% of patients (bleeding was considered major if it was accompanied by a decrease in hemoglobin levels by 2 g/L or more, required transfusion of 2 or more units of blood components, and also if it was retroperitoneal or intracranial) . Some of these cases were fatal.

As with the use of other anticoagulants, bleeding may occur when using enoxaparin sodium, especially in the presence of risk factors that contribute to the development of bleeding, during invasive procedures or the use of drugs that impair hemostasis (see “Special Instructions” and “Interaction”).

When describing bleeding, the sign “*” means an indication of the following types of bleeding: hematoma, ecchymoses (except those developed at the injection site), wound hematomas, hematuria, nosebleeds, gastrointestinal bleeding (see below).

Very common: bleeding* when preventing venous thrombosis in surgical patients and treating deep vein thrombosis with or without pulmonary embolism.

Often - bleeding* when preventing venous thrombosis in patients on bed rest and treating unstable angina, non-Q wave myocardial infarction and ST-segment elevation myocardial infarction.

Uncommon: retroperitoneal bleeding and intracranial hemorrhage in patients treated for deep vein thrombosis with or without pulmonary embolism, as well as in the treatment of ST-segment elevation myocardial infarction.

Rarely - retroperitoneal bleeding during the prevention of venous thrombosis in surgical patients and the treatment of unstable angina and myocardial infarction without a Q wave.

Thrombocytopenia and thrombocytosis

Very often - thrombocytosis (platelet count in peripheral blood - >400·109/l) in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without pulmonary embolism.

Often - thrombocytosis in the treatment of patients with acute myocardial infarction with ST segment elevation.

Thrombocytopenia in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without pulmonary embolism, as well as in acute ST-segment elevation myocardial infarction.

Uncommon: thrombocytopenia in the prevention of venous thrombosis in patients on bed rest and in the treatment of unstable angina and non-Q wave myocardial infarction.

Very rarely - immune-allergic thrombocytopenia in the treatment of patients with acute myocardial infarction with ST segment elevation.

Other clinically significant adverse reactions, regardless of indication

These undesirable reactions, presented below, are grouped by system-organ classes, given with an indication of the frequency of their occurrence defined above and in decreasing order of their severity.

From the immune system: often - allergic reactions; rarely - anaphylactic and anaphylactoid reactions (see also below subsection Data obtained after the drug was released on the market ).

From the liver and biliary tract: very often - increased activity of liver enzymes, mainly increased activity of transaminases, more than three times the ULN).

From the skin and subcutaneous tissues: often - urticaria, itching, erythema; infrequently - bullous dermatitis.

General disorders and disorders at the injection site: often - 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; uncommon - irritation at the injection site, skin necrosis at the injection site.

Laboratory and instrumental data: rarely - hyperkalemia.

Data obtained after the drug entered the market

The following adverse reactions were observed during post-marketing use of Clexane®. These adverse reactions have been spontaneously reported and their frequency has been defined as “frequency unknown” (cannot be determined from available data).

From the immune system: anaphylactic/anaphylactoid reactions, including shock.

From the nervous system: headache.

Vascular: When using enoxaparin sodium against the background of spinal/epidural anesthesia or spinal puncture, cases of spinal hematoma (or neuraxial hematoma) have been reported. These reactions led to the development of neurological disorders of varying severity, including persistent or irreversible paralysis (see "Special Instructions").

From the blood or lymphatic system: hemorrhagic anemia; cases of development of immune-allergic thrombocytopenia with thrombosis (in some cases, thrombosis was complicated by the development of organ infarction or limb ischemia - see “Special Instructions”, subsection Monitoring the number of platelets in peripheral blood); eosinophilia.

On the part of the skin and subcutaneous tissues: cutaneous vasculitis and skin necrosis may develop at the injection site, which is usually preceded by the appearance of purpura or erythematous papules (infiltrated and painful - in these cases, therapy with Clexane® should be discontinued); the formation of hard inflammatory nodules-infiltrates at the injection site of the drug is possible, which disappear after a few days and are not grounds for discontinuation of the drug; alopecia.

From the liver and biliary tract: hepatocellular liver damage; cholestatic liver damage.

From the musculoskeletal and connective tissue side: osteoporosis with long-term therapy (more than 3 months).

Special instructions for the use of the drug Clexane

Low molecular weight heparins are not interchangeable drugs, since they differ in molecular weight, specific activity against factor Xa, and dosage regimen. Clexane, like other anticoagulants, should be used with caution in conditions that are accompanied by an increased risk of bleeding, namely: with hemostasis disorders, a history of peptic ulcers, recent hemorrhagic stroke, uncontrolled severe hypertension (arterial hypertension), diabetic retinopathy, neurosurgical or ophthalmic surgical interventions, simultaneous use of drugs that affect hemostasis. During prophylactic treatment of patients over 65 years of age, no increased bleeding was observed, however, when using the drug in therapeutic doses, there may be a risk of developing hemorrhagic complications. Since there are not enough controlled clinical studies in pregnant women, enoxaparin sodium should be prescribed during pregnancy only if there is a vital indication. It is not recommended to use Clexane for the treatment of pregnant women with prosthetic heart valves. It is recommended to stop breastfeeding during treatment with the drug. Not used in pediatric practice. In patients with low body weight (less than 45 kg in women and 57 kg in men), the risk of developing hemorrhagic complications increases, which requires monitoring the patient. In order to reduce the risk of bleeding after percutaneous coronary angioplasty, the catheter providing vascular access should be removed no earlier than 6–8 hours after subcutaneous administration of enoxaparin. The next dose of enoxaparin can be administered only 6–8 hours after removal of the catheter. When performing spinal or epidural anesthesia with the use of enoxaparin sodium at a dose of 4000 anti-Xa IU/kg once a day, cases of the development of neuraxial hematomas and associated neurological disorders were rarely observed. The risk of developing such complications increases with the use of enoxaparin sodium in high doses, the use of permanent postoperative epidural catheters, or the simultaneous use of drugs that affect hemostasis, in particular NSAIDs, during repeated punctures. When combined with spinal or epidural anesthesia and enoxaparin, it is best to install and remove the catheter before administering enoxaparin. When performing spinal or epidural anesthesia, it is best to insert and remove the catheter when the anticoagulant effect of enoxaparin sodium is low: 10–12 hours after administration of a dose of 4000 anti-Xa IU/kg or less, or 24 hours after administration of the drug in high doses (100 anti-Xa IU/kg 2 times a day or 150 anti-Xa IU/kg once a day). The next administration of enoxaparin sodium should be carried out no earlier than 2 hours after removal of the catheter. Strict medical monitoring of the patient's neurological status is necessary. If signs of a spinal hematoma appear, appropriate treatment should be immediately prescribed (if necessary, spinal cord decompression). Medical supervision is required when prescribing the drug to patients with a history of heparin-induced thrombocytopenia with or without thrombosis. It is recommended to determine the platelet count before and throughout the course of treatment. If the platelet count decreases by 30–50% of the initial value, the drug should be discontinued immediately. Enoxaparin sodium in doses used for the prevention of venous thromboembolism does not significantly affect bleeding time and other parameters of blood coagulation, including platelet aggregation or fibrinogen binding to platelets. When using the drug in higher doses, the aPTT and activated clot formation time may increase. However, the increase in these indicators does not directly depend on the increase in the antithrombotic activity of enoxaparin and does not require constant monitoring.

Clexane: contraindications

First of all, individual intolerance to the components of the injection should be taken into account. If any negative reactions to heparin preparations have been noted, Clexane is used strictly under the supervision of a physician, starting with a minimum single dose.

Other contraindications are:

• aneurysms;
• bleeding;
• bleeding disorders;
• pregnancy, if the expectant mother has an artificial heart valve installed;
• children's age (up to 18 years).

Patients with:

• stomach ulcer;
• hemophilia;
• thrombocytopenia;
• history of ischemic stroke;
• arterial hypertension;
• diabetes mellitus;
• bacterial endocarditis;
• pericarditis;
• kidney damage;
• the presence of extensive wounds on the body.

Clexane is not prescribed to women if less than 6 months have passed since childbirth, and to people who underwent eye surgery less than 3 months ago.

Drug interactions Clexane

Due to the increased risk of bleeding, Clexane should not be used simultaneously with acetylsalicylic acid and other NSAIDs in high doses, ticlopidine, clopidogrel, dextran 40, corticosteroids, thrombolytics, anticoagulants, and other antithrombotic drugs, including glycoprotein IIb/IIIa antagonists. If it is necessary to use such combinations, careful clinical and laboratory monitoring should be carried out, however, today there is experience in the safe combined use of enoxaparin sodium with the above drugs.

Use during pregnancy and breastfeeding

There is no information that enoxaparin sodium crosses the placental barrier during the second trimester of pregnancy in humans. There is no relevant information regarding the first and third trimesters of pregnancy. Since there are no adequate and well-controlled studies in pregnant women, and animal studies do not always predict the response to enoxaparin sodium during pregnancy in humans, it should be used during pregnancy only when there is an urgent need for its use, as determined by a physician. .

It is unknown whether unchanged enoxaparin sodium is excreted into breast milk in humans. Breastfeeding should be stopped while the mother is being treated with Clexane.

Clexane overdose, symptoms and treatment

As a specific antidote, slow intravenous administration of protamine sulfate (hydrochloride) is indicated at the rate of 1 mg of protamine per 1 mg of Clexane (if enoxaparin sodium was administered over the previous 8 hours). However, even with the introduction of protamine sulfate in a high dose, the effect of enoxaparin sodium is not completely neutralized (maximum - up to 60%). Since neutralization may be temporary (due to the absorption characteristics of low molecular weight heparins), the dose of protamine must be divided into several injections (from 2 to 4) over 24 hours.

Compound

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