Name:

Clexane

Pharmacological
action:

A drug low molecular weight heparin(molecular weight about 4500 daltons: less than 2000 daltons -< 20%, от 2000 до 8000 дальтон - >68%, more than 8000 daltons -< 18%).
Enoxaparin sodium is obtained by alkaline hydrolysis of heparin benzyl ester isolated from the mucous membrane of the small intestine of pigs.
Its structure is characterized by a non-reducing 2-O-sulfo-4-enpyrazinosuronic acid moiety and a reducing 2-N,6-O-disulfo-D-glucopyranoside moiety.
The structure of enoxaparin contains about 20% (ranging from 15% to 25%) 1,6-anhydro derivative in the reducing portion of the polysaccharide chain.
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-III), providing anticoagulant activity in humans.

In addition to anti-Xa/IIa activity, additional anticoagulant and anti-inflammatory properties of enoxaparin sodium have also been identified both in healthy humans and patients, and in animal models.
This includes AT-III-dependent inhibition of other coagulation factors such as factor VIIa, activation of tissue factor pathway inhibitor (TFP) release, and decreased release of von Willebrand factor from the vascular endothelium into the bloodstream. These factors provide the anticoagulant effect of enoxaparin sodium in general.
When using the drug in prophylactic doses, it slightly changes the aPTT, almost has no effect on platelet aggregation and the level of fibrinogen binding 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 body weight for a double dose and 1.5 mg/kg body weight for a single dose. introduction accordingly.
The average maximum anti-Xa activity of plasma 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, 40 mg and 1 mg/kg and 1.5 mg/kg respectively.

Pharmacokinetics
The pharmacokinetics of enoxaparin in the indicated dosage regimens is linear.
Suction and distribution
After repeated subcutaneous injections of enoxaparin sodium at a dose of 40 mg and at a dose of 1.5 mg/kg body weight 1 time/day in healthy volunteers, Css is achieved by day 2, and AUC is on average 15% higher than after a single administration. After repeated subcutaneous injections of enoxaparin sodium at a daily dose of 1 mg/kg body weight 2 times/day, Css is achieved after 3-4 days, with AUC on average 65% higher than after a single dose and average Cmax values ​​of 1.2 IU, respectively. /ml and 0.52 IU/ml.
The bioavailability of enoxaparin sodium after subcutaneous administration, assessed on the basis of anti-Xa activity, is close to 100%. The Vd of enoxaparin sodium (based on anti-Xa activity) is approximately 5 liters and is close to the blood volume.
Metabolism
Enoxaparin sodium is mainly biotransformed in the liver by desulfation and/or depolymerization to form low molecular weight substances with very low biological activity.

Removal
Enoxaparin sodium is a drug with low clearance. After intravenous administration for 6 hours at a dose of 1.5 mg/kg body weight, the average clearance of anti-Xa in plasma is 0.74 l/h.
The elimination of the drug is monophasic. T1/2 is 4 hours (after a single subcutaneous injection) and 7 hours (after repeated administration of the drug). 40% of the administered dose is excreted by the kidneys, with 10% unchanged.
Pharmacokinetics in special clinical situations
There may be a delay in the elimination of enoxaparin sodium in elderly patients due to decreased renal function.
In patients with impaired renal function, a decrease in the clearance of enoxaparin sodium is observed. In patients with mild (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-50 ml/min) renal impairment, after repeated subcutaneous administration of 40 mg enoxaparin sodium 1 time/day, there is an increase in anti-Xa activity, represented by AUC . In patients with severe renal impairment (creatinine clearance less than 30 ml/min), with repeated subcutaneous administration of the drug at a dose of 40 mg 1 time/day, the AUC at steady state is on average 65% higher.
In patients with excess body weight, with subcutaneous administration of the drug, the clearance is slightly less. If you do not adjust the dose taking into account the patient's body weight, then after a single subcutaneous injection of enoxaparin sodium at a dose of 40 mg, anti-Xa activity will be 50% higher in women weighing less than 45 kg and 27% higher in men with weight body weight less than 57 kg, compared with patients with normal average body weight.

Indications for
application:

Prevention of venous thrombosis and embolism during surgical interventions, especially orthopedic and general surgical operations;
- prevention of venous thrombosis and thromboembolism in patients on bed rest due to acute therapeutic diseases (acute heart failure, chronic heart failure in the stage of decompensation of functional class III or IV according to the NYHA classification, acute respiratory failure, severe acute infection, acute rheumatic diseases in combination with one of the risk factors for venous thrombosis);
- treatment of deep vein thrombosis with or without thromboembolism of the pulmonary artery;
- prevention of thrombus formation in the extracorporeal circulatory system during hemodialysis (usually with a session duration of no more than 4 hours);
- treatment of unstable angina and myocardial infarction without a Q wave in combination with acetylsalicylic acid;
- treatment of acute ST-segment elevation myocardial infarction in patients undergoing medical treatment or subsequent percutaneous coronary intervention.

Mode of application:

Clexane is intended only for subcutaneous administration, administering it intramuscularly is contraindicated.
Prevention of thrombosis during surgical interventions
For abdominal operations, 20-40 mg once a day subcutaneously, the initial dose is administered 2 hours before surgery.
For orthopedic operations, 40 mg once a day subcutaneously, the initial dose is administered 12 hours before surgery.
An alternative regimen for administering Clexane 30 mg twice a day is possible, the initial dose is administered 12-24 hours after surgery.
The course of therapy is 7-10 days, but if necessary can be extended as long as the risk of thrombosis remains (usually no longer than 5 weeks).
Prevention of thromboembolism and venous thrombosis during forced long-term bed rest
It is recommended to use Clexane in a dose of 40 mg once, subcutaneously, for a course of therapy of 6-14 days.

Prevention of thrombosis during hemodialysis
It is recommended to administer Clexane at a dose of 1 mg/kg body weight once a day; in the presence of risk factors for bleeding, it is recommended to reduce the dose to 0.5 mg/kg body weight once a day if double vascular access is possible or 0.75 mg if a single vascular access is available.
In this procedure, Clexane is injected into the arterial part of the shunt before hemodialysis begins. One dose of Clexane is sufficient for a four-hour session; for a longer hemodialysis session, additional administration of the drug at the rate of 0.5 - 1 mg/kg body weight may be required.
Treatment of deep vein thrombosis
It is recommended to administer Clexane at a dose of 1.5 mg/kg body weight once a day or at a dose of 1 mg/kg body weight twice a day. In the presence of thromboembolic complications, it is recommended to administer Clexane at a dose of 1 mg/kg body weight twice a day.
The average course of therapy is 10 days.

Treatment of coronary heart disease (unstable angina, myocardial infarction without the presence of a pathological Q wave)
It is recommended to administer Clexane at a dose of 1 mg/kg body weight twice a day, simultaneously with the administration of acetylsalicylic acid at a dose of 100-325 mg once a day.
The course of therapy is 2-8 days.
For patients with renal failure, correction is required only when creatinine clearance is less than 30 ml/min.
In this case, the drug is administered at the rate of 1 mg/kg body weight for therapeutic purposes and 20 mg once a day for prophylactic purposes. For mild or moderate deficiency, Clexane can be administered in the usual dosage.
The administration of Clexane should be carried out when the patient is in a supine position, the drug is injected subcutaneously deep (the entire length of the needle vertically) into the inferolateral or superolateral part of the anterior abdominal wall on the left or right.
The release form of Clexane is a pre-filled syringe that is completely ready for use. There is no need to remove air bubbles from the syringe, this avoids loss of the drug.

Side effects:

The side effects of enoxaparin sodium were studied in more than 15,000 patients participating in clinical trials.
Prevention of venous thrombosis and embolism during general surgery and orthopedic operations - 1776 patients.
Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases - 1169 patients.
Treatment of deep vein thrombosis with or without pulmonary embolism - 559 patients.
Treatment of unstable angina and myocardial infarction without Q wave - 1578 patients.
Treatment of myocardial infarction with ST segment elevation - 10,176 patients. 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, the dose was 40 mg subcutaneously once.
When treating deep vein thrombosis with or without pulmonary embolism, patients received enoxaparin sodium at the rate of 1 mg/kg body weight subcutaneously every 12 hours or 1.5 mg/kg body weight sc once a day.
In the treatment of unstable angina and myocardial infarction without a Q wave, the dose of enoxaparin sodium was 1 mg/kg body weight subcutaneously every 12 hours, and in the case of myocardial infarction with ST-segment elevation - 30 mg by bolus administration followed by a dose of 1 mg/day. kg body weight s.c. every 12 hours.
Determination of the frequency of adverse reactions: very often (≥1/10), often (≥1/100 -<1/10), нечасто (≥1/1000 - <1/100), редко (≥1/10 000 - <1/1000), очень редко (<1/10 000).

Bleeding
Bleeding was the most common side effect.
It occurred in 4.2% of cases and was considered significant if it was accompanied by a decrease in hemoglobin content by 2 g/l or more, required transfusion of 2 or more doses 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, especially in the presence of concomitant risk factors that contribute to the development of bleeding, during invasive procedures or the use of drugs that impair hemostasis.
Very often - bleeding during the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without thromboembolism.
Often - bleeding during the prevention of venous thrombosis in patients on bed rest and during the treatment of angina pectoris, myocardial infarction without a Q wave and myocardial infarction with ST segment elevation.
Uncommon: retroperitoneal bleeding and intracranial bleeding in patients treated for deep vein thrombosis with or without thromboembolism, as well as ST-segment elevation myocardial infarction.
Rarely - retroperitoneal bleeding in the prevention of venous thrombosis in surgical patients and in the treatment of angina pectoris, myocardial infarction without a Q wave.
When using Clexane against the background of spinal/epidural anesthesia and postoperative use of penetrating catheters, cases of the formation of neuraxial hematomas have been described, leading to neurological disorders of varying severity, including long-term or irreversible paralysis.

Thrombocytopenia and thrombocytosis
Very often - thrombocytosis in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without thromboembolism.
Often - thrombocytopenia in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without thromboembolism, as well as in myocardial infarction with ST segment elevation.
Uncommon - thrombocytopenia in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina pectoris, myocardial infarction without a Q wave.
Very rarely - autoimmune thrombocytopenia during myocardial infarction with ST segment elevation.
In rare cases, the development of autoimmune thrombocytopenia in combination with thrombosis. In some of them, thrombosis was complicated by organ infarction or limb ischemia.

Others
Very often - increased activity of liver transaminases.
Often - allergic reactions, urticaria, itching, redness of the skin, hematoma and pain at the injection site.
Uncommon: 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, preceded by the appearance of purpura or erythematous painful papules. 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.

Contraindications:

Conditions and diseases in which there is a high risk of bleeding (threatened abortion, cerebral aneurysm or dissecting aortic aneurysm /except for surgical intervention/, hemorrhagic stroke, uncontrolled bleeding, severe enoxaparin- or heparin-induced thrombocytopenia);
- age under 18 years (efficacy and safety have not been established);
- hypersensitivity to enoxaparin, heparin and its derivatives, including other low molecular weight heparins.

Use not recommended drug in pregnant women with artificial heart valves.
Carefully used for the following conditions:
- hemostasis disorders (including hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease);
- severe vasculitis;
- peptic ulcer of the stomach and duodenum or other erosive and ulcerative lesions of the gastrointestinal tract;
- recent ischemic stroke;
- uncontrolled severe arterial hypertension;
- diabetic or hemorrhagic retinopathy;
- severe diabetes mellitus;
- recent or proposed neurological or ophthalmological surgery;
- performing spinal or epidural anesthesia (potential danger of hematoma development);
- spinal puncture (recently undergone);
- recent birth;
- bacterial endocarditis (acute or subacute);
- pericarditis or pericardial effusion;
- renal and/or liver failure;
- intrauterine contraception;
- severe trauma (especially the central nervous system);
- open wounds with a large wound surface;
- simultaneous use of drugs that affect the hemostatic system.
There is no data on the clinical use of Clexane in the following conditions: active tuberculosis, radiation therapy (recently administered).

When prescribing the drug for prophylactic purposes, there was no tendency to increase bleeding.
When prescribing the drug for therapeutic purposes, there is a risk of bleeding in older patients (especially those over 80 years of age).
Recommended Carrying out careful monitoring of the patient's condition.
It is recommended that the use of drugs that can impair hemostasis (salicylates, acetylsalicylic acid, NSAIDs, including ketorolac; dextran with a molecular weight of 40 kDa, ticlopidine, clopidogrel; corticosteroids, thrombolytics, anticoagulants, antiplatelet agents, including antagonists of glycoprotein receptors IIb/IIIa) should be discontinued until starting treatment with enoxaparin sodium, unless their use is strictly indicated. If combinations of enoxaparin sodium with these drugs are indicated, careful clinical observation and monitoring of relevant laboratory parameters should be carried out.

In patients with impaired renal function there is a risk of bleeding as a result of increased anti-Xa activity of enoxaparin sodium.
In patients with severe renal impairment (CK< 30 мл/мин) рекомендуется проводить коррекцию дозы как при профилактическом, так и терапевтическом назначении препарата. Хотя не требуется проводить коррекцию дозы у пациентов с легким и умеренным нарушением функции почек (КК 30-50 мл/мин или КК 50-80 мл/мин), рекомендуется проведение тщательного контроля состояния таких пациентов.
An increase in the anti-Xa activity of enoxaparin sodium when administered prophylactically in women weighing less than 45 kg and in men weighing less than 57 kg may lead to an increased risk of bleeding.
Risk of autoimmune thrombocytopenia induced by heparin also exists with the use of low molecular weight heparins.
If thrombocytopenia develops, it is usually detected between 5 and 21 days after initiation of enoxaparin sodium therapy.
In this regard, it is recommended to regularly monitor the platelet count before starting treatment with the drug and during its use. If there is a confirmed significant decrease in platelet count (by 30-50% compared to the initial value), it is necessary to immediately discontinue enoxaparin sodium and transfer the patient to another therapy.

Spinal/epidural anesthesia
As with the use of other anticoagulants, cases of neuraxial hematomas have been described when using the drug Clexane against the background of spinal/epidural anesthesia with the development of persistent or irreversible paralysis.
The risk of these events is reduced when using the drug at a dose of 40 mg or lower. The risk increases with increasing dosage of the drug, as well as with the use of penetrating epidural catheters after surgery, or with the concomitant use of additional drugs that have the same effect on hemostasis as NSAIDs.
The risk also increases with trauma or repeated lumbar puncture, or in patients with a history of spinal surgery or spinal deformity.
To reduce the risk of bleeding from the spinal canal during epidural or spinal anesthesia, it is necessary to take into account the pharmacokinetic profile of the drug.
It is best to install or remove a catheter when the anticoagulant effect of enoxaparin sodium is low.

Installation or removal of the catheter should be carried out 10-12 hours after using the drug Clexane in prophylactic doses to prevent deep vein thrombosis. In cases where patients receive higher doses of enoxaparin sodium (1 mg/kg 2 times/day or 1.5 mg/kg 1 time/day), these procedures should be postponed for a longer period of time (24 hours). Subsequent administration of the drug should be carried out no earlier than 2 hours after removal of the catheter.
If the physician prescribes anticoagulant therapy during epidural/spinal anesthesia, the patient should be closely monitored for any neurological signs and symptoms, such as: back pain, sensory and motor disturbances (numbness or weakness in the lower extremities), bowel and/or bladder functions.
The patient should be instructed to immediately inform the doctor if the above symptoms occur.
If signs or symptoms consistent with a spinal cord hematoma are detected, prompt diagnosis and treatment are necessary, including spinal decompression if necessary.

Heparin-induced thrombocytopenia
Clexane should be prescribed with extreme caution to patients with a history of heparin-induced thrombocytopenia, with or without thrombosis.
The risk of thrombocytopenia caused by heparin may persist for several years. If heparin-induced thrombocytopenia is suspected based on history, in vitro platelet aggregation tests are of limited value in predicting the risk of its development. The decision to prescribe Clexane in this case can only be made after consultation with an appropriate specialist.
Percutaneous coronary angioplasty
In order to reduce the risk of bleeding associated with invasive vascular manipulation in the treatment of unstable angina and non-Q wave myocardial infarction, the catheter should not be removed for 6-8 hours after subcutaneous administration of Clexane. The next calculated 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 invasion in order to promptly identify signs of bleeding and hematoma formation.
Artificial heart valves
No studies have been conducted to reliably assess the effectiveness and safety of Clexane in preventing thromboembolic complications in patients with artificial heart valves. The use of the drug for this purpose is not recommended.

Laboratory tests
At doses used for the prevention of thromboembolic complications, Clexane does not significantly affect bleeding time and blood coagulation parameters, as well as platelet aggregation or their binding to fibrinogen.
As the dose increases, the aPTT and clotting time may prolong. The increase in aPTT and clotting time are not in direct linear relationship with the increase in the antithrombotic 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 the case of the development of acute infection, acute rheumatic conditions, prophylactic administration of enoxaparin sodium is justified only if the above conditions are combined with one of the listed risk factors for venous thrombus formation: age over 75 years, malignant neoplasms, history of thrombosis and embolism, obesity, hormonal therapy, heart failure , chronic respiratory failure.
Impact on the ability to drive vehicles and operate machinery
Clexane does not affect the ability to drive vehicles and machines.

Interaction
other medicinal
by other means:

Clexane cannot be mixed with other drugs!
You should not alternate the use of enoxaparin sodium and other low molecular weight heparins, because they differ from each other in production method, molecular weight, specific anti-Xa activity, units of measurement and dosage. And, as a consequence of this, the drugs have different pharmacokinetics and biological activities (anti-IIa activity, interaction with platelets).
With systemic salicylates, acetylsalicylic acid, NSAIDs (including ketorolac), dextran with a molecular weight of 40 kDa, ticlopidine and clopidogrel, systemic corticosteroids, thrombolytics or anticoagulants, and other antiplatelet drugs (including glycoprotein IIb/IIIa antagonists), the risk of bleeding increases.

Pregnancy:

Clexane should not be used during pregnancy unless the expected benefit to the mother outweighs the potential risk to the fetus.
There is no information that enoxaparin sodium crosses the placental barrier in the second trimester; there is no information regarding the first and third trimesters of pregnancy.
When using Clexane during lactation, breastfeeding should be stopped.

Overdose:

Symptoms: Accidental overdose by IV, extracorporeal or subcutaneous administration can lead to hemorrhagic complications. When taken orally, even in large doses, absorption of the drug is unlikely.
Treatment: slow intravenous administration of protamine sulfate is indicated as a neutralizing agent, the dose of which depends on the dose of Clexane administered.
It should be taken into account that 1 mg of protamine neutralizes the anticoagulant effect of 1 mg of enoxaparin if Clexane was administered no more than 8 hours before the administration of protamine. 0.5 mg of protamine neutralizes the anticoagulant effect of 1 mg of Clexane if it was administered more than 8 hours ago or if a second dose of protamine is necessary. : water d/i.

Low molecular weight heparin drug.
Drug: CLEXANE®
Active substance of the drug: enoxaparin sodium
ATX code: B01AB05
KFG: Direct anticoagulant - low molecular weight heparin
Registration number: P No. 014462/01
Registration date: 09.18.08
Owner reg. cert.: SANOFI-AVENTIS France (France)

1 syringe
enoxaparin sodium
2000 anti-Ha ME

0.2 ml - syringes (2) - blisters (1) - cardboard packs.
0.2 ml - syringes (2) - blisters (5) - cardboard packs.

The solution for injection is clear, colorless to pale yellow.

1 syringe
enoxaparin sodium
4000 anti-Ha ME

0.4 ml - syringes (2) - blisters (1) - cardboard packs.
0.4 ml - syringes (2) - blisters (5) - cardboard packs.

The solution for injection is clear, colorless to pale yellow.

1 syringe
enoxaparin sodium
6000 anti-Ha ME

0.6 ml - syringes (2) - blisters (1) - cardboard packs.

The solution for injection is clear, colorless to pale yellow.

1 syringe
enoxaparin sodium
8000 anti-Ha ME

0.8 ml - syringes (2) - blisters (1) - cardboard packs.
0.8 ml - syringes (2) - blisters (5) - cardboard packs.

The solution for injection is clear, colorless to pale yellow.

1 syringe
enoxaparin sodium
10000 anti-Ha ME

1 ml - syringes (2) - blisters (1) - cardboard packs.

The description of the drug is based on the officially approved instructions for use.

Pharmacological action of Clexane

Low molecular weight heparin (molecular weight about 4500 daltons). It is characterized by high activity against coagulation factor Xa (anti-Xa activity of approximately 100 IU/ml) and low activity against coagulation factor IIa (anti-IIa or antithrombin activity of approximately 28 IU/ml).

When the drug is used in prophylactic doses, it slightly changes the activated partial thromboplastin time (aPTT), has virtually no effect on platelet aggregation and the level of fibrinogen binding 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 body weight for a double dose and 1.5 mg/kg body weight for a single dose. introduction accordingly.

The average maximum anti-Xa activity of plasma 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, 40 mg and 1 mg/kg and 1.5 mg/kg respectively.

Pharmacokinetics of the drug.

Pharmacokinetics of the drug.

enoxaparin in the indicated dosage regimens is linear.

Suction and distribution

After repeated subcutaneous injections of enoxaparin sodium at a dose of 40 mg and at a dose of 1.5 mg/kg body weight 1 time/day in healthy volunteers, Css is achieved by day 2, and AUC is on average 15% higher than after a single administration. After repeated subcutaneous injections of enoxaparin sodium at a daily dose of 1 mg/kg body weight 2 times/day, Css is achieved after 3-4 days, with AUC on average 65% higher than after a single dose and average Cmax values ​​of 1.2 IU, respectively. /ml and 0.52 IU/ml.

The bioavailability of enoxaparin sodium after subcutaneous administration, assessed on the basis of anti-Xa activity, is close to 100%. The Vd of enoxaparin sodium (based on anti-Xa activity) is approximately 5 liters and is close to the blood volume.

Metabolism

Enoxaparin sodium is mainly biotransformed in the liver by desulfation and/or depolymerization to form inactive metabolites.

Removal

Enoxaparin sodium is a drug with low clearance. After intravenous administration for 6 hours at a dose of 1.5 mg/kg body weight, the average clearance of anti-Xa in plasma is 0.74 l/h.

The elimination of the drug is monophasic. T1/2 is 4 hours (after a single subcutaneous injection) and 7 hours (after repeated administration of the drug). 40% of the administered dose is excreted in the urine, with 10% unchanged.

Pharmacokinetics of the drug.

in special clinical cases

There may be a delay in the elimination of enoxaparin sodium in elderly patients due to decreased renal function.

In patients with impaired renal function, a decrease in the clearance of enoxaparin sodium is observed. In patients with minor (creatinine clearance 50-80 ml/min) and moderate (creatinine clearance 30-50 ml/min) renal impairment, after repeated subcutaneous administration of 40 mg enoxaparin sodium 1 time/day, there is an increase in anti-Xa activity, represented by AUC . In patients with severe renal impairment (creatinine clearance less than 30 ml/min), with repeated subcutaneous administration of the drug at a dose of 40 mg 1 time/day, the AUC at steady state is on average 65% higher.

In patients with excess body weight, with subcutaneous administration of the drug, the clearance is slightly less.

Indications for use:

Prevention of venous thrombosis and thromboembolism, especially in orthopedics and general surgery;

Prevention of venous thrombosis and thromboembolism in patients with acute therapeutic diseases who are on bed rest (chronic heart failure of functional class III or IV according to the NYHA classification, acute respiratory failure, acute infection, acute rheumatic diseases in combination with one of the risk factors for venous thrombus formation);

Treatment of deep vein thrombosis with or without pulmonary embolism;

Treatment of unstable angina and myocardial infarction without a Q wave in combination with acetylsalicylic acid;

Prevention of thrombosis formation in the extracorporeal circulation system during hemodialysis.

The drug is administered subcutaneously. The drug cannot be administered intramuscularly!

To prevent venous thrombosis and thromboembolism, patients with moderate risk (abdominal surgery) are prescribed Clexane 20-40 mg (0.2-0.4 ml) subcutaneously 1 time per day. The first injection is given 2 hours before surgery.

High-risk patients (orthopedic surgery) are prescribed 40 mg (0.4 ml) s.c. 1 time/day, with the first dose administered 12 hours before surgery or 30 mg (0.3 ml) s.c. 2 times/day with the beginning of administration 12-24 hours after surgery.

The duration of treatment with Clexane is 7-10 days. If necessary, therapy can be continued as long as the risk of thrombosis or embolism remains (for example, in orthopedics, Clexane is prescribed at a dose of 40 mg 1 time / day for 5 weeks).

For the prevention of venous thrombosis in patients with acute therapeutic conditions who are on bed rest, 40 mg is prescribed 1 time / day for 6-14 days.

For the treatment of deep vein thrombosis, 1 mg/kg is administered subcutaneously every 12 hours (2 times/day) or 1.5 mg/kg 1 time/day. In patients with complicated thromboembolic disorders, the drug is recommended to be used at a dose of 1 mg/kg 2 times a day.

The average duration of treatment is 10 days. It is advisable to immediately begin therapy with indirect anticoagulants, while Clexane therapy must be continued until a sufficient anticoagulant effect is achieved, i.e. The INR should be 2.0-3.0.

For unstable angina and myocardial infarction without a Q wave, the recommended dose of Clexane is 1 mg/kg subcutaneously every 12 hours. At the same time, acetylsalicylic acid is prescribed at a dose of 100-325 mg 1 time/day. The average duration of therapy is 2-8 days (until the patient’s clinical condition stabilizes).

To prevent the formation of a blood clot in the extracorporeal circulation system during hemodialysis, the dose of Clexane is on average 1 mg/kg body weight. If there is a high risk of bleeding, the dose should be reduced to 0.5 mg/kg body weight with double vascular access or 0.75 mg/kg with single vascular access.

During hemodialysis, the drug should be injected into the arterial site of the shunt at the beginning of the hemodialysis session. One dose is usually sufficient for a four-hour session, however, if fibrin rings are detected during longer hemodialysis, you can additionally administer the drug at the rate of 0.5-1 mg/kg body weight.

If renal function is impaired, it is necessary to adjust the dose of the drug depending on the QC. When CC is less than 30 ml/min, Clexane is administered at the rate of 1 mg/kg body weight 1 time/day for therapeutic purposes and 20 mg 1 time/day for prophylactic purposes.

Dosage and method of administration of the drug.

does not apply to cases of hemodialysis. When CC is more than 30 ml/min, no dose adjustment is required, however, laboratory monitoring of therapy should be carried out more carefully.

Rules for introducing the solution

It is advisable to carry out injections with the patient lying down. Clexane is administered deeply subcutaneously. When using pre-filled 20 mg and 40 mg syringes, do not remove air bubbles from the syringe before injection to avoid loss of the drug. Injections should be performed alternately into the left or right superolateral or inferolateral parts of the anterior abdominal wall.

The needle must be inserted vertically along its entire length into the skin, holding the fold of skin between the thumb and forefinger. The skin fold is released only after the injection is completed. Do not massage the injection site after administering the drug.

Side effects of Clexane:

Bleeding

If bleeding develops, it is necessary to discontinue the drug, establish the cause and begin appropriate treatment.

In 0.01-0.1% of cases, hemorrhagic syndrome may develop, including retroperitoneal and intracranial bleeding. Some of these cases were fatal.

When Clexan is used against the background of spinal/epidural anesthesia and postoperative use of penetrating catheters, cases of spinal cord hematoma have been described (in 0.01-0.1% of cases), which leads to neurological disorders of varying severity, including persistent or irreversible paralysis.

Thrombocytopenia

In the first days of treatment, mild transient asymptomatic thrombocytopenia may develop. In less than 0.01% of cases, immune thrombocytopenia may develop in combination with thrombosis, which can sometimes be complicated by organ infarction or limb ischemia.

Local reactions

After subcutaneous administration, pain may be observed at the injection site, and in less than 0.01% of cases, hematoma at the injection site. In some cases, the formation of solid inflammatory infiltrates containing the drug is possible, which resolve after a few days, without requiring discontinuation of the drug. In 0.001%, skin necrosis may develop at the injection site, preceded by purpura or erythematous plaques (infiltrated and painful); in this case, the drug should be discontinued.

In 0.01-0.1% - skin or systemic allergic reactions. There have been cases of allergic vasculitis (less than 0.01%), requiring discontinuation of the drug in some patients.

A reversible and asymptomatic increase in liver enzyme activity is possible.

Contraindications to the drug:

Conditions and diseases in which there is a high risk of bleeding (threatened abortion, cerebral aneurysm or dissecting aortic aneurysm /except for surgical intervention/, hemorrhagic stroke, uncontrolled bleeding, severe enoxaparin- or heparin-induced thrombocytopenia);

Age up to 18 years (efficacy and safety have not been established);

Hypersensitivity to enoxaparin, heparin and its derivatives, including other low molecular weight heparins;

Use with caution in the following conditions: hemostasis disorders (including hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease), severe vasculitis, gastric and duodenal ulcers or other erosive and ulcerative lesions of the gastrointestinal tract, recent ischemic stroke, uncontrolled severe arterial hypertension, diabetic or hemorrhagic retinopathy, severe diabetes mellitus, recent or proposed neurological or ophthalmic surgery, spinal or epidural anesthesia (potential risk of hematoma development), lumbar puncture (recent), recent childbirth, bacterial endocarditis (acute or subacute), pericarditis or pericardial effusion, renal and/or liver failure, intrauterine contraception, severe trauma (especially the central nervous system), open wounds with a large wound surface, simultaneous use of drugs that affect the hemostatic system.

The company does not have data on the clinical use of Clexane in the following conditions: active tuberculosis, radiation therapy (recent).

Use during pregnancy and lactation.

Clexane should not be used during pregnancy unless the expected benefit to the mother outweighs the potential risk to the fetus. There is no information that enoxaparin crosses the placental barrier in the second trimester, and there is no information regarding the first and third trimesters of pregnancy.

When using Clexane during lactation, breastfeeding should be stopped.

Special instructions for the use of Clexane.

When prescribing the drug for prophylactic purposes, there was no tendency to increase bleeding. When prescribing the drug for therapeutic purposes, there is a risk of bleeding in older patients (especially those over 80 years of age). Close monitoring of the patient's condition is recommended.

Before starting therapy with this drug, it is recommended to discontinue other drugs that affect the hemostatic system due to the risk of bleeding: salicylates, incl. acetylsalicylic acid, NSAIDs (including ketorolac); dextran 40, ticlopidine, clopidogrel, corticosteroids, thrombolytics, anticoagulants, antiplatelet agents (including glycoprotein IIb/IIIa receptor antagonists), except in cases where their use is necessary. If it is necessary to use Clexane in combination with these drugs, special caution must be observed (careful monitoring of the patient’s condition and relevant laboratory blood parameters).

In patients with impaired renal function, there is a risk of bleeding as a result of increased anti-Xa activity. Because this increase increases significantly in patients with severe renal impairment (creatinine clearance less than 30 ml/min); dose adjustment is recommended for both prophylactic and therapeutic use of the drug. Although no dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance greater than 30 ml/min), careful monitoring of the condition of such patients is recommended.

An increase in the anti-Xa activity of enoxaparin when administered prophylactically in women weighing less than 45 kg and in men weighing less than 57 kg may lead to an increased risk of bleeding.

The risk of immune thrombocytopenia caused by heparin also exists with the use of low molecular weight heparins. If thrombocytopenia develops, it is usually detected between 5 and 21 days after initiation of enoxaparin sodium therapy. In this regard, it is recommended to regularly monitor the platelet count before starting treatment with enoxaparin sodium and during its use. If there is a confirmed significant decrease in platelet count (by 30-50% compared to the initial value), it is necessary to immediately discontinue enoxaparin sodium and transfer the patient to another therapy.

Spinal/epidural anesthesia

As with the use of other anticoagulants, cases of spinal cord hematoma have been described when using Clexane during spinal/epidural anesthesia with the development of persistent or irreversible paralysis. The risk of these events is reduced when using the drug at a dose of 40 mg or lower. The risk increases with increasing dosage of the drug, as well as with the use of penetrating epidural catheters after surgery, or with the concomitant use of additional drugs that have the same effect on hemostasis as NSAIDs. The risk also increases with traumatic exposure or repeated spinal puncture.

To reduce the risk of bleeding from the spinal canal during epidural or spinal anesthesia, it is necessary to take into account the pharmacokinetic profile of the drug. It is best to install or remove a catheter when the anticoagulation effect of enoxaparin sodium is low.

Installation or removal of the catheter should be carried out 10-12 hours after the use of prophylactic doses of Clexane for deep vein thrombosis. In cases where patients receive higher doses of enoxaparin sodium (1 mg/kg 2 times/day or 1.5 mg/kg 1 time/day), these procedures should be postponed for a longer period of time (24 hours). Subsequent administration of the drug should be carried out no earlier than 2 hours after removal of the catheter.

If the physician prescribes anticoagulation therapy during epidural/spinal anesthesia, the patient should be closely monitored for any neurological signs and symptoms, such as: back pain, sensory and motor disturbances (numbness or weakness in the lower extremities), bowel and/or bladder functions. The patient should be instructed to immediately inform the doctor if the above symptoms occur. If signs or symptoms consistent with a brainstem hematoma are detected, prompt diagnosis and treatment is necessary, including spinal decompression if necessary.

Heparin-induced thrombocytopenia

Clexane should be prescribed with extreme caution to patients with a history of heparin-induced thrombocytopenia, with or without thrombosis.

The risk of thrombocytopenia caused by heparin may persist for several years. If the history suggests heparin-induced thrombocytopenia, in vitro platelet aggregation tests are of limited value in predicting the risk of its development. The decision to prescribe Clexane in this case can only be made after consultation with an appropriate specialist.

Percutaneous coronary angioplasty

In order to reduce the risk of bleeding associated with invasive vascular manipulation in the treatment of unstable angina, the catheter should not be removed for 6-8 hours after subcutaneous administration of Clexane. The next calculated dose should be administered no earlier than 6-8 hours after removal of the catheter. The injection site should be monitored to promptly identify signs of bleeding and hematoma formation.

Artificial heart valves

No studies have been conducted to reliably assess the effectiveness and safety of Clexane in preventing thromboembolic complications in patients with artificial heart valves, therefore the use of the drug for this purpose is not recommended.

Laboratory tests

At doses used for the prevention of thromboembolic complications, Clexane does not significantly affect bleeding time and overall coagulation parameters, as well as platelet aggregation or their binding to fibrinogen.

As the dose increases, the aPTT and clotting time may prolong. The increase in aPTT and clotting time are not in direct linear relationship with the increase in the antithrombotic 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 the event of the development of an acute infection or acute rheumatic conditions, prophylactic administration of enoxaparin sodium is justified only in the presence of risk factors for venous thrombus formation (age over 75 years, malignant neoplasms, history of thrombosis and embolism, obesity, hormonal therapy, heart failure, chronic respiratory failure).

Impact on the ability to drive vehicles and operate machinery

Clexane does not affect the ability to drive a car or use machinery.

Drug overdose:

Symptoms Accidental overdose with IV, extracorporeal or subcutaneous administration can lead to hemorrhagic complications. When taken orally, even in large doses, absorption of the drug is unlikely.

Treatment: slow intravenous administration of protamine sulfate is indicated as a neutralizing agent, the dose of which depends on the dose of Clexane administered. It should be taken into account that 1 mg of protamine neutralizes the anticoagulant effect of 1 mg of enoxaparin if Clexane was administered no more than 8 hours before the administration of protamine. 0.5 mg of protamine neutralizes the anticoagulant effect of 1 mg of Clexane if it was administered more than 8 hours ago or if a second dose of protamine is necessary. If more than 12 hours have passed after the administration of Clexane, then the administration of protamine is not required. However, even with the introduction of large doses of protamine sulfate, the anti-Xa activity of Clexane is not completely neutralized (maximum by 60%).

Interaction of Clexane with other drugs.

With simultaneous use of Clexane with drugs that affect hemostasis (salicylates / with the exception of unstable angina and non-ST segment elevation myocardial infarction /, other NSAIDs / including ketorolac/, dextran 40, ticlopidine, corticosteroids for systemic use, thrombolytics, anticoagulants, antiplatelet agents / including antagonists of glycoprotein receptors IIb/IIIa/), hemorrhagic complications may develop. If the use of such a combination cannot be avoided, enoxaparin should be used under close monitoring of blood clotting parameters.

You should not alternate the use of enoxaparin sodium and other low molecular weight heparins, because they differ from each other in the method of production, molecular weight, specific anti-Xa activity, units of measurement and doses. These drugs therefore have different

Pharmacokinetics of the drug.

Biological activity (anti-IIa activity and platelet interaction).

Pharmaceutical interactions

Clexane solution cannot be mixed with other drugs.

Terms of sale in pharmacies.

The drug is available with a prescription.

Terms of storage conditions for the drug Clexane.

List B. The drug should be stored out of the reach of children at a temperature not exceeding 25°C. Shelf life - 3 years.

Today we will talk about the drug Clexane. Many have heard about it, but few know whether you really need it and in what cases is it prescribed?

Clexane is a drug that provides you with an antithrombotic effect. During pregnancy, hormonal levels change greatly, and with it the most common problems of pregnant women are anemia (when they start prescribing you iron, etc., which corrects your hemoglobin) and increased blood clotting, which increases every month. In fact, this is a common concern of nature, which thus prevents pregnant women from severe blood loss during childbirth.

But if a pregnant woman is predisposed to thrombosis, this can be dangerous for both mother and baby (hypoxia, miscarriage). Therefore, after carrying out the appropriate tests, I can prescribe Clexane to the pregnant woman. The main active ingredient of the drug is enoxaparin sodium - a substance that, when it enters the blood, reaches a concentration after a couple of hours and thins the blood.

Clexane is available only in injection form, sold as a disposable syringe. The volume of the syringe may be different, and you will need the dose that the doctor prescribes for you: 0.2 ml, 0.4 ml, 0.6 ml, 0.8 ml. or 1 ml. The injection may be clear or yellowish, but don't let that bother you.

The contents of the syringe are injected immediately and the syringe itself is then thrown away; using it to inject other liquids is strictly prohibited.

Why is it prescribed to pregnant women: indications for use

The list of mandatory tests for an expectant mother may not always include a check for blood clots, which are very dangerous. This test is carried out in the form of a coagulogram - a study of blood clotting. But if your obstetrician-gynecologist notices some symptoms, you will definitely be recommended to do this test.

Symptoms in pregnant women usually include:

• constant swelling of the legs;
• pain in the calves or in the hollow behind the knees;
• pain in the lower leg or thigh;
• hemorrhoids with severe pain.

And according to reviews from pregnant women, why they were prescribed Clexane, these were precisely these symptoms. Therefore, be sure to inform your doctor about all unusual conditions in your body, this is very important: the sooner the treatment is adjusted, the better and easier your birth will be.

If the doctor discovers that the blood values ​​are different from the norm, he must intervene. As a rule, those drugs that dissolve blood clots and thin the blood. Blood clots are not good because they can be located anywhere, including in the placental vessels, which will disrupt the flow of nutrients from mother to child and can lead to hypoxia and even miscarriage.

Clexane is prescribed only by a specialist after a comprehensive analysis of all factors. Clexane is most often not prescribed from the 1st trimester, but from the second it is mandatory if we are talking about:

• treatment of blood clots;
• with thrombosis after surgery;
• with heart attack and angina pectoris.

Clexane injections into the stomach during pregnancy are prescribed only after special tests and are carried out under the careful and regular supervision of a gynecologist and with constant monitoring of blood counts. Using Clexane on your own is strictly prohibited, especially during pregnancy. Only a competent specialist can regulate this process, correct it and stop it if it is possible to try to do without drugs, which, of course, is always better for the unborn baby.

Clexane: contraindications and side effects

Clexane is a very serious drug that should not be joked with, so if you have been prescribed it, do not be alarmed, there is nothing wrong with it, except for the need to correct your condition and preparation for childbirth, but be sure to listen carefully and write down all the doctor’s instructions.

Clexane has quite a few contraindications:

• risk of early birth;
• hemorrhagic stroke;
• tuberculosis in the active phase;
• hypertension;
• presence of a cardiac prosthesis;
• age under 18 years;
• heavy weight;
• neoplasms;
• disorders of the liver or kidneys;
• diabetes;
• open wounds;
• stomach ulcer.

There are also serious nuances when stopping the drug. The dose of Clexane should be reduced gradually. But if there is a threat of miscarriage, its use is stopped immediately. In any case, again, this is all the competence of the doctor.

Side effects of Clexane

• Allergic reaction;
• swelling at the injection site;
• skin problems at the injection site;
• headache;
• neurological problems;
• hematomas (due to incorrect injection technique);
• hyperkalemia.

If the drug is abused on its own, much more severe problems can occur, such as liver cirrhosis, hemorrhagic lesions or osteoporosis.

Clexane during pregnancy: consequences for the child

We never tire of repeating that Clexane can be used only after a thorough examination. If we talk about the effect on the fetus, there is no evidence that enoxaparin can penetrate the placenta, but there are no serious studies that would confirm the safety of the drug for a child.

Therefore, no one is in a hurry to immediately prescribe this remedy to a pregnant woman, but there are cases when it is simply necessary. For example, if a doctor sees thrombosis of the placenta beginning, this poses a serious danger to the child. At the beginning of pregnancy, this causes miscarriages, and in subsequent trimesters it leads to hypoxia, premature aging of the placenta and early birth.

Clexane: instructions for use during pregnancy

Clexane is available as an injection. The ampoules have different doses, which are prescribed only by the doctor in order to avoid side effects and so that the treatment is not excessive, but precise. If the doctor sees a possibility of developing thrombosis in a pregnant woman, then there is a need for preventive purposes to give 1 injection per day, 40 ml for 10-15 days. If treatment is being carried out and the problem already exists, then Clexane is injected once a day, and the volume is calculated based on the weight of the pregnant woman (1.5 mg per 1 kg).

As for the injections themselves, they are given differently from a regular injection. Clexane is injected into the stomach, and to achieve the correct effect, you need to know the rules of administration. By the way, don’t let the word “stab in the stomach” scare you, it’s even less painful than in a muscle. And you can give the injection yourself. Therefore, let’s look at how to inject Clexane into the stomach during pregnancy.

1. Before you start the injection, you need to wash your hands very well and sit comfortably, or better yet, lie on your back.
2. Treat the injection site well.
3. Remove the cap from the syringe.
4. As in a regular injection, in this one you don’t need to press on the piston to release air bubbles, as we always do, everything is already provided for, and we can lose drops of the expensive drug.
5. Gather the skin on the abdomen with your thumb and forefinger to create a fold. The injection site should be at least 5-6 cm from the navel.
6. Insert the needle along its entire length perpendicular to the surface of the abdomen.
7. Inject the entire drug, then leave the fold alone and remove the needle without deviating its degree.

Do not give the next injections where there is already a mark from the previous injection. Give injections to different places in the abdomen each time.

Important! Do not rub the injection site. It is forbidden to administer Clexane intramuscularly.

Analogues of Clexane during pregnancy

In addition to Clexane, there are many antithrombotic drugs that are also actively used depending on the circumstances - in the postoperative period and at other times, but not all of these drugs can be used during pregnancy.

Complete analogues of clexane are:

• Novoparin;
• Warfarin;
• Hemapaxan;
• Wessel Due F.;
• Anfiber;
• Enoxarin;
• Fragmin;
• Angioflux;
• Fraxiparine.

Analogs of Clexane differ in composition, mass of substance, and release form. All of them have different effects on the body of a pregnant woman. Therefore, you should never prescribe such medications yourself. Only a doctor can combine all your tests, which contain a great many different nuances, indicators, numbers, and prescribe you exactly that drug, and not that one.

The prescription of Fraxiparine is quite common and many are interested in which is better - Clexane or Fraxiparine during pregnancy. We certainly cannot answer this question in any way, the compositions are very similar, but for some pregnant women Fraxiparine is not suitable or, on the contrary, Clexane. And the most important thing is that the gynecologist, as a rule, consults with a hematologist (in any case, he should do this) and if the necessary tests are available, only they decide which drug to prescribe and in what dose.