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Instruction for use: Clexane
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Dosage form: Solution for injection
Active substance: Enoxaparinum natrium
ATX
B01AB05 Enoxaparin
Pharmacological group
Anticoagulants
The nosological classification (ICD-10)
I00 Rheumatic fever without mention of heart involvement: Acute rheumatism; Rheumatic arthritis acute; Rheumatism is active; Rheumatic fever; Acute attack of rheumatic joint disease
I20.0 Unstable angina: heberden disease; Angina pectoris; The attack of angina pectoris; recurrent angina; Spontaneous angina; Stable angina pectoris; Angina rest; Angina progressing; Angina mixed; Angina spontaneous; stable angina; Chronic stable angina; Angina Syndrome X
I21 Acute myocardial infarction: Myocardial infarction in the acute phase; Acute Myocardial Infarction; Myocardial infarction with pathologic Q wave and without; Myocardial infarction complicated by cardiogenic shock; Infarction left ventricular; Transmural myocardial infarction; Myocardial infarction netransmuralny (subendocardial); Netransmuralny myocardial infarction; Subendocardial myocardial infarction; The acute phase of myocardial infarction; Acute myocardial infarction;Sub-acute phase of myocardial infarction; Subacute phase of myocardial infarction; Thrombosis of the coronary arteries (the arteries); Threatened myocardial infarction; Myocardial infarction without Q wave
I26 Pulmonary embolism: Recurrent thromboembolism of the pulmonary artery; Recurrent pulmonary embolism; Thromboembolism of the branches of the pulmonary artery; Thromboembolism of the lungs; Thromboembolism of the pulmonary artery (PE); Thrombosis of the pulmonary artery; Thromboembolism; Thromboembolism of the pulmonary artery; Thromboembolism; Pulmonary embolism; Thromboembolism of the pulmonary artery and its branches; Thromboembolism of pulmonary vessels; Embolism of the lung; Embolism of the pulmonary artery; Acute massive thromboembolism of the pulmonary artery
I50 Heart failure: Exacerbation of chronic heart failure; Shortness of breath with acute heart failure; Acute heart failure; Acute heart failure; Heart failure on the background of intoxication; Heart failure on the background of infections; Acute Heart Failure; Chronic myocardial insufficiency; Cardiac dyspnea
I50.0 Congestive heart failure: anasarca heart; Decompensated congestive heart failure; Congestive heart failure; Congestive heart failure with high afterload; Congestive chronic heart failure; Cardiomyopathy with severe chronic heart failure; Compensated chronic heart failure; Swelling with circulatory failure; Edema of cardiac origin; Swelling of the heart; Edematous syndrome in diseases of the heart; Edematous syndrome in congestive heart failure; Edematous syndrome in heart failure; Edematous syndrome in heart failure or liver cirrhosis; right ventricular failure; Congestive Heart Failure; Heart failure stagnant; Heart failure with low cardiac output; Heart failure is a chronic; Cardiac edema; Chronic decompensated heart failure; Chronic Congestive Heart Failure; Chronic heart failure; Change of liver function in heart failure
I74 Embolism and arterial thrombosis: Thrombosis of effort (stress); Arterial thrombosis; Arteriothrombosis; Subacute and chronic arterial thrombosis; Subacute thrombosis of peripheral arteries; Postoperative thrombosis; Vascular thrombosis; Vascular embolism; Thrombosis of aortocoronary shunt; Arterial thrombosis; Thrombosis of arteries; Coronary artery thrombosis; Coronary thrombosis; Thrombosis of blood vessels; Thrombosis with ischemic stroke; Thrombosis with general surgical operations; Thrombosis in Oncology Operations; Vascular thrombosis; Thrombus formation in the postoperative period; Thrombotic complications; Thromboembolic diseases; Thromboembolic syndrome; Thromboembolic complication in the postoperative period; Thromboembolism of arteries; Partial vascular thrombosis; Embolism; Embolism of arteries
I82 Embolism and thrombosis of other veins: Recurrent venous thrombosis; Postoperative thrombosis; Venous thrombosis; Acute venous thromboembolism; Recurrent vein thrombosis; Venous thrombosis; Thrombosis of veins of internal organs; Venous thrombosis; Deep vein thrombosis; Thrombosis of blood vessels; Vascular thrombosis; Thrombosis of veins; Deep vein thrombosis; Thromboembolic diseases; Thromboembolism of veins; Severe venous thrombosis; Embolism; Embolism of veins; Thromboembolic complications
J96 Respiratory failure, not elsewhere classified: Hypoxic states; Hypoxia; Respiratory failure; Oxygen deficiency; Insufficiency of breathing; Insufficient oxygenation of the blood; Acute hypoxia; Acute respiratory failure; Acute hypoxic condition; Psychogenic dyspnea; Hypoxic syndrome; Inhibition of respiration in pneumonia and other infectious diseases; Inhibition of the respiratory center in pneumonia and other infectious diseases; Chronic hypoxia; Tachypnea
Z100 * CLASS XXII Surgical practice: Abdominal surgery; adenomectomy; Amputation; Coronary angioplasty; Angioplasty of the carotid arteries; Antiseptic skin treatment for wounds; Antiseptic Hand; Appendectomy; atherectomy; Balloon coronary angioplasty; Vaginal hysterectomy; The coronary bypass; Interventions in the vagina and cervix; Interventions on the bladder; Intervention in the mouth; Restoration and reconstructive surgery; Hand hygiene of medical personnel; Gynecologic surgery; Gynecological intervention; Gynecological surgery; Hypovolemic shock during operations; Disinfection of purulent wounds; Disinfection of wounds edges; Diagnostic intervention; Diagnostic procedures; Cervical Diathermocoagulation; Long-surgery; Replacing the fistula catheters; Infection in orthopedic surgery; Artificial heart valve; cystectomy; Short-term outpatient surgery; Short-term operation; Short surgical procedures; Krikotireotomiya; Blood loss during surgery; Bleeding during surgery and in the postoperative period; Kuldotsentez; laser photocoagulation; laser coagulation; retinal laser coagulation; Laparoscopy; Laparoscopy in Gynecology; CSF fistula; Small gynecological operations; Small surgical procedures; Mastectomy and subsequent plastic; mediastinotomy; Microsurgical operations on the ear; Mukogingivalnye operation; suturing; Minor surgery; neurosurgical operation; Immobilization of the eyeball in ophthalmic surgery; testectomy; pancreatectomy; Perikardektomiya; The period of rehabilitation after surgery; The period of convalescence after surgery; Percutaneous transluminal coronary angioplasty; Pleural thoracentesis; Pneumonia postoperative and posttraumatic; Preparation for surgical procedures; Preparation for surgery; Preparation of the surgeon's hands before surgery; Preparation of the colon for surgical procedures; Postoperative aspiration pneumonia in neurosurgical and thoracic surgery; Postoperative nausea; Postoperative bleeding; postoperative granuloma; postoperative shock; The early postoperative period; myocardial revascularization; Radiectomy; gastric Resection; bowel resection; uterine Resection; liver Resection; enterectomy; Resection of part of the stomach; Reocclusion of the operated vessel; Bonding tissues during surgical procedures; Removal of sutures; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity; Condition after gastrectomy; Status after resection of the small intestine; Condition after tonsillectomy; Condition after removal of the duodenum; Condition after phlebectomy; Vascular surgery; Splenectomy; Sterilization of surgical instruments; Sterilization of surgical instruments; sternotomy; Dental surgery; Dental intervention in periodontal tissues; strumectomy; Tonsillectomy; Thoracic surgery; Thoracic surgery; total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinektomiya; Removal of a tooth; cataract surgery; Removal of cysts; tonsillectomy; Removal of fibroids; Removing the mobile primary teeth; Removing polyps; Removing broken tooth; Removal of the uterus body; Removal of sutures; Fistula likvoroprovodyaschih ways; Frontoetmoidogaymorotomiya; Surgical infection; Surgical treatment of chronic limb ulcers; Surgery; The surgery in the anal area; The surgery on the colon; Surgical practice; The surgical procedure; Surgical interventions; Surgery on the gastrointestinal tract; Surgical procedures on the urinary tract; Surgical procedures on the urinary system; Surgical intervention of the genitourinary system; Surgical procedures on the heart; Surgical manipulation; surgery; Surgery on the veins; Surgical intervention; Vascular surgery; Surgical treatment of thrombosis; Surgery; cholecystectomy; Partial gastric resection; hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass; tooth Extirpation; Extirpation of milk teeth; pulpectomy; pulsative cardiopulmonary bypass; tooth Extraction; teeth Extraction; cataract extraction; Electrocoagulation; endourological intervention; episiotomy; Etmoidotomiya; Complications after tooth extraction
Z49.1 Aids that include extracorporeal dialysis: hemodialysis; Chronic hemodialysis; Extracorporeal circulation; Thrombosis of hemodialysis shunt
Composition
| 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; 10,000 anti-Xa IU / 1 ml |
| In a syringe | Pre-filled syringes | ||||
| 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/1,0 ml | |
| Active substance: enoxaparin sodium (Heb.F., ND firm) | 20 mg* | 40 mg* | 60 mg* | 80 mg* | 100 mg* |
| Solvent: Water for Injection (Hearth.F.) | to 0,2 ml | to 0,4 ml | to 0,6 ml | to 0,8 ml | to 1,0 ml |
Transparent solution from colorless to pale yellow.
Pharmachologic effect
Mode of action - Antithrombotic.
Pharmacodynamics
Enoxaparin sodium is a low molecular weight heparin with an average molecular weight of about 4500 Da: less than 2000 Da - <20%, from 2000 to 8000 Daltons -> 68%, more than 8000 Da - <18%. Enoxaparin sodium is obtained by alkaline hydrolysis of benzyl ester of heparin isolated from the mucosa of the small intestine of a pig. Its structure is characterized by a nonreducing fragment of 2-O-sulfo-4-enapyrazinosuronic acid and a reducing fragment of 2-N, 6-O-disulfo-D-glucopyranoside. The structure of enoxaparin contains about 20% (ranging from 15 to 25%) of the 1,6-anhydro derivative in the reducing fragment of the polysaccharide chain. In a purified in vitro system, sodium enoxaparin has anti-Xa activity (about 100 IU / ml) and low anti-IIa or antithrombin activity (about 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 sodium enoxaparin have been identified both in healthy individuals and patients, and in animal models. This includes AT-III-dependent inhibition of other clotting factors-as factor VIIa, activation of the release of the tissue factor pathway inhibitor (PTF), as well as a reduction in vWF release from the vascular endothelium into the bloodstream. These factors provide an anticoagulant effect of sodium enoxaparin as a whole.
When used in prophylactic doses, it slightly changes the APTT, practically does not affect the aggregation of platelets and the level of binding of fibrinogen to platelet receptors.
Anti-IIa activity in plasma is about 10 times lower than anti-Xa activity. The mean maximum anti-IIa activity is observed approximately 3-4 hours after SC administration and reaches 0.13 and 0.19 IU / ml after repeated administration of 1 mg / kg - with double administration and 1.5 mg / kg - with Single entry, respectively.
The average maximum anti-Xa plasma activity is observed 3-5 h after the SC administration and is approximately 0.2; 0.4; 1.0 and 1.3 anti-Xa IU / ml after SC administration 20, 40 mg and 1 mg / kg and 1.5 mg / kg, respectively.
Pharmacokinetic
The pharmacokinetics of enoxaparin in these dosage regimens is linear. The variability within and between groups of patients is low. After repeated administration of 40 mg of enoxaparin sodium once a day and after the administration of enoxaparin sodium at a dose of 1.5 mg / kg once a day in healthy volunteers, the equilibrium concentration is reached by day 2, the area under the pharmacokinetic curve on average 15% higher than after a single injection. After repeated injections of sodium enoxaparin at a daily dose of 1 mg / kg twice a day, the equilibrium concentration is achieved after 3-4 days, the area under the pharmacokinetic curve averaging 65% higher than after a single administration and the mean Cmax values are respectively 1.2 and 0.52 IU / ml.
Bioavailability of sodium enoxaparin for n / k introduction, estimated on the basis of anti-Xa activity, is close to 100%.
The volume of distribution of anti-Xa activity of enoxaparin sodium is approximately 5 liters and approaches the blood volume.
Enoxaparin sodium is a preparation with low clearance. After intravenous administration for 6 hours at a dose of 1.5 mg / kg, the average value of anti-Xa clearance in plasma is 0.74 l / h.
Excretion of the drug is monophasic with T1 / 2 4 hours (after a single SC administration) and 7 hours (after repeated administration of the drug).
Enoxaparin sodium is mainly metabolized in the liver by desulfating and / or depolymerizing to form low molecular weight substances with very low biological activity. Kidney excretion of active fragments of the drug is approximately 10% of the administered dose and total excretion of active and inactive fragments is approximately 40% of the administered dose.
It is possible to delay the excretion of sodium enoxaparin in elderly patients as a result of a decrease in renal function with age.
A decrease in the clearance of enoxaparin sodium in patients with decreased renal function was noted. After repeated administration of 40 mg of enoxaparin sodium, the activity of anti-Xa, represented by the area under the pharmacokinetic curve, in patients with insignificant (Cl creatinine 50-80 ml / min) and moderate (Cl creatinine 30-50 ml / Min) impaired renal function.In patients with severe renal dysfunction (Cl creatinine <30 ml / min), the area under the pharmacokinetic curve in equilibrium is an average of 65% higher with a repeated SC administration of 40 mg once a day.
In people with excessive body weight with n / to the introduction 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 administration of 40 mg of enoxaparin sodium, anti-Xa activity will be 50% higher in women with a body weight of less than 45 kg and 27% higher in men with body weight less than 57 kg compared with patients with normal average body weight.
Indication of the drug Clexane
Prevention of venous thrombosis and embolism during surgical interventions, especially in orthopedic and general surgical operations;
Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic illnesses, including acute heart failure and decompensation of chronic heart failure (NYHA grade III or IV), acute respiratory failure, and severe acute infections and acute rheumatic diseases in Combination with one of the risk factors for venous thrombosis (see "Special instructions");
Treatment of deep vein thrombosis with pulmonary embolism or without pulmonary arterial thromboembolism;
Prevention of thrombus formation in the extracorporeal circulation system during hemodialysis (usually with a session duration of no more than 4 hours);
Treatment of unstable angina and myocardial infarction without Q wave in combination with acetylsalicylic acid;
Treatment of acute myocardial infarction with ST segment elevation in patients subject to medical treatment or subsequent percutaneous coronary intervention.
Contraindications
Increased sensitivity to enoxaparin sodium, heparin or its derivative, including other low molecular weight heparins;
Active bleeding, as well as conditions and diseases in which there is a high risk of bleeding: threatening abortion, cerebral aneurysms or exfoliating aortic aneurysm (with the exception of surgical intervention), hemorrhagic stroke, uncontrolled bleeding, severe enoxaparin and heparin-induced thrombocytopenia ;
The use of Clexane® in pregnant women with artificial heart valves (lack of clinical experience) is not recommended;
Age to 18 years (efficiency and safety not established).
With caution: violations of hemostasis (including hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease, etc.), severe vasculitis; Peptic ulcer of the stomach or duodenum or other erosive-ulcerative lesions of the gastrointestinal tract; Recent ischemic stroke; Uncontrolled severe arterial hypertension; Diabetic or hemorrhagic retinopathy; Severe diabetes mellitus; Recent or alleged neurologic or ophthalmic surgery; Carrying out spinal or epidural anesthesia (a potential risk of developing a hematoma), spinal puncture (recently transferred); Recent childbirth; Endocarditis bacterial (acute or subacute); Pericarditis or pericardial effusion; Renal and / or liver failure; Intrauterine contraception (IUD); Severe trauma (especially the CNS), open wounds on large surfaces; Simultaneous administration of drugs that affect the hemostasis system.
The company does not have data on the clinical use of the drug Ñlexane ® in the following diseases: active tuberculosis, radiation therapy (recently transferred).
Pregnancy and breast-feeding
The information that enoxaparin sodium penetrates through the placental barrier during the second trimester of pregnancy in humans, no. There is no relevant information regarding the I and III trimesters of pregnancy. Since there are no adequate and well-controlled studies in pregnant women, and animal studies do not always predict a reaction to sodium enoxaparin during pregnancy in humans, it should be used during pregnancy only when there is an urgent need for its use established by a doctor.
It is not known whether unchanged sodium enoxaparin is excreted in human breast milk. Breastfeeding should be stopped during the treatment of the mother with Clexane®.
Side effects
A study of the adverse effects of enoxaparin sodium was conducted in more than 15,000 patients participating in clinical trials, including 1776 patients, in the prevention of venous thrombosis and embolism in general surgical and orthopedic operations; In 1169 patients - in 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 pulmonary embolism; In 1578 patients - in the treatment of unstable angina and myocardial infarction without a Q wave; In 10176 patients - in the treatment of myocardial infarction with ST segment elevation.
The mode of administration of sodium enoxaparin differed depending on the indications. In the prevention of venous thrombosis and embolism with general surgical and orthopedic operations or patients on a bed rest, 40 mg p / c was administered once a day. In the treatment of deep vein thrombosis with pulmonary embolism or without it, patients received enoxaparin sodium at a rate of 1 mg / kg SC every 12 hours or 1.5 mg / kg SC once daily. In the treatment of unstable angina and myocardial infarction without a Q-wave, the dose of enoxaparin sodium was 1 mg / kg SC every 12 hours, and in the case of myocardial infarction with ST-segment elevation, 30 mg bolus injection followed by 1 mg / kg n / K every 12 hours.
Undesirable reactions were classified according to the frequency of occurrence as follows: very frequent (≥1 / 10); Frequent (≥1 / 100 - <1/10); Infrequent (≥1 / 1000 - <1/100); Rare (≥1 / 10000 - <1/1000); Very rare (<1/10000), or the frequency is unknown (according to available data, the frequency of occurrence of an undesirable reaction cannot be estimated). The undesirable reactions observed after the release of the drug on the market were assigned to the parameter "frequency unknown".
Vascular disorders
Bleeding
In clinical studies, bleeding was the most common adverse reaction. These included large bleeding observed in 4.2% of patients (bleeding was considered large if accompanied by a decrease in hemoglobin content of 2 g / l or more, requiring transfusion of 2 or more doses of blood components, and also if it was retroperitoneal or intracranial) . Some of these cases were lethal.
As with the use of other anticoagulants, the use of sodium enoxaparin may cause bleeding, especially if there are risk factors that contribute to the development of bleeding, during invasive procedures or the use of drugs that disrupt hemostasis (see "Special instructions" and "Interactions").
In the description of bleeding, the sign "*" means an indication of the following types of bleeding: hematoma, ecchymosis (except developed at the injection site), wound hematomas, hematuria, nasal bleeding, gastrointestinal hemorrhage (see below).
Very often bleeding * in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with or without pulmonary embolism.
Often - bleeding * in the prevention of venous thrombosis in patients on bed rest and treatment of unstable angina, myocardial infarction without Q wave and myocardial infarction with ST segment elevation.
Infrequent - retroperitoneal bleeding and intracranial hemorrhage in patients with or without deep vein thrombosis with or without pulmonary embolism, as well as in the treatment of myocardial infarction with ST segment elevation.
Rarely - retroperitoneal bleeding in 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 (the number of platelets in the 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 elevation of the ST segment.
Thrombocytopenia in the prevention of venous thrombosis in surgical patients and the treatment of deep vein thrombosis with pulmonary embolism or without it, as well as with acute myocardial infarction with ST segment elevation.
Infrequent - thrombocytopenia in the prevention of venous thrombosis in patients on bed rest, and in the treatment of unstable angina and myocardial infarction without a Q wave.
Very rarely - immuno-allergic thrombocytopenia in the treatment of patients with acute myocardial infarction with ST segment elevation.
Other clinically relevant adverse reactions, regardless of the indications
These undesirable reactions, presented below, are grouped according to the system-organ classes, given with the indication of the frequency of their occurrence defined above and in order of decreasing their severity.
From the immune system: often - allergic reactions; Seldom - anaphylactic and anaphylactoid reactions (see also below section Data obtained after the release of the drug on the market).
On the part of the liver and bile ducts: very often - an increase in the activity of liver enzymes, mainly an increase in the activity of transaminases, more than three times higher than UGN).
From the skin and subcutaneous tissues: often - hives, itching, erythema; Infrequently, bullous dermatitis.
General disorders and disorders at the injection site: often - hematoma at the injection site, pain at the injection site, edema at the injection site, bleeding, hypersensitivity reactions, inflammation, formation of seals at the injection site; Infrequent - irritation at the injection site, necrosis of the skin at the injection site.
Laboratory and instrumental data: rarely - hyperkalemia.
Data obtained after the release of the drug on the market
The following adverse reactions were noted during the post-marketing application of Clexane®. There were spontaneous reports of these adverse reactions, and their frequency was defined as "the frequency is unknown" (it cannot be established from the available data).
From the immune system: anaphylactic / anaphylactoid reactions, including shock.
From the side of the nervous system: headache.
From the side of the vessels: with the use of sodium enoxaparin on the background of spinal / epidural anesthesia or spinal puncture, there were cases of development of spinal hematoma (or neuraxial hematoma). These reactions led to the development of neurological disorders of varying severity, including persistent or irreversible paralysis (see "Special instructions").
On the part of the blood or lymphatic system: hemorrhagic anemia; Cases of development of immuno-allergic thrombocytopenia with thrombosis (in some cases, thrombosis was complicated by the development of an organ infarction or limb ischemia - see "Special instructions", subsection Control of platelet count in peripheral blood); Eosinophilia.
From the skin and subcutaneous tissues: at the injection site, skin vasculitis, skin necrosis, 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 solid inflammatory nodules-infiltrates at the injection site of the drug, which disappear after a few days and are not grounds for discontinuing the drug; alopecia.
From the liver and biliary tract: hepatocellular liver damage; Cholestatic liver damage.
From the musculoskeletal and connective tissue: osteoporosis with prolonged therapy (more than 3 months).
Interaction
The drug Clexane ® cannot be mixed with other drugs.
When used simultaneously with drugs that affect hemostasis (systemic salicylates, acetylsalicylic acid, NSAIDs (including ketorolac), dextran with a molecular weight of 40 kDa, ticlopidine and clopidogrel, systemic SCS, thrombolytics or anticoagulants, other antiplatelet drugs (including glycoprotein IIb / IIIa), the risk of bleeding increases (see "Special instructions").
Dosing and Administration
Except for special cases (see below Treatment of myocardial infarction with ST-segment elevation, medication or with percutaneous coronary intervention, and prevention of thrombus formation in the extracorporeal circulation system during hemodialysis), sodium enoxaparin is administered deeply. Injections should preferably be performed in the prone position. When using pre-filled syringes for 20 and 40 mg to avoid loss of the drug before the injection does not need to remove air bubbles from the syringe. Injections should be performed alternately in the left or right anterolateral or posterolateral area of the abdominal wall. The needle must be inserted vertically (not sideways) the entire length, into the skin fold, collected and held between the thumb and forefinger. Skin fold is released only after the injection is completed. Do not massage the injection site after injection.
The pre-filled disposable syringe is ready for use.
The drug cannot be administered in / m.
Prevention of venous thrombosis and embolism during surgical interventions, especially in orthopedic and general surgical operations
Patients with a moderate risk of developing thrombosis and embolism (for example, abdominal surgery) the recommended dose of Clexane® is 20 or 40 mg once a day SC. The first injection should be done 2 hours before surgery.
Patients with a high risk of developing thrombosis and embolism (for example, in orthopedic operations) the drug is recommended at a dose of 40 mg once a day sc, with the administration of the first dose 12 hours before surgery, or at a dose of 30 mg twice a day with the onset Administration after 12-24 h after the operation.
The duration of treatment with Clexane® is on average 7-10 days. If necessary, therapy can continue as long as there is a risk of developing thrombosis and embolism and the patient will not go on an outpatient schedule. In orthopedic operations, it may be advisable after the initial therapy to continue treatment by administering Clexan® at a dose of 40 mg once daily for 3 weeks.
The specific features of using Clexane® for spinal / epidural anesthesia, as well as procedures for coronary revascularization, are described in the section "Special instructions".
Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic illnesses
The recommended dose of Clexane® is 40 mg once a day, for at least 6 days. The therapy should be continued until the patient completely switches to an outpatient treatment (maximum for 14 days).
Treatment of deep vein thrombosis with pulmonary embolism or pulmonary embolism
The drug is administered SC at a rate of 1.5 mg / kg once a day or 1 mg / kg 2 times a 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. Immediately begin therapy with indirect anticoagulants, while treatment with Clexane® should be continued until the therapeutic anticoagulant effect is achieved (the INR values should be 2-3).
Prophylaxis of thrombus formation in the extracorporeal circulation system during hemodialysis
The recommended dose of Clexane® is on average 1 mg / kg. At a high risk of bleeding, the dose should be reduced to 0.5 mg / kg with dual vascular access or up to 0.75 mg with single vascular access.
When hemodialysis, the drug Clexane® should be injected into the arterial part of the shunt at the beginning of the hemodialysis session. A single dose, as a rule, is sufficient for a 4-hour session, however, if the fibrin rings are detected with a longer hemodialysis, the drug can be additionally administered at the rate of 0.5-1 mg / kg.
Treatment of unstable angina and myocardial infarction without a Q wave
The drug Clexane® is administered at a rate of 1 mg / kg every 12 hours, sc, with the simultaneous use of acetylsalicylic acid in a dose of 100-325 mg once a day. The average duration of therapy is at least 2 days and continues until the patient's clinical condition is stabilized. Usually, the drug is administered for 2 to 8 days.
Treatment of acute myocardial infarction with ST segment elevation, medication or with percutaneous coronary intervention
Treatment begins with a single intravenous bolus administration of enoxaparin sodium at a dose of 30 mg.
Immediately after it is administered enoxaparin sodium at a dose of 1 mg / kg. Next, the drug is given SC at 1 mg / kg every 12 hours (maximum 100 mg of sodium enoxaparin for each of the first two subcutaneous injections, then 1 mg / kg for the remaining subcutaneous doses, ie, with a body weight of more than 100 kg Single dose may exceed 100 mg). Patients 75 years of age and older do not have an initial IV bolus injection. The drug is administered SC at a dose of 0.75 mg / kg every 12 hours (maximum 75 mg of sodium enoxaparin for each of the first two injections, then 0.75 mg / kg for the remaining SC doses, E. With a body weight of more than 100 kg, a single dose may exceed 75 mg).
When combined with thrombolytic agents (fibrin-specific and fibrin-specific), sodium enoxaparin should be administered in the range of 15 minutes before the onset of thrombolytic therapy and up to 30 minutes after it. As soon as possible after the detection of acute myocardial infarction with ST-segment elevation, patients should be prescribed acetylsalicylic acid simultaneously, and if there are no contraindications, take acetylsalicylic acid (in doses of 75-325 mg) should be continued daily for at least 30 days.
The recommended duration of treatment with Clexane® is 8 days or until discharge from the hospital (if the hospitalization period is less than 8 days). Intravenous bolus administration of sodium enoxaparin should be performed through a venous catheter. Enoxaparin sodium should not be mixed or injected with other medications. In order to avoid the presence of traces of other drugs in the infusion system and their interaction with sodium enoxaparin, the venous catheter should be washed with a sufficient amount of 0.9% sodium chloride solution or 5% dextrose solution before and after intravenous bolus administration of sodium enoxaparin. Enoxaparin sodium can be safely administered with 0.9% sodium chloride solution and 5% dextrose solution.
For bolus administration of 30 mg enoxaparin sodium in the treatment of acute myocardial infarction with ST segment elevation, 60, 80 and 100 mg glass syringes remove excess amount of the drug so that only 30 mg (0.3 ml) remain in them. A dose of 30 mg can be directly administered iv.
To perform IV bolus administration of enoxaparin sodium through a venous catheter, pre-filled syringes for the administration of the drug 60, 80 and 100 mg can be used. It is recommended to use 60 mg syringes, because This reduces the amount of drug removed from the syringe. 20 mg syringes are not used; In them there is not enough preparation for the bolus administration of 30 mg of enoxaparin sodium. 40 mg syringes are not used; On them there are no divisions, and therefore it is impossible to accurately measure the amount of 30 mg.
In patients undergoing percutaneous coronary intervention, in the event that the last SC injection of enoxaparin sodium was performed less than 8 hours before the balloon catheter inserted into the site of the narrowing of the coronary artery, additional administration of sodium enoxaparin is not required. If the last penicillin injection of sodium enoxaparin was carried out more than 8 hours before the balloon catheter was inflated, an additional intravenous bolus administration of sodium enoxaparin should be performed at a dose of 0.3 mg / kg.
To increase the accuracy of additional intravenous bolus injection of small volumes into the 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.
Table 1
Volumes to be administered intravenously after dilution
| Weight, kg | The required dose (0.3 mg / kg), mg | The volume of solution diluted to a concentration of 3 mg / ml, ml |
| 45 | 13,5 | 4,5 |
| 50 | 15 | 5 |
| 55 | 16,5 | 5,5 |
| 60 | 18 | 6 |
| 65 | 19,5 | 6,5 |
| 70 | 21 | 7 |
| 75 | 22,5 | 7,5 |
| 80 | 24 | 8 |
| 85 | 25,5 | 8,5 |
| 90 | 27 | 9 |
| 95 | 28,5 | 9,5 |
| 100 | 30 | 10 |
Patients with renal insufficiency
Severe renal impairment (Cl creatinine less than 30 mL / min). The dose of sodium enoxaparin is reduced in accordance with tables 2 and 3 below, In these patients there is an increase in system exposure (duration of action) of the drug.
When using the drug with a therapeutic purpose, the following correction of the dosing regimen is recommended.
Table 2
| Normal dosing regimen | Dosing regimen for severe renal failure |
| 1 mg / kg SC twice a day | 1 mg / kg SC once a day |
| 1.5 mg SC once a day | 1 mg / kg SC once a day |
| Treatment of acute myocardial infarction with ST-segment elevation in patients <75 years | |
| Once: bolus iv in the dose of 30 mg plus 1 mg / kg p / k; Followed by SC administration at a dose of 1 mg / kg 2 times per day (maximum 100 mg for each of the first two n / kinjections) | One time: bolus iv injection at a dose of 30 mg plus 1 mg / kg sc, followed by a sc administration at a dose of 1 mg / kg 1 time per day (max 100 mg for the first n / kynektsii) |
| Treatment of acute myocardial infarction with ST-segment elevation in patients ≥75 years of age and older | |
| 0.75 mg / kg SC twice a day, without initial bolus administration (maximum 75 mg for each of the first two kinases) | 1 mg / kg p / q once a day without an initial bolus (maximum 100 mg for the first injection) |
| Normal dosing regimen | Dosing regimen for severe renal failure |
| 40 mg SC once a day | 20 mg SC once a day |
| 20 mg SC once a day | 20 mg SC once a day |
The recommended dosage adjustment is not used for hemodialysis.
With a mild (Cl creatinine 50-80 ml / min) and moderate (Cl creatinine 30-50 ml / min), renal dysfunction is not required, but patients should be under close medical supervision.
Patients with impaired liver function. Due to the lack of clinical studies, caution should be exercised when administering enoxaparin sodium to patients with impaired hepatic function.
Instructions for self-administered injection of Clexane® (pre-filled syringe with needle safety system)
1. Wash hands and skin area (place for injection), in which the patient will administer the drug, with soap and water. Dry it.
2. Take a comfortable sitting or lying position and relax. Make sure that the patient clearly sees the place in which the drug will be injected. It is best to use a reclining chair, a chaise longue or a bed, covered with cushions for support.
3. Choose a place for an injection in the right or left side of the abdomen. This place should be at least 5 cm from the navel towards the sides. Do not perform an independent injection at a distance of 5 cm from the navel or around the existing scars or bruises. Alternate injection sites in the right and left abdomen, depending on where the drug was administered the previous time.
4. Wipe the place for injection with a tampon moistened with alcohol.
5. Carefully remove the cap from the syringe needle with Clexane®. To postpone the cap. The syringe is pre-filled and ready for use. Do not press the plunger to expel air bubbles before inserting the needle into the injection site. This can lead to loss of the drug. After removing the cap, do not allow the needle to touch any objects. This is necessary to maintain the sterility of the needle.
6. Hold the syringe in the hand that the patient is writing, as he holds the pencil, and with the other hand gently squeeze the alcohol-rubbed insertion site to form a fold of skin between the thumb and forefinger. Hold the skin fold all the time until the drug is injected.
7. Hold the syringe in such a way that the needle is pointing down (vertically at an angle of 90 °). Insert the needle for its entire length into the skin fold.
8. Press the piston with your finger. This will ensure the introduction of the drug into the subcutaneous adipose tissue of the abdomen. Hold the skin fold all the time until the patient enters the drug.
9. Remove the needle by pulling it back without deviating from the axis. The protective mechanism automatically closes the needle. Now you can stop holding the skin fold. The safety system that starts the protective mechanism is activated only after the entire contents of the syringe are inserted by pressing the piston for the entire length of its stroke.
10. To prevent bruising, do not rub the injection site after injection.
11. Place the used syringe with the protective mechanism in the container for sharp objects. Close the container tightly and keep it out of the reach of children.
When using the drug, adhere strictly to the recommendations given in this description, as well as the directions of the doctor or pharmacist. If you have any questions, contact your doctor or pharmacist.
Video instructions for self-using a syringe with a protective mechanism can be viewed using a QR code.
Overdose
Symptoms: a random overdose of Ñlexane® (with IV, p / k or extracorporeal application) can lead to hemorrhagic complications. When ingested, even large doses of absorption of the drug is unlikely.
Treatment: anticoagulant effects can be largely neutralized by slow intravenous administration of protamine sulfate, the dose of which depends on the dose of Clexane® administered. 1 mg protamine sulphate neutralizes the anticoagulant activity of 1 mg Clexane® if sodium enoxaparin 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 needed. If, after the administration of enoxaparin sodium, 12 hours or more have passed, no introduction of protamine is required. However, even with the introduction of large doses of protamine sulfate, anti-Xa activity of Clexane® is not completely neutralized (maximal by 60%).
Special instructions
Are common
Low molecular weight heparins are not interchangeable, because They differ in the production process, molecular weight, specific anti-Xa activity, dosage units and dosing regimen, which are associated with differences in their pharmacokinetics and biological activity (antithrombin activity and interaction with platelets).
Therefore, it is required to strictly follow the recommendations for use for each drug belonging to the class of low molecular weight heparins.
Bleeding
As with the use of other anticoagulants, with the use of the drug Clexane ® possible development of bleeding of any location (see "Side effects"). When developing bleeding it is necessary to find its source and conduct appropriate treatment.
Bleeding in elderly patients. With the use of Clexane® in preventive doses in elderly patients, there was no tendency to increase bleeding. When using the drug in therapeutic doses in elderly patients (especially at the age of> 80 years) there is an increased risk of bleeding. It is recommended that careful monitoring of the condition of such patients is made (see "Pharmacokinetics" and "Method of administration and dose", subsection Elderly patients).
Simultaneous use of other drugs that affect hemostasis
It is recommended that the use of drugs capable of disturbing hemostasis (salicylates, including acetylsalicylic acid, NSAIDs, including ketorolac, dextran with a molecular mass of 40 kDa, ticlopidine, clopidogrel, GCS, thrombolytics, anticoagulants, antiplatelet agents, including glycoprotein receptor antagonists IIb / IIIa) was discontinued before treatment with enoxaparin sodium, except in cases where their use is strictly shown. If combinations of sodium enoxaparin with these preparations are shown, careful clinical observation and monitoring of relevant laboratory parameters should be carried out.
Renal insufficiency
In patients with impaired renal function, there is a risk of bleeding as a result of an increase in the systemic exposure of enoxaparin sodium.
In patients with severe renal dysfunction (Cl creatinine less than 30 ml / min), dose adjustment is recommended, both for prophylactic and therapeutic use of the drug. Although dose adjustments are not required in patients with mild to moderate renal impairment (Cl creatinine 30-50 or 50-80 mL / min), careful monitoring of the condition of such patients is recommended (see "Pharmacokinetics" and "Dosage and Administration" , Subsection Patients with renal insufficiency).
Low body weight
An increase in the anti-Xa activity of enoxaparin sodium in its preventive use in women with a body weight of less than 45 kg and in men weighing less than 57 kg may lead to an increased risk of bleeding.
It is recommended that careful monitoring of the condition of such patients is made.
Patients with obesity
Patients with obesity have an increased risk of developing thrombosis and embolism. The safety and efficacy of enoxaparin in prophylactic doses in obese patients (BMI more than 30 kg / m2) has not been fully determined, and there is no consensus on dose adjustment. These patients should be carefully monitored 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 exists even when low molecular weight heparins are used. In the case of thrombocytopenia, it usually develops between the 5th and 21st days after initiation of sodium enoxaparin therapy. In this regard, it is recommended that the number of platelets in the peripheral blood be monitored regularly before treatment with Clexane® and during its use. In the presence of a confirmed significant decrease in the number of platelets (by 30-50% compared with the initial index), it is necessary to immediately cancel enoxaparin sodium and transfer the patient to another therapy.
Spinal / epidural anesthesia
The cases of the appearance of neuroaxial hematomas with the use of Clexane® with simultaneous spinal / epidural anesthesia with the development of long-lasting or irreversible paralysis are described. The risk of occurrence of these phenomena decreases with the use of the drug in a dose of 40 mg or lower.
The risk increases with higher doses of Clexane®, as well as with the use of permanent catheters after surgery, or with the simultaneous use of additional drugs that affect hemostasis, such as NSAIDs (see "Interaction"). The risk also increases with a traumatically performed or repeated spinal puncture or in patients who have a history of referring to the transferred operations in the spine or deformity of the spine. To reduce the possible risk of bleeding associated with the use of sodium enoxaparin and epidural or spinal anesthesia / analgesia, the pharmacokinetic profile of the drug should be considered (see Pharmacokinetics). It is better to install or remove a catheter with a low anticoagulant effect of enoxaparin sodium, but the exact time to achieve a sufficient reduction in the anticoagulant effect in different patients is unknown.
The insertion or removal of the catheter should be performed at least 12 hours after the administration of lower doses of Clexane® (20 mg once a day, 30 mg once or twice daily, 40 mg once a day) and, at a minimum, 24 hours after the administration of higher doses of Clexan® (0.75 mg / kg 2 times a day, 1 mg / kg 2 times a day, 1.5 mg / kg 1 time per day). At these time points, anti-Xa activity of the drug still continues to be detected, and the time delays do not guarantee that the development of the neuroaxial hematoma will be avoided. Patients receiving sodium enoxaparin at doses of 0.75 mg / kg 2 times a day or 1 mg / kg 2 times a day, with this (twice-daily) dosing regimen, do not administer the second dose in order to increase Interval before installing or replacing the catheter.
Similarly, consideration should be given to the possibility of delaying the introduction of the next dose of the drug for at least 4 hours, based on an assessment of the benefit / risk ratio (risk of thrombosis and bleeding during the procedure, taking into account the presence of risk factors in patients). However, it is not possible to give clear recommendations on the timing of the next dose of enoxaparin sodium after removal of the catheter. It should be noted that in patients with Cl creatinine less than 30 ml / min, excretion of sodium enoxaparin is slowed. Therefore, this category of patients should consider doubling the time from catheter removal: at least 24 hours for lower doses of enoxaparin sodium (30 mg once daily) and at least 48 hours for higher doses (1 mg / Kg / day).
If anticoagulant therapy is used at the time of epidural / spinal anesthesia or lumbar puncture, the patient should be monitored continuously to detect any neurological symptoms such as back pain, impaired sensory and motor functions (numbness or weakness in the lower extremities), a violation Function of the intestine and / or bladder. The patient should be instructed about the need to inform the physician immediately if any of the above symptoms occur. When suspected of the symptoms characteristic of the hematoma of the spinal cord, urgent diagnosis and treatment is needed, including, if necessary, decompression of the spinal cord.
Heparin-induced thrombocytopenia
With extreme caution, Clexane® should be used in patients who have a history of heparin-induced thrombocytopenia in combination with or without thrombosis.
The risk of heparin-induced thrombocytopenia can persist for several years. If anamnesis is supposed to have heparin-induced thrombocytopenia, platelet aggregation tests in vitro are of limited importance in predicting the risk of its development. The decision on the use of Clexane® in this case can be taken only after consulting with the appropriate specialist.
Percutaneous coronary angioplasty
In order to minimize the risk of bleeding associated with invasive vascular instrumental manipulation in the treatment of unstable angina and myocardial infarction without Q wave and acute myocardial infarction with ST segment elevation, these procedures should be performed at intervals between the administration of Clexane®. This is necessary in order to achieve hemostasis after percutaneous coronary intervention. When using a closure device, the introductory femoral artery can be removed immediately. When using manual compression, the femoral artery introducer should be removed 6 hours after the last IV or injection of sodium enoxaparin. If treatment with sodium enoxaparin continues, the next dose should be administered no earlier than 6-8 hours after removal of the introductory femoral artery. It is necessary to monitor the place of introduction of the introducer, in order to detect signs of bleeding and formation of a hematoma in time.
Patients with mechanical heart valves
The use of Clexane® for the prevention of thrombosis in patients with mechanical heart valves has not been adequately studied. There are separate reports on the development of thrombosis of heart valves in patients with mechanical heart valves on the background of therapy with enoxaparin sodium for the prevention of thrombosis. Assessment of these reports is limited due to the presence of competing factors contributing to the development of thrombosis of artificial heart valves, including the underlying disease, and because of the lack of clinical data.
Pregnant women with mechanical artificial heart valves. The use of the drug Clexane® for the prevention of thrombosis in pregnant women with mechanical artificial heart valves has been studied insufficiently. In a clinical study of pregnant women with mechanical heart valves using sodium enoxaparin at a dose of 1 mg / kg twice a day to reduce the risk of thrombosis and embolism, in 2 out of 8 women a thrombus formed, blocking the heart valves and the death of the mother and fetus. There are separate post-marketing reports on thrombosis of heart valves in pregnant women with mechanical heart valves treated with enoxaparin for the prevention of thrombosis. Pregnant women with mechanical artificial heart valves have a high risk of developing thrombosis and embolism.
Laboratory Tests
In the doses used to prevent thromboembolic complications, the Clexane® preparation does not significantly affect bleeding time and blood clotting parameters, as well as platelet aggregation or binding to fibrinogen.
When the dose is raised, APTT and the activated clotting time can be prolonged. The increase in APTT and activated clotting time is not in a direct linear relationship with the increase in anticoagulant activity of the drug, so there is no need to monitor them.
Prevention of venous thrombosis and embolism in patients with acute therapeutic illnesses, who are on a bed rest
In the case of acute infection, acute rheumatic conditions, the prophylactic use of sodium enoxaparin 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; Thrombosis and embolism in the anamnesis; obesity; Hormonal therapy; heart failure; Chronic respiratory failure.
Impact on the ability to drive vehicles and engage in other potentially hazardous activities. Does not affect.
Release form
Solution for injection, 2000 anti-Ha IU / 0.2 ml; 4000 anti-Ha IU / 0.4 mL; 6000 anti-Ha IU / 0.6 ml; 8000 anti-HamE / 0.8 ml; 10,000 anti-Ha IU / 1 ml.
1 kind of packaging: 4000 anti-Ha IU / 0.4 ml. 0.2 ml or 0.4 ml or 0.6 ml or 0.8 ml or 1 ml solution of the drug in a glass syringe (type I) respectively. 2 syringes per blister. For 1 or 5 blisters in a cardboard box.
2 Packing type: 0.2 ml or 0.4 ml or 0.6 ml or 0.8 ml or 1 ml solution of the drug in a glass syringe (type I) with a protective needle system, respectively. 2 syringes per blister. For 1 or 5 blisters in a cardboard box.
Manufacturer
1. Sanofi Winthrop Industrie, France. 180, rue Jean Jaures, 94702 Maisons-Alfort Cedex, France.
2. Sanofi Winthrop Industrie, France. Boulevard Industriel, Zone Industrielle, 76580 Le Trait, France.
A legal entity in whose name a registration certificate is issued. Sanofi-Aventis France, France.
Claims of consumers should be sent to the address in Russia: 125009, Moscow.
In the case of drug packaging at ZAO Sanofi-Aventis Vostok, Russia, customer complaints should be sent to the following address: 302516, Russia, Oryol Region, Orlovsky District, Bolshekulikovskoe Village.
In the case of drug packaging at OJSC Pharmstandard-UfaVITA, Russia, customer complaints should be sent to: 125009, Moscow.
Conditions of supply of pharmacies
On prescription.
Storage conditions of the drug Clexane
At a temperature not higher than 25 °.
Keep out of the reach of children.
The shelf life of the drug Clexane
3 years.
Do not use beyond the expiration date printed on the package.
