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Instruction for use: Enixum
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Dosage form: Solution for injection
Active substance: Enoxaparinum natrium
ATX
B01AB05 Enoxaparin
Pharmacological group
Anticoagulants
The nosological classification (ICD-10)
A49 Bacterial infection of unspecified site: Bacterial infection; Infectious diseases
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
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
I82.9 Embolism and thrombosis of unspecified vein: Venous embolism; Venous thrombosis; Diseases caused by blood clots in the vessels; Acute vascular occlusion; Acute venous thrombosis; Acute thrombosis of veins; Thrombosis; Thromboembolism; Phlebothrombosis; Embolism
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
J96.0 Acute respiratory failure: Shock lung; Insufficient respiration acute
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 1 syringe (0.2 ml)
active substance: Enoxaparin sodium 2000 anti-Xa IU (20 mg)
Excipient: water for injection - up to 0.2 ml
Solution for injection 1 syringe (0.3 ml)
active substance: Enoxaparin sodium 3000 anti-Xa IU (30 mg)
Excipient: water for injection - up to 0.3 ml
Solution for injection 1 syringe (0.4 ml)
active substance: Enoxaparin sodium 4000 anti-Xa IU (40 mg)
Excipient: water for injection - up to 0.4 ml
Solution for injection 1 syringe (0.5 ml)
active substance: Enoxaparin sodium 5000 anti-Xa IU (50 mg)
Excipient: water for injection - up to 0.5 ml
Solution for injection 1 syringe (0.6 ml)
active substance: Enoxaparin sodium 6000 anti-Xa IU (60 mg)
Excipient: water for injection - up to 0.6 ml
Solution for injection 1 syringe (0.7 ml)
active substance: Enoxaparin sodium 7000 anti-Xa IU (70 mg)
Excipient: water for injection - up to 0.7 ml
Solution for injection 1 syringe (0.8 ml)
active substance: Enoxaparin sodium 8000 anti-Xa IU (80 mg)
Excipient: water for injection - up to 0.8 ml
Solution for injection 1 syringe (1 ml)
active substance: Enoxaparin sodium 10,000 anti-Xa IU (100 mg)
Excipient: water for injection - up to 1 ml
Description of dosage form
Colorless or yellowish, or brownish-yellowish transparent liquid.
Characteristic
Enoxaparin sodium is a low
molecular weight heparin. The average molecular weight is about 4500 Da: less than 2000 Da - <20%, from 2000 to 8000 Da -> 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 the 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 sodium enoxaparin contains about 20% (ranging from 15 to 25%) of the 1,6-anhydro derivative in the reducing fragment of the polysaccharide chain.
Pharmachologic effect
Mode of action - Antithrombotic.
Pharmacodynamics
In vitro, sodium enoxaparin has high activity against coagulation factor Xa (anti-Xa activity of about 100 IU / ml) and low activity against coagulation factor IIa (anti-IIa or antithrombin activity of about 28 IU / ml). This anticoagulant activity is mediated by antithrombin III. In addition to anti-Xa / IIa activity, additional anticoagulant and anti-inflammatory properties of sodium enoxaparin have been identified in both humans and animal models that include AT-III-dependent inhibition of other coagulation factors such as factor VIIa, activation of the release of the tissue factor pathway inhibitor, As well as a decrease in the release of von Willebrand factor from the vascular endothelium into the bloodstream. These factors provide an anticoagulant effect of sodium enoxaparin as a whole.
When used in prophylactic doses, enoxaparin sodium slightly changes the APTT, has almost no effect on platelet aggregation and the degree of binding of fibrinogen to the platelet receptors.
Anti-IIa activity in plasma is about 10 times lower than anti-Xa activity. The average 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 a double injection and 1.5 mg / kg - When administered once, respectively.
The average maximum anti-Xa activity of the plasma is observed 3-5 h after the SC administration and is approximately 0.2, 0.4, 1 and 1.3 anti-Xa IU / ml after the SC administration 20, 40 Mg and 1 and 1.5 mg / kg, respectively.
Pharmacokinetic
The pharmacokinetics of enoxaparin sodium in therapeutic doses is linear. The variability within and between groups of patients is low. After a single administration of Enixum® at a dose of 1 mg / kg Cmax is (0.49 ± 0.07) IU / ml, Tmax is 3.19 ± 1.08 h, AUC0-24 = 4.44 + 0 , 91 IU × ml / h. According to the literature, after repeated administration of enoxaparin sodium at a dose of 40 mg 1 time per day and after the administration of enoxaparin sodium at a dose of 1.5 mg / kg once a day, Css is achieved by the 2nd day, with AUC in An average of 15% higher than after a single injection. After repeated injections of sodium enoxaparin in a daily dose of 1 mg / kg 2 times a day, Css is achieved in 3-4 days, with AUC on average 65% higher than after a single injection. Bioavailability of sodium enoxaparin for n / k introduction, estimated on the basis of anti-Xa activity, is close to 100%.
The Vd of the anti-Xa activity of sodium enoxaparin 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.
Enoxaparin sodium is mainly metabolized in the liver by desulfating and / or depolymerizing to form low molecular weight substances with very low biological activity.
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).
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.
Patients of advanced age. Excretion slowed due to a physiological decline in kidney function. This change does not affect the dosing and administration regimen in preventive therapy, if the kidney function of such patients remains within acceptable limits, i.e. Reduced slightly.
Impaired renal function. The clearance of sodium enoxaparin decreases in patients with decreased renal function. A decrease in the clearance of enoxaparin sodium in renal failure was noted. After repeated administration of 40 mg of sodium enoxaparin, the activity of anti-Xa, represented by AUC in mild (Cl creatinine 50-80 ml / min) and moderate (Cl creatinine 30-50 ml / min) renal failure, occurs 1 time per day. In patients with severe renal insufficiency (Cl creatinine less than 30 ml / min), the AUC in the equilibrium state is on average 65% higher with the repeated SC administration of 40 mg of the drug once a day.
Patients with excessive body weight. In people with excessive body weight with n / to the introduction of the drug, the clearance is slightly less. If the dose is not adjusted to take into account the patient's body weight, then after a single administration of 40 mg of enoxaparin sodium, the anti-Xa activity will be 50% higher in women weighing less than 45 kg and 27% higher in men with body weight Less than 57 kg compared to patients with normal average body weight.
Indication of the drug Enixum
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; Acute infectious diseases; Acute stage of rheumatic diseases in combination with one of the risk factors for venous thrombosis (see "Special instructions");
Treatment of deep vein thrombosis, which is accompanied or not accompanied by pulmonary embolism of the pulmonary artery;
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 large 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 cases of surgical intervention in this regard);
Recently suffered hemorrhagic stroke;
Uncontrolled bleeding;
Thrombocytopenia in combination with a positive in vitro test for antiplatelet antibodies in the presence of sodium enoxaparin;
The use of sodium enoxaparin is not recommended for the prevention of thrombosis in pregnant women with mechanical heart valves (lack of clinical experience);
Age to 18 years (efficiency and safety not established).
With caution: hemostasis disorders (including hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease), severe vasculitis; Peptic ulcer of the stomach or duodenum or other erosive-ulcerative lesions of the gastrointestinal tract in the anamnesis; Recent ischemic stroke; Uncontrolled severe arterial hypertension; Diabetic or hemorrhagic retinopathy; Severe diabetes mellitus; A recent or alleged neurologic or ophthalmic operation; 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; Severe trauma (especially the CNS), open wounds on large surfaces; Simultaneous administration of drugs that affect the hemostasis system; Heparin-induced thrombocytopenia (in the anamnesis) in combination with or without thrombosis.
There are no data on the clinical use of the drug in the following diseases: active tuberculosis, radiation therapy (recently transferred).
Pregnancy and breast-feeding
At present, the available clinical data are insufficient to determine the possible teratogenic or fetotoxic effects of enoxaparin sodium when administered for prophylactic purposes during pregnancy. Enixum® should not be used during pregnancy, except when the potential benefit to the mother exceeds the possible risk to the fetus.
During drug treatment, spinal or epidural anesthesia should not be performed. If epidural anesthesia is planned, preventive treatment with sodium enoxaparin should be discontinued, if possible, at least 12 hours before anesthesia.
Enoxaparin sodium is not recommended for pregnant women with prosthetic heart valves.
For the duration of treatment with enoxaparin sodium breastfeeding should be discontinued.
Side effects
WHO classification of unwanted drug reactions by frequency of occurrence: very often - ≥1 / 10; Often - ≥1 / 100- <1/10; Infrequently - ≥1 / 1000- <1/100; Rarely - ≥1 / 10000- <1/1000; Very rarely - <1/10000.
Bleeding: bleeding may occur, especially in the presence of concomitant risk factors - organic changes with a tendency to bleeding, age, renal insufficiency, low body weight and some combinations of medications (see "Interaction"). In clinical trials, large bleedings (leading to clinically significant complications and / or accompanied by a 2 g / l or greater decrease in Hb and / or requiring the transfusion of 2 or more blood components) were administered in 4.2% of patients with enoxaparin, and in some These cases were lethal. Possible pinpoint hemorrhages (petechiae), ecchymosis. Very often - bleeding in the prevention of venous thrombosis during surgical interventions and treatment of deep vein thrombosis with PE or without it; Often - bleeding in the prevention of venous thrombosis in patients on bed rest due to acute therapeutic diseases, and in the treatment of unstable angina and myocardial infarction without a Q wave; Infrequent - retroperitoneal bleeding or intracranial hemorrhage in the treatment of deep vein thrombosis with PE or without it; Rarely - retroperitoneal bleeding in the prevention of venous thrombosis in surgical patients and in the treatment of unstable angina and myocardial infarction without a Q wave. In case of bleeding, it is necessary to cancel the injection of the drug, establish the cause of the bleeding and begin appropriate therapy. When sodium enoxaparin was applied against the background of spinal / epidural anesthesia and postoperative use of penetrating catheters, cases of neuraxial hematomas (0.01-0.1% of cases), which resulted in neurologic disorders of varying severity, including long-persistent or irreversible paralysis (see " Special instructions").
Thrombocytopenia and thrombocytosis: during the first days after the initiation of therapy, slightly transient asymptomatic thrombocytopenia may develop. Very often - thrombocytosis in the prevention of venous thrombosis during surgical interventions and the treatment of deep vein thrombosis with PE or without it; Often - thrombocytopenia in the prevention of venous thrombosis during surgical interventions and the treatment of deep vein thrombosis with PE or without it; Infrequently - thrombocytopenia in the prevention of venous thrombosis in patients on bed rest due to acute therapeutic illnesses, and in the treatment of unstable angina and myocardial infarction without Q wave; Very rarely - it is possible to develop autoimmune thrombocytopenia in combination with thrombosis, which was sometimes complicated by an organ infarction or limb ischemia.
Allergic reactions: often - hives, itching, redness of the skin; Rarely - anaphylactic and anaphylactoid reactions, allergic vasculitis.
From the skin and the reaction at the injection site: often - hematoma, pain at the injection site; Rarely - bullous dermatitis; Very rarely - necrosis of the skin, which is preceded by the appearance of purpura or infiltrated and painful erythematous plaques. In these cases, drug therapy should be discontinued. In some cases, at the injection site, the formation of solid inflammatory nodules-infiltrates containing the drug, which disappear in a few days and are not grounds for drug withdrawal.
From the CVS: rarely - thrombosis of artificial heart valves (usually with inadequate dosage).
Changes in laboratory indicators: very often - an asymptomatic and reversible increase in hepatic transaminase activity (AST and ALT more than 3 times higher than UGN); Rarely - hypoaldosteronism, hyperkalemia (especially in patients with CRF and diabetes mellitus, metabolic acidosis).
Other: in case of prolonged treatment, the risk of developing osteoporosis increases.
Interaction
Do not mix Eniksum® with other medications in the same syringe.
When used simultaneously with other drugs that affect hemostasis (salicylates, including acetylsalicylic acid, NSAIDs, including ketorolac, dextran with a molecular mass of 40 kDa, ticlopidine, clopidogrel, systemic GCS, thrombolytics or anticoagulants, other antiplatelet drugs, including antagonists Glycoprotein IIb / IIIa receptors), the risk of bleeding increases (see "Special instructions").
Dosing and Administration
SC to (deep), in special cases (see below) in the arterial contour during the hemodialysis session and IV.
The drug cannot be administered IM.
Prevention of venous thrombosis and embolism during surgical interventions, especially in orthopedic and general surgical operations: for patients with a moderate risk of developing thrombosis and embolism (general surgical operations), the recommended dose of the drug is 20-40 mg once a day SC. The first injection is performed 2 hours before surgery.
For patients with a high risk of thrombosis and embolism (orthopedic surgery), the recommended dose is 40 mg once a day; The first dose is administered 12 hours before surgery or 30 mg 2 times a day with the onset of administration 12-24 hours after the operation.
The duration of treatment is an average of 7-10 days. If necessary, therapy can continue as long as there is a risk of developing thrombosis and embolism (for example, in orthopedics, Enixum® is used 40 mg once a day for 5 weeks).
Specific features of the drug for spinal / epidural anesthesia, as well as for percutaneous coronary angioplasty (PTCA) are described in the section "Special instructions".
Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic illness: the recommended dose of enoxaparin sodium is 40 mg once a day for six to 14 days.
Treatment for deep vein thrombosis that is accompanied or not accompanied by PE: Enixum® is administered SC, at a rate of 1.5 mg / kg once a day or at a dose of 1 mg / kg 2 times a day. In patients with complicated thromboembolic disorders, the drug is recommended to be applied at a dose of 1 mg / kg 2 times a day.
The duration of treatment is an average of 10 days. It is advisable immediately to begin therapy with anticoagulants for oral administration, while therapy with enoxaparin should be continued until a sufficient anticoagulant effect is achieved, i.e. INR should be 2-3. If necessary, control of the anticoagulant effect should be evaluated for anti-Xa activity.
Prevention of thrombus formation in the extracorporeal circulation system during hemodialysis: the dose of enoxaparin sodium is 1 mg / kg. For patients with a high risk of bleeding, the dose should be reduced to 0.5 mg / kg with dual vascular access or 0.75 mg / kg with single-vessel access.
When hemodialysis, Enixum® should be inserted 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, when fibrin rings are detected (for example, with a longer hemodialysis), an additional 0.5-1 mg / kg dose of Enixum® can be added.
Treatment of unstable angina and myocardial infarction without Q-wave in combination with acetylsalicylic acid: Enixum® is administered at a dose of 1 mg / kg every 12 hours, with simultaneous administration of acetylsalicylic acid at a dose of 100-325 mg once a day.
The average duration of treatment is 2-8 days (until the patient's clinical condition is stabilized).
Treatment of acute myocardial infarction with ST segment elevation in patients subject to medical treatment or subsequent percutaneous coronary intervention: treatment is started with intravenous bolus administration of enoxaparin sodium at a dose of 30 mg and immediately after it (within 15 minutes) is performed sc administration Enoxaparin sodium at a dose of 1 mg / kg (and with the first two injections the maximum can be 100 mg of sodium enoxaparin). Then, all subsequent subcutaneous doses are administered every 12 hours at a rate of 1 mg / kg (ie, with a body weight of more than 100 kg, the dose may exceed 100 mg).
Persons 75 years of age or older do not have an initial IV bolus injection.
Enoxaparin sodium is given SC at a dose of 0.75 mg / kg every 12 hours (and with the first two injections, 75 mg of sodium enoxaparin can be administered as often as possible). Then, all subsequent SC or doses are administered every 12 hours at a rate of 0.75 mg / kg (with a weight of more than 100 kg, the dose may exceed 75 mg).
When combined with thrombolytic agents (fibrin-specific and fibrin-specific), sodium enoxaparin should be administered in the range from 15 minutes before the onset of thrombolytic therapy to 30 minutes after it. As soon as possible after the detection of acute myocardial infarction, with the rise of the ST segment should simultaneously start taking acetylsalicylic acid and, if there are no contraindications, continue for at least 30 days at doses from 75 to 325 mg daily.
The recommended duration of treatment with the drug is 8 days or until the patient leaves the hospital if the hospitalization period is less than 8 days.
Bolus administration of sodium enoxaparin should be performed through a venous catheter, and sodium enoxaparin should not be mixed or administered together with other medications. In order to avoid the presence of traces of other drugs in the system and their interaction with sodium enoxaparin, the venous catheter should be washed with a sufficient amount of 0.9% sodium chloride solution or dextrose 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 of sodium enoxaparin, in the treatment of acute myocardial infarction with ST segment elevation, 40, 60, 80 and 100 mg glass syringes remove excess amount of the drug so that only 30 mg (0.3 ml) remain. A dose of 30 mg can be directly administered iv. To perform IV bolus administration of enoxaparin sodium through a venous catheter, prefilled syringes can be used for the administration of the drug without a device for needle protection of 40, 60, 80 and 100 mg. 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 is inflated, an additional bolus administration of sodium enoxaparin at a dose of 0.3 mg / kg should be performed IV.
To increase the accuracy of additional bolus injection of small volumes into the venous catheter during percutaneous coronary interventions, it is recommended to dilute the drug with an infusion solution (0.9% sodium chloride solution or 5% dextrose solution) to a concentration of 3 mg / ml. It is recommended to dilute the solution immediately before use.
To obtain a solution of enoxaparin sodium at a concentration of 3 mg / ml using a prefilled syringe, it is recommended to use a container with an infusion solution, from which a part of the solution is extracted with a conventional syringe to the required volume. Enoxaparin sodium (the contents of the syringe for the SC administration) is introduced into the infusion solution remaining in the container.
Table 1
| The volume of pre-filled syringe, ml | The amount of infusion solution left in the tank, ml |
| 0,3 | 10 |
| 0,6 | 20 |
Volumes to be administered IV after dilution
| Body weight, kg | The required amount based on the 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 |
Renal insufficiency. In case of severe impairment of renal function (Cl of endogenous creatinine less than 30 ml / min), the dose of Enixum® should be adjusted, In these patients, the drug accumulates (see Table 3, 4).
Table 3
Recommendations for correcting the dosage regimen when using the drug with a therapeutic purpose
| The usual 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 / kg SC once a day | 1 mg / kg SC once a day |
| Once: bolus IV administration 30 mg plus 1 mg / kg sc; With the subsequent sc administration at a dose of 1 mg / kg 2 times a day | Once: bolus IV administration 30 mg plus 1 mg / kg sc; With a subsequent SC administration at a dose of 1 mg / kg 1 time per day |
| Elderly patients over the age of 75 years (only with acute myocardial infarction with ST-segment elevation) | |
| 0.75 mg / kg SC 2 times a day without the initial bolus administration | 1 mg / kg SC once a day without the initial bolus administration |
| The usual dosing regimen | Dosing regimen for severe renal failure |
| 40 mg / kg SC once a day | 20 mg / kg SC once a day |
| 20 mg / kg SC once a day | 20 mg / kg SC once a day |
This dosage regimen is not applicable in case of hemodialysis.
With a mild (Cl creatinine 50-80 ml / min) and moderate (Cl creatinine 30-50 ml / min) renal failure, dose adjustment is not required, but more careful laboratory monitoring of therapy.
Liver failure. Due to the lack of clinical studies, caution should be exercised when administering enoxaparin sodium to patients with impaired hepatic function.
Technique of the introduction
The pre-filled disposable syringe is ready for use.
Injections should preferably be performed in the prone position. Enixum® is injected deeply into the penis. When using pre-filled syringes for 20, 30 and 40 mg before the injection, do not remove air bubbles from the syringe to avoid loss of the drug. Injections should be carried out alternately in the left or right upper- or lower-side part of the anterior abdominal wall.
The needle must be inserted vertically (not sideways) over its entire length into the thickness of the skin, holding the fold of the skin with the thumb and forefinger until the injection is complete. Do not massage the injection site after injection.
Overdose
Symptoms: hemorrhagic complications in case of accidental overdose with SC to the administration of enoxaparin sodium. When ingested, even large doses of absorption of the drug is unlikely.
Treatment: neutralize the action of sodium enoxaparin slow IV the administration of protamine sulfate (or hydrochloride). Before using protamine sulfate, due to the possibility of side effects (in particular anaphylactic shock), you must carefully weigh the benefit / risk ratio.
1 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of sodium enoxaparin if the drug was administered no more than 8 hours before the administration of protamine sulfate.
0.5 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of sodium enoxaparin if it is injected more than 8 hours ago or if a second dose of protamine sulfate is required.
If after the administration of enoxaparin sodium passed 12 hours or more, administration of protamine sulfate is not required. However, even with the administration of large doses of protamine sulfate, the anti-Xa activity of sodium enoxaparin is not completely neutralized (up to a maximum of 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 dosage 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 the use of 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 Eniksum ®, the development of bleeding of any localization is possible (see "Side effects"). With the development of bleeding it is necessary to find its source and prescribe the appropriate treatment.
Bleeding in elderly patients. With the use of enoxaparin sodium in preventive doses in elderly patients, there was no tendency to increase bleeding. When using sodium enoxaparin in therapeutic doses in elderly patients (especially at the age of 80 years and older) 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", Older patients).
Simultaneous use of other drugs that affect hemostasis
It is recommended that the use of drugs that affect hemostasis (salicylates, including acetylsalicylic acid, NSAIDs, including ketorolac, dextran with a molecular 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 when their use is necessary. 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 impairment of renal function (Cl creatinine less than 30 ml / min), there is a significant increase in exposure to sodium enoxaparin, so it is recommended that dose adjustments be carried out both for prophylactic and therapeutic use of the drug. Although dose adjustment is not required in patients with mild to moderate renal impairment (Cl creatinine 30-50 mL / min or 50-80 mL / min), careful monitoring of the condition of such patients is recommended (see "Pharmacokinetics" and "Method of Use And doses ", Patients with renal insufficiency).
Low body weight
There was an increase in the exposure of sodium enoxaparin in its preventive use in women weighing less than 45 kg and men weighing less than 57 kg, which 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 sodium enoxaparin in prophylactic doses in obese patients (BMI greater than 30 kg / m2) is not fully determined, and there is no consensus on dose adjustment. It is necessary to closely monitor the condition of these patients for the development of symptoms and signs of thrombosis and embolism.
Control of the number of platelets in the peripheral blood
The risk of developing antibody-mediated heparin-induced thrombocytopenia exists even when low molecular weight heparins are used. If thrombocytopenia develops, it is usually detected between the 5th and 21st days after initiation of sodium enoxaparin therapy. Therefore, it is recommended that the number of platelets in the peripheral blood be monitored regularly before initiation of treatment with Enixum® and during its administration. 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 occurrence of neuroaxial hematomas with the use of sodium enoxaparin are described with simultaneous spinal / epidural anesthesia with the development of long-lasting or irreversible paralysis. The risk of occurrence of these phenomena decreases with application of enoxaparin sodium in a dose of 40 mg or less.
The risk increases with higher doses of enoxaparin sodium, as well as with the use of permanent catheters after surgery or with the simultaneous use of additional drugs that affect hemostasis, such as NSAIDs (see "Interaction"). 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, it is necessary to take into account the pharmacokinetic profile of the drug (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 Enixum® (20 mg once daily, 30 mg once or twice daily, 40 mg once daily) and at least 24 hours after Administration of higher doses of the drug Enixum® (0.75 mg / kg 2 times a day, 1 mg / kg 2 times a day, 1.5 mg / kg once a day). At these time points, the anti-Xa activity of sodium enoxaparin 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 twice a day, with this (twice-daily) dosing regimen, do not enter a second dose in order to increase the interval before installation Or replacement of the catheter. Similarly, consideration should be given to the possibility of delaying the introduction of the next dose of enoxaparin sodium for at least 4 hours, based on an assessment of the benefit / risk ratio (risk of thrombosis and bleeding during the procedure, taking into account the presence of risk factors in patients). However, it is 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 per 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 doctor 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, the Enixum® drug should be used in patients who have a history of heparin-induced thrombocytopenia in combination with or without thrombosis.
The risk of developing 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 to use Enixum® in this case can be taken only after consultation with the appropriate specialist.
Percutaneous coronary angioplasty
In order to minimize the risk of bleeding associated with invasive vascular instrumental manipulation in the treatment of unstable angina and myocardial infarction without Q wave and acute myocardial infarction with ST-segment elevation, these procedures should be performed at intervals between the administration of Enixum®. 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 sodium enoxaparin treatment is continued, then 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 artificial heart valves The use of sodium enoxaparin for the prevention of thrombosis in patients with mechanical heart valves is not well understood. There are separate reports on the development of thrombosis of heart valves in patients with mechanical heart valves on the background of the appointment of 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 sodium enoxaparin for the prevention of thrombosis in pregnant women with mechanical artificial heart valves has been studied insufficiently. In a clinical study in pregnant women with mechanical heart valves using sodium enoxaparin at a dose of 1 mg / kg 2 times a day to reduce the risk of thrombosis and embolism, 2 in 8 women developed a blood clot that blocked the valves of the heart 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 sodium 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 doses used to prevent thromboembolic complications, sodium enoxaparin does not significantly affect bleeding time and blood coagulation, 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 direct linear dependence on 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 performance of potentially hazardous activities requiring special attention and speed of reactions. There is no data indicating a negative effect of sodium enoxaparin on the ability to drive vehicles and engage in other potentially hazardous activities that require an increased concentration of attention and speed of psychomotor reactions.
Release form
Solution for injection, 10,000 anti-Xa IU (100 mg) / ml. 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8 or 1 ml in sterile glass syringes, graduated or not graduated; With a needle, protective cap, with an additional automatic or non-automatic device to protect the needle after using the syringe or without it. 1 or 2 syringes in a contoured cell pack of PVC or PET film and a film of a composite material or a polypropylene film or a PE film or a polymer-coated packaging paper, or a paper for packaging medical products, or an aluminum lacquered foil. 1 or 5 contoured cell packs with a coating in a pack of cardboard.
Manufacturer
CJSC "PharmFirma" Sotex ". 141345, Russia, Moscow Region, Sergiev Posad Municipal District, sp. Bereznyakovskoe.
Name of the legal entity in whose name the registration certificate issued by CJSC "PharmFirma" Sotex ".
Complaints of consumers should be addressed to the manufacturer's address.
Conditions of supply of pharmacies
On prescription.
Storage conditions of the drug Enixum
At a temperature not higher than 25 °(Do not freeze).
Keep out of the reach of children.
The shelf life of the drug Enixum
2 years.
Do not use beyond the expiration date printed on the package.
