Description
Pharmacological action of
Enoxaparium sodium – low molecular weight heparin. The average molecular weight is about 4,500 daltons: less than 2,000 daltons – <20%, from 2,000 to 8,000 daltons -> 68%, more than 8,000 daltons – <18%. Enoxaparium sodium is obtained by alkaline hydrolysis of heparin gasoline ester isolated from the mucous membrane of the pig ² ¢s small intestine. Its structure is characterized by a non-reducing fragment of 2-0-sulfo-4-enpyrazinosuronic acid and a recovering fragment of 2-14.6-0-disulfo-0-glucopyranoside. The structure of sodium enoxaparin contains about 20% (ranging from 15% to 25%) of the 1,6-anhydron derivative in the reducing fragment of the polysaccharide chain. Pharmacodynamics of In vitro sodium enoxaparium has high activity against coagulation factor Xa (anti-Xa activity of approximately 100 IU / ml) and low activity against coagulation factor (ant-IIa or anti-thrombin activity of approximately 28 IU / ml). This anticoagulant activity is mediated by antithrombin III (AT-III). In addition to anti-Xa / IIa activity, additional anticoagulant and anti-inflammatory properties of enoxaparp sodium were found both in humans and in animal models, which include AT-III-dependent inhibition of other coagulation factors, such as Vila factor, activation of tissue factor pathway inhibitor release, as well as a decrease in the release of von Willebrand factor from vascular endothelium into the bloodstream. These factors provide the anticoagulant effect of enoxaparin sodium in general. When used in prophylactic doses, epoxaparin sodium slightly changes the activated partial thromboplas type time (APTT). has virtually no effect on platelet aggregation and the degree of binding of fibrinogen to 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 subcutaneous administration and reaches 0.13 IU / ml and 0.19 IU / ml after repeated administration of 1 mg / kg of body weight – with double administration and 1.5 mg / kg of body weight body – with a single administration, respectively. The average maximum anti-Xa plasma activity is observed 3-5 hours after subcutaneous administration of the drug and is approximately 0.2 0.4 1.0 and 1.3 anti-XA ME / ml after subcutaneous administration of 20 mg, 40 mg and 1 mg / kg and 1.5 mg / kg, respectively Indications – prevention of venous thrombosis and embolism during surgical interventions, especially during orthopedic and general surgical operations – prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases (including acute cardiac insufficiency (III or IV class NYHA), acute respiratory failure acute infectious diseases acute stages of rheumatic diseases combined 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 – treatment of unstable angina pectoris and myocardial infarction without Q wave in combination with acetylsalicylic acid – prevention of thrombosis in the extracorporeal circulatory system during hemodialysis (usually with rodolzhitelnosti session is not more than 4 hours) – treatment of acute myocardial infarction with ST segment elevation in patients to be medicated or following percutaneous coronary intervention. Contraindications – Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins – active large bleeding, as well as conditions and diseases in which there is a high risk of bleeding: threatened abortion, cerebral aneurysms or aortic dissection (except in the case of surgical intervention on this issue). recent hemorrhagic stroke, uncontrolled bleeding, thrombocytopenia in combination with a positive test in vitro for antiplatelet antibodies in the presence of enoxaparin sodium – sodium eioxaparin is not recommended for the prevention of thrombosis in pregnant women with mechanical artificial heart valves (clinical experience) – age up to 18 years (efficacy and safety not established). Precautions: Conditions at which there is a potential risk of bleeding: – hemostatic disorders (including hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease, etc.), severe vasculitis – peptic ulcer of the stomach or duodenum or other – erosive and ulcerative lesions of the gastrointestinal tract in the history of – recent history of ischemic stroke – uncontrolled severe arterial hypertension srdlkrp diabetes mellitus – previous or suspected neurological or ophthalmic surgery – spinal or epidural anesthesia (potential risk of hematoma), spinal puncture (recently transferred): – recent birth – bacterial endocarditis (acute or subacute): – pericarditis or pericardial effusion – renal and / or liver failure – intrauterine contraception (IUD) – severe trauma (especially the central nervous system (CNS)), open wounds on large surfaces – concomitant use of drugs that affect the heme system – heparin-induced thrombocytopenia (history) in combination with or without thrombosis. There are no data on the clinical use of enoxaparin sodium in the following diseases: active tuberculosis, radiation therapy (recently transferred). Special instructions General Low molecular weight heparins are not interchangeable because they differ in production process, molecular weight, specific anti-Xa activity, dosage units and dosage regimen, which are related to differences in their pharmacokinetics and biological activity (antithrombin activity interaction with platelets). The floor needs to strictly comply with the recommendations for the use of each drug belonging to the class of low molecular weight heparins. Bleeding As with other anticoagulants, with the use of the drug Enixum ® 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 When using enoxaparin sodium in prophylactic doses in elderly patients, there was no tendency to increase bleeding. When using enoxaparin sodium in therapeutic doses in elderly patients (especially those aged 80 years and older), there is an increased risk of bleeding. It is recommended that careful monitoring of the condition of such patients be carried out (see Pharmacokinetics and Method of Use at a Dose, Subsection of Elderly Patients). Concomitant use of no other drugs affecting hemostasis Recommended. to the use of drugs that affect hemostasis (salicylates. including acetylsalicylic acid. NSAIDs, including ketorolac, dextrin with a molecular weight of 40 kDa, ticlopidine, clopidogrel, glucocorticosteroids, thrombolytics, anticoagulants, antiplatelet agents, including antagonists of glycoprotein reviewers IIb / IIIa), was discontinued prior to treatment with sodium enoxaparin, unless their use is necessary. If a combination of enoxaparin sodium with these drugs is indicated, careful clinical observation and monitoring of relevant laboratory parameters should be carried out. Renal failure In patients with impaired renal function, there is a risk of bleeding due to an increase in systemic exposure of enoxaparin sodium In patients with severe impaired renal function (creatinine clearance less than 30 ml / min), a significant increase in the exposure of enoxaparin sodium is noted, Insertion or removal of a catheter should be performed at least 12 hours after the administration of lower doses of Enixum ® (20 mg once a day, 30 mg once or twice a day. 40 mg once a day) and at least , 24 hours after the administration of higher doses of Enixum ® (0.75 mg / kg body weight twice a day. 1 mg / kg body weight twice a day. 1.5 mg / kg once a day). At these time points, the anti-Xa activity of sodium enoxanarin still continues to be detected, and delays in time are not a guarantee. that the development of neuroaxial hematoma can be avoided. Patients receiving enoxaparin sodium at doses of 0.75 mg / kg body weight twice a day or 1 mg / kg body weight twice a day, in this (twice a day) dosage regimen, a second dose should not be administered in order to , to detect signs of bleeding and hematoma in a timely manner. Patients with mechanical artificial heart valves The use of enoxaparin sodium for the prevention of thrombosis in patients with mechanical artificial heart valves is not well understood. There are separate reports on the development of heart valve thrombosis in patients with mechanical artificial heart valves during therapy with sodium epoxaparin to prevent thrombosis. Evaluation 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 due to insufficient clinical data. acute rheumatic conditions, the prophylactic use of enoxaparin sodium is justified only if the above conditions are combined with one of the following risk factors for venous thrombosis: age more than 75 years malignant neoplasms: history of thrombosis and embolism obesity hormone therapy heart failure chronic respiratory failure. Impact on the ability to drive transp. Wed and fur .: There is no data indicating a negative effect of enoxaparin sodium on the ability to drive vehicles and engage in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions. Composition 1 syringe (0.7 ml) contains 7,000 anti-XA IU (70 mg) excipients as an active ingredient: water for injection – up to 0.7 ml. Dosage and administration of Except in special cases (see below Treatment of myocardial infarction with ST segment elevation, medication or with percutaneous coronary intervention and Prevention of thrombosis in the extracorporeal circulatory system during hemodialysis), enoxaparin sodium is administered. Injections are preferably carried out in a patient lying position. Injections should be carried out alternately in the left or right anterolateral or posterolateral surface of the abdomen. The needle must be inserted vertically (not from the side) into the skin fold for the entire length, assembled and held until the injection is completed between the thumb and forefinger. Skin fold released only after completion of the injection. Do not massage the injection site after drug administration. A pre-filled disposable syringe is ready to use. The drug can not be administered intramuscularly! Prevention of venous thrombosis and embolism during surgical interventions, especially during orthopedic and general surgical operations For patients with a moderate risk of developing thrombosis and embolism (general surgery), the recommended dose of the drug is 20 mg once a day subcutaneously. The first injection is made 2 hours before surgery. For patients with a high risk of thrombosis and embolism (general and orthopedic surgery), the drug is recommended at a dose of 40 mg once a day subcutaneously, the first dose is administered 12 hours before surgery, or 30 mg 2 times a day with the start of administration 12-24 hours after surgery. The duration of treatment with the drug on average is 7-10 days. If necessary, therapy can be continued until there is a risk of developing thrombosis and embolism (for example, in orthopedics, enoxaparin sodium is used 40 mg once a day for 5 weeks). Peculiarities of prescribing the drug in spinal / epidural anesthesia, as well as in percutaneous coronary angioplasty, are described in the Special Instructions section. Prevention of venous thrombosis and embolism in patients on bed rest due to acute therapeutic diseases Recommended dose of enoxaparin sodium is 40 mg once daily subcutaneously for 6-14 days. Treatment of deep vein thrombosis, which is accompanied or not accompanied by pulmonary thromboembolism Enixum ® is administered subcutaneously at a rate of 1.5 mg / kg once a day or at a dose of 1 mg / kg twice a day. In patients with complicated thromboembolic disorders, the drug is recommended to be used at a dose of 1 mg / kg twice a day. Duration of treatment is an average of 10 days. It is advisable to immediately start anticoagulant therapy for oral administration, while enoxaparin sodium therapy should be continued until a sufficient anticoagulant effect is achieved, i.e. INR should be 2.0-3.0. If necessary, control of the anticoagulant effect should be evaluated by anti-Xa activity. Treatment of unstable angina pectoris and myocardial infarction without Q wave in combination with acetylsalicylic acid Enixum ® is administered at a rate of 1 mg / kg body weight every 12 hours subcutaneously, with the appointment of acetylsalicylic acid inside at a dose of 100-325 mg once a day. The average duration of treatment is 2-8 days (until stabilization of the clinical condition of the patient). Treatment of myocardial infarction with ST-segment elevation, medication or with percutaneous coronary intervention Treatment begins with an intravenous bolus of enoxaparin sodium at a dose of 30 mg and immediately after it (within 15 minutes) is administered subcutaneously at a dose of 1 mg / kg (and during the first two subcutaneous injections, 100 mg of enoxaparin sodium can be administered as much as possible). Then, all subsequent subcutaneous doses are administered every 12 hours at a rate of 1 mg / kg (i.e., with a body weight of more than 100 kg, the dose may exceed 100 mg). In persons 75 years of age and older, the initial intravenous bolus is not used. Enoxaparin sodium is administered subcutaneously at a dose of 0.75 mg / kg every 12 hours (moreover, during the first two subcutaneous injections, 75 mg of enoxaparin sodium can be administered as much as possible). Then, all subsequent subcutaneous doses are administered every 12 hours at a rate of 0.75 mg / kg (i.e., with a body weight of more than 100 kg, the dose may exceed 75 mg). When combined with thrombolytics (fibrin-specific and fibrin-specific), enoxaparin sodium should be administered in the range from 15 minutes before starting thrombolytic therapy to 30 minutes after it. After the detection of acute myocardial infarction with an ST segment elevation, acetylsalicylic acid should be started at the same time as soon as possible, which, in the absence of contraindications, should continue for at least 30 days in doses of 75 to 325 mg daily. The recommended duration of treatment with the drug is 8 days or until the patient is discharged from the hospital if the hospitalization period is less than 8 days. The bolus administration of enoxaparin sodium should be given through a venous catheter, and enoxaparin sodium should not be mixed or administered with other drugs. In order to avoid the presence of traces of other drugs in the system and their interaction with enoxaparin sodium, the venous catheter should be flushed with a sufficient amount of 0, 9% sodium chloride or dextrose solution before and after intravenous bolus administration of enoxaparin sodium. Enoxaparin sodium is compatible with 0.9% sodium chloride solution and 5% dextrose solution. For bolus administration of 30 mg of enoxaparin sodium in the treatment of acute myocardial infarction with ST segment elevation, 60 mg, 80 mg and 100 mg of excess syringe are removed from glass syringes so that only 30 mg (0.3 ml) remains in them. A dose of 30 mg can be directly administered intravenously. For intravenous bolus administration of enoxaparin sodium through a venous catheter, pre-filled syringes for subcutaneous administration of 60 mg, 80 mg and 100 mg can be used. 60 mg syringes are recommended, as this reduces the amount of drug removed from the syringe. 20 mg syringes are not used, since they do not have enough drug for the bolus administration of 30 mg of enoxaparin sodium. 40 mg syringes are not used, since there are no divisions on them and therefore it is impossible to accurately measure the amount of 30 mg. In patients undergoing transdermal coronary intervention, if the last subcutaneous injection of enoxaparin sodium was performed less than 8 hours before the balloon catheter was introduced into the site of the coronary artery narrowing, additional administration of enoxaparin sodium is not required. If the last subcutaneous injection of enoxaparin sodium was administered more than 8 hours before the balloon catheter was inflated, an additional intravenous bolus injection of enoxaparin sodium at a dose of 0.3 mg / kg should be performed. 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 to a concentration of 3 mg / ml. Dilution of the solution is recommended immediately before administration. To obtain a solution of enoxaparin sodium with a concentration of 3 mg / ml using a pre-filled syringe, it is recommended to use a container with an infusion solution, from which part of the solution is removed using a regular syringe to the required volume. Enoxaparin sodium (the contents of the hypodermic syringe) is injected into the remaining infusion solution. Volume of pre-filled syringe Amount of infusion solution left in the container 0.3 ml 10 ml 0, 6 ml 20 ml The contents of the diluted sodium enoxaparin solution container are mixed gently. For injection, the required volume of diluted solution of enoxaparin sodium is extracted using a syringe, which is calculated by the formula: Volume of diluted solution = Patient’s body weight (kg) x 0.1 or using the table below. Volumes to be administered intravenously after dilution Patient body weight (kg) Required dose (0.3 mg / kg) [mg] Required volume of solution diluted to 3 mg / ml [ml] 45 13.5 4.5 50 Diluted solution volume = Patient body weight (kg) x 0.1 or using the table below. Volumes to be administered intravenously after dilution Patient body weight (kg) Required dose (0.3 mg / kg) [mg] Required volume of solution diluted to 3 mg / ml [ml] 45 13.5 4.5 50 Diluted solution volume = Patient body weight (kg) x 0.1 or using the table below. Volumes to be administered intravenously after dilution Patient body weight (kg) Required dose (0.3 mg / kg) [mg] Required volume of solution diluted to 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 7.5 8 85 25.5 8.5 90 27 9 95 28.5 9.5 100 30 10 Prevention of blood clots in the extracorporeal system more than 4 hours) The dose of enoxaparin sodium averages 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 to 0.75 mg with single vascular access. For hemodialysis, Enixum ® should be injected into the arterial area of the shunt at the beginning of the hemodialysis session. A single dose is usually enough for a four-hour session, however, if fibrin rings are detected with longer hemodialysis, you can additionally enter the drug at a rate of 0.5-1 mg / kg. Elderly patients With the exception of treatment for myocardial infarction with ST-segment elevation (see above), for all other indications of reduced doses of enoxaparin sodium in elderly patients, if they do not have impaired renal function, it is not required. Patients with renal failure Severe renal impairment (endogenous creatinine clearance less than 30 ml / min). The dose of enoxaparin sodium is reduced in accordance with the tables below, since the accumulation of the drug occurs in these patients. When using the drug for therapeutic purposes, the following correction of the dosage regimen is recommended: Normal dosing regimen Dosing regimen for severe renal failure 1 mg / kg subcutaneously 2 times a day 1 mg / kg subcutaneously 1 time per day 1.5 mg subcutaneously once a day 1 mg / kg subcutaneously once a day day Treatment of acute myocardial infarction with ST segment elevation in patients <75 years of age Once: bolus intravenous administration of 30 mg plus 1 mg / kg subcutaneously followed by subcutaneous administration at a dose of 1 mg / kg twice a day (maximum 100 mg for each the first two subcutaneous injections) Once: intravenous bolus administration of 30 mg plus 1 mg / kg subcutaneously followed by subcutaneous administration at a dose of 1 mg / kg once a day (maximum 100 mg for the first subcutaneous injection) Treatment of acute myocardial infarction with ST segment elevation in patients> 75 years old
0, 75 mg / kg subcutaneously 1 mg / kg subcutaneously twice a day without initial bolus injection (maximum 75 mg for each of the first two subcutaneous injections)
1 mg / kg subcutaneously once a day without initial bolus injection (maximum 100 mg for the first subcutaneous injection)
When using the drug for prophylactic purposes, the following correction of the
dosing regimen is recommended. Normal dosing regimen
Dosing regimen for severe renal failure
40 mg subcutaneously once a day
20 mg subcutaneously once a day
20 mg subcutaneously once daily
20 mg subcutaneously once daily
recommended correction mode can not be applied during hemodialysis.
In case of mild (creatinine clearance of 50-80 ml / min) and moderate (creatinine clearance of 30- 50 ml / min) renal failure, dose adjustment is not required, however, laboratory monitoring of therapy should be carried out more carefully.
Patients with liver failure
Due to the lack of clinical trials, caution should be exercised when using enoxaparin sodium in patients with impaired liver function.
Side effects
Side effects were classified by frequency 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). Bleeding Bleeding is possible, especially if there are concomitant risk factors: organic changes with a tendency to bleed, age, renal failure, low body weight, and some drug combinations (see Interactions with other drugs). With the development of bleeding, it is necessary to cancel the administration of the drug, establish the cause of the bleeding and begin the appropriate therapy. Very frequent – bleeding in the prevention of venous thrombosis, in surgical patients and the treatment of deep vein thrombosis with or without thromboembolism. Frequent – bleeding in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina pectoris, myocardial infarction without Q wave and myocardial infarction with ST segment elevation. Infrequent – retroperitoneal hemorrhages and intracranial bleeding in patients treating deep vein thrombosis with or without thromboembolism, as well as myocardial infarction with ST segment elevation. Rare – retroperitoneal bleeding in the prevention of venous thrombosis in surgical patients and in the treatment of angina pectoris, myocardial infarction without Q wave. When using enoxaparin sodium against the background of spinal / epidural anesthesia and postoperative use of penetrating catheters, rare cases of the formation of neuroaxial hematomas are described leading to neurological disorders of varying severity, including long-lasting or irreversible paralysis (see. Special instructions). Thrombocytopenia and platelet Very frequent – thrombocytosis in the prevention of venous thrombosis in surgical patients and in the treatment of deep vein thrombosis with or without thromboembolism. Frequent – thrombocytopenia. In the prevention of venous thrombosis in surgical patients and in the treatment of deep vein thrombosis with or without thromboembolism, as well as in myocardial infarction with ST segment elevation. Infrequent – thrombocytopenia in the prevention of venous thrombosis in patients on bed rest and in the treatment of angina pectoris, myocardial infarction without Q wave. Very rare – autoimmune thrombocytopenia in myocardial infarction with ST segment elevation. In rare cases, the development of autoimmune thrombocytopenia in combination with thrombosis has been reported. In some of them, thrombosis was complicated by heart attack or limb ischemia (see section Special instructions). Other Very often – increased activity of hepatic transaminases. Often – allergic reactions, urticaria, itching, redness of the skin, bruising and pain at the injection site. Infrequently – skin (bullous rashes), inflammatory reaction at the injection site, skin necrosis at the injection site. Rarely – anaphylactic and anaphylactoid reactions, hyperkalemia. Skin necrosis may develop at the injection site, preceded by the appearance of purpura or erythematous painful papules. In these cases, drug therapy should be discontinued. The formation of solid inflammatory nodules-infiltrates at the injection site of the drug is possible, which disappear after a few days and are not grounds for drug withdrawal. Overdose Symptoms: hemorrhagic complications in case of accidental overdose with subcutaneous administration of enoxaparin sodium. In case of accidental ingestion of even large doses, absorption of the drug is unlikely. Treatment: neutralize the effect of enoxaparin sodium by slow intravenous (iv) administration of protamine sulfate. 1 mg of protamine sulfate neutralizes the anticoagulant effect of 1 mg of enoxaparin sodium, if the drug was administered no more than 8 hours before the administration of protamine sulfate. 0.5 mg protamine sulfate neutralizes the anticoagulant effect of 1 mg enoxaparin sodium if it was administered more than 8 hours ago or if a second dose of protamine sulfate is needed. If, however, 12 hours or more have passed after the administration of enoxaparin sodium, administration of protamine sulfate is not required. However, even with the introduction of large doses of protamine sulfate, anti-Xa, the activity of enoxaparin sodium is not completely neutralized (by a maximum of 60%). Storage conditions At a temperature not exceeding 25 ° C. Do not freeze. Keep out of the reach of children. Expiration 2 years. Do not use after the expiration date indicated on the package. Deystvuyuschee substances noksaparyn sodium Terms and conditions prescription dosage form injection Appointment Adult prescription Indications Infarction and Stroke Prevention, From Angina, To Prevent Thrombosis, Prevention Of Acute Myocardial Infarction
