Fragmin solution for intravenous and subcutaneous administration of 5000 IU syringes 0.2 ml 10 pcs
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Active ingredients
Dalteparin Sodium
Release form
Solution
Composition
Active ingredient: dalteparin sodium Concentration of active ingredient (IU): 5000 ME
Pharmacological effect
Anticoagulant direct action. is a low molecular weight heparin isolated in the process of controlled depolymerization (with nitrous acid) of sodium heparin from the mucous membrane of the small intestine of the pig and subjected to additional purification using ion-exchange chromatography. consists of sulfated polysaccharide chains with an average molecular weight of 5000 daltons; while 90% have a molecular weight of from 2000 to 9000 daltons; the degree of sulfation is from 2 to 2.5 per disaccharide. binds plasma antithrombin, as a result of which it inhibits the activity of factor xa and thrombin. the anticoagulant effect of dalparin sodium is primarily due to inhibition of factor xa; at the time of blood clotting affects slightly. compared to heparin, it has a weak effect on platelet adhesion and, thus, has less impact on primary hemostasis.
Pharmacokinetics
Pharmacokinetic parameters of sodium dalteparin do not change depending on the administered dose of the drug. Absorption After subcutaneous injection, the bioavailability of sodium dalteparin is about 90%. Excretion of T1 / 2 after IV administration is 2 hours, after subcutaneous administration - 3-5 hours Sodium is excreted mainly by the kidneys, but the biological activity of the fragments excreted in the urine is not well understood. In the urine less than 5% of anti-Xa activity is detected. The clearance of anti-Xa activity of dalteparin from plasma after a single intravenous bolus administration at a dose of 30 and 120 IU (anti-Xa) / kg averages 24.6 ± 5.4 and 15.6 ± 2.4 ml / h / kg, respectively, and T1 / 2 - 1.47 ± 0.3 and 2.5 ± 0.3 hours. Pharmacokinetics in special clinical situations in patients with uremia T1 / 2 increases. In patients with chronic renal failure receiving treatment with hemodialysis, after a single IV dose of 5000 IU / 2, determined by anti-Xa activity, was 5.7 ± 2 h and was significantly higher than in healthy vol. ltsev. Accordingly, in such patients a more pronounced cumulation of the drug can be expected.
Indications
treatment of acute thrombosis of deep veins and pulmonary thromboembolism; prevention of blood coagulation in the extracorporeal circulation during hemodialysis or hemofiltration in patients with acute or chronic renal failure; prevention of thrombosis during surgical interventions; mobility (including in conditions requiring bed rest), unstable angina and myocardial infarction carda (without Q wave on ECG), long-term treatment (up to 6 months) in order to prevent the recurrence of venous thrombosis and pulmonary thromboembolism in patients with oncological diseases.
Contraindications
hypersensitivity to dalteparin sodium or other low molecular weight heparins and / or heparin; immune thrombocytopenia (caused by a history of heparin or suspicion of its presence); bleeding (clinically significant, for example, from the organs of the gastrointestinal tract against the background of gastric ulcer and / or duodenal ulcer, intracranial bleeding); pronounced disorders of the blood coagulation system; septic endocarditis; recent injuries or operative interventions on the organs of the central nervous system, organs of sp and / or hearing; due to an increased risk of bleeding, high doses of Fragmin (for example, for the treatment of acute deep vein thrombosis, pulmonary thromboembolism, unstable angina and myocardial infarction without a Q-wave on an ECG) cannot be prescribed to patients who are planned to have spinal or epidural anesthesia, or other procedures involving lumbar puncture.
Precautionary measures
The drug should be kept out of the reach of children.
Use during pregnancy and lactation
When used in pregnant women, there was no adverse effect on the course of pregnancy, as well as on the health of the fetus and newborn. When using Fragmin during pregnancy, the risk of adverse effects on the fetus is assessed as low. However, since the possibility of adverse effects cannot be completely ruled out, Fragmin can be prescribed only by strict indications,when the intended benefit to the mother exceeds the potential risk. If it is necessary to use Fragmin during pregnancy, it is necessary to monitor the anticoagulant activity of the drug. In experimental studies, no teratogenic or fetotoxic effect of the drug has been identified.
Dosage and administration
Fragmin can not be administered intramuscularly! Treatment of acute deep vein thrombosis and pulmonary thromboembolism Fragmin is injected subcutaneously 1-2 times a day. You can immediately begin therapy with indirect anticoagulants (vitamin K antagonists). This combination therapy should be continued until the prothrombin index reaches a therapeutic level (this is usually observed no earlier than after 5 days). Patients can be treated on an outpatient basis in the same doses that are recommended for treatment in a hospital setting. Administration once a day - a dose of 200 IU / kg body weight is injected subcutaneously. A single daily dose should not exceed 18,000 ME. Monitoring of the anticoagulant activity of the drug can not be carried out. Administration 2 times a day - 100 IU / kg body weight subcutaneously 2 times a day. It is possible not to carry out monitoring of anticoagulant activity, but it should be borne in mind that it may be necessary in the treatment of special groups of patients (see the section "Special Instructions"). The recommended maximum concentration of the drug in the blood plasma should be 0.5-1 ME anti-Xa / ml. Prevention of blood coagulation in the extracorporeal circulation during hemodialysis or hemofiltration Fragmin should be administered intravenously (IV) by selecting a dosing regimen from the following. Patients with chronic renal failure, or patients without the risk of bleeding. Such patients usually require a slight dose adjustment, and therefore most patients do not need to perform full monitoring of anti-Xa level. With the introduction of the recommended doses during hemodialysis, a plasma level is usually reached equal to 0.5 -1 IU anti-Xa / ml. With the duration of hemodialysis or hemofiltration of not more than 4 hours - in / in the jet of 30-40 IU / kg body weight, followed by in / in the drip of 10-15 IU / kg / hour,or once intravenously in a jet at a dose of 5000 ME.If the duration of hemodialysis or hemofiltration is more than 4 hours, intramuscular injection of 30-40 IU / kg body weight, followed by intravenous drip injections of 10-15 IU / kg / hour. Patients with acute renal failure, or patients with a high risk of bleeding In / in the jet of 5 -10 IU / kg body weight, followed by IV drip injections of 4-5 IU / kg / hour. In patients who undergo hemodialysis for acute renal failure, the drug is characterized by a narrower therapeutic index than in patients on chronic hemodialysis (in connection with which they need adequate monitoring of the level of anti-Xa). The recommended maximum plasma level should be 0.2 - 0.4 IU anti-Xa / ml). Prevention of thrombosis during surgery Fragmin should be administered subcutaneously. Monitoring of anticoagulant activity is generally not required. When using the drug in recommended doses, maximum plasma concentrations range from 0.1 to 0.4 IU anti-Xa / ml. When performing operations in general surgical practice, patients with the risk of developing thromboembolic complications - subcutaneously 2500 ME 2 hours before surgery, then after surgeries - subcutaneously at 2500 IU / day (every morning) for the entire period while the patient is on bed rest (usually 5-7 days). Patients with additional risk factors for developing thromboembolic complications (for example, patients with malignant tumors Yami) - Fragmin should be used during the entire period while the patient is on bed rest (usually 5-7 days or more). 1. At the start of therapy the day before surgery: 5000 ME p / c the evening before the operation, then 5000 ME p / c every evening after the surgery. 2. At the beginning of therapy at the time of surgery: 2500 ME n / a 2 hours before the operation and 2500 ME n / a in 8-12 hours, but not earlier than 4 hours after the end of the operation. Then, from the next day, 5,000 IU of c / c are administered every morning. When performing orthopedic operations (for example, during hip joint arthroplasty), Fragmin should be administered for up to 5 weeks after surgery by selecting one of the dosing regimens listed below. 1. At the beginning of therapy the evening before the operation: 5000 ME p / c the evening before the operation, then 5000 ME p / c every evening after the operation. 2At the beginning of therapy on the day of the operation: 2500 ME n / a 2 hours before the operation and 2500 ME n / a 8-12 hours, but not earlier than 4 hours after the end of the operation. Then, from the next day, every morning - 5,000 ME p / k. 3. At the beginning of therapy after surgery: 2500 ME n / a after 4-8 hours after surgery, but not earlier than 4 hours after the end of the operation. Then, from the next day, 5000 IU p / c per day. Prevention of thromboembolic complications in patients with a therapeutic disease in the acute phase and limited mobility (including in conditions requiring bed rest) Fragmin should be administered subcutaneously with 5000 IU once day, usually within 12-14 days or longer (in patients with ongoing restriction of mobility). Monitoring of anticoagulant activity is generally not required. Unstable angina pectoris and myocardial infarction (without Q-wave on the ECG) Monitoring of anticoagulant activity is usually not required, but it should be borne in mind that it may be necessary in the treatment of special groups of patients (see section "Special Instructions"). The recommended maximum concentration of the drug in plasma should be 0.5-1 ME anti-Xa / ml (at the same time it is advisable to carry out therapy with acetylsalicylic acid in a dose of from 75 to 325 mg / day). Fragmin is administered subcutaneously at 120 IU / kg body weight every 12 hours. The maximum dose should not exceed 10,000 IU every 12 hours. Therapy should be continued until the patient’s clinical condition becomes stable (usually at least 6 days), or longer (at the discretion of the physician). Then it is recommended to switch to long-term therapy with Fragmin in a constant dose until revascularization (percutaneous interventions or aorta-coronary bypass surgery). The total duration of therapy should not exceed 45 days. The dose of Fragmin is selected taking into account the patient's sex and body weight: Women weighing less than 80 kg and men weighing less than 70 kg should be administered at 5000 IU every 12 hours; Women weighing 80 kg or more and men weighing Long bodies of 70 kg and more should be administered 7500 IU every 12 hours. Long-term treatment to prevent the recurrence of venous thrombosis in patients with oncological diseases. 1 month. Administration 1 time per day - 200 IU / kg body weight subcutaneously. A single daily dose should not exceed 18,000 ME.2-6 months. Administration once a day - at a dose of about 150 IU / kg body weight subcutaneously, using fixed dose syringes (Table 1). Table 1. Determining the dose of Fragmin depending on the weight body for a treatment period of 2 to 6 months.Body weight, kg Dose of Fragmin, ME less than 56 750057-68 1000069-82 / µl For platelet count from 50,000 / µl to 100,000 / µl, the dose of the drug should be reduced by 17% -33% relative to the initial dose, depending on the patient's body weight (Table 2). When restoring the platelet count to a level greater than 100,000 / μl, the drug should be administered in full dose. Table 2. Fragmin dose reduction with thrombocytopenia is 50,000 / μL-100000 / μL. Body weight, kg Planned dose of Fragmin, ME Reduced dose of Fragmin Dose reduction,% less than 56 7500 5000 3357-68 10000 7500 2569-82 12500 10000 2083-98 15000 12500 17 more than 99 18000 15000 17 Kidney failure - In case of significant renal failure determined by level creatinine as exceeding a 3-fold increase in the upper limit of normal, Fragmin's dose should be adjusted to maintain a therapeutic level of anti-Xa IU / ml (range 0.5-1.5 IU / ml), measured over 4-6 hours after dalteparin administration. If the level of anti-Xa is lower or higher than the therapeutic range, the dose of Fragmin should be increased or decreased accordingly a, the measurement of anti-Xa should be repeated after the administration of 3-4 new doses. Dose adjustment should be made before reaching the anti-Xa therapeutic level.
Side effects
The following side effects are noted (on average in 1% of patients): bleeding, hematoma at the injection site, reversible non-immune thrombocytopenia, pain at the injection site, allergic reactions, as well as a transient increase in liver transaminases (ACT, ALT). Several cases of immune thrombocytopenia have been reported (with or without thrombotic complications), as well as cases of skin necrosis, anaphylactic reactions, the development of spinal or epidural hematomas, peritoneal and intracranial bleeding, some of which were fatal.
Overdose
Symptoms: with an excessive dose may develop hemorrhagic complications. In case of overdose in most cases, bleeding of the skin and mucous membrane, gastrointestinal tract and urogenital tract are possible.Decrease in blood pressure, hematocrit and other symptoms may indicate latent bleeding. Treatment: in case of bleeding, use Fragmin to assess the severity of bleeding and the risk of thrombosis. The anti-coagulant effect of Fragmin can be eliminated by administering protamine sulfate, which is a means of emergency treatment. 1 mg of protamine sulfate partially neutralizes the effect of 100 ME (anti-Xa) sodium dalteparin (and, although there is a complete neutralization of the induced increase in blood clotting time, from 25% to 50% of the anti-Xa activity of sodium dalteparin remains.
Interaction with other drugs
With simultaneous use with drugs that affect hemostasis, such as thrombolytic agents (alteplaza, streptokinase, urokinase), indirect anticoagulants, vitamin K antagonists, NSAIDs (including acetylsalicylic acid, indomethacin), as well as inhibitors of platelet function, anticoagulants, anticoagulants, anti-coagulants, and anti-coagulants. Fragmin may increase (the risk of bleeding increases). Pharmaceutical interaction Fragmin is compatible with isotonic sodium chloride solution (9 mg / ml), isotonic dextrose (glucose) solution (50 mg / ml).
special instructions
The drug should not be injected intramuscularly! When conducting neuroaxial anesthesia (epidural / spinal anesthesia) or when performing spinal puncture in patients who receive anticoagulant therapy or in whom it is planned to conduct anticoagulant therapy using low molecular weight heparins for the prevention of thromboembolic complications, there is an increased risk of using thromboembolic complications. or epidural hematoma, which in turn can lead to prolonged or permanent paralysis. The risk of such complications increases with the use of permanent epidural catheters for the introduction of analgesics or with the simultaneous use of drugs that affect hemostasis (NSAIDs, platelet function inhibitors, other anticoagulants). The risk also increases with injuries and repeated epidural or lumbar punctures. In such cases, patients should be constantly monitored for the timely detection of pathological neurological symptoms.When neurological pathology appears, it is shown that spinal cord decompression is urgent. There are no clinical data on the use of Fragmin in pulmonary thromboembolism in patients with circulatory disorders, arterial hypotension or shock. In the case of rapid development during therapy with Fragmin thrombocytopenia or in the body count. / μl is recommended to conduct an in vitro test for anti-platelet antibodies in the presence of heparin or low molecular weight heparins. If the results of such an in vitro test turn out to be positive or doubtful, or if the testing has not been carried out at all, then Fragmin should be canceled. As a rule, Fragmin’s anticoagulant activity is not monitored. However, it should be carried out with the use of Fragmin in children, patients with a body weight below normal or obese, pregnant women, as well as an increased risk of bleeding or re-thrombosis. Blood samples should be collected for the analysis of Fragmin activity during the period when the maximum concentration is reached the drug in the blood plasma (3-4 hours after the s / c injection). To determine the activity of anti-Xa, the method of choice is laboratory tests that use a chromogenic substrate. Tests should not be used to determine APTT and thrombin time, since these tests are relatively insensitive to the activity of dalteparin sodium. Increasing the dose of Fragmin to increase APTT can lead to bleeding. The units of Fragmin, unfractionated heparin and other low-molecular-weight heparins are not equivalent, therefore, when replacing one drug with another, correction of the dosing regimen is required. When using multi-dose vials, unused solution should be destroyed after 14 days after the first needle piercing. Use in pediatrics There are only limited safety information and effect. and the use of Fragmin in pediatric practice. When using Fragmin in children, it is necessary to control the level of anti-Xa activity.