Fragmin injection 2500me/0,2ml syringe №1

Dosage form

Solution for iv and p / to the introduction

Composition

0.2 ml of solution for IV and SC injection contains: dalteparin sodium 2500 IU anti-Xa.
Excipients: sodium chloride, sodium hydroxide or hydrochloric acid q.s., water d / u.

Packing

In a single-use syringe 0.2 ml solution. In the package 10 syringes.

Mechanism of action

Fragmin - direct acting anticoagulant. It 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 5,000 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. It binds plasma antithrombin, and therefore inhibits the activity of factor Xa and thrombin. The anticoagulant effect of dalparin sodium is primarily due to the inhibition of factor Xa; at the time of blood clotting affects slightly. Compared with heparin, it has a weak effect on platelet adhesion and, thus, has less effect on primary hemostasis.

Indications and usage

- acute deep vein thrombosis;
- pulmonary embolism;
- 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;
- unstable stenocardia and myocardial infarction (without Q wave on the ECG).

Contraindications

- bleeding (clinically significant, for example, from the gastrointestinal tract on the background of gastric ulcer and duodenal ulcer, intracranial bleeding);
- a history of immune thrombocytopenia (caused by heparin) or suspicion of it;
- recent injuries or surgeries on the central nervous system, organs of vision, hearing;
- septic endocarditis;
- severe disorders of the blood coagulation system;
- hypersensitivity to sodium dalteparin or to other low molecular weight heparins and / or to heparin.
Due to the high risk of bleeding Fragmin in high doses (used for example for the treatment of acute deep vein thrombosis, pulmonary thromboembolism, unstable angina and myocardial infarction without Q wave on the ECG) cannot be prescribed to patients undergoing spinal or epidural anesthesia or other procedures accompanied by lumbar puncture.

Pregnancy and Breastfeeding

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 excluded, Fragmin can only be prescribed for strict indications when the intended benefit to the mother outweighs the potential risk.
If necessary, the use of Fragmin during pregnancy should be monitored anticoagulant activity of the drug.
In experimental studies revealed no teratogenic or fetotoxic effect of the drug.
It is not established whether dalteparin sodium is excreted in breast milk.

Dosage and administration

Fragmin can not enter the / m!
For the treatment of acute deep vein thrombosis and pulmonary thromboembolism Fragmin injected s / c 1-2 times / day. In this case, you can immediately begin therapy with indirect anticoagulants. This combination therapy should be continued until the prothrombin index reaches a therapeutic level (usually not earlier than after 5 days). Patients can be treated on an outpatient basis in doses recommended for inpatient therapy. When administered once a day, the dose is 200 IU / kg body weight. A single dose should not exceed 18,000 IU. With the introduction of 2 times / day a single dose of 100 IU / kg. Monitoring of the anticoagulant activity of the drug can not be carried out, but it should be borne in mind that this may be necessary in the treatment of certain groups of patients.The recommended maximum concentration of the drug in plasma should be 0.5-1 IU anti-Xa / ml.
For the prevention of blood coagulation in the extracorporeal circulation during hemodialysis or hemofiltration Fragmin injected into / in.
Patients with chronic renal failure or patients without a risk of bleeding in history as a rule, a slight correction of the dosing regimen is required, so there is no need for frequent monitoring of the anti-Xa level. With the introduction of the recommended doses during hemodialysis, an anti-Xa activity level of 0.5–1 IU / ml is usually achieved. With a duration of hemodialysis or hemofiltration of not more than 4 hours, the drug is administered intravenously in streams of 30-40 IU / kg body weight, followed by intravenous drip injections at a rate of 10-15 IU / kg / h, or once streamed at 5000 IU. With the duration of hemodialysis or hemofiltration for more than 4 hours, it is carried out in / in the jet injection of the drug in a dose of 30–40 IU / kg followed by the introduction of 10–15 IU / kg / h.
When using Fragmin in patients with acute renal failure or in patients with a high risk of bleeding the drug is administered intravenously in a jet at the rate of 5-10 IU / kg, followed by intravenous drip injections at a rate of 4-5 IU / kg / h. When conducting emergency hemodialysis, a more thorough monitoring of the level of anti-Xa activity is required, since the range of therapeutic doses for such patients is much narrower. The level of anti-Xa activity should be in the range of 0.2-0.4 IU / ml.
For the prevention of thrombosis during surgical interventions Fragmin enter s / c. 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 an operation in general surgical practice in patients at risk of developing thromboembolic complications the drug is injected s / c at a dose of 2500 IU 2 hours before the operation, then after the operation at 2500 IU / day (every morning) during the entire period while the patient is on bed rest (usually 5-7 days). Patients with additional risk factors for the development of thromboembolic complications (including patients with malignant tumors) Fragmin should be used during the entire period while the patient is on bed rest. At the same time, at the beginning of therapy the day before the operation, Fragmin is injected s / c in a dose of 5,000 IU in the evening before the operation, then after the operation, 5,000 IU each evening. At the beginning of therapy on the day of the operation, n / a 2500 IU is administered 2 hours before the operation and 2500 IU after 8-12 hours, but not earlier than 4 hours after the end of the operation; then from the next day every morning at 5000 IU.
When performing orthopedic operations (for example, for hip joint arthroplasty) Fragmin should be administered for up to 5 weeks after surgery, selecting one of the alternative dosing regimens. At the beginning of therapy on the evening before the operation, a single dose for sc infusion is 5000 IU, and the drug is administered on the evening before the operation and then every evening after the operation.At the start of therapy on the day of surgery, Fragmin is injected s / c at a dose of 2500 IU 2 hours before the operation and 2500 IU after 8-12 hours, but not earlier than 4 hours after the end of the operation; then from the next day every morning at 5000 IU.
At the beginning of therapy after surgery the drug is injected s / c at a dose of 2500 IU after 4-8 hours after surgery; then from the next day to 5000 IU / day.
With unstable angina or myocardial infarction without a pathological Q wave The recommended maximum plasma concentration of the drug should be 0.5-1 IU anti-Xa / ml (at the same time it is advisable to carry out therapy with Acetylsalicylic acid at a dose of 75 to 325 mg / day). Fragmin is injected at a dose of 120 IU / kg body weight every 12 hours. The maximum dose should not exceed 10,000 IU / 12 hours. Therapy should be continued until the clinical condition is stable (usually at least 6 days) or longer. (at the discretion of the doctor). Then it is recommended to switch to long-term therapy with Fragmin in a constant dose until revascularization (percutaneous interventions or aorto-coronary bypass surgery). The total duration of therapy should not exceed 45 days. The dose of Fragmin is selected taking into account the gender and body weight of the patient. Women weighing less than 80 kg and men weighing less than 70 kg should be administered subcutaneous doses of 5,000 IU every 12 hours. Women weighing 80 kg or more and men weighing 70 kg or more should be administered 7,500 IU. every 12 hours

From the hemopoietic system and blood coagulation system: rarely, reversible non-immune thrombocytopenia, bleeding (when used in high doses); in some cases, immune thrombocytopenia (with or without thrombotic complications); development of spinal or epidural hematoma.
From the digestive system: in some cases, a transient increase in liver transaminase activity.
Local reactions: hematoma at the injection site, pain; rarely - skin necrosis.
Other: in some cases - Anaphylactic reactions .

The drug can not be administered in / m!
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 carry out anticoagulant therapy using low molecular weight heparins for the prevention of thromboembolic complications, there is an increased risk of developing spinal or epidural anesthesia or an adulitis. a queue 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. Such patients should be monitored for timely detection.pathological neurological symptoms. When a 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.
With the rapid development of thrombocytopenia with thrombocytopenia or thrombocytopenia with platelet count less than 10,000 / μl, it is recommended that an in vitro test for antiplatelet antibodies in the presence of heparin or low molecular weight heparins is recommended. If the results of such an in vitro test turn out to be positive or doubtful, or the testing has not been carried out at all, then Fragmin should be canceled.
In monitoring the anticoagulant activity of Fragmin, as a rule, there is no need. However, it should be carried out with the use of Fragmin in patients with a body weight below normal or obese, as well as with an increased risk of bleeding or thrombosis. Blood samples for the analysis of Fragmin's activity should be taken during the period when the maximum concentration of the drug in the blood plasma is reached (3-4 hours after s / c injection).
Laboratory tests that use a chromogenic substrate are used to determine anti-Xa activity. Tests should not be used to determine activated partial thromboplastin time (APTT) and thrombin time, since these tests are relatively insensitive to the activity of dalteparin sodium. Increasing the dose of Fragmin in order to increase the APTT can lead to bleeding.
The units of action of Fragmin, unfractionated heparin and other low-molecular-weight heparins are not equivalent, therefore, when replacing one drug with another, it is necessary to correct the dosage regimen.
Use in pediatrics: Only limited information is available on the safety and efficacy of Fragmin in pediatric practice. When using Fragmin in children, it is necessary to control the level of anti-Xa activity.

With simultaneous use with drugs that affect hemostasis, such as NSAIDs , thrombolytic agents, other anticoagulants, as well as inhibitors of platelet function, it is possible to enhance the anti-clotting effect of Fragmin.
When combined with the use of Fragmin antihistamines, cardiac glycosides, tetracyclines, Ascorbic acid may weaken the action of Fragmin.
Pharmaceutical interaction. Fragmin is compatible with isotonic sodium chloride solution (9 mg / ml), isotonic glucose solution (50 mg / ml).

Treatment: The anticoagulant effect of dalteparin sodium can be eliminated by administering protamine sulphate (an emergency treatment tool). 1 mg of protamine partially inhibited 100 ME of dalteparin sodium (and although there is a complete neutralization of the induced increase in clotting time, but from 25 to 50% of the anti-Xa activity of dalteparin sodium still persists).

Keep out of the reach of children at a temperature not exceeding 30 ° C.