Expiration date: 08/2025
Release form and composition:
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.2 ml
dalteparin sodium 2500 IU (anti-XA)
Auxiliary substances: sodium chloride, sodium hydroxide or hydrochloric acid q.s. the water d/and.
0.2 ml single-dose glass syringes (5) - blisters (2) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.2 ml
dalteparin sodium 5000 IU (anti-XA)
Auxiliary substances: sodium hydroxide or hydrochloric acid q.s. the water d/and.
0.2 ml single-dose glass syringes (5) - blisters (2) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.3 ml
dalteparin sodium 7500 IU (anti-XA)
Auxiliary substances: water d/and.
0.3 ml single-dose glass syringes (5) - blisters (2) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.4 ml
dalteparin sodium 10 000 IU (anti-XA)
Auxiliary substances: water d/and.
0.4 ml single-dose glass syringes (5) - blisters (1) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
1 ml
dalteparin sodium 10 000 IU (anti-XA)
Auxiliary substances: sodium chloride, sodium hydroxide or hydrochloric acid q.s. the water d/and.
1 ml - ampoules (10) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.5 ml
dalteparin sodium 12 500 IU (anti-XA)
Auxiliary substances: water d/and.
0.5 ml single-dose glass syringes (5) - blisters (1) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.6 ml
dalteparin sodium 15 000 IU (anti-XA)
Auxiliary substances: water d/and.
0.6 ml single-dose glass syringes (5) - blisters (1) - packs of cardboard.
Solution for the on/in and s/to the introduction transparent, colourless or with a yellowish tint.
0.72 ml
dalteparin sodium 18 000 IU (anti-XA)
Auxiliary substances: water d/and.
0.72 ml single-dose glass syringes (5) - blisters (1) - packs of cardboard.
Pharmacological action:
The anticoagulant of direct action. Is a low molecular weight heparin, selected in the controlled depolymerization (with nitrous acid) heparin sodium from mucous membrane of the small intestine of the pig and subjected to further purification using ion-exchange chromatography. Composed of sulfated polysaccharide chains having an average molecular weight of 5000 daltons, 90% have a molecular weight from 2000 to 9000 daltons, the degree of sulfation is from 2 to 2.5 babies.
Binds antithrombin plasma, resulting in inhibits the activity of factor XA and thrombin. Anticoagulant effect of sodium dalteparine due primarily to inhibition of factor XA the clotting time is affected slightly. Compared with heparin exerts a mild influence on the adhesion of platelets and, thus, has less effect on primary hemostasis.
Pharmacokinetics:
Pharmacokinetic parameters of dalteparin sodium do not change depending on the administered dose of the drug.
Suction
After p/to the introduction of the bioavailability of dalteparin sodium is about 90%.
Excretion
T1/2 after in/in the introduction is 2 h, after p/to the introduction - 3-5 p.m. Dalteparin sodium excreted by the kidney, but the biological activity of the fragments that are excreted in the urine, poorly understood. In the urine is less than 5% of anti-Xa activity. Clearance of anti-Xa activity dalteparin from plasma after a single on/in the introduction of the drug in bolus at a dose of 30 and 120 IU (anti-Xa)/kg is an average of 24.6±5.4 and 15.6±2.4 ml/h/kg, respectively, and T1/2 is 1.47±0.3 and 2.5±0.3 h
Pharmacokinetics in special clinical cases
In patients with uremia T1/2 increases.
In patients with chronic renal failure, receiving hemodialysis, after a single on/in the introduction of dalteparin sodium in the dose of 5000 ME T1/2, determined by anti-Ha activity, was 5.7±2 h and was significantly higher than in healthy volunteers. Accordingly, such patients can expect a more pronounced accumulation of the drug.
Indications:
— acute deep vein thrombosis
— pulmonary embolism
— prevention of blood clotting in the extracorporeal circulation during hemodialysis or hemofiltration in patients with acute or chronic renal failure
— prevention of thrombosis during surgery
— prevention of thromboembolic complications in patients with therapeutic disease in the acute phase and limited mobility (including the conditions requiring bed rest)
— unstable angina and myocardial infarction (without pathological Q wave on ECG)
— long-term treatment (up to 6 months) to prevent recurrence of venous thrombosis and pulmonary thromboembolism in patients with cancer.
Dosing regimen:
Fragmin® issue/m!
Treatment of acute deep vein thrombosis and pulmonary embolism
Fragmin® is injected p/to 1-2 times/day. You can immediately begin therapy with indirect anticoagulants (vitamin K antagonists). Such combination therapy should continue for as long as the prothrombin index reaches a therapeutic level (usually no earlier than 5 days). Treating patients in the outpatient setting can be given in doses recommended for treatment in hospitals.
With the introduction of 1 times/day dose, component 200 IU/kg of body weight, injected n/a. Single dose should not exceed 18 000 IU. Monitoring of anticoagulant activity of the drug may be waived.
With the introduction of 2 times/day is administered 100 IU/kg body weight n/a. Monitoring of anticoagulant activity of the drug may be dispensed, but be aware that this may be necessary when treating certain groups of patients. The recommended maximum concentration of drug in plasma should be 0.5-1 IU anti-XA/ml.
Prevention of clotting in the extracorporeal circulation during hemodialysis or hemofiltration
Fragmin® injected I/V.
Patients with chronic renal insufficiency or to patients without risk of bleeding, as a rule, requires a slight correction mode, so in most cases there is no need for frequent monitoring of the level of anti-XA. With the introduction of the recommended dose during hemodialysis is usually achieved the level of activity of anti-XA 0.5-1 IU/ml. the duration of hemodialysis or hemofiltration is not more than 4 h the drug is injected in/in struino 30-40 IU/kg body weight followed in/to drip introduction with a speed of 10-15 IU/kg/h or momentary bolus dose of 5000 IU. If the duration of hemodialysis or hemofiltration for more than 4 hours performed in bolus infusion dose rate of 30-40 IU/kg, followed in/to drip introduction with a speed of 10-15 IU/kg/h.
When applying Fragmin in patients with acute renal insufficiency or in patients with high risk of bleeding the drug is injected in/in struino the rate of 5-10 IU/kg, followed in/to drip introduction with a speed of 4-5 IU/kg/h When conducting emergency hemodialysis (acute renal failure) requires more careful monitoring of the level of activity of anti-Ha, as the range of therapeutic doses for such patients is much narrower than that for patients on chronic hemodialysis. Recommended maximum activity level of anti-XA in plasma should be in the range of 0.2-0.4 IU/ml.
Prevention tromboobrazovania with surgical interventions
Fragmin® enter n/K. the monitoring of the anticoagulation activity, as a rule, is not required. In applying the drug in the recommended doses, Cmax in plasma ranged from 0.1 to 0.4 IU anti-XA/ml.
During the operation in General surgical practice in patients with risk of thromboembolic complications the drug is injected p/to the dose 2500 IU for 2 hours before surgery, then after surgery, 2500 IU/day (every morning) during the whole period while the patient is on bedrest (usually 5-7 days).
Patients with additional risk factors of thromboembolic complications (including cancer patients) Fragmin® should be used during the entire period while the patient is on bedrest (usually 5-7 days or more). Thus at the beginning of therapy the day before surgery Fragmin® is injected p/to a dose of 5000 IU evening before surgery, then after surgery, 5000 IU every night. At the beginning of therapy to the day of the operation, enter n/a 2500 IU 2 hours before surgery and 2500 IU every 8-12 hours, but not earlier than 4 h after the end of the operation then the next day every morning 5000 IU.
When carrying out orthopaedic operations (such as hip replacement) Fragmin® should be administered for up to 5 weeks after the operation by selecting one of the alternate modes of dispensing. At the beginning of therapy the drug is administered at a dose of 5000 IU s/C the night before surgery, then 5000 IU every evening after the surgery. At the beginning of therapy on day of surgery Fragmin® is injected p/to the dose 2500 IU for 2 hours before surgery and 2500 IU every 8-12 hours, but not earlier than 4 h after the operation and then the next day in the morning 5000 IU.
At the beginning of therapy after surgery, the drug is injected p/to the dose 2500 IU 4-8 hours after surgery, but not earlier than 4 h after the operation and then the next day n/a on 5000 IU/day.
Prevention of thromboembolic complications in patients with therapeutic disease in the acute phase and limited mobility (including the conditions requiring bed rest)
Fragmin® should be administered s/C at 5000 IU 1 time/day usually for 12-14 days or longer (patients with continuing limitation). Monitoring of anticoagulant activity, as a rule, is not required.
Unstable angina or myocardial infarction without pathological Q wave on ECG
Monitoring of anticoagulant activity, as a rule, is not required, but it should be borne in mind that it may be required in the treatment of special patient groups. The recommended Cmax of the drug in plasma should be 0.5-1 IU anti-XA/ml (at the same time it is expedient to conduct therapy with acetylsalicylic acid at a dose of 75 to 325 mg/day). Fragmin® enter n/a 120 IU/kg of body weight every 12 hours Maximum dose should not exceed 10 000 IU/12 h Therapy should continue as long as the patient's clinical condition will not be stable (usually at least 6 days) or longer (at the discretion of the physician). Then it is recommended to go to long-term therapy with Frimenom in a constant dose until the time of the revascularization (percutaneous intervention or coronary artery bypass grafting). The total duration of therapy should not exceed 45 days.
Fragmin dose is selected taking into account gender and body weight of the patient. Women with a body weight of t 80 kg and men weighing 70 kg t the drug should enter n/a on 5000 IU every 12 h. Women with body weight ge 80 kg and men weighing 70 kg ge, enter 7500 IU s/C every 12 hours.
Long-term treatment to prevent recurrence of venous thrombosis in patients with cancer
1 month - designated n/a in a dose of 200 IU/kg body weight 1 times/day. Maximum daily dose of 18 000 ME.
2-6 months - appoint s/to the dose of approximately 150 IU/kg body weight 1 times/day, using syringes with fixed dose, in accordance with table 1.
Table 1. Determination of the dose Fragmin® depending on body mass for the period of treatment is 2-6 months.
| Body weight (kg) | Dose Fragmin (IU) |
| before 56 | 7500 |
| 57-68 | 10000 |
| 69-82 | 12500 |
| 83-98 | 15000 |
| above 99 | 18000 |
In thrombocytopenia, which developed on the background of chemotherapy with a platelet count of 50 000 t/l application Fragmin should be suspended until the increase in the number of platelets more than 50,000/µl. For a platelet count of 50,000/µl to 100,000/µl the dose should be reduced by 17-33% relative to the initial dose, depending on body mass of the patient in accordance with table 2. When restoring platelet count to the level of ge 100 000/µl, the drug should be administered in full dose.
Table 2. Dose reduction of the drug Fragmin® for thrombocytopenia 50 000/µl and 100,000/µl
| Body weight (kg) | The planned dose Fragmin (IU) | Reduced dose Fragmin (IU) | Dose reduction (%) |
| before 56 | 7500 | 5000 | 33 |
| 56-68 | 10000 | 7500 | 25 |
| 89-92 | 12500 | 10000 | 20 |
| 83-98 | 15000 | 12500 | 17 |
| above 99 | 18000 | 15000 | 17 |
In renal failure, severe with creatinine level more than 3 times exceeding the ULN, the dose should be adjusted Fragmin thus, to maintain a therapeutic level of anti-XA 1 IU/ml (range 0.5-1.5 IU/ml), determined 4-6 h after drug administration. If the level of anti-Ha above or below therapeutic range, the dose Fragmin should respectively increase or decrease, and measurement of anti-XA should be repeated after the introduction of 3-4 new doses. Dose adjustment should be carried out to achieve a therapeutic level of anti-Ha.
Side effects:
Side effects observed at an average of 1% of patients.
From the hematopoietic system and blood coagulation: bleeding, hematoma at the injection site, reversible non-immune thrombocytopenia, bleeding in some cases of immune thrombocytopenia (with or without thrombotic complications) development of spinal or epidural hematoma, peritoneal and intracranial hemorrhage, some with fatal outcome.
From the digestive system: transient increase in liver transaminases (AST, ALT).
Local reactions: soreness at the injection site in some cases - skin necrosis.
Other: allergic reactions, in some cases, - anaphylactic reactions.
Contraindications:
— immune thrombocytopenia (heparin-induced) history or suspected it
— bleeding (clinically significant, for example, from the gastrointestinal tract on the background of gastric ulcer and/or duodenal ulcer, intracranial bleeding)
— expressed violations of the blood coagulation system
— bacterial endocarditis
— recent injury or surgery on the Central nervous system, organs of vision, hearing
— hypersensitivity to the preparation components
— hypersensitivity to other low molecular weight heparins and/or heparin.
Due to increased risk of bleeding Fragmin® in high doses (used, for example, for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina and myocardial infarction without pathological Q wave on ECG) should not be prescribed to patients who are planned spinal or epidural anesthesia or other procedures involving lumbar puncture.
With caution, especially in patients in the early postoperative period, should be appointed Fragmin® at high doses (e.g., for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina and myocardial infarction without the Q wave on the ECG) with caution should designate Fragmin® patients with a high risk of bleeding, including patients with thrombocytopenia, disorders of platelets, severe liver or renal insufficiency, uncontrolled hypertension, hypertensive or diabetic retinopathy.
Pregnancy and lactation:
When administered to a pregnant was not identified adverse effects on pregnancy and the health of the fetus and newborn. When applying Fragmin in pregnancy, the risk of adverse effects on the fetus is assessed as low. However, since the possibility of adverse effects cannot be ruled out completely, Fragmin® can be prescribed only under strict indications, when the expected benefit to the mother outweighs the potential risk.
If necessary, use Fragmin during pregnancy it is necessary to monitor anticoagulant activity of the drug.
In experimental studies have not revealed teratogenic or fetotoksi?eskoe effect of the drug.
Is not installed, selects whether dalteparin sodium in breast milk.
Special instructions:
The drug issue/m!
When conducting neuroaxial anesthesia (epidural/spinal anesthesia) or when performing a lumbar puncture in patients who are receiving anticoagulant therapy or who have planned to pursue anticoagulant therapy using low molecular weight heparins for prevention of thromboembolic complications, there is an increased risk of spinal or epidural hematoma, which in turn may result in prolonged or permanent paralysis. The risk of such complications increases with the use of permanent epidural catheters for administration of analgesics or with simultaneous use of drugs that affect hemostasis (NSAIDs, inhibitors of the functions of platelets, other blood thinners). The risk increases in case of injury and repeated epidural or spinal punctures the. In such cases, patients should be under constant surveillance for the timely identification of pathological neurological symptoms. With the appearance of neurological pathology shows emergency conducting decompression of the spinal cord.
There are no clinical data on the use of Fragmin when pulmonary embolism in patients with circulatory disorders, hypotension, or shock.
With the rapid development of the therapy with Frimenom thrombocytopenia or thrombocytopenia with platelet count less than 100,000/µl is recommended in all vitr test for antiplatelet antibody in the presence of heparin or low molecular weight heparins. If the results of such a test in all vitr is positive or questionable, or testing is generally not performed, Fragmin® should be abolished.
In monitoring anticoagulant activity Fragmin usually not necessary. However, it should be conducted when applying Fragmin in children, patients with body weight below normal or obese, pregnant women, and also with increased risk of bleeding or re-thrombosis.
The sampling of blood for analysis of the activity Fragmin should be made in a period when maximum concentration of drug in plasma (3-4 h after s/to the injections).
To determine the activity of anti-XA method of choice are laboratory tests, which use a chromogenic substrate. You should not use tests to determine the APTT and thrombin time, as these tests are relatively insensitive to the activity of dalteparin sodium. Higher doses Fragmin to increase the APTT may result in bleeding.
Units of operation Fragmin, unfractionated heparin and other low molecular weight heparins are not equivalent, therefore, the replacement of one drug while others need to make a correction mode.
When using multi-dose vials of unused solution should be destroyed after 14 days after first piercing the tube with a needle.
Use in Pediatrics
There are only limited data on the safety and efficacy of Fragmin in pediatric practice. When applying Fragmin in children it is necessary to monitor the level of anti-XA activity.
Overdose:
Symptoms: excessive doses may develop hemorrhagic complications. Overdose in most cases, possible bleeding of the skin and mucous sheath, gastrointestinal tract and urogenital tract. The decrease in blood pressure, decrease in hematocrit and other symptoms may indicate a hidden bleeding.
Treatment: in case of bleeding application of Fragmin should pause to assess the severity of bleeding and risk of thrombosis.
Anticoagulant effect Fragmin can be eliminated by the introduction of Protamine sulfate, which is a means of emergency therapy. 1 mg of Protamine sulfate partially neutralizes the effect of 100 ME(anti-Ha) of dalteparin sodium (and, although there is a complete neutralization of the induced increase in clotting time of blood, from 25% to 50% of anti-XA activity dalteparin sodium still remains.
Drug interactions:
While the use of drugs affecting hemostasis such as thrombolytic preparations (alteplase, streptokinase, urokinase), indirect anticoagulants, vitamin K antagonists, NSAIDs (including acetylsalicylic acid, indomethacin), and inhibitors of platelet function, anticoagulant effects Fragmin may increase (increased risk of bleeding).
Pharmaceutical interaction
Fragmin® is compatible with isotonic sodium chloride solution (9 mg/ml), isotonic solution of dextrose (glucose) (50 mg/ml).
Terms and conditions of storage:
Drug ampoules should be stored at temperature not exceeding 30°C, the injector at a temperature not exceeding 25°C. shelf Life - 3 years.
The drug should be stored out of reach of children.
