Fragmin solution 5000 anti-Xa IU/0.2 ml syringes, 10 pcs.

Composition

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of 0.2 ml solution for intravenous and subcutaneous administration contains:

dalteparin sodium 5000 IU anti-Ha.

Auxiliary substances:

sodium chloride,

sodium hydroxide or hydrochloric acid q. s.,

d/i water.

Pharmacological action

Fragmin is a direct-acting anticoagulant.

It is a low-molecular-weight heparin isolated during controlled depolymerization (with nitrous acid) of sodium heparin from the mucosa of the small intestine of pigs and subjected to additional purification using ion exchange chromatography. It consists of sulfated polysaccharide chains with an average molecular weight of 5,000 daltons; 90% have a molecular weight of 2,000 to 9,000 daltons; the degree of sulfation is from 2 to 2.5 per disaccharide.

Binds plasma antithrombin, thereby inhibiting the activity of factor Xa and thrombin.

The anticoagulant effect of dalteparin sodium is primarily due to inhibition of factor Xa; it has little effect on blood clotting time. Compared to heparin, it has a weak effect on platelet adhesion and, thus, has a smaller effect on primary hemostasis.

Indications

-acute deep vein thrombosis; – pulmonary embolism; – prevention of blood clotting in the extracorporeal circulation system during hemodialysis or hemofiltration in patients with acute or chronic renal failure; – prevention of thrombosis during surgical interventions– – unstable angina and myocardial infarction (without Q wave on the ECG).

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 excluded, Fragmin can only be prescribed for 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. No teratogenic or fetotoxic effects of the drug were detected in experimental studies. It has not been established whether dalteparin sodium is excreted in breast milk.

Contraindications

– bleeding (clinically significant, for example, from the blood on the background of gastric ulcer and duodenal ulcer, intracranial bleeding);– immune thrombocytopenia (heparin-induced) in a history of, or suspected it;– a recent injury or surgery on the Central nervous system, organs of vision, hearing; septic endocarditis;– pronounced violations of the blood coagulation system;– hypersensitivity to dalteparin sodium or other low molecular weight heparins and/or heparin.

Due to the high risk of bleeding, Fragmin in high doses (used, for example, for the treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina, and non-Q-wave myocardial infarction on the ECG) should not be prescribed to patients who are scheduled to undergo spinal or epidural anesthesia, or other procedures accompanied by lumbar puncture.

Side effects

From the hematopoietic and 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 the activity of hepatic transaminases.

Local reactions: hematoma at the injection site, soreness; rarely-skin necrosis.

Other: in some cases-anaphylactic reactions.

Interaction

When used concomitantly with drugs that affect hemostasis, such as NSAIDs, thrombolytics, other anticoagulants, as well as platelet function inhibitors, it is possible to increase the anticoagulant effect of Fragmin.

The combined use of Fragmin with antihistamines, cardiac glycosides, tetracyclines, ascorbic acid may weaken the effect of Fragmin.

Pharmaceutical interaction. Fragmin is compatible with isotonic sodium chloride solution (9 mg / ml), isotonic glucose solution (50 mg / ml).

How to take, course of administration and dosage

of Fragmin can not be administered intravenously!

For the treatment of acute deep vein thrombosis and pulmonary embolism, Fragmin is administered subcutaneously 1-2 times a day. In this case, you can immediately start therapy with indirect anticoagulants. This combination therapy should be continued until the prothrombin index reaches a therapeutic level (usually not earlier than 5 days). Treatment of patients on an outpatient basis can be carried out at the doses recommended for inpatient therapy. When administered 1 time / day, the dose is 200 IU/kg of body weight. A single dose should not exceed 18,000 IU. When administered 2 times / day, a single dose is 100 IU / kg. Monitoring of the anticoagulant activity of the drug may not be necessary, but it should be taken into account that this may be necessary in the treatment of certain groups of patients. The recommended maximum concentration of the drug in blood plasma should be 0.5-1 IU of anti-Xa/ml.

To prevent blood clotting in the extracorporeal circulatory system during hemodialysis or hemofiltration, Fragmin is administered intravenously.

Patients with chronic renal failure or patients without a history of bleeding risk usually require minor adjustments to the dosage regimen, so there is no need for frequent monitoring of anti-Xa levels. When the recommended doses are administered during hemodialysis, an anti-Xa activity level of 0.5-1 IU/ml is usually achieved. When the duration of hemodialysis or hemofiltration is not more than 4 hours, the drug is administered intravenously in a jet of 30-40 IU/kg of body weight, followed by intravenous drip administration at a rate of 10-15 IU / kg/h, or a single jet at a dose of 5000 IU. If the duration of hemodialysis or hemofiltration is longer than 4 hours, the drug is administered intravenously in a jet at a dose of 30-40 IU / kg, followed by 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 at a rate of 5-10 IU/kg, followed by intravenous drip administration at a rate of 4-5 IU/kg/h. When performing emergency hemodialysis, more careful monitoring of anti-Xa activity is required, since the therapeutic dose range for such patients is much narrower. The level of anti-Xa activity should be in the range of 0.2-0.4 IU / ml.

To prevent thrombosis during surgical interventions, Fragmin is administered subcutaneously. Monitoring of anticoagulant activity is usually not required. When using the drug at the recommended doses, the maximum plasma concentrations range from 0.1 to 0.4 IU of anti-Xa/ml.

When performing surgery in general surgical practice in patients at risk of developing thromboembolic complications, the drug is administered subcutaneously at a dose of 2500 IU 2 hours before surgery, then after surgery 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 (including patients with malignant tumors) Fragmin should be used for the entire period while the patient is on bed rest. At the same time, when starting therapy the day before the operation, Fragmin is administered subcutaneously at a dose of 5000 IU in the evening before the operation, then after the operation,5000 IU every evening. At the beginning of therapy on the day of the operation,2500 IU is administered subcutaneously 2 hours before the operation and 2500 IU in 8-12 hours, but not earlier than 4 hours after the operation is completed; then, from the next day,5000 IU is administered every morning.

When performing orthopedic operations (for example, hip replacement), Fragmin should be administered for up to 5 weeks after surgery, choosing one of the alternative dosage regimens. When starting therapy in the evening before surgery, a single dose for subcutaneous administration is 5000 IU, and the drug is administered in the evening before surgery and then every evening after surgery. At the beginning of therapy on the day of surgery, Fragmin is administered subcutaneously at a dose of 2500 IU 2 hours before surgery and 2500 IU in 8-12 hours, but not earlier than 4 hours after the end of the operation; then from the next day every morning 5000 IU.

At the beginning of therapy after surgery, the drug is administered subcutaneously at a dose of 2500 IU 4-8 hours after surgery; then from the next day to 5000 IU / day. In patients 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 of anti-Xa/ml (at the same time, it is advisable to conduct therapy with acetylsalicylic acid at a dose of 75 to 325 mg / day). Fragmin is administered subcutaneously at 120 IU / kg of 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 at a constant dose until revascularization (percutaneous interventions or coronary artery bypass grafting). The total duration of therapy should not exceed 45 days. The dose of Fragmin is selected based on the patient’s gender and body weight. Women with a body weight of less than 80 kg and men with a body weight of less than 70 kg should be administered subcutaneously 5000 IU every 12 hours. Women with a body weight of 80 kg or more and men with a body weight of 70 kg or more should be administered 7500 IU every 12 hours.

Overdose

Treatment: the anticoagulant effect of dalteparin sodium can be eliminated by the introduction of protamine sulfate (an emergency treatment).

1 mg of protamine partially inhibits 100 IU of dalteparin sodium (and although the induced increase in clotting time is completely neutralized,25 to 50% of the anti-Xa activity of dalteparin sodium is still preserved).

Special instructions

The drug should not be administered intravenously!

When performing neuroaxial anesthesia (epidural / spinal anesthesia) or performing spinal puncture in patients who are receiving anticoagulant therapy or who are planning to undergo anticoagulant therapy using low-molecular-weight heparins to prevent thromboembolic complications, there is an increased risk of developing spinal 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 administration 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 constantly monitored for the timely detection of pathological neurological symptoms. If neurological pathology appears, urgent spinal cord decompression is indicated.

There are no clinical data on the use of Fragmin for pulmonary embolism in patients with circulatory disorders, hypotension or shock.

If thrombocytopenia develops rapidly during Fragmin therapy or if thrombocytopenia with a platelet count of less than 10,000/µl, it is recommended to conduct an in vitro test for antiplatelet antibodies in the presence of heparin or low-molecular-weight heparins. If the results of such an in vitro test are positive or questionable, or no testing has been performed at all, Fragmin should be discontinued.

Monitoring of the anticoagulant activity of Fragmin is usually unnecessary. However, it should be performed when using Fragmin in patients with a lower body weight or with obesity, as well as with an increased risk of bleeding or thrombosis. Blood samples should be collected for analysis of Fragmin activity during the period when the maximum concentration of the drug in blood plasma is reached (3-4 hours after subcutaneous injection).

To determine the activity of anti-Xa, the method of choice is laboratory tests that use a chromogenic substrate. Tests for determining activated partial thromboplastin time (APTT) and thrombin time should not be used, as these tests are relatively insensitive to the activity of dalteparin sodium. Increasing the dose of Fragmin to increase APTT may lead to bleeding.

Units of action of Fragmin, unfractionated heparin and other low-molecular-weight heparins are not equivalent, so when replacing one drug with another, it is necessary to adjust the dosage regimen.

Pediatric use: There is only limited information on the safety and efficacy of Fragmin in pediatric practice. When using Fragmin in children, it is necessary to monitor the level of anti-Xa activity.

Form of production

Solution for intravenous and subcutaneous administration

Storage conditions

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

Shelf

life is 3 years.

Active ingredient

Dalteparin sodium

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion

Purpose

For adults as directed by your doctor

Indications

Prevention of thrombosis, Prevention of heart attacks and strokes

Weight

Weight: 89 g.