Fragmin, 5000 anti-xa me/0.2 ml 0.2 ml syringes 10 pcs.

Fragmin is a direct-acting anticoagulant.

It is a low molecular weight heparin isolated by controlled depolymerization (with nitric acid) of sodium heparin from pig small intestinal mucosa and further purified by ion-exchange chromatography. It consists of sulfated polysaccharide chains having an average molecular weight of 5,000 dalton, with 90% having a molecular weight of 2,000 to 9,000 dalton; the degree of sulfation is 2 to 2.5 per disaccharide.

Binds plasma antithrombin, whereby it inhibits factor Xa and thrombin activity.

The anticoagulation effect of dalteparin sodium is primarily due to inhibition of factor Xa; it has little effect on the clotting time. Compared with heparin, it has little effect on platelet adhesion and thus has less effect on primary hemostasis.

Indications

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

Active ingredient

Composition

0.2 ml of solution for intravenous and p/n injection contains:

dalteparin sodium 5000 IU anti-Xa.

Auxiliary Ingredients:

Sodium chloride,

Sodium hydroxide or hydrochloric acid q.s.,

water d/i.

How to take, the dosage

Fragmin should not be administered by injection!

Fragmin is administered p/cm 1-2 times/day for the treatment of acute deep vein thrombosis and pulmonary embolism. Therapy with indirect anticoagulants may be started immediately. Such combination therapy should be continued until prothrombin index reaches therapeutic level (usually not earlier than in 5 days). Treatment of patients in outpatient settings can be performed in doses recommended for inpatient therapy. When administered once daily, the dose is 200 IU/kg body weight. A single dose should not exceed 18,000 IU. When administered 2 times/day the single dose is 100 IU/kg. Monitoring of anticoagulative activity of the drug may be omitted, but it should be taken into account that this may be required for the treatment of certain groups of patients. The recommended maximum plasma concentration of the drug should be 0.5-1 IU anti-Xa/ml.

Fragmin is administered intravenously to prevent blood clotting in the extracorporeal circulation system during hemodialysis or hemofiltration.

Patients with chronic renal insufficiency or patients without a history of risk of bleeding usually require minor dosing adjustments, so there is no need for frequent monitoring of anti-Xa levels. When recommended doses are administered during hemodialysis, anti-Xa activity levels of 0.5-1 IU/ml are usually achieved. If duration of hemodialysis or hemofiltration is less than 4 hours, the drug is administered by IV drip of 30-40 IU/kg body weight followed by IV drip of 10-15 IU/kg/h, or a single drip of 5000 IU. If the duration of hemodialysis or hemofiltration is longer than 4 hours, the drug is administered by intravenous jetting 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 at high risk of bleeding, the drug is administered by intravenous jetting at a rate of 5-10 IU/kg followed by intravenous drip infusion at a rate of 4-5 IU/kg/h. When performing emergency hemodialysis, more careful monitoring of anti-Xa activity levels is required because the range of therapeutic doses for these patients is much narrower. The anti-Xa activity level should be in the range of 0.2-0.4 IU/ml.

Fragmin is administered p/k to prevent thrombosis during surgical interventions. Monitoring of anticoagulation activity is usually not required. When the drug is used in the recommended doses, the maximum plasma concentrations are 0.1 to 0.4 IU anti-Xa/ml.

When performing surgery in general surgical practice in patients at risk for thromboembolic complications, the drug is administered p/k in a dose of 2500 IU 2 hours before surgery, then 2500 IU/day (every morning) after surgery for as long as the patient is on bed rest (usually 5-7 days). In patients with additional risk factors for thromboembolic complications (including patients with malignant tumors), Fragmin should be used for the entire period when the patient is on bed rest. When therapy is started the day before surgery, Fragmin is administered p/k in a dose of 5000 IU the evening before surgery and 5000 IU every evening after surgery. When therapy is initiated on the day of surgery, Fragmin is administered p/k 2500 IU 2 hours before surgery and 2500 IU 8-12 hours later, but not earlier than 4 hours after the end of surgery; then from the next day each morning at 5000 IU.

In orthopedic surgery (e.g., hip arthroplasty), Fragmin should be administered for up to 5 weeks after surgery, choosing one of the alternative dosing regimens. When starting therapy the evening before surgery, the single dose for p/u administration is 5000 IU and the drug is administered the evening before surgery and then every evening after surgery. When therapy begins on the day of surgery Fragmin is administered by mouth in a dose of 2500 IU 2 hours before surgery and 2500 IU 8-12 hours later, but not earlier than 4 hours after the end of surgery; then from the next day on each morning for 5000 IU.

When therapy is started after surgery the drug is administered by injection in a dose of 2500 IU 4-8 hours after surgery; then from the next day onwards in a dose of 5000 IU/day.
In unstable angina or myocardial infarction without pathological Q-wave, the recommended maximum drug concentration in plasma should be 0.5-1 IU anti-Xa/ml (therapy with acetylsalicylic acid at a dose of 75 to 325 mg/day is advisable simultaneously). Fragmin is administered p/k at 120 IU/kg body weight every 12 hours. The maximum dose should not exceed 10,000 IU/12 h. Therapy should be continued until the clinical condition is 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 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 adjusted to the gender and body weight of the patient. Women with body weight less than 80 kg and men with body weight less than 70 kg should administer the drug by injection and by injection of 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 receive 7,500 IU every 12 hours.

Interaction

In concomitant use with drugs that affect hemostasis, such as NSAIDs, thrombolytics, other anticoagulants, and platelet function inhibitors, the anticoagulant effect of Fragmin may be increased.

In co-administration of Fragmin with 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).

Special Instructions

The drug should not be administered by injection!

When performing neuroaxial anesthesia (epidural/spinal anesthesia) or when performing a spinal tap in patients who receive anticoagulant therapy or in whom anticoagulant therapy with low molecular weight heparin is planned for the prevention of thromboembolic complications, there is an increased risk of 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 inhibitors, other anticoagulants). The risk also increases with trauma and repeated epidural or lumbar punctures. Such patients should be constantly monitored for the timely detection of pathological neurological symptoms. When neurological pathology appears, urgent spinal cord decompression is indicated.

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

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

Monitoring of the anticoagulation activity of Fragmin is generally not necessary. However, it should be performed when Fragmin is used in patients who are underweight or obese, or who are at increased risk of bleeding or thrombosis. Blood sampling for the analysis of Fragmin activity should be performed during the period when the maximum concentration of the drug in plasma is reached (3-4 hours after p/u injection).

To determine anti-Xa activity, laboratory tests using a chromogenic substrate are the method of choice. Activated partial thromboplastin time (APT) and thrombin time tests should not be used because these tests are relatively insensitive to dalteparin sodium activity. Increasing the dose of Fragmin to increase the ACTV may result in bleeding.

The units of action of Fragmin, unfractionated heparin and other low molecular weight heparins are not equivalent, so dosing adjustments must be made when substituting one drug for another.

Pediatric use: There is only limited data 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.

Contraindications

– bleeding (clinically significant, such as from the gastrointestinal tract against the background of gastric and duodenal ulcer disease, intracranial bleeding);
– immune thrombocytopenia (caused by heparin) in the anamnesis or suspected of it;
– Recent trauma or surgical interventions on CNS, organs of vision, hearing;
– Septic endocarditis;
– Significant coagulation disorders;
– Hypersensitivity to dalteparin sodium or other low molecular weight heparin and/or to heparin.

Because of the high risk of bleeding, Fragmin in high doses (e.g. for treatment of acute deep vein thrombosis, pulmonary embolism, unstable angina and myocardial infarction without Q-wave on ECG) should not be administered to patients who are going to have spinal or epidural anesthesia or other procedures accompanied by lumbar puncture.

Side effects

Blood and coagulation system: rare – reversible non-immune thrombocytopenia, bleeding (when used in high doses); in individual cases – immune thrombocytopenia (with or without thrombotic complications); development of spinal or epidural hematoma.

Digestive system disorders: in some cases – transient increase in liver transaminase activity.

Local reactions: hematoma at the injection site, pain; rarely – skin necrosis.

Others: in some cases – anaphylactic reactions.

Overdose

Treatment: The anticoagulant effect of sodium dalteparin can be reversed by administration of protamine sulfate (an emergency treatment).

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

Pregnancy use

An adverse effect on the course of pregnancy and on the health of the fetus and the newborn has not been detected during use in pregnant women. When Fragmin is used during pregnancy, the risk of adverse effects on the fetus is evaluated as low. However, because the possibility of adverse effects cannot be completely excluded, Fragmin may be prescribed only for strict indications when the expected benefits to the mother exceed the potential risks.

If it is necessary to use Fragmin in pregnancy, the anticoagulation activity of the drug should be monitored.
No teratogenic or fetotoxic effects of the drug were found in experimental studies.
Whether dalteparin sodium is excreted with the breast milk has not been determined.