Fragmin, 2500 anti-xa me/0.2 ml 0.2 ml syringes 10 pcs.

Fragmin has anticoagulant effect.

The anticoagulant effect is primarily due to inhibition of factor Xa, it has little effect on the clotting time.

Fragmin has little effect on platelet adhesion, so has little effect on primary hemostasis.

Pharmacokinetics

The bioavailability after subcutaneous administration is approximately 90%; pharmacokinetic parameters are independent of dose.

The T1/2 after intravenous administration of the drug is 2 hours; after subcutaneous administration, it is 3-5 hours.

In patients with uremia the T1/2 of the drug is prolonged. It is excreted mainly by the kidneys.

Indications

Active ingredient

Composition

0.2 ml of solution for injection contains:

the active ingredient:

dalteparin sodium 2500 IU,

excipients:

water for injection;

sodium chloride;

sodium hydroxide or hydrochloric acid q.s.

How to take, the dosage

The dosing regimen of Fragmin is set individually. Fragmin is administered subcutaneously, intravenously (by trickle or drip).

In the treatment of acute deep vein thrombosis and pulmonary embolism, subcutaneously, 200 IU/kg once daily or 100 IU/kg twice daily. Monitoring of antiplatelet activity may be omitted, but it should be borne in mind that it may be necessary when treating special groups of patients. The recommended plasma Cmax should be 0.5-1 IU of anti-Xa/ml. In this case, therapy with indirect anticoagulants (vitamin K antagonists) can be started immediately. Such combination therapy should be continued until prothrombin index reaches the therapeutic level (usually not earlier than after 5 days). Treatment of patients on an outpatient basis can be carried out in the same doses as recommended for inpatient treatment.

For prevention of blood clotting in the extracorporeal circulation system during hemodialysis or hemofiltration – intravenously, choosing a dosing regimen from those listed below.

Patients with chronic renal insufficiency or patients without risk of bleeding usually require minor dose adjustments, so most patients do not need frequent monitoring of anti-Xa levels. When recommended doses are administered during hemodialysis, plasma levels of 0.5-1 ME anti-Xa/ml are usually achieved.

If the duration of hemodialysis or hemofiltration is less than 4 hours, a single intravenous stream at a dose of 5000 ME or the same regimen as for procedures longer than 4 hours may be used.

If the duration of hemodialysis or hemofiltration is longer than 4 hours, the regimen is an intravenous drip of 30-40 ME/kg followed by an intravenous drip of 10-15 ME/kg/h.

Patients with acute renal failure or patients at high risk of bleeding – intravenous IU 5-10 IU/kg followed by intravenous drip infusion of 4-5 IU/kg/h. In patients undergoing hemodialysis for acute renal failure, the drug has a narrower therapeutic index than in patients on chronic hemodialysis, due to which they need adequate monitoring of anti-Xa levels. The recommended maximum plasma level should be 0.2-0.4 ME anti-Cha/ml.

For the prevention of thrombosis in surgical procedures, subcutaneously. Monitoring of antithrombotic activity is usually not required. When the drug is used in the recommended doses, the Cmax in plasma is 0.1 to 0.4 ME anti-Xa/ml.

In general surgical practice: patients at risk for thromboembolic complications, subcutaneously 2500 ME 2 hours before surgery, then after surgery, subcutaneously 2500 ME/day (every morning) for as long as the patient is on bed rest (usually 5-7 days); patients with additional risk factors for thromboembolic complications (eg, patients with malignancies) should use Fragmin for as long as the patient is on bed rest (usually 5-7 days or more).

1. When starting therapy the day before surgery: 5000 ME subcutaneously the evening before surgery, then 5000 ME subcutaneously each evening after surgery.

2 When therapy starts on the day of surgery: 2500 ME subcutaneously 2 hours before surgery and 2500 ME subcutaneously 8-12 hours later, but not earlier than 4 hours after the end of surgery. Then from the next day onwards 5,000 ME subcutaneously each morning.

In orthopedic surgeries (such as hip arthroplasty), Fragmin should be administered up to 5 weeks after surgery by choosing one of the dosing regimens listed below.

1. When starting therapy the evening before surgery: 5000 ME subcutaneously the evening before surgery, then 5000 ME subcutaneously each evening after surgery.

2. When starting therapy on the day of surgery: 2500 ME subcutaneously 2 hours before surgery and 2500 ME subcutaneously 8-12 hours later, but not earlier than 4 hours after the end of surgery. Then, starting the next day, 5,000 ME subcutaneously every morning.

In unstable angina and myocardial infarction (without a Q-tooth on the ECG), monitoring of anticoagulation activity is usually not required, but it should be kept in mind that it may be necessary when treating special patient groups. The recommended plasma Cmax should be 0.5-1 ME of anti-Xa/ml (concomitant therapy with acetylsalicylic acid at a dose of 75 to 325 mg/day is advisable). Fragmin is administered subcutaneously at 120 IU/kg every 12 hours. The maximum dose should not exceed 10000 ME every 12 hours. The therapy should be continued until the patient’s clinical condition becomes stable (usually at least 6 days), or longer (at the doctor’s discretion). Then it is recommended to switch to long-term therapy with Fragmin in 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 for patient’s sex and body weight:

Women weighing less than 80 kg and men weighing less than 70 kg should receive 5000 ME subcutaneously every 12 hours;

Women weighing 80 kg or more and men weighing 70 kg or more should receive 7500 ME subcutaneously every 12 hours.

Interaction

In concomitant use with drugs that affect hemostasis, such as: thrombolytics, other anticoagulants, NSAIDs, as well as platelet function inhibitors, the anticoagulant effect of Fragmin may be enhanced; concomitant use with antihistamines, cardiac glycosides, tetracyclines, ascorbic acid weakens the effect of dalteparin.

Compatibility with solutions for intravenous administration. Fragmin is compatible with isotonic sodium chloride solution (9 mg/ml) and isotonic dextrose solution (50 mg/ml).

Special Instructions

Caution should be exercised when prescribing Fragmin to patients at increased risk of bleeding; this group includes patients with thrombocytopenia, impaired platelet function, severe hepatic or renal impairment, uncontrolled arterial hypertension, hypertensive or diabetic retinopathy.

The data on the efficacy and safety of Fragmin in pediatrics are limited. Anti-Xa levels should be monitored if such use is necessary.

. When epidural or spinal anesthesia or spinal tap is performed in patients who receive anticoagulant therapy or in whom anticoagulant therapy with low molecular weight heparins or heparinoids for prevention of thromboembolic complications is planned, there is an increased risk of epidural or spinal 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, such as NSAIDs, platelet inhibitors and other anticoagulants. The risk also increases with trauma and with repeated epidural or lumbar punctures. In such cases, patients should be monitored for the timely detection of abnormal neurological symptoms. If neurological pathology is detected, emergency intervention (spinal cord decompression) is indicated.

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

Particular attention should be given to patients in whom rapid development of thrombocytopenia or thrombocytopenia with platelet counts less than 100,000/μL is noted during treatment with Fragmin. In such cases, an in vitro test for antiplatelet antibodies in the presence of heparin or low molecular weight heparin is recommended. If the result of this test is positive or questionable, or no test has been performed at all, treatment with Fragmin should be discontinued.

Monitoring of the antiplatelet activity of Fragmin is not usually necessary, but may be necessary when treating special groups of patients: children, patients with body weight below normal or with obesity, pregnant women, and patients at increased risk of bleeding or recurrent thrombosis. Blood sampling for the analysis of Fragmin activity should be performed during the period when the maximum concentration of the drug in the blood plasma is reached (3-4 hours after subcutaneous 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 here because these tests are relatively insensitive to dalteparin sodium activity. Increasing the dose of Fragmin in order 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 dose adjustments must be made when replacing one drug with another. If multi-dose vials are used, the unused solution must be destroyed 14 days after the first needle puncture.

Contraindications

Side effects

Adverse events occur in an average of 1% of patients.

Hematopoietic and coagulation system disorders: bleeding, hematoma at the injection site, reversible non-immune thrombocytopenia, bleeding; in individual cases – immune thrombocytopenia (with or without thrombotic complications); development of spinal or epidural hematoma, peritoneal and intracranial bleeding, some of them with fatal outcome.

Digestive system disorders: transient increase of liver transaminases activity (AST, ALT).

Local reactions: soreness at the injection site; in some cases – skin necrosis.

Others: allergic reactions; in some cases – anaphylactic reactions.

Overdose

Symptoms: bleeding.

Treatment: administration of protamine (1 mg inhibits 100 IU of dalteparin).

Pregnancy use

The use of Fragmin in pregnancy is possible if the expected effect of therapy exceeds the potential risk to the fetus.

It has not been established whether Fragmin is excreted into the mother’s milk.