Instructions for use FRAXIPARINE

Instructions for use FRAXIPARINE

The drug is administered subcutaneously (except for use during hemodialysis). This dosage form is intended for adults

. The drug is not administered intramuscularly. 1 ml of Fraxiparine is equivalent to approximately 9500 IU of the anti-Xa factor activity of nadroparin calcium.

Prevention of thromboembolism in surgery

These recommendations apply to surgical procedures performed under general anesthesia.

The frequency of use of the drug is 1 injection/day.

The dose is determined by the degree of risk of thromboembolism in a specific clinical situation and depends on the patient’s body weight and the type of operation.

With moderate thrombogenic risk

, as well as in patients
without an increased risk of thromboembolism,
effective prevention of thromboembolic disease is achieved by administering the drug at a dose of 2850 IU/day (0.3 ml). The initial injection is administered 2 hours before surgery, then nadroparin is administered 1 time/day. Treatment is continued for at least 7 days and during the period of risk of thrombosis until the patient is transferred to an outpatient regimen.

With increased thrombogenic risk (hip and knee surgeries)

the dose of Fraxiparine depends on the patient’s body weight. The drug is administered at a dose of 38 IU/kg before surgery, i.e. 12 hours before the procedure, then after the operation, i.e. starting 12 hours after the end of the procedure, then 1 time per day until 3 days after the operation inclusive. Then, starting from the 4th day after surgery, 1 time/day at a dose of 57 IU/kg during the period of risk of thrombosis until the patient is transferred to an outpatient regimen. Minimum duration is 10 days.

Doses of Fraxiparine depending on body weight are presented in the table.

When prescribing the drug to non-surgical patients with a high risk of thrombus formation, usually located in intensive care units (with respiratory failure and/or respiratory tract infections and/or heart failure), the dose of nadroparin depends on the patient’s body weight and is indicated in the table below. The drug is administered 1 time/day. Nadroparin is used throughout the entire period of risk of thrombosis.

In cases where the risk of thromboembolism associated with the type of operation (especially oncological operations) and/or with the individual characteristics of the patient (especially with a history of thromboembolic disease) appears to be increased, a dose of 2850 IU (0.3 ml) may be sufficient, but the dose should be adjusted individually.

Duration of treatment.

Treatment with Fraxiparine in combination with the technique of traditional elastic compression of the lower extremities should be continued until the patient’s motor activity is completely restored. In general surgery, the duration of use of Fraxiparine is up to 10 days in the absence of a particular risk of venous thromboembolism associated with the individual characteristics of the patient. If the risk of thromboembolic complications is present after the recommended period of treatment, it is necessary to continue preventive treatment, primarily with oral anticoagulants.

However, the clinical effectiveness of long-term treatment with low molecular weight heparins or vitamin antagonists has not yet been determined.

Prevention of blood coagulation in the extracorporeal circulation system during hemodialysis

Fraxiparine should be administered intravascularly into the arterial shunt of the dialysis loop.

In patients receiving repeated hemodialysis sessions

,
prevention of coagulation in the extracorporeal purification loop
is achieved by administering an initial dose of 65 IU/kg into the arterial line of the dialysis loop at the beginning of the session.

This dose, administered as a single intravascular bolus injection, is only suitable for dialysis sessions lasting no more than 4 hours. Subsequently, the dose can be adjusted depending on the individual response of the patient, which varies greatly.

Doses of the drug depending on body weight are presented in the table.

If necessary, the dose can be changed in accordance with the specific clinical situation and the technical conditions of dialysis. In patients with an increased risk of bleeding, dialysis sessions can be performed by reducing the dose of the drug by 2 times.

Treatment of deep vein thrombosis (DVT)

Any suspicion of deep vein thrombosis should be immediately confirmed by the results of appropriate tests.

The frequency of use of the drug is 2 injections/day with an interval of 12 hours.

A single dose of Fraxiparine is 85 IU/kg.

The dose of Fraxiparine depending on body weight in patients weighing more than 100 kg or less than 40 kg has not been determined. In patients weighing more than 100 kg, the effectiveness of LMWH may be reduced. On the other hand, in patients weighing less than 40 kg, the risk of bleeding may be increased. In such cases, special clinical monitoring is required.

Recommended doses are presented in the table.

Duration of treatment.

Treatment with LMWH should be promptly replaced with oral anticoagulants unless the latter are contraindicated. The duration of treatment with LMWH should not exceed 10 days, including the period of transition to vitamin K antagonists, except in cases where difficulties arise in stabilizing INR. Therefore, treatment with oral anticoagulants should be started as early as possible.

Treatment of unstable angina/myocardial infarction without pathological Q wave on ECG

Fraxiparine is administered subcutaneously at 86 IU/kg 2 times a day (with an interval of 12 hours) in combination with acetylsalicylic acid (recommended doses for oral administration are 75-325 mg after an introductory minimum dose of 160 mg).

An initial dose of 86 IU/kg is administered intravenously as a bolus, followed by the same dose subcutaneously. The recommended duration of treatment is 6 days until the patient's condition stabilizes.

Doses of Fraxiparine depending on body weight are presented in the table.

To prevent blood clots

in
patients with moderate renal failure (creatinine clearance ≥ 30 ml/min and < 60 ml/min),
no dose reduction is required.
In patients with severe renal failure (creatinine clearance <30 ml/min),
the dose should be reduced by 25%.

In the treatment of thromboembolism, unstable angina and myocardial infarction without a pathological Q wave

in
patients with mild to moderate renal impairment,
the dose should be reduced by 25%.
Nadroparin is contraindicated in patients with severe renal failure
.

Rules for administering the drug

It is preferable to inject with the patient lying down, into the subcutaneous tissue of the anterolateral or posterolateral abdominal girdle, alternately from the right and left sides. Injection into the thigh is allowed.

To avoid loss of the drug when using syringes, do not remove air bubbles before injection.

The needle should be inserted perpendicularly, and not at an angle, into the pinched fold of skin, held between the thumb and index finger until the end of the solution. Do not rub the injection site after injection. Graduated syringes are designed to select the dose depending on the patient’s body weight.

After administering the drug, you should use the syringe needle protection system:

• holding the used syringe in one hand by the protective housing, pull the holder with the other hand to release the latch and slide the cover to protect the needle until it clicks. The used needle is completely protected.

Fraxiparine overdose, symptoms and treatment

The main clinical sign of overdose with subcutaneous or intravenous administration is bleeding. In this case, it is necessary to determine the number of platelets and other indicators of blood clotting. Patients with minor bleeding very rarely require specific treatment measures. As a rule, it will be sufficient to reduce the dose or delay the administration of the next dose of nadroparin. In severe cases, the use of protamine sulfate is indicated. The drug largely neutralizes the anticoagulant effect of nadroparin, but some anti-Xa activity remains. When determining the amount of protamine sulfate required for administration, the following calculation is used: 0.6 ml of protamine sulfate neutralizes approximately 950 IU of the anti-factor Xa activity of nadroparin. In this case, it is necessary to take into account the time that has passed since the administration of heparin, since a reduction in the dose of the antidote may be necessary.

Interaction

The development of hyperkalemia may depend on the simultaneous presence of several risk factors. Drugs that cause hyperkalemia: potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine and tacrolimus, trimethoprim. The risk of developing hyperkalemia increases when the above-mentioned drugs are combined with Fraxiparine.

The combined use of Fraxiparine with drugs that affect hemostasis, such as acetylsalicylic acid, NSAIDs, vitamin K antagonists, fibrinolytics and dextran, leads to a mutual enhancement of the effect.

In addition, it should be taken into account that platelet aggregation inhibitors (except for acetylsalicylic acid as an analgesic and antipyretic drug, i.e. in doses over 500 mg): NSAIDs, abciximab, acetylsalicylic acid in antiplatelet doses (50–300 mg) at Cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Side effects

The most common side effect is the formation of a subcutaneous hematoma at the injection site. In some cases, the appearance of dense nodules is observed, which does not indicate heparin encapsulation, which disappear after a few days.

Large doses of Fraxiparine can provoke bleeding of various localizations and mild thrombocytopenia (type I), which usually disappears with further therapy. A temporary moderate increase in the level of liver enzymes (ALT, AST) is possible.

Skin necrosis and allergic reactions occur rarely. Several cases of anaphylactic reactions and immune thrombocytopenia (type II) associated with arterial and/or venous thrombosis or thromboembolism have been reported.

Use during pregnancy and breastfeeding

Experiments on animals have not shown the teratogenic effect of nadroparin calcium; however, in the first trimester of pregnancy it is preferable to avoid prescribing Fraxiparine, both in a prophylactic dose and in the form of a course of treatment.

During the II and III trimesters of pregnancy, Fraxiparine can be used only in accordance with the doctor's recommendations for the prevention of venous thrombosis (when comparing the benefits to the mother with the risk to the fetus). Course treatment is not used during this period.

If the use of epidural anesthesia is considered, it is recommended, as far as possible, to withhold prophylactic heparin treatment at least 12 hours before anesthesia.

Since absorption of the drug in the gastrointestinal tract in newborns is, in principle, unlikely, treatment with Fraxiparine in nursing mothers is not contraindicated.

Pharmacokinetics

Pharmacokinetic properties are determined based on changes in plasma anti-Xa factor activity. After subcutaneous administration, almost 100% of the drug is rapidly absorbed. Cmax in plasma is achieved between 3 and 4 hours if nadroparin calcium is used in a regimen of 2 injections per day. When using nadroparin calcium in a regimen of 1 injection per day, Cmax is achieved between 4 and 6 hours after administration. Metabolism occurs mainly in the liver (desulfation, depolymerization). After subcutaneous administration, T1/2 of anti-Xa factor activity of low molecular weight heparins is higher than in the case of unfractionated heparins and is 3–4 hours.

As for anti-factor IIa activity, when low molecular weight heparins are used, it disappears from the plasma faster than anti-factor Xa activity.

Excretion occurs primarily by the kidneys, in its original or slightly modified form.

At-risk groups

In elderly patients, since renal function is physiologically reduced, elimination slows down. This does not affect the dose and regimen of administration of the drug for prophylactic purposes as long as the renal function of these patients remains within acceptable limits, i.e. slightly damaged.

Before starting treatment with LMWH, renal function should be systematically assessed in elderly patients over 75 years of age using the Cockroft formula.

Mild to moderate renal failure (Cl >30 ml/min): in some cases it may be useful to monitor the level of anti-Xa factor activity in the blood to exclude the possibility of overdose during a course of drug use.

Hemodialysis: Low molecular weight heparin is injected into the arterial line of the dialysis loop in sufficiently high doses to prevent clotting in the loop. In principle, pharmacokinetic parameters do not change, except in the case of overdose, when the passage of the drug into the systemic circulation may lead to an increase in anti-Xa factor activity associated with end-phase renal failure.

Pharmacodynamics

Nadroparin calcium is characterized by higher anti-Xa factor compared to anti-IIa factor or antithrombotic activity. The ratio between the two activities for nadroparin is in the range of 2.5–4.

In prophylactic doses, nadroparin does not cause a significant decrease in activated partial thrombin time (aPTT).

During a course of treatment during the period of maximum activity, the aPTT can be extended to a value 1.4 times higher than the standard one. This prolongation reflects the residual antithrombotic effect of nadroparin calcium.