Fraxiparin® [Nadroparin calcium]

Pharmacological properties

nadroparin - a low molecular weight heparin obtained from standard heparin by depolymerization, is a glycosaminoglycan with an average molecular weight of 4300 da. nadroparin exhibits a high level of plasma protein binding to antithrombin iii. this affinity causes accelerated inhibition of factor xa and is the main reason for the high antithrombotic activity of nadroparin. another mechanism of the antithrombotic activity of nadroparin is the stimulation of a tissue conduction factor inhibitor, activation of fibrinolysis by direct release of a tissue plasminogen activator from epithelial cells, modification of hemorheological parameters (decrease in blood viscosity and platelet fluidity and membrane granulocytes). nadroparin has a high level of correlation between anti-ha and anti-iia activity. It has an immediate and prolonged antithrombotic effect. Compared with non-fractional heparin, nadroparin has less effective effect on platelet function and aggregation and very little on primary hemostasis.

Pharmacokinetics is determined by measuring the anti-Xa factor activity of blood plasma.

Bioavailability. After SC administration C_max in blood plasma is reached after 3-5 hours. Bioavailability is almost complete (about 88%).

After iv administration, the maximum anti-Xa activity is reached after 10 min with T_½ 2 hours

After SC administration of T_½ is about 3.5 hours. However, anti-Xa activity persists for at least 18 hours after injection of nadroparin at a dose of 1900 anti-XA ME.

Special patient groups

Elderly patients. Since the physiological function of the kidneys decreases with age, the elimination process slows down. The possibility of developing renal failure in this group of patients should be taken into account and the dose of the drug should be adjusted accordingly.

Renal failure. Clinical studies on the pharmacokinetic parameters of nadroparin when given iv in patients with various degrees of renal failure indicate a correlation between nadroparin clearance and creatinine clearance. Average AUC and T_½ with moderate renal failure (creatinine clearance 36–43 ml / min) increased by 52 and 39%, respectively, the average plasma clearance decreased to 63% of the norm. Wide individual variability was noted. In patients with severe renal failure (creatinine clearance 10–20 ml / min) AUC and T_½ increased to 95 and 112%, respectively, compared with those of healthy volunteers. Plasma clearance in severe renal failure was reduced to 50% compared with patients with normal renal function. In patients with severe renal failure (creatinine clearance 3–6 ml / min) undergoing hemodialysis, AUC and T_½ increased by 62 and 65%, respectively, compared with healthy volunteers. Plasma clearance in patients with severe renal failure undergoing hemodialysis decreased to 67% in patients with normal renal function.

Indications

Prevention of thromboembolic complications resulting from general or orthopedic surgery in patients at high risk of thromboembolic complications. treatment of deep vein thrombosis. prevention of blood coagulation during hemodialysis. treatment of unstable angina pectoris and myocardial infarction without a pathological q wave per ECG in combination with acetylsalicylic acid.

Application

Particular attention should be paid to specific recommendations on the dosage of each individual drug in the group of low molecular weight heparins, since different units of measurement (IU or mg) are used to determine the doses of these drugs. therefore, nadroparin cannot be used as a substitute for another low molecular weight heparin during the course of treatment.special care and adherence to specific instructions for use for each form of nadroparin release are necessary.

Fraxiparin is not intended for intramuscular administration. Platelet count control is needed in the treatment of nadroparin.

Special recommendations should be followed regarding the time of dosing of nadroparin during spinal / epidural anesthesia or lumbar puncture (see SPECIAL INSTRUCTIONS).

The technique of s / c introduction. It is recommended to administer a subcutaneous injection of Fraxiparin in a patient position lying in the anterolateral region of the abdominal wall, alternately to the right and left. To avoid drug loss, do not remove air bubbles from a pre-filled syringe before injection. The needle is inserted perpendicular to the surface of the body (and not at an angle) into the skin fold taken with the thumb and forefinger (hold during the introduction of the solution).

Prevention of Thromboembolic Complications

General surgery. The recommended dose of Fraxiparin is 0.3 ml (2850 IU of anti-Xa factor activity), administered s.c. 2 hours before surgery. Further doses are administered once a day on subsequent days.

Orthopedic surgery. The drug is administered sc in doses depending on the patient’s body weight (table). Doses are selected based on 38 IU of anti-Xa factor activity per 1 kg of body weight and based on 57 IU of anti-Xa factor activity per 1 kg of patient body weight from the 4th postoperative day. The initial dose is administered 12 hours before surgery, the second - 12 hours after surgery. Subsequent doses are administered once a day during the entire period of risk and until the patient is transferred to outpatient treatment.

The maximum duration of treatment for general surgery is 10 days, except in cases of increased risk of thromboembolic complications.

If the risk of thromboembolic complications is still high after completing the recommended duration of treatment, prophylactic treatment should be continued, in particular with oral anticoagulants. However, it should be borne in mind that the clinical benefits of long-term treatment with low molecular weight heparin or a vitamin K antagonist have not yet been studied.

Treatment of deep vein thrombosis. Any suspicion of deep vein thrombosis should be confirmed by appropriate analyzes.

It is recommended to use Fraxiparin s / c 2 times a day (every 12 hours). The dose is calculated according to the patient’s body weight, as shown in the table, based on 0.01 ml (85 anti-Xa factor activity) per 1 kg of patient’s body weight.

Dosage for patients whose body weight is 100 kg or 40 kg has not been investigated. In patients with a body weight of 100 kg, the effectiveness of treatment with low molecular weight heparin can be reduced, in patients with a body weight of 40 kg, the risk of bleeding increases. Special clinical observation is required.

Treatment with Fraxiparin should be replaced as soon as possible with oral anticoagulants, if there are no contraindications. The duration of treatment with Fraxiparin should not exceed 10 days, including the stabilization period when switching to vitamin K antagonists, unless it is difficult to stabilize. Treatment with oral anticoagulants should be started as soon as possible.

Prevention of blood coagulation during hemodialysis. The dose of nadroparin is selected individually, taking into account also the technical conditions for hemodialysis.

As a rule, nadroparin is used as a one-time bolus intravascular injection of an extracorporeal circuit into the arterial shunt at the beginning of each hemodialysis session. The initial dose is 65 IU of anti-Xa factor activity per 1 kg of patient body weight. In patients without an increased risk of bleeding, the initial dose is calculated according to body weight and is sufficient for a hemodialysis session lasting up to 4 hours (table below).

With an increased risk of bleeding, the dose should be reduced by half.

Treatment of unstable angina pectoris and myocardial infarction without pathological Q wave on an ECG. The use of nadroparin s / c 2 times a day (every 12 hours) in combination with acetylsalicylic acid (recommended dose: 75–325 mg orally after a minimum initial loading dose of 160 mg) is recommended. The usual duration of treatment is 6 days before clinical stabilization.

The initial dose is administered as an iv bolus injection, subsequent doses are given s.c. The dose is calculated based on the patient’s body weight based on 86 IU of anti-Xa factor activity per 1 kg of the patient’s body weight (table below).