Zibor® [Bemiparin sodium]

Pharmacological properties

bemiparin sodium is a low molecular weight heparin obtained as a result of depolymerization of sodium heparin isolated from pig intestinal mucosa. the average molecular weight (mm) of bemiparin is about 3,600 da. the percentage of molecular chains with mm 2000 is 35%. the percentage of molecular chains with mm 2000–6000 yes varies in the range of 50–75%. the proportion of molecular chains with mm 6000 yes is 15%. the anti-ha factor activity of bemiparin is 80–120 Iu antifactor-ha per 1 mg of dry matter, and the anti-iiia factor activity is 5–20 me of antifactor iia per 1 mg of dry matter. the ratio of anti-ha-factor / anti-ii-factor activity is about 8. in animal experiments, bemiparin sodium showed anticoagulation effect and moderate hemorrhagic effect. the use of bemiparin sodium in humans confirms its anticoagulant activity and, subject to the recommended dose, does not significantly increase the coagulation time.

Pharmacokinetics The pharmacokinetic properties of bemiparin were studied by measuring the anti-Xa factor activity in blood plasma using the amidolytic method using the І International WHO standard for low molecular weight heparin (National Institute for Biological Standards and Control - National Institute of Biological Standards and Control). The processes of absorption and excretion correspond to linear kinetics of the first order.

Suction. Bemiparin sodium is rapidly absorbed after sc injection with a bioavailability of 96%. The maximum anti-Xa factor activity in blood plasma after administration of the drug in prophylactic doses (2500 and 3500 IU) is achieved 2-3 hours after sc administration of bemiparin sodium with a maximum activity of about 0.34 ± 0.08 and 0.45 ± 0.07 IU of anti-Xa factor / ml, respectively. Anti-IIa factor activity does not occur when prescribing these doses. The maximum anti-Xa factor activity in blood plasma when administered in doses of 5000; 7500; 10,000 and 12,500 IU are achieved 3-4 hours after s / c injection of bemiparin with a maximum activity of about 0.54 ± 0.06; 1.22 ± 0.27; 1.42 ± 0.19 and 2.03 ± 0.25 IU of anti-Xa factor / ml, respectively. Anti-IIa factor activity of about 0.01 IU / ml was detected upon administration at doses of 7500; 10,000 and 12,500 IU.

T_½ when administered in doses of 2500–1200 IU, bemiparin is about 5–6 hours; therefore, bemiparin should be prescribed once a day. Currently, there is no data on the ability of bemiparin to bind to plasma proteins, its metabolism and excretion in humans.

Indications

Prevention of venous thromboembolism with a high degree of risk during surgical interventions. prevention of blood coagulation in the extracorporeal circulation system during hemodialysis. prophylaxis of venous thromboembolism in non-surgical patients with a high risk of developing venous thromboembolism. secondary prevention of recurrence of venous thromboembolism in patients with deep vein thrombosis and transient risk factors.

Application

Zibor 2500 and Tsibor 3500. warning: various drugs of the group of low molecular weight heparins do not necessarily show equivalent effectiveness, therefore, for each such drug, a specific dosage regimen and method of application must be observed.

Adults

General surgery with a moderate risk of venous thromboembolism. On the day of surgery, 2500 IU of the drug is administered by sc injection 2 hours before or 6 hours after the end of the operation, and on the next days, sc is administered at 2500 IU every 24 hours. thromboembolism or until the patients motor activity is completely restored. Typically, such prophylactic treatment is performed at least 7–10 days after surgery to reduce the risk of thromboembolism.

In patients undergoing extensive orthopedic surgery, prophylactic treatment should be continued for up to 35 days. In patients operated on for cancer of the abdominal cavity or pelvis, up to 28 days, provided there is an increased risk of thromboembolism and a low risk of bleeding.

With hemodialysis: prevention of blood coagulation in the extracorporeal circuit. In patients who undergo repeated hemodialysis for a duration of no more than 4 hours, provided there is no risk of bleeding, coagulation prophylaxis in the extracorporeal circuit during the dialysis procedure is achieved by a single dose of the drug by bolus injection into the arterial bed at the beginning of the hemodialysis session. For patients with a body weight of 60 kg, the dose is 2500 IU of the antifactor-Xa, and with a body weight of 60 kg - 3500 IU of the antifactor-Xa.

Prevention of venous thromboembolism in non-surgical patients with a moderate and high risk of developing venous thromboembolism (for example, patients with acute diseases). The recommended dose of bemiparin is 2500 anti-Xa factor per day s / c (moderate risk) and 3500 anti-Xa factor per day s / c (high risk). Preventive treatment is carried out according to the doctor’s decision during the period of the patient’s risk or during his immobilization.

Secondary prevention of recurrence of venous thromboembolism in patients with deep vein thrombosis and transient risk factors. Bemiparin can be used in a fixed dose of 3500 IU / day (maximum duration of treatment is up to 3 months) for patients receiving anticoagulant treatment for deep vein thrombosis with or without pulmonary embolism, as a therapeutic alternative to oral anticoagulants or when contraindicated.

Patients of advanced age. No dose adjustment is required.

Persons with impaired liver and kidney function. A limited amount of data does not allow for recommendations regarding dosage adjustment of bemiparin sodium for these patients.

Mode of application. The technique of sc injection. Pre-filled syringes are ready for immediate use and do not require sterilization before injection. The drug is injected into the subcutaneous fat layer of the anterolateral region of the abdomen or the posterolateral portion of the lower back, alternately on the right and left sides. The needle is inserted to the full depth perpendicularly, and not at an angle, to the fold of skin that is formed by the thumb and forefinger. The fold of the skin is not straightened, it should be held until the end of the injection. The injection site should not be rubbed.

Contraindications

Known hypersensitivity to bemiparin sodium or heparin or substances of porcine origin; confirmed thrombocytopenia immunologically due to heparin or suspicion of it, or a history of it; bleeding or an increased risk of bleeding due to a blood clotting disorder; severe violations of the liver and pancreas; injuries or surgical interventions in the field of central nervous system, organ of vision or organ of hearing over the past 2 months; ICE in the framework of heparin-induced thrombocytopenia; acute bacterial endocarditis and chronic endocarditis; pathological conditions with a high risk of bleeding, such as active peptic ulcer, hemorrhagic stroke, cerebral aneurysm, or cerebral neoplasia.

Side effects

More often reported adverse reactions such as hematoma and / or ecchymosis at the injection site, which were observed in about 15% of patients receiving cibor. prolonged use of heparin can cause the development of osteoporosis. adverse reactions are classified by organ systems and frequency: very often (≥1 / 10), often (≥1 / 100 - 1/10), sometimes (≥1 / 1000 - 1/100); rarely (≥1 / 10,000 - 1/1000), very rarely (1/10 000) and unknown (impossible to estimate based on available data).

The frequency of adverse reactions when using bemiparin corresponds to the frequency of adverse reactions detected when using other drugs of the low molecular weight heparin group, and is given below:

special instructions

The package contains a single dose of the drug. after use, unused contents of the package must be destroyed. do not use the drug if the protective film is opened or damaged. use only a clear, colorless or yellowish, particle-free solution.

Do not administer by i / m injection. Due to the risk of developing hematomas, IM injections of other drugs should be avoided during treatment with bemiparin.

Caution should be exercised when prescribing the drug to patients with liver or kidney failure, uncontrolled hypertension, a history of gastric and duodenal ulcers, thrombocytopenia, kidney stones or urolithiasis, vascular disorders of the membrane and retina of the eye, as well as other organic disorders associated with an increased risk the development of bleeding, as well as when patients undergo spinal or epidural anesthesia or lumbar puncture.

Bemiparin, like other drugs of the low molecular weight heparin group, can inhibit the secretion of aldosterone by the adrenal glands, which can lead to hyperkalemia, especially in patients with diabetes mellitus, chronic renal failure, metabolic acidosis, with an increased level of potassium in the blood plasma or in patients taking potassium-sparing drugs. The risk of developing hyperkalemia increases in proportion to the duration of therapy, but such hyperkalemia is usually transient. In patients at risk, it is necessary to determine the level of electrolytes in blood plasma before prescribing bemiparin and regularly monitor it during treatment, especially if the duration of therapy is more than 7 days.

Sometimes, at the beginning of treatment with bemiparin, a mild transient thrombocytopenia of type I develops (the number of platelets is 100,000 / mm³-150,000 / mm³) associated with the temporary activation of platelets. As a rule, this condition does not cause complications, so bemiparin therapy can be continued.

In rare cases, bemiparin therapy develops severe type II immune thrombocytopenia with platelet counts well below 100,000 / mm³. Such a reaction usually occurs between the 5th and 21st day of therapy. In patients with a history of heparin-induced thrombocytopenia, this complication may develop faster.It is recommended to determine the platelet count before the start of treatment with bemiparin (on the 1st day of therapy), then regularly with an interval of 3-4 days and after the end of the drug. With a significant decrease in platelet count (30–50%), which is combined with positive or unknown in vitro tests for the presence of antiplatelet antibodies in the presence of bemiparin or other drugs of low molecular weight heparin and / or heparin, bemiparin should be immediately discontinued and alternative treatment should be prescribed.

When prescribing bemiparin, as in the case of the appointment of other drugs of low molecular weight heparin, cases of skin necrosis were noted, sometimes with previous erythema or painful erythematous spots. In such cases, bemiparin must be withdrawn immediately.

Prophylactic use of bemiparin in combination with epidural or spinal