CLEXANE INJECTION FOR SYRINGES 20MG/0,2ML

Dosage form

Injection

Composition

1 syringe for injection contains: Enoxaparin sodium 2000 anti-Xa ME.

Packaging

In 1 syringe 0.2 ml solution. In 1 blister 2 syringes. In a cardboard bundle one blister.

Mechanism of action

Clexane is a low molecular weight Heparin preparation (molecular weight about 4,500 daltons). It is characterized by high activity against blood coagulation factor Xa (anti-Xa activity of approximately 100 IU / ml) and low activity against coagulation factor IIa (anti-IIa or antithrombin activity of approximately 28 IU / ml).

When using the drug in prophylactic doses, it slightly changes the activated partial thromboplastin time (APTT), has practically no effect on platelet aggregation and on the level of fibrinogen binding to platelet receptors.

Anti-IIa activity in plasma is about 10 times lower than anti-Xa activity. The average maximum anti-IIa activity is observed approximately 3-4 hours after s / c injection and reaches 0.13 IU / ml and 0.19 IU / ml after repeated administration of 1 mg / kg of body weight with double administration and 1.5 mg / kg of body weight with a single dose. introduction respectively.

The average maximum anti-Xa plasma activity is observed 3–5 hours after s / c injection and is approximately 0.2, 0.4, 1.0, and 1.3 anti-Xa IU / ml after s / c administration 20, 40 mg and 1 mg / kg and 1.5 mg / kg, respectively.

Indications and usage

- Prevention of venous thrombosis and thromboembolism, especially in orthopedics and general surgery.
- Prevention of venous thrombosis and thromboembolism in patients with acute therapeutic diseases on bed rest (chronic heart failure of the third or fourth functional class according to the NYHA classification, acute respiratory failure, acute infection, acute rheumatic diseases in combination with one of the risk factors of venous thrombosis).
- Treatment of deep vein thrombosis with or without pulmonary embolism.
- Treatment of unstable angina and myocardial infarction without Q wave in combination with Acetylsalicylic acid.
- Prevention of the formation of thrombosis in the system of extracorporeal circulation during hemodialysis.

Contraindications

- Conditions and diseases in which there is a high risk of bleeding:
- Threatening abortion.
- Aneurysm of cerebral vessels or dissecting aortic aneurysm (with the exception of surgical intervention).
- Hemorrhagic stroke.
- Uncontrolled bleeding.
- Severe enoxaparin- or heparin-induced thrombocytopenia.

It is used with caution in disorders of hemostasis, including: hemophilia, thrombocytopenia, hypocoagulation, von Willebrand disease.

The company does not have data on the clinical use of the drug Clexan in the following conditions: active tuberculosis, radiation therapy (recently conducted).

Pregnancy and Breastfeeding

Clexane should not be used during pregnancy unless the intended benefits to the mother outweigh the potential risk to the fetus. There is no information that enoxaparin penetrates the placental barrier in the second trimester, there is no information regarding the first and third trimesters of pregnancy.

When applying Clexane during lactation, breastfeeding should be stopped.

Dosage and administration

The drug is injected s / c. The drug can not be administered in / m!

For the prevention of venous thrombosis and thromboembolism: patients with moderate risk (abdominal surgery) are prescribed Clexane at 20-40 mg (0.2-0.4 ml) s / c 1 time / day. The first injection is made 2 hours before surgery; patients with high risk (orthopedic surgery) are prescribed 40 mg (0.4 ml) s / c 1 time / day. while the first dose is administered 12 hours before the operation or 30 mg (0.3 ml) n / a 2 times / day. with the beginning of introduction in 12-24 h after operation.

The duration of treatment with Clexane is 7-10 days. If necessary, therapy can be continued as long as the risk of thrombosis or embolism persists (for example, in Clexan orthopedics, a dose of 40 mg is prescribed 1 time per day for 5 weeks).

For the prevention of venous thrombosis in patients with acute therapeutic conditions on bed rest, they are prescribed 40 mg 1 time / day. within 6-14 days.

For the treatment of deep vein thrombosis, 1 mg / kg infusion is administered every 12 hours (2 times / day) or 1.5 mg / kg 1 time / day. In patients with complicated thromboembolic disorders, the drug is recommended to be used at a dose of 1 mg / kg 2 times / day. The average duration of treatment is 10 days. It is desirable to immediately begin therapy with indirect anticoagulants, while therapy with Clexane should be continued until a sufficient anticoagulant effect is achieved, i.e. INR should be 2.0-3.0.

With unstable angina and myocardial infarction without a Q wave, the recommended dose of Clexane is 1 mg / kg every 12 hours. At the same time, acetylsalicylic acid is prescribed at a dose of 100-325 mg 1 time / day. The average duration of therapy is 2-8 days (until the patient’s clinical condition stabilizes).

For the prevention of thrombus formation in the extracorporeal circulation system during hemodialysis, the dose of Clexane is on average 1 mg / kg body weight. With a high risk of bleeding, the dose should be reduced to 0.5 mg / kg body weight with a double vascular approach or 0.75 mg / kg with a single vascular approach. In hemodialysis, the drug should be injected into the arterial area of ​​the shunt at the beginning of the hemodialysis session. A single dose is usually sufficient for a four-hour session, however, if fibrin rings are detected during longer hemodialysis, the drug can be additionally administered at a rate of 0.5–1 mg / kg body weight.

Use in patients with impaired renal function: In case of impaired renal function, it is necessary to adjust the dose of the drug, depending on CC.When QA is less than 30 ml / min, Clexane is administered at the rate of 1 mg / kg of body weight 1 time / day. with the purpose of treatment and 20 mg 1 time / day. with the preventive purpose. Dosing regimen does not apply to cases of hemodialysis. When QC more than 30 ml / min, dose adjustment is not required, but laboratory monitoring of therapy should be carried out more carefully.

The rules of the introduction of the solution: Injections are preferably carried out in the position of the patient lying down. Clexane is injected deep subcutaneously. When using pre-filled syringes for 20 mg and 40 mg before injection, it is not necessary to remove air bubbles from the syringe to avoid loss of the drug. Injections should be carried out alternately in the left or right upper side or lower side of the anterior abdominal wall. The needle must be inserted vertically for the entire length into the skin, holding the skin fold between the thumb and index fingers. A skin fold is released only after completion of the injection. Do not massage the injection site after the injection.

Adverse reactions

Bleeding: With the development of bleeding, it is necessary to cancel the drug, establish the cause and start the appropriate treatment. In 0.01-0.1% of cases, hemorrhagic syndrome may develop, including retroperitoneal and intracranial bleeding. Some of these cases were lethal. When Clexane is used on the background of spinal / epidural anesthesia and postoperative use of penetrating catheters, hematomas of the spinal cord are described (in 0.01-0.1% of cases), which leads to neurological disorders of various manifestations, including persistent or irreversible paralysis.

Thrombocytopenia: in the first days of treatment, a slight transient asymptomatic thrombocytopenia may develop. In less than 0.01% of cases, the development of immune thrombocytopenia is possible in combination with thrombosis, which can sometimes be complicated by organ infarction or limb ischemia.

Local reactions: after s / c administration, pain at the injection site can be observed, in less than 0.01% of cases, hematoma at the injection site. In some cases, the formation of solid inflammatory infiltrates containing the drug, which dissolve after a few days, without the abolition of the drug is not required. In 0.001% at the injection site, skin necrosis may occur, preceded by purpura or erythematous plaques (infiltrated and painful); in this case, the drug should be discontinued.

Other: in 0.01-0.1% - skin or systemic allergic reactions. There have been cases of allergic vasculitis (less than 0.01%), which required discontinuation of the drug in some patients. Perhaps a reversible and asymptomatic increase in liver enzymes.

When prescribing the drug for the purpose of prevention, no tendency to increased bleeding was found. When prescribing a drug for therapeutic purposes, there is a risk of bleeding in older patients (especially in people older than 80 years). It is recommended to conduct a careful observation of the patient's condition.

Before starting treatment with this drug, it is recommended to cancel other drugs that affect the hemostatic system due to the risk of bleeding: salicylates, incl.acetylsalicylic acid, NPVS (including ketorolac); dextran 40, ticlopidine, Clopidogrel , corticosteroids, thrombolytics, anticoagulants, antiplatelet agents (including antagonists of glycoprotein IIb / IIIa receptors), except when they are necessary. If necessary, the combined use of Clexan with these drugs should be especially careful (careful monitoring of the patient and the relevant laboratory blood parameters).

An increase in anti-Xa activity of enoxaparin in its prophylactic administration in women weighing less than 45 kg and in men weighing less than 57 kg may lead to an increased risk of bleeding.

The risk of immune thrombocytopenia caused by heparin also exists when using low molecular weight heparins. If thrombocytopenia develops, it is usually detected between the 5th and 21st days after the start of therapy with enoxaparin sodium. In this regard, it is recommended to regularly monitor the number of platelets prior to treatment with enoxaparin sodium and during its use. If there is a confirmed significant reduction in the number of platelets (by 30-50% compared with baseline), it is necessary to immediately cancel sodium enoxaparin and transfer the patient to another therapy.

As with the use of other anticoagulants, described cases of spinal hematoma when using Clexane on the background of spinal / epidural anesthesia with the development of persistent or irreversible paralysis. The risk of these phenomena is reduced when using the drug at a dose of 40 mg or lower.The risk increases with increasing dosage of the drug, as well as with the use of penetrating epidural catheters after surgery, or with the concomitant use of additional drugs that have the same effect on hemostasis as NSAIDs. The risk also increases with traumatic exposure or repeated spinal puncture. To reduce the risk of bleeding from the spinal canal during epidural or spinal anesthesia, it is necessary to consider the pharmacokinetic profile of the drug. The installation or removal of the catheter is best done with a low anticoagulant effect of enoxaparin sodium. Installation or removal of the catheter should be carried out after 10-12 h after the application of prophylactic doses of Clexane for deep vein thrombosis. In cases where patients receive higher doses of enoxaparin sodium (1 mg / kg 2 times / day or 1.5 mg / kg 1 time / day), these procedures should be postponed for a longer period of time (24 hours). Subsequent administration of the drug should be carried out no earlier than 2 hours after removal of the catheter. If the doctor prescribes anticoagulant therapy during epidural / spinal anesthesia, very careful monitoring of the patient is necessary to identify any neurological signs and symptoms, such as: back pain, impaired sensory and motor functions (numbness or weakness in the lower extremities), disorders bowel and / or bladder function.The patient must be instructed to immediately inform the physician when the above symptoms occur. If signs or symptoms characteristic of a brain stem hematoma are found, urgent diagnosis and treatment is necessary, including spinal decompression if necessary.

With extreme caution, Clexane should be prescribed to patients in the history of which there is evidence of heparin-induced thrombocytopenia, in combination with or without thrombosis. The risk of heparin-induced thrombocytopenia may persist for several years. If heparin-induced thrombocytopenia is assumed anamnestically, then in vitro platelet aggregation tests are of limited value in predicting the risk of its development. The decision on the appointment of Clexane in this case can be taken only after consulting with the appropriate specialist.

In order to reduce the risk of bleeding associated with invasive vascular manipulation in the treatment of unstable angina, the catheter should not be removed within 6-8 hours after subcutaneous injection of Clexan. The next estimated dose should be administered no earlier than 6-8 hours after the catheter is removed. The injection site should be monitored in order to timely detect signs of bleeding and hematoma formation.

Studies have not been conducted to reliably assess the efficacy and safety of Clexane in preventing thromboembolic complications in patients with artificial heart valves, therefore, the use of the drug for this purpose is not recommended.

In doses used for the prevention of thromboembolic complications, Clexane does not significantly affect bleeding time and overall clotting rates, as well as platelet aggregation or binding to fibrinogen. At higher doses, the APTT and clotting time can be prolonged. The increase in APTT and clotting time are not directly linearly dependent on the increase in the antithrombotic activity of the drug, so there is no need to monitor them.

In the case of acute infection, acute rheumatic conditions, prophylactic administration of enoxaparin sodium is justified only if there are risk factors for venous thrombosis (over 75 years of age, malignant tumors, thrombosis and embolism in history, obesity, hormone therapy, heart failure, chronic respiratory failure).

Clexane does not affect the ability to drive and mechanisms.

With simultaneous use of Clexane with drugs that affect hemostasis (salicylates / with the exception of unstable angina and myocardial infarction without ST-segment elevation /, other NSAIDs / including Ketorolac /, dextran 40, ticlopidine, GCS for systemic use, thrombolytics, anticoagulants, anti-antigens, anti-coagulants, anti-coagulant, anti-coagulant including antagonists of glycoprotein IIb / IIIa /) receptors, hemorrhagic complications may develop. If the use of such a combination cannot be avoided,Enoxaparin should be used under close monitoring of blood clotting parameters.

Do not alternate the use of enoxaparin sodium and other low molecular weight heparins, since they differ from each other in the way of production, molecular weight, specific anti-Xa activity, units of measure and doses. These drugs, therefore, have different pharmacokinetics, biological activity (anti-IIa activity and platelet interaction).

Clexane solution should not be mixed with other drugs.

Symptoms: Accidental overdose with IV, extracorporeal or SC injection may lead to hemorrhagic complications. When ingestion, even in large doses, the absorption of the drug is unlikely.
Treatment: Slow iv administration of protamine sulfate is shown as a neutralizing agent, the dose of which depends on the dose of Clexan administered. It is necessary to take into account that 1 mg of protamine neutralizes the anticoagulant effect of 1 mg of enoxaparin, if Clexane was administered no more than 8 hours before administration of protamine. 0.5 mg of protamine neutralizes the anticoagulant effect of 1 mg of Clexane if it was administered more than 8 hours ago or if a second dose of protamine is to be administered. If, after administration of Clexane, more than 12 hours have passed, then the introduction of protamine is not required. However, even with the introduction of large doses of protamine sulfate, the anti-Xa activity of Clexane is not completely neutralized (maximum 60%).

The drug should be stored at a temperature not higher than 25 ° C.

Clexane