Clexane (enoxaparin sodium) syringes

Release form and composition:

Solution for injection transparent, from colorless to pale yellow.

1 syringe contains: enoxaparin sodium is 2000 anti-XA IU

0.2 ml – syringes (2) – blisters (1) – packs of cardboard.

0.2 ml – syringes (2) – blisters (5) – packs of cardboard.

Solution for injection transparent, from colorless to pale yellow.

1 syringe contains: enoxaparin sodium 4000 anti-XA IU

0.4 ml syringes (2) – blisters (1) – packs of cardboard.

0.4 ml syringes (2) – blisters (5) – packs of cardboard.

Solution for injection transparent, from colorless to pale yellow.

1 syringe contains: enoxaparin sodium 6000 anti-XA IU

0.6 ml syringes (2) – blisters (1) – packs of cardboard.

Solution for injection transparent, from colorless to pale yellow.

1 syringe contains: enoxaparin sodium 8000 anti-XA IU

0.8 ml syringes (2) – blisters (1) – packs of cardboard.

0.8 ml syringes (2) – blisters (5) – packs of cardboard.

Solution for injection transparent, from colorless to pale yellow.

1 syringe contains: enoxaparin sodium 10000 anti-XA IU

1 ml syringes (2) – blisters (1) – packs of cardboard.

Pharmacological action:

The preparation of low molecular weight heparin (molecular weight of about 4500 Dalton: less than 2000 Dalton – t 20%, from 2000 to 8000 daltons – gt68%, more than 8,000 Dalton – t 18%). Enoxaparin sodium get alkaline hydrolysis of benzyl ester of heparin isolated from the mucosa of the small intestine of the pig. Its structure is characterized by nonrecoverable fragment of 2-O-sulfo-4-operatinguranium acid and recovering a fragment of 2-N,6-O-disulfo-D-glucopyranoside. The enoxaparin structure contains about 20% (from 15% to 25%) 1,6-angelofrevenge in recovering the fragment of the polysaccharide chain.

Characterized by high activity against factor XA of blood coagulation (anti-XA activity is approximately 100 IU/ml) and low activity against the coagulation factor IIa (anti-IIa or antitrombina the activity of approximately 28 IU/ml).

In applying the drug in prophylactic doses, it only slightly changes the activated partial thromboplastin time (APTT), virtually no effect on platelet aggregation and binding of fibrinogen to receptors on platelets.

Anti-IIa activity in the plasma is about 10 times lower than anti-XA activity. The mean maximum anti-IIa activity is observed approximately 3-4 h after s/to the introduction and reaches 0.13 IU/ml and 0.19 IU/ml after repeated administration of 1 mg/kg body weight in repeated introduction and 1.5 mg/kg body weight in single administration, respectively.

Average maximum anti-XA activity of plasma is observed 3-5 h after s/to the introduction of the drug and is approximately 0.2, 0.4, 1.0 and 1.3 anti-XA IU/ml after p/to the introduction of a 20, 40 mg and 1 mg/kg and 1.5 mg/kg, respectively.

Pharmacokinetics:

The pharmacokinetics of enoxaparin in these dosing regimens is linear.

Absorption and distribution

After repeated s/C injection of enoxaparin sodium in a dose of 40 mg and at a dose of 1.5 mg/kg body weight 1 times/day in healthy volunteers Css achieved for day 2, and AUC by an average of 15% higher than after a single injection. After repeated s/C injection of enoxaparin sodium in a daily dose of 1 mg/kg of body weight 2 times/day Css is achieved after 3-4 days, and AUC on average 65% higher than after a single injection and the mean values of Cmax are, respectively, 1.2 IU/ml and 0.52 IU/ml.

The bioavailability of enoxaparin sodium when s/to the introduction, estimated on the basis of anti-XA activity, is close to 100%. Vd of enoxaparin sodium (anti-XA activity) is approximately 5 years and is approaching the volume of blood.

Metabolism

Enoxaparin sodium biotransformiroetsa mainly in the liver by desulfation and/or depolymerization with the formation of active metabolites.

Excretion

Enoxaparin sodium is a drug with low ground clearance. After the on/in the introduction for 6 h at a dose of 1.5 mg/kg of body weight the average value of the clearance of anti-XA in plasma is 0.74 l/h.

Excretion of the drug is monophasic in nature. T1/2 is 4 h (after a single p/to the introduction) and 7 h (after repeated administration of the drug). 40% of the administered dose are excreted by the kidneys, and 10% in an unmodified form.

Pharmacokinetics in special clinical cases

Possible delayed elimination of enoxaparin sodium in elderly patients as a result of declining renal function.

In patients with renal impairment, the reduction in the clearance of enoxaparin sodium. In patients with minor (QC 50-80 ml/min) and moderate (QC 30-50 ml/min) impaired renal function after repeated p/to the introduction 40 mg of enoxaparin sodium 1 times/day is an increase in the activity of anti-Ha, represented the AUC. In patients with severe impaired renal function (KK less 30 ml/min) when re s/to the introduction of the drug in a dose 40 mg 1 times/day AUC at steady state an average of 65% above.

In patients with excessive body weight when s/to the introduction of the drug clearance is somewhat less. If you do not do correction doses, given the body mass of the patient after a single p/to the introduction of enoxaparin sodium in a dose of 40 mg anti-Xa activity is 50% higher in women with body weight less than 45 kg or 27% higher in men with body weight less than 57 kg, compared with patients with a normal average body mass.

Indications:

— prevention of venous thrombosis and thromboembolism, especially in orthopedic and General surgical operations

— prevention of venous thrombosis and thromboembolism in patients on bed rest, because of acute internal diseases (congestive heart failure, chronic heart failure in the decompensation stage III or IV functional class NYHA classification, acute respiratory failure, severe acute infection, acute rheumatic disease in combination with one of the risk factors of venous thrombosis)

— prevention of clot formation in the extracorporeal circulation during hemodialysis (generally, if the duration of the session not more than 4 hours)

— treatment of unstable angina and myocardial infarction without Q-wave in combination with acetylsalicylic acid

— treatment of acute myocardial infarction with ST-segment elevation in patients subject to medical treatment or further percutaneous coronary intervention.

Dosing regimen:

Except for special cases (treatment of myocardial infarction with ST-segment elevation, medical or with percutaneous coronary intervention and prevention of clotting in the extracorporeal circulation during hemodialysis), enoxaparin sodium is administered by deep n/a. Injection is preferably carried out with the patient supine. When using pre-filled syringes of 20 mg and 40 mg to avoid loss of the drug before injection is not necessary to remove the air bubbles from the syringe. Injection should be carried out alternately in the left or right anterolateral or posterolateral region of the abdominal wall. The needle must enter vertically (not side) in the skin fold of the entire length, collected and held until the end of injection between the thumb and forefinger. The skin fold is released only after completion of the injection. You should not massage the injection site after drug administration.

Pre-filled disposable syringe is ready for use.

The drug issue/m!

Prevention of venous thrombosis and embolism during surgery, especially in orthopedic and General surgical operations

Patients with a moderate risk of thrombosis and embolism (surgical operation) Clexane the recommended dose is 20-40 mg 1 time/day n/a. the First injection is made 2 hours before surgery.

Patients with a high risk of thrombosis and embolism (orthopedic surgery) the drug is recommended at a dose of 40 mg 1 time/day n/a, the first dose is administered 12 hours before surgery, or 30 mg 2 times/day p/to the beginning of the introduction in 12-24 hours after surgery.

The duration of treatment Clexane on average 7-10 days. If necessary, therapy can continue as long as there remains a risk of thrombosis and embolism (e.g. in Orthopaedics Lexan® appointed dose 40 mg 1 times/day for 5 weeks).

Features purpose Clexane with spinal/epidural anesthesia, as well as in the procedures of coronary revascularization described in section aquОсобые указанияraqu.

Prevention of venous thrombosis and embolism in patients who are on bed rest due to acute therapeutic diseases

Clexane the recommended dose is 40 mg 1 time/day s/C for 6-14 days.

Treatment of deep vein thrombosis with pulmonary embolism with or without pulmonary embolism

The drug is injected p/to is based 1.5 mg/kg body weight 1 times/day or at a dose of 1 mg/kg of body weight 2 times/day. Have

patients with complicated thromboembolic disorders, the product is recommended at a dose of 1 mg/kg 2 times/day.

The duration of treatment averages 10 days. It is desirable to immediately begin therapy with anticoagulants, during therapy with this Clexane must continue to achieve adequate anticoagulant effect, i.e., the MHO should be 2-3.

Prevention of clotting in the extracorporeal circulation during hemodialysis

Dose Clexane averages 1 mg/kg of body weight. At high risk of bleeding dose should be reduced to 0.5 mg/kg body weight in a double vascular access or 0.75 mg for single vascular access.

In hemodialysis, the drug should be administered into the arterial portion of the shunt at the beginning of the hemodialysis session. One dose usually enough for a 4-hour session, however, upon detection of fibrin rings in case of prolonged hemodialysis may be added, the preparation is 0.5-1 mg/kg of body weight.

Treatment of unstable angina and myocardial infarction without Q wave

Clexane ® is injected at the rate of 1 mg/kg of body weight every 12 hours n/a, while the appointment of acetylsalicylic acid at a dose of 100-325 mg 1 times/day. The average duration of treatment is 2-8 days (until stabilization of the clinical condition of the patient).

Treatment of myocardial infarction with ST-segment elevation, medical or with percutaneous coronary intervention

Start treatment with I/V bolus administration of enoxaparin sodium in a dose of 30 mg and immediately after (within 15 min) conduct p/to the introduction of enoxaparin sodium in a dose of 1 mg/kg (and in the holding of the first two s/C injection may be administered a maximum of 100 mg enoxaparin sodium). Then all subsequent p/to the dose introduced every 12 h at the rate of 1 mg/kg of body weight (i.e., body weight more than 100 kg the dose may exceed 100 mg).

In persons 75 years and older not applicable to initial/bolus. Enoxaparin sodium is injected p/to a dose of 0.75 mg/kg every 12 hours (and, during the first two s/C injection may be administered a maximum of 75 mg enoxaparin sodium). Then all subsequent p/to the dose introduced every 12 h from the calculation of the 0.75 mg/kg of body weight (i.e., body weight more than 100 kg the dose may exceed 75 mg).

In combination with thrombolytic drugs (fibrin-specific and fibrin-non-specific) enoxaparin sodium should be administered between 15 minutes before the start of thrombolytic therapy up to 30 min after it. As soon as possible after identification of acute myocardial infarction with ST-segment elevation should also begin taking acetylsalicylic acid and, if there are no contraindications, it should last for at least 30 days in doses of 75 to 325 mg daily.

The recommended duration of treatment is 8 days or until the patient’s discharge from hospital, if the hospitalization period is less than 8 days.

Bolus enoxaparin sodium should be conducted through a venous catheter and enoxaparin sodium should not be mixed or administered together with other drugs. In order to avoid the presence in the system, traces of other medicinal substances and their interactions with enoxaparin sodium for venous catheter should be washed with a sufficient quantity of 0.9% solution of sodium chloride or dextrose before and after in/in the bolus injection enoxaparin sodium. Enoxaparin sodium may be safely administered with 0.9% solution of sodium chloride and 5% dextrose solution.

To conduct a bolus administration of a 30 mg enoxaparin sodium in the treatment of acute myocardial infarction with ST-segment elevation of glass syringes 60 mg, 80 mg and 100 mg remove the excess amount of the drug so that they had only 30 mg (0.3 ml). The dose of 30 mg may be directly entered.

For holding in/bolus administration of enoxaparin sodium to the venous catheter can be used pre-filled syringes for subcutaneous injection 60 mg, 80 mg and 100 mg. it is Recommended to use syringes, 60 mg, as this reduces the amount removed from the syringe of the drug. Syringes of 20 mg are not used, because they cannot afford the medication for bolus administration of a 30 mg enoxaparin sodium. Syringes of 40 mg are not used, since they have no division and therefore it is impossible to accurately measure the quantity of 30 mg.

In patients who undergo percutaneous coronary intervention, if the last SC injection of enoxaparin sodium was carried out in less than 8 hours before inflating inserted in place of narrowing of a coronary artery balloon catheter, additional administration of enoxaparin sodium is not required. If the last SC injection of enoxaparin sodium was conducted more than 8 hours before inflating the balloon catheter must be made within/additional bolus of enoxaparin sodium in a dose of 0.3 mg/kg.

To improve accuracy, an additional bolus administration of small volumes into the venous catheter when carrying out percutaneous coronary interventions, it is recommended to dilute the drug to a concentration of 3 mg/ml Dilution is recommended directly before use.

To obtain the solution of enoxaparin sodium with a concentration of 3 mg/ml using a pre-filled syringe of 60 mg is recommended to use a container of infusion solution 50 ml (that is, 0.9% sodium chloride solution or 5% dextrose solution). From the container with infusion solution with a conventional syringe is extracted and removed 30 ml of solution. Enoxaparin sodium (contents of the syringe for s/C injection 60 mg) is introduced in the remaining capacity in 20 ml infusion solution. The contents of the tank with a diluted solution of enoxaparin sodium gently stirred. For administration with a syringe extracted the necessary volume of diluted solution of enoxaparin sodium, which is calculated by the formula:

The volume of the diluted solution = body Weight of patient (kg) x 0.1 or using the table given below.

The amounts that should be entered in the/in line after dilution

With the exception of the treatment of myocardial infarction with ST-segment elevation (see above) for all other indications of lower doses of enoxaparin sodium in patients of advanced age, if they have no impairment of renal function, is not required.

Patients with severely impaired renal function (KK less 30 ml/min) dose of enoxaparin sodium is reduced in accordance with the following tables, because in these patients there is an accumulation of the drug.

When using the drug for therapeutic purposes, it is recommended that the correction mode:

The usual dosing regimen dosing regimen in severe renal failure

1 mg/kg n/a 2 times/day 1 mg/kg p/to 1 times/day

1.5 mg p/to 1 times/day 1 mg/kg p/to 1 times/day

Once: bolus, in/in the introduction of 30 mg plus 1 mg/kg s/C, followed by subcutaneous injection at a dose of 1 mg/kg 2 times/day one: bolus, in/in the introduction of 30 mg plus 1 mg/kg s/C, followed by subcutaneous injection at a dose of 1 mg/kg 1 time/day

Elderly patients aged gt75 years (only in acute myocardial infarction with ST-segment elevation)

0.75 mg/kg n/a 2 times/day without an initial bolus injection of 1 mg/kg p/to 1 times/day without an initial bolus injection

When using the drug prophylactically, it is recommended that the correction mode

The usual dosing regimen dosing regimen in severe renal failure

40 mg p/to 1 times/day 20 mg p/to 1 times/day

20 mg p/to 1 times/day 20 mg p/to 1 times/day

Recommended correction dosing regimen is not applicable for kidney dialysis.

With a light (QC 50-80 ml/min) and moderate (QC 30-50 ml/min) impaired renal function dose adjustment is not required, but should be more careful to conduct laboratory control of therapy.

In the absence of clinical studies, caution should be exercised in the appointment of enoxaparin sodium to patients with impaired liver function.

Side effects:

Bleeding

As the use of other anticoagulants may cause bleeding, especially when there are concomitant risk factors such as organic lesions, contributing to the development of bleeding, invasive procedures or the use of drugs in violation of hemostasis. With the development of bleeding it is necessary to cancel the administration of the drug, to determine the cause of bleeding and to initiate appropriate therapy.

It was reported the development of severe bleeding, including retroperitoneal and intracranial hemorrhage (with a frequency of 0.01-0.1%).

Some of these cases were fatal.

When applying Clexane on the background of the spinal/epidural anesthesia and postoperative use of penetrating catheters described the cases of the formation of neuroaxial hematomas (0.01-0.1% of cases), leading to neurological disorders of varying severity, including long-lasting or irreversible paralysis.

Thrombocytopenia

During the first days after the start of therapy may develop slightly severe, transient, asymptomatic thrombocytopenia. In rare cases (less than 0.01%) been reported on the development of autoimmune thrombocytopenia in combination with thrombosis. In rare cases, thrombosis was complicated by organ infarction or limb ischemia.

Local reactions

After p/to the introduction Clexane may experience pain at the injection site, less than 0.01% of cases, hematoma at the injection site. In some cases, the injection site, the formation of firm inflammatory nodules-infiltrates containing the drug, which disappears in a few days and are not grounds for withdrawal of the drug. In 0.001% of cases at the injection site may develop skin necrosis, which is preceded by the appearance of purpura or painful erythematous papules. In these cases, therapy should be discontinued Clexane.

Other

Rarely observed cutaneous (bullous eruptions) and systemic allergic reactions, including anaphylactic and anaphylactoid reactions (with a frequency of 0.01-0.1%). There have been cases of allergic vasculitis (less than 0.01%). Some patients may require discontinuation of treatment.

Described asymptomatic and reversible elevation of liver enzymes.

Reported cases of hyperkalemia with the use of heparin and low molecular weight heparins.

As the use of low molecular weight heparin, we cannot exclude the risk of osteoporosis in the case of prolonged treatment.

Contraindications:

— States and diseases in which there is a high risk of bleeding (threatening abortion, aneurysm of blood vessels o