Gemapaksan

General characteristics. Structure:

Active agent: эноксапарин sodium – 2000 ME/0,2 ml (20 mg); 4000 ME/0,4 ml (40 mg); 6000 ME/0,6 ml (60 mg). Excipients: water for injections.

DESCRIPTION: 
transparent, colourless or light yellow solution.

Pharmacological properties:

Enoksaparin of sodium represents heparin with a low molecular weight with activity high Anti-ha (100 ME/mg) and low anti-IIa or activity of antithrombin (28 ME/mg). At the doses demanded for various indications эноксапарин sodium does not increase a bleeding time. At preventive doses, эноксапарин sodium does not cause noticeable change of the activated partial tromboplastinovy time (APTT). It does not influence neither aggregation of thrombocytes, nor linkng of fibrinogen with thrombocytes.

Pharmacokinetics. Pharmacokinetic parameters were studied by means of action time Anti-ha of activity of plasma, and also anti-IIa of activity in the recommended dose ranges.
Absolute bioavailability of an enoksaparin of sodium after hypodermic introduction is close to 100%. Average maximum anti-Хa activity of plasma was observed during from 3 to 5 hours after a subcutaneous injection. The pharmacokinetics of an enoksaparin of sodium probably has linear character in the recommended dose ranges.
Even if it was reported about a difference of pharmacokinetic indicators in an equilibrium state between one-time and repeated introduction, this difference is expected and is in limits of therapeutic ranges. Average maximum anti-IIa activity of plasma was observed during from 3 to 4 hours after hypodermic introduction.
Enoksaparin of sodium is initially metabolized in a liver.
The elimination half-life for Anti-ha activity makes approximately of 4 o'clock after one-time introduction and till 7 o'clock - after repeated introduction. The renal clearance of active metabolites makes about 10% of the entered dose, and the general renal excretion makes 40% of a dose.
At people of advanced age as, function of kidneys decreases with age, removal can be reduced.
At patients with a heavy renal failure (the clearance of creatinine <30 ml/min.) of AUC considerably increases after repeated hypodermic introduction 4000 Anti-ha of ME of 1 times a day.

Indications to use:

The solution for injections containing 2000 ME anti-Ha/0,2 of ml and 4000 ME anti-Ha/0,4 of ml is shown for the following cases:
- Prevention of venous thromboses and a thromboembolism (especially at orthopedic and surgeries);
- Prevention of venous thromboses and a thromboembolism at the patients who are on a bed rest (XCH III or the IV class NYHA, acute respiratory insufficiency, acute infections or acute rheumatic diseases in combination with one of risk factors of venous thrombosis: age more than 75 years, cancer, thromboses and thromboembolisms in the anamnesis, obesity, hormonal therapy, HSN, chronic respiratory insufficiency).

The solution for injections containing 6000 ME anti-Ha/0,6 of ml is shown for:  
- Treatment of a deep vein thrombosis, with an embolism and without vascular embolism of lungs;
- Treatment of unstable stenocardia and myocardial infarction without Q tooth on an ECG, at reception together with acetylsalicylic acid;
- Prevention of hypercoagulation in system of extracorporal circulation when carrying out a hemodialysis.

Route of administration and doses:

Subcutaneously and in an arterial contour during the hemodialysis session.
Prevention of venous thromboses and thromboembolism at surgical patients At patients with average risk of developing of a thrombembolia (for example, at operations of an abdominal cavity), the recommended dose of an enoksaparin of sodium 2000 ME/0,2 of ml or 4000 ME/0,4 ml of 1 times a day.

In the general surgery the first injection has to be made in 2 hours prior to surgical intervention.
Patients with high risk have development of thromboses and a thromboembolism (for example, in orthopedic surgery), the recommended dose of an enoksaparin of sodium makes 4000 ME/0,4 ml of 1 times a day, beginning in 12 hours prior to surgical intervention, or 3000 ME (30 mg) 2 times a day in 12-24 h after operation.
Concerning the special recommendations concerning intervals of administration of drug for spinal/epidural anesthesia and procedures of chrezkozhny coronary revascularization see the section "Special Instructions".

Duration treatment enoksapariny sodium usually makes from 7 to 10 days. More prolonged treatment can be required by some patients, and it has to be continued until there is a risk of development of thrombosis and thromboembolism (in orthopedics apply in a dose 4000 ME/0,4 ml of 1 times a day within 5 weeks).
Prevention of venous thromboses and thromboembolism at the therapeutic patients who are on a bed rest the Recommended dose of an enoksaparin of sodium makes 4000 ME/0,4 ml of 1 times a day within 6-14 days.

Treatment of a deep vein thrombosis, with a thromboembolism and without thromboembolism of a pulmonary artery Enoksaparin of sodium is entered in a dose of 150 ME/kg of body weight (1,5 mg/kg) of 1 times a day or 100 ME/kg (1 mg/kg) 2 times a day. For patients with the complicated thromboembolic disturbances the dose of 100 ME/kg 2 times a day is recommended.
Duration treatment makes 10 days. It is desirable to begin at once therapy with peroral anticoagulants, at the same time therapy enoksapariny sodium needs to be continued before achievement of sufficient anticoagulating effect (the International Normalized Relation 2-3). Treatment of unstable stenocardia and myocardial infarction without tooth Q Recommended dose of an enoksaparin of sodium makes 100 ME/kg of body weight each 12 hours at co-administration of acetylsalicylic acid in a dose of 100-325 mg of 1 times a day.

The average duration of therapy makes 2-8 days (before stabilization of a clinical condition of the patient). Prevention of hypercoagulation in system of extracorporal circulation when carrying out a hemodialysis
 The recommended dose of an enoksaparin of sodium makes 100 ME/kg of body weight.
For patients with high risk of bleeding the dose has to be lowered to 50 ME/kg at double vascular access or to 75 ME/kg at unary vascular access. During a hemodialysis эноксапарин sodium it has to be entered into an arterial contour at the beginning of the hemodialysis session. One dose, as a rule, is enough for a 4-hour session.
However, at detection of fibrinous rings at more long hemodialysis it is possible to enter 50-100 ME/kg of body weight in addition.

Special categories of patients 
• Patients of advanced age: dose adjustment is not required if function of kidneys is only not broken.
• At the expressed renal failure the dose is adjusted depending on the size of clearance of creatinine: at clearance of creatinine the preventive dose makes less than 30 ml/min. 2000 ME 1 times a day; a therapeutic dose - 100 ME/kg of body weight of 1 times a day.
• At a slight and moderate renal failure: dose adjustment is not required. The way of introduction Gemapaksan is entered by means of a deep subcutaneous injection at preventive and therapeutic treatment and into an arterial contour during the hemodialysis session.

IT IS IMPOSSIBLE TO ADMINISTER THE DRUG INTRAMUSCULARY.
Before an injection the air bubble should not appear. It is more preferable to do a subcutaneous injection when the patient is in situation "lying". Gemapaksan is entered serially into the left or right anterolateral and posterolateral parts of a front abdominal wall.
At an injection the needle should be entered perpendicularly, but not under an inclination, at all its length the thickness of skin clamped pleated between big and index fingers. The fold of skin should be held until the end of an injection. After an injection the injection site cannot be pounded.

Features of use:

• Heparins with a low molecular weight should not be used on an interchangeable basis as they differ on process of their production, the molecular weight, activity specific Anti-ha, units of action and a dosage. Accurate observance of the specific application instruction of each drug is necessary.
• Spinal/epidural anesthesia

 At purpose of anticoagulating therapy during spinal/epidural anesthesia especially careful, constant observation of patients is necessary for identification of any neurologic symptoms (median dorsodynias, disturbance of touch and motor functions, including numbness or weakness in the lower extremities, dysfunction of digestive tract and/or bladder).

At identification of the symptoms characteristic of a brainstem hematoma, urgent diagnosis and the treatment including if necessary a spinal decompression are necessary.

Exceptional cases of developing of a hematoma of a spinal cord at treatment are described enoksapariny sodium against the background of spinal/epidural anesthesia with development of persistent paralysis.

The risk of emergence of these phenomena decreases at use of drug in a dose to 4000 ME. The risk increases at increase in a dose of drug, and also when using of the getting epidural catheters after operation or at the accompanying use of the additional medicines exerting impact on a hemostasis (including NPVP).

The risk also increases at a traumatic or repeated spinal puncture.
During epidural or spinal anesthesia, it is better to make introduction and removal of a catheter when anticoagulating effect of an enoksaparin of sodium low: in 10–12 hours after use of preventive doses of drug or in 24 hours after introduction of higher doses (100 Anti-ha body weight ME/kg 2 times a day or 150 Anti-ha ME/kg of body weight of 1 times a day).

The subsequent administration of drug has to be carried out not earlier than in 2 h after removal of a catheter. 
• The thrombocytopenia caused by use of heparin At decrease in number of thrombocytes is lower than norm for 30-50%, and also at emergence of symptoms of internal bleeding (the melena or detection is fresher than blood in Calais, vomiting blood, hypochromia anemia) эноксапарин sodium cancel. At the thrombocytopenia induced by heparin in the anamnesis эноксапарин sodium appoint in exceptional cases because of risk of the immunoallergic trombotichesky thrombocytopenia which is shown for 5-21 days after introduction. The risk of the thrombocytopenia caused by heparin can remain within several years.
• Procedures of chrezkozhny coronary revascularization For reduction of risk of bleeding at treatment of the acute coronary syndrome assuming surgical invasive methods of treatment with disturbance of integrity of a vascular wall, introduction of an enoksaparin of sodium has to be carried out not less than in 6-8 hours prior to manipulation or 6-8 hours later after the carried-out manipulation.
• Artificial valves of heart patients have no sufficient data about efficiency and safety of use of drug for prevention of tromboembolic episodes with artificial valves of heart.
• Laboratory tests At the doses used for prevention of venous thromboses and a thromboembolism эноксапарин sodium does not influence significantly a bleeding time and the general indicators of a blood coagulation, and also aggregation of thrombocytes or their linkng with fibrinogen. At higher doses, there can be an increase in AChTV and the activated blood clotting time.

Side effects:

Dot hemorrhages (petechias), ecchymomas, it is rare – a hemorrhagic syndrome (including retroperitoneal and intracranial bleedings, up to a lethal outcome), a hyperemia and morbidity in an injection site, it is rare – a hematoma, emergence of dense inflammatory nodes (resolve in several days, the termination of treatment is not required); seldom – a skin necrosis in an injection site to which the purpura or erythematic plaques precedes (infiltrirovanny and painful); symptomless thrombocytopenia (in the first days of treatment), it is rare – immunoallergic thrombocytopenia (for 5-21 days of treatment) with development of ricochet thromboses (heparin trombotichesky thrombocytopenia) which can be complicated by a heart attack of body or ischemia of an extremity; asymptomatic reversible increase in activity of "hepatic" transaminases.

Seldom – system and skin allergic reactions. At traumatic carried out spinal/epidural anesthesia (the probability increases when using a constant postoperative epidural catheter) – an intra spinal hematoma (seldom) which can lead to temporary or constant paralysis.

Interaction with other medicines:

To avoid possible interaction with other medicines, inform your attending physician on other drugs which you use now.
It is recommended before an initiation of treatment using an enoksaparin of sodium to interrupt use of drugs which influence a hemostasis if there are only no strict indications for this purpose.

The combination to antagonists of vitamin K, antiagregant (including acetylsalicylic acid and its derivatives, blockers of glycoprotein receptors of IIb/IIIa), by Sulfinpyrazonum, valproic acid, ketorolaky and other NPVP (non-steroidal anti-inflammatory drugs), dextrans with a high molecular weight, klopidogrely, tiklopidiny, glucocorticosteroids (systemic action), a trombolitikama is not recommended.

As well as in case of other heparins with a low molecular weight, in need of the combined use with these medicines careful control of a condition of the patient and indicators of a hemostasis is required. It is impossible to mix drug in one syringe with other medicines!

Contraindications:

Drug cannot be used: 
• at the known hypersensitivity (allergy) to a sodium enoksaparin, heparin or other heparins with a low molecular weight;
• at aneurism of vessels of a brain or the stratifying aortic aneurysm (except for surgical intervention);
• at the hemorrhagic stroke (established or suspected) and at high risk of uncontrollable bleeding;
• at heavy uncontrollable arterial hypertension;
• at a heavy enoksaparin-or geparinindutsirovanny thrombocytopenia (for the last months);
• at children's age (due to the lack of data on safety and efficiency of use of drug for this category of patients).

WITH CARE 
 Carrying out spinal or epidural anesthesia (potential danger of development of a hematoma); the states connected with danger of bleeding – disturbance in system of a blood coagulation (including hemophilia, thrombocytopenia, hypocoagulation, an angiohemophilia, etc.); recent childbirth, heavy diabetes mellitus, endocarditis bacterial (acute or subacute), the peptic ulcer of a stomach or a 12-perstny gut or other erosive cankers of a GIT, the intrauterine contraception, neurologic or ophthalmologic operation (which is recently postponed or assumed), a pericardis or a pericardiac exudate, radiation therapy (recently postponed), renal and/or liver failure, a diabetic or hemorrhagic retinopathy, a spinal puncture (recently postponed), severe injury (especially TsNS), active tuberculosis, diseases of respiratory system or an urinary path (in an aggravation stage), a heavy vasculitis, open wounds on big surfaces, arterial hypertension.

PREGNANCY AND PERIOD OF FEEDING BY THE BREAST 
 There is no confirmation that эноксапарин sodium gets through a placental barrier. However, it has to be used during pregnancy only in urgent cases.
Enoksaparin of sodium is not recommended for use for pregnant women with artificial valves of heart (see the section "Special Instructions").
As a precautionary measure, the nursing mothers accepting эноксапарин sodium need to recommend to avoid feeding by a breast.

Overdose:

Symptoms: bleeding.
Treatment: protamin sulfate (1 mg of protamin of sulfate neutralizes anti-IIA the activity caused by 1 mg of an enoksaparin of sodium); high doses neutralize Anti-ha activity of an enoksaparin of sodium for 60%.

Storage conditions:

At a temperature not over 25 ºС. To store in the place, unavailable to children! Period of validity 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Solution for hypodermic introduction. On 2000 ME/0,2 ml, 4000 ME/0,4 ml or 6000 ME/0,6 ml in the syringes with a single dose consisting: from a syringe body of glass Type I, with the attached needle from stainless steel; a rigid protective cap of a needle from natural rubber and stiren-butadiene-rubber mix; elastomeric stopper of the piston (chlorbutyl rubber); piston: blue color (for a dosage of 2000 ME/0,2 ml); red color (for a dosage of 4000 ME/0,4 ml); white transparent color (for a dosage of 6000 ME/0,6 ml).

The syringe (for a dosage of 6000 ME/0,6 ml) in addition has graduation, each division corresponds to 0,025 ml. On two filled syringes PVC the packaging sealed by a paper foil are packed in planimetric. 3 planimetric PVC of packaging together with the application instruction in a cardboard pack.