Fraksiparin forte

General characteristics. Structure:

Solution for injections transparent or poorly opalescent, colourless or poorly painted.

 1 syringe
Active ingredient: надропарин calcium of 11 400 ME Anti-ha

Excipients: hydroxide calcium solution of 1% or Acidum hydrochloricum diluted 8% (for maintenance of level рН) - q.s. to рН 4.5-7.5, water for and - to 0.6 ml.

Solution for injections transparent or poorly opalescent, colourless or poorly painted.

 1 syringe
Active ingredient: надропарин calcium of 15 200 ME Anti-ha

Excipients: hydroxide calcium solution of 1% or Acidum hydrochloricum diluted 8% (for maintenance of level рН) - q.s. till 4.5-7.5, water for and - to 0.8 ml.

Solution for injections transparent or poorly opalescent, colourless or poorly painted.

 1 syringe
Active ingredient: надропарин calcium of 19 000 ME Anti-ha

Excipients: hydroxide calcium solution of 1% or Acidum hydrochloricum diluted 8% (for maintenance of level рН) - q.s. - to рН 4.5-7.5, water for and - to 1 ml.

Pharmacological properties:

Anticoagulant of direct action - heparin low-molecular.

Nadroparin of calcium is characterized by higher activity concerning blood-coagulation factors Ha in comparison with activity concerning IIA blood-coagulation factors. It has both the immediate, and prolonged anticoagulating activity.

In comparison with unfractionated heparin, надропарин calcium has smaller influence on functions of thrombocytes and on their aggregation and has a little expressed influence on primary hemostasis.

In preventive doses does not cause the expressed decrease in the activated partial thrombin time (APTT).

At course treatment in the period of the maximum activity of AChTV it can be extended to the value, by 1.4 times exceeding standard. Such prolongation reflects residual anticoagulating effect of a nadroparin of calcium.

Action mechanism

Nadroparin of calcium is the low-molecular heparin (NMG) received by way of a depolymerization from standard heparin. It represents гликозаминогликан with an average molecular weight about 4300 дальтон.

Nadroparin of calcium shows high ability to linkng with antithrombin III (ATIII). This binding leads to the accelerated inhibition of blood-coagulation factors Ha, than and the high anticoagulating potential of a nadroparin of calcium is caused. Other mechanisms providing anticoagulating action of a nadroparin of calcium include activation of inhibitor of a way of a fabric factor (TFPI), activation of a fibrinolysis by means of direct release of the activator of fabric plasminogen from endothelial cells and modification of rheological properties of blood (decrease in viscosity of blood and increase in permeability of membranes of thrombocytes and granulocytes).

 

Pharmacokinetics. Pharmacokinetic properties are defined on the basis of change anti-Ha - factor activity of plasma.

Absorption

After п / to introduction maximum anti-Ha - factor activity (Cmax) is reached in 3-5 h.

Later in/in introductions of Cmax in plasma it is reached within the first 10 min.

Distribution

After п / to introduction надропарин calcium it is almost completely soaked up (about 88%).

At in introduction maximum anti-Ha - factor activity is reached less than in 10 min., T1/2 makes about 2 h.

Metabolism

Metabolism happens generally in a liver (a desulfatirovaniye, a depolymerization).

Removal

T1/2 after п / to introduction makes about 3.5 h. However anti-Ha - factor activity remains during at least 18 h after an injection of a nadroparin of calcium in a dose 1900 Anti-ha of ME.

At in/in T1/2 makes about 2 h.

Pharmacokinetics in special clinical cases

At elderly patients, in connection with possible depression of function of kidneys, elimination of a nadroparin of calcium can be slowed down. The possible renal failure in this group of patients demands assessment and the corresponding dose adjustment.

In the clinical trials devoted to studying of pharmacokinetics of a nadroparin of calcium at in introduction to patients with a renal failure of various weight correlation between clearance of a nadroparin of calcium and clearance of creatinine was established. When comparing of the received values with indicators at healthy volunteers, it was established that AUC it1/2 at patients with a renal failure of moderate degree (clearance of creatinine of 36-43 ml/min.) were raised for 52 and 39% respectively, and the plasma clearance of a nadroparin of calcium is reduced to 63% of normal values. At patients with a heavy renal failure (clearance of creatinine of 10-20 ml/min.) AUC and T1/2 were raised for 95 and 112% respectively, and the plasma clearance of a nadroparin of calcium is reduced to 50% of normal values. At patients with heavy renal failures (clearance of creatinine of 3-6 ml/min.) which are on a hemodialysis, AUC and T1/2 were raised for 62 and 65% respectively, and the plasma clearance of a nadroparin of calcium is reduced to 67% of normal values.

Results of a research showed that small accumulation of a nadroparin of calcium can be observed at patients with a renal failure of moderate degree (clearance of creatinine more or is equal 30 ml/min. and less than 50 ml/min.), therefore, Fraksiparin Forta should reduce a drug dose by 25-33% at such patients receiving it for the purpose of treatment of a thromboembolism. Drug Fraksiparin Forta is contraindicated to patients with a heavy renal failure, for the purpose of treatment of these states.

Indications to use:

— treatment of thromboses and thromboembolisms.

Route of administration and doses:

For п / to introduction.

Drug is not intended to Fraksiparin Forta for introduction in oil.

At treatment by drug to Fraksiparin Forta clinical monitoring of quantity of thrombocytes has to be carried out.

When carrying out spinal/epidural anesthesia / the spinal puncture needs to study the data presented in the section "Special Instructions" also.

Special attention should be paid to specific application instructions for each medicine belonging to the class of low-molecular heparins (NMG) since in them various units of dosing can be used (PIECE or mg). Owing to what drug alternation to Fraksiparin Forta with other NMG is inadmissible at prolonged treatment. It is also necessary to pay attention to what drug is used — Fraksiparin or Fraksiparin Forta since it influences the dosing mode.

The graduated syringes are intended for selection of a dose depending on the body weight of the patient.

The equipment п / to introduction

It is preferable to administer the drug in position of the patient "lying", in hypodermic fabric of a perednebokovy or posterolateral surface of an abdominal wall, serially from the right and left side. Introduction to a hip is allowed.

In order to avoid loss of drug when using syringes it is not necessary to delete vials of air before an injection.

The needle should be entered perpendicularly, but not at an angle, into previously created fold of skin which needs to be held between big and index fingers until the end of administration of solution. It is not necessary to pound a drug injection site after an injection.

Adults

At treatment of thromboembolic states it is necessary to appoint peroral anticoagulants as soon as possible, on condition of lack of contraindications to them. Drug Fraksiparin Forta should continue treatment before achievement of the MNO target values.

The recommended dosing mode: 1 time / п / to, the usual duration of a course — 10 days. The dose depends on the body weight of the patient and body weight ME/kg is provided below in the table, at the rate of 171 Anti-ha.

The body weight of the patient          is 1 times/days duration there are 10 days 
                                                 Volume, ml               Anti-ha ME  
<                                                 50 0.4                          7600
                                               50-59 0.5                         9500
                                               60-69 0.6                        11 400
                                              70-79 0.7                        13 300
                                              80-89 0.8                        15 200
>                                                 90 0.9                        17 100

Children and teenagers aged up to 18 years

Fraksiparin Forta is not recommended to use drug at children and teenagers, i.e. so far there are not enough data on efficiency and safety, for definition of a dose at patients 18 years are younger.

Patients of advanced age

Correction of the mode of dosing, except for patients with a renal failure is not required from patients of advanced age. Prior to treatment by drug Fraksiparin Forta is recommended to carry out assessment of function of kidneys.

Renal failures

At patients with renal failures of moderate severity (clearance of creatinine of 30-50 ml/min.) receiving drug to Fraksiparin Forta for treatment of a thromboembolism, the dose should be lowered by 25%. Drug Fraksiparin Forta is contraindicated to patients with a heavy renal failure.

Patients with an abnormal liver function

Special researches for this group of patients were not conducted.

Features of use:

The heparin-induced thrombocytopenia

As at use of heparins there is a possibility of development of thrombocytopenia (heparin - the induced thrombocytopenia), during all course of treatment drug Fraksiparin Forta needs to monitorirovat quantity of thrombocytes.

It was reported about exceptional cases of thrombocytopenia, sometimes heavy which could be connected with arterial or venous thromboses that it is important to consider in the following cases:

— at thrombocytopenia;

— at considerable reduction of maintenance of thrombocytes (for 30-50% in comparison with a reference value);

— at negative dynamics from thrombosis concerning which the patient receives treatment;

— at the thrombosis which developed against the background of drug use;

— at the IDCS.

In these cases drug Fraksiparin Forta should stop treatment.

The specified effects of the immunoallergic nature usually are noted between 5 and 21 day of treatment, but can arise earlier if the patient has heparin - the induced thrombocytopenia in the anamnesis.

In the presence heparin - the induced thrombocytopenia in the anamnesis (against the background of unfractionated or low-molecular heparins), treatment by drug to Fraksiparin Forta if necessary can be appointed. However in this situation strict clinical monitoring and, at least, daily measurement of number of thrombocytes are shown. When developing thrombocytopenia Fraksiparin Forta should stop drug use immediately.

If against the background of heparins (unfractionated or low-molecular) there is thrombocytopenia, then it is necessary to consider the possibility of purpose of anticoagulants of other groups. If other drugs are unavailable, then use of other low-molecular heparin is possible. At the same time it is necessary to watch daily number of thrombocytes in blood. If symptoms of the beginning thrombocytopenia continue to be observed after drug replacement, then it is necessary to stop treatment as soon as possible. It is necessary to remember that the control of aggregation of thrombocytes based on in vitro tests has limited value at diagnosis heparin - the induced thrombocytopenia.

Patients of advanced age

Before an initiation of treatment drug Fraksiparin Forta needs to estimate function of kidneys.

Renal failure

At patients with a moderate renal failure (the clearance of creatinine more or is equal to 30 ml/min. and less than 50 ml/min.) the attending physician has to accept the decision on need of a dose decline, weighing risk of bleedings on the one hand and thromboembolisms on the other hand.

Hyperpotassemia

Heparins can suppress secretion of Aldosteronum that can lead to a hyperpotassemia, especially patients with the increased potassium concentration in blood or at patients with risk have increases in content of potassium in blood (including patients with a diabetes mellitus, a chronic renal failure, a metabolic acidosis or the patients accepting drugs which can cause a hyperpotassemia (for example, APF, NPVP inhibitors)). The risk of a hyperpotassemia increases at long therapy, but we will usually turn at cancellation. At the patients who are in risk group it is necessary to control potassium concentration in blood.

Spinal/epidural anesthesia / a spinal puncture and the accompanying medicines

The risk of developing of spinal/epidural hematomas increases at persons with the established epidural catheters or the accompanying use of other medicines which can affect a hemostasis, such as NPVP, antiagregant or other anticoagulants. The risk, apparently, also increases when carrying out traumatic or repeated epidural or spinal punctures. Thus, the question of the combined use of neuroaxial blockade and anticoagulants has to be solved individually after ratio assessment advantage/risk in the following situations:

— at patients who already receive anticoagulants need of spinal or epidural anesthesia has to be proved;

— at patients to whom elective surgical intervention using spinal or epidural anesthesia is planned need of administration of anticoagulants has to be proved.

When carrying out a lumbar puncture or spinal/epidural anesthesia there have to pass at least 12 h between administration of drug to Fraksiparin Forta for the purpose of prevention or 24 h for the purpose of treatment and introduction or removal of a spinal/epidural catheter or needle. At patients with a renal failure increase in these intervals can be considered. Careful observation of the patient for the purpose of identification of signs and symptoms of neurologic disturbances is necessary. At detection of disturbances in the neurologic status of the patient, urgent corresponding therapy is required.

Salicylates, NPVP and antiagregant

At prevention or treatment venous thromboembolisms, and also at prevention of a blood coagulation in system of extracorporal blood circulation at a hemodialysis simultaneous use of drug is not recommended to Fraksiparin Forta with such drugs as NPVP (including acetylsalicylic acid and other salicylates) and antiagregant since it can increase risk of development of bleedings.

Allergy to latex

The basis of a needle of previously filled syringe may contain dry natural latex which can cause allergic reaction in patients with hypersensitivity to latex.

Skin necrosis

About cases of a necrosis of skin it was reported very seldom. The skin necrosis is usually preceded by a purpura or an infiltrirovanny or painful erythematic spot which can be followed or not be followed by the general symptoms. In such cases drug Fraksiparin Forta should cancel treatment immediately.

Influence on ability to driving of motor transport and to control of mechanisms

There are no data on drug influence to Fraksiparin Forta on ability to manage vehicles, mechanisms.

Side effects:

The undesirable phenomena given below are listed depending on anatomo-physiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1/10), it is frequent (≥1/100 and <1/10), infrequently (≥1/1 000 and <1/100), is rare (≥1/10 000 and <1/1000), is very rare (<1/10 000, including separate cases). Categories of frequency were created on the basis of clinical trials of drug and post-registration observations.

From hemopoietic and lymphatic system: very often - bleedings of various localizations, are more often at patients with other risk factors; seldom - thrombocytopenia (including heparin - the induced thrombocytopenia), a thrombocytosis; very seldom - an eosinophilia, reversible after drug withdrawal.

From immune system: very seldom - hypersensitivity reactions (including a Quincke's edema and skin reactions), anaphylactoid reactions.

From a metabolism: very seldom - the reversible hyperpotassemia connected with effect of genarin to suppress secretion of Aldosteronum, especially at patients from risk group.

From a liver and biliary tract: often - the increase in activity of hepatic transaminases having usually passing character.

Local reactions: very often - education п / to a hematoma in the place of an injection. Emergence of the dense small knots which are not meaning heparin encapsulation which disappear in several days is in certain cases observed; often - reactions in an injection site; seldom - calcification in an injection site. Calcification meets at patients with disturbance of exchange of calcium and phosphates, for example, in certain cases at a chronic renal failure more often.

From generative organs: very seldom - a priapism.

From skin and a hypodermic fatty tissue: seldom - rash, urticaria, an erythema, an itch; very seldom - a skin necrosis, usually in an injection site.

Interaction with other medicines:

Development of a hyperpotassemia can depend on simultaneous presence of several risk factors. The medicines causing a hyperpotassemia: potassium salts, kaliysberegayushchy diuretics, APF inhibitors, blockers of receptors of angiotensin II, NPVP, heparins (low-molecular or unfractionated), cyclosporine and такролимус, Trimethoprimum. Danger of development of a hyperpotassemia increases at a combination of above-mentioned means with drug to Fraksiparin Forta.

Combined use of drug to Fraksiparin Forta with the drugs influencing a hemostasis such as acetylsalicylic acid, NPVP, indirect anticoagulants, fibrinolitik and a dextran, leads to mutual strengthening of effect.

Besides, it is necessary to take into account that antiagregant (except acetylsalicylic acid as analgeziruyushchy and febrifugal medicine, i.e. in a dose over 500 mg): абциксимаб, acetylsalicylic acid in antiagregantny doses (50-300 mg) at cardiological and neurologic indications, берапрост, klopidogret, эптифибатид, илопрост, тиклопидин, тирофибан — strengthen risk of development of bleeding.

Fraksiparin Forta should appoint drug with care to the patients receiving indirect anticoagulants, system GKS and dextrans. At purpose of indirect anticoagulants to the patients receiving drug to Fraksiparin Forta, it is necessary to continue its use before stabilization of an indicator of MHO to required value.

Contraindications:

— symptoms of bleeding or the increased risk of bleeding connected with disturbance of a hemostasis (except for the IDCS which is not caused by heparin);

— organic lesions of bodies with tendency to bleeding (for example, an aggravation of a peptic ulcer of a stomach and duodenum);

— intracraneal hemorrhages;

— acute septic endocarditis;

— thrombocytopenia (at use of a nadroparin in the anamnesis);

— a renal failure of heavy degree (KK <30 ml/min.) at the patients receiving drug to Fraksiparin Forta for the purpose of treatment of a thromboembolism, unstable stenocardia and a myocardial infarction without Q tooth;

— children's age up to 18 years (in connection with insufficiency of data);

— hypersensitivity to drug or other low-molecular heparins and/or heparin in the anamnesis.

Fraksiparin Forta should appoint drug in the following situations with care, in connection with the increased risk of bleedings:

— at a liver failure;

— at a renal failure;

— at heavy arterial hypertension;

— at round ulcers in the anamnesis or other diseases with the increased risk of bleeding;

— at disturbances of blood circulation in a choroid and a retina of an eye;

— in the postoperative period after a head and spinal cord operations or in the eyes;

— at patients with a body weight less than 40 kg;

— in case of duration of treatment exceeding recommended (10 days);

— in case of non-compliance with the recommended treatment conditions (in particular durations and establishments of a dose on the basis of body weight for course use);

— at a combination with the drugs strengthening risk of bleeding.

 

Drug FRAKSIPARIN use FORTE at pregnancy and feeding by a breast

There are no data on influence of a nadroparin of calcium on fertility.

Animal experiments did not show teratogenic or fetotoksichesky effects of a nadroparin of calcium, nevertheless, now there are only limited data concerning penetration of a nadroparin of calcium through a placenta at the person. Therefore purpose of drug is not recommended to Fraksiparin Forta at pregnancy, except cases when the potential advantage for mother exceeds risk for a fruit.

Now there are only limited data on allocation of a nadroparin of calcium in breast milk. In this regard use of a nadroparin of calcium during breastfeeding is not recommended.

 

Use at abnormal liver functions

Special researches for this group of patients were not conducted.

 

Use at renal failures

At patients with renal failures of moderate severity (clearance of creatinine of 30-50 ml/min.) receiving drug to Fraksiparin Forta for treatment of a thromboembolism, the dose should be lowered by 25%. Drug Fraksiparin Forta is contraindicated to patients with a heavy renal failure.

 

Use for elderly patients

Correction of the mode of dosing, except for patients with a renal failure is not required from patients of advanced age. Prior to treatment by drug Fraksiparin Forta is recommended to carry out assessment of function of kidneys.

Use for children

It is contraindicated:

— children's age up to 18 years (in connection with insufficiency of data).

Overdose:

Symptoms: the main sign of overdose at п / to introduction is bleeding.

Treatment: it is necessary to watch number of thrombocytes and other parameters of coagulant system of blood. Insignificant bleedings do not demand special therapy, happens usually enough to lower or delay the subsequent dose of drug to Fraksiparin Forta.

Protamin sulfate has the expressed neutralized effect in relation to anticoagulating effects of heparin, however some anti-Ha - factor activity can remain. Use of protamin of sulfate is necessary only in hard cases.

0.6 the ml of protamin of sulfate neutralizes about 950 Anti-ha ME of a nadroparin of calcium. The dose of protamin of sulfate is calculated taking into account time which passed after administration of heparin with a possible dose decline of an antidote.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 30 °C. Not to freeze. A period of validity - 3 years.

Issue conditions:

According to the recipe

Packaging:

• solution for инъекц. 11 400 ME anti-Ha/0.6 of ml: syringes one-dose 2 or 10

• solution for инъекц. 15 200 ME anti-Ha/0.8 of ml: syringes one-dose 2 or 10

• solution for инъекц. 19 000 ME anti-Ha/1 of ml: syringes one-dose 2 or 10.