FRAKSIPARIN

Active material: Nadroparin calcium
When ATH: B01AB06
CCF: The anticoagulant of direct action – Heparin nizkomolyekulyarnyi
ICD-10 codes (testimony): I20.0, I21, i26, I74, I82
When CSF: 01.12.11.06.02
Manufacturer: GLAXO WELLCOME PRODUCTION (France)

Pharmaceutical form, composition and packaging

The solution for the p / to the introduction clear, slightly opalescent, colorless or light yellow.

Excipients: solution of calcium hydroxide or dilute hydrochloric acid (to pH 5.0-7.5), water d / and (to 0.3 ml).

0.3 ml – single-dose syringes (2) – blisters (1) – packs cardboard.
0.3 ml – single-dose syringes (2) – blisters (5) – packs cardboard.

The solution for the p / to the introduction clear, slightly opalescent, colorless or light yellow.

Excipients: solution of calcium hydroxide or dilute hydrochloric acid (to pH 5.0-7.5), water d / and (to 0.4 ml).

0.4 ml – single-dose syringes (2) – blisters (1) – packs cardboard.
0.4 ml – single-dose syringes (2) – blisters (5) – packs cardboard.

The solution for the p / to the introduction clear, slightly opalescent, colorless or light yellow.

Excipients: solution of calcium hydroxide or dilute hydrochloric acid (to pH 5.0-7.5), water d / and (to 0.6 ml).

0.6 ml – single-dose syringes (2) – blisters (1) – packs cardboard.
0.6 ml – single-dose syringes (2) – blisters (5) – packs cardboard.

The solution for the p / to the introduction clear, slightly opalescent, colorless or light yellow.

Excipients: solution of calcium hydroxide or dilute hydrochloric acid (to pH 5.0-7.5), water d / and (to 0.8 ml).

0.8 ml – single-dose syringes (2) – blisters (1) – packs cardboard.
0.8 ml – single-dose syringes (2) – blisters (5) – packs cardboard.

The solution for the p / to the introduction clear, slightly opalescent, colorless or light yellow.

Excipients: solution of calcium hydroxide or dilute hydrochloric acid (to pH 5.0-7.5), water d / and (to 1 ml).

1 ml – single-dose syringes (2) – blisters (1) – packs cardboard.
1 ml – single-dose syringes (2) – blisters (5) – packs cardboard.

Pharmacological action

Nadroparin calcium is a low molecular weight heparin (LMWH), obtained by depolymerization of standard heparin, glikozoaminoglikanov is an average molecular weight 4300 Dalton.

Exhibits high binding to plasma proteins antithrombin III (AT III). This binding leads to an accelerated inhibition of factor Xa, and this is due to the high antithrombotic potential of nadroparin.

Other mechanisms, providing antithrombotic effect of nadroparin, transformation include activation of tissue factor inhibitor (TFPI), Direct activation of fibrinolysis by releasing tissue plasminogen activator of endothelial cells and modification of the rheological properties of the blood (lowering blood viscosity and increased permeability of membranes of platelets and granulocytes).

Nadroparin calcium characterized by a higher anti-factor Xa activity than anti-factor IIa or antithrombotic activity and has both immediate, and prolonged antithrombotic activity.

In comparison with unfractionated heparin nadroparin has less influence on the platelet function and aggregation, and Just noticeable effect on primary hemostasis.

The preventive doses nadroparin does not cause significant decrease APTT.

In exchange treatment in the period of maximum activity may increase to a value of APTT, in 1.4 times the standard. Such prolongation reflects the residual antithrombotic effect of nadroparin calcium.

Pharmacokinetics

The pharmacokinetic properties are determined on the basis of changes in anti-factor Xa activity of plasma.

Absorption

After p / to the introduction of C_max plasma levels achieved after 3-5 no, nadroparin almost completely absorbed (about 88%). The on / in the introduction of the maximum anti-Xa activity is achieved in less than 10 m, T_1/2 is about 2 no.

Metabolism

It is metabolized primarily in the liver by desulfation and depolymerization.

Deduction

After p / to the introduction of T_1/2 is about 3.5 no. However, anti-Xa activity is maintained for at least 18 hours after injection in a dose of nadroparin 1900 anti-Ha ME.

Pharmacokinetics in special clinical situations

Elderly patients due to physiological deterioration of kidney function slows down the elimination of nadroparin. Possible renal failure in this group of patients require evaluation and appropriate dose adjustment.

In clinical studies on the pharmacokinetics of nadroparin at / in a patient with renal failure of varying severity has been a correlation between nadroparin clearance and creatinine clearance. When comparing the values ​​obtained with the parameters in healthy volunteers has been found, that the AUC and T_1/2 in patients with renal insufficiency, mild (CC 36-43 ml / min) We were raised to 52% and 39% respectively, and plasma clearance of nadroparin reduced to 63% from normal values. Patients with severe renal insufficiency (CC 10-20 ml / min) AUC and T_1/2 We were raised to 95% and 112% respectively, and plasma clearance of nadroparin reduced to 50% from normal values. Patients with severe renal insufficiency (CC 3-6 ml / min) and hemodialysis, AUC and T_1/2 We were raised to 62% and 65% respectively, and plasma clearance of nadroparin reduced to 67% from normal values.

The results showed, that a small nadroparina accumulation may occur in patients with renal insufficiency, or mild to moderate severity (CC ≥ 30 ml / min < 60 ml / min). Hence, Fraksiparina dose should be reduced by 25% patients, receiving Fraksiparin to treat thromboembolism, unstable angina / myocardial infarction without Q wave. Patients with severe renal insufficiency in order to treat these conditions is contraindicated Fraksiparin.

In patients with renal failure or moderate in applying Fraksiparina to prevent thromboembolism nadroparina accumulation does not exceed that of patients with normal renal function, receiving therapeutic doses Fraksiparin. In applying Fraksiparina to prevent reduction of the dose in these patients is not required. Patients with severe renal insufficiency, Fraksiparin receiving prophylactic doses, should decrease the dose 25%.

Low molecular weight heparin is administered into the arterial line loop dialysis in doses high enough to, to prevent clotting of blood in the dialysis loop. Pharmacokinetic parameters were essentially unchanged, except in the case of overdose, when the passage of the drug into the systemic circulation can lead to increased anti-factor Xa activity, Conditionality final phase of renal failure.

Testimony

- Prevention of thromboembolic complications (surgical and orthopedic surgery; in patients with a high risk of thrombosis in acute respiratory and / or heart failure in the ICU);

- Treatment of venous thromboembolism;

- Prevention of clotting during hemodialysis;

- Treatment of unstable angina and myocardial infarction without Q wave.

Dosage regimen

When s / to the introduction of the drug is preferably administered with the patient lying, in n / a tissue of the anterolateral or posterolateral surface of the abdomen, alternately on the right and left hand. Allowed the introduction of the thigh.

To avoid the loss of drug when using syringes should not remove air bubbles before injection.

The needle should be introduced perpendicularly, rather than at an angle, jammed into a fold of skin, formed between the thumb and index finger. Fold should be maintained throughout the period of administration. Do not rub the injection site after the injection of the drug.

To prevention of thromboembolism in general surgical practice The recommended dose is Fraksiparina 0.3 ml (2850 anti-Ha ME) n / a. The drug was administered 2-4 hours before the operation, then – 1 time / day. Treatment is continued for at least 7 days or for the entire period of increased risk of thrombogenesis, to transfer the patient to outpatient treatment.

To prevention of thromboembolism in orthopedic surgery Fraksiparin administered s / c at a dose, established depending on the body weight of the patient based 38 anti-Ha ME / kg, which can be increased to 50% at the 4th postoperative day. The initial dose is prescribed for 12 hours before the operation, 2-Dose – through 12 h after surgery. Next Fraksiparin continue to apply 1 time / day during the period of increased risk of thrombosis to transfer the patient to outpatient treatment. The minimum duration of therapy – 10 days.

Patients with a high risk of thrombosis (usually, We are in intensive care units and intensive care / respiratory failure and / or infection of the respiratory tract and / or heart failure /) Fraksiparin appointed n / a 1 times / day dose, established depending on the body weight of the patient. Fraksiparin apply during the period of risk of thrombosis.

At the treatment of unstable angina and myocardial infarction without Q wave Fraksiparin appointed n / a 2 times / day (every 12 no). The duration of treatment is generally 6 days. In clinical studies, patients with unstable angina / myocardial infarction without Q wave Fraksiparin administered in combination with acetylsalicylic acid at a dose of 325 mg / day.

The initial dose is administered in a single I / bolus injection, subsequent doses administered s / c. Dose set depending on the rate of body weight 86 anti-Ha ME / kg.

At treatment of thromboembolism oral anticoagulants (in the absence of contraindications) should be appointed as soon as possible. Therapy Fraksiparinom not stop until it reaches the target values ​​of the prothrombin time. The drug is prescribed n / a 2 times / day (every 12 no), the usual duration of the course – 10 days. The dose depends on the body weight of the patient based 86 anti-Xa IU / kg body weight.

Prevention of clotting in the extracorporeal circuit during hemodialysis

Fraksiparina dose must be set individually for each patient, taking into account the technical conditions of dialysis.

Fraksiparin introduced singly into the arterial line loops in the beginning of each dialysis session. For patients without increased risk of bleeding recommended starting dose adjusted according to body weight, but sufficient for a 4-hour dialysis session.

In patients with increased risk of bleeding is possible to use half the recommended dose.

If dialysis session lasts longer 4 no, can be introduced additional small doses Fraksiparina.

During the subsequent dialysis dose should be selected depending on the effects observed.

It should observe the patient during dialysis due to the possible occurrence of bleeding or thrombotic indication system for dialysis.

In elderly patients correction dose is not required (except in patients with impaired renal function). Prior to treatment Fraksiparinom recommended to monitor renal function.

In patients renal insufficiency easy and moderate severity (CC ≥ 30 ml / min < 60 ml / min) to prevention of thrombotic events reducing the dose is not required, in patients with severe renal insufficiency (CC < 30 ml / min) the dose should be reduced by 25%.

In Patients with mild to moderate renal insufficiency to treatment of thromboembolism or thromboembolism prophylaxis in patients with a high risk of thrombosis (unstable angina and myocardial infarction without Q wave) the dose should be reduced by 25%, patients with severe renal insufficiency drug is contraindicated.

In patients with impaired liver function special studies on the drug were not carried out.

Side effect

Adverse reactions are shown depending on the frequency of occurrence: Often (>1/10), often (>1/100, < 1/10), sometimes (>1/1000, < 1/100), rarely (>1/10 000, < 1/1000), rarely (< 1/10 000).

From the blood coagulation system: Often – bleeding of different localization, more frequently in patients with other risk factors.

From the hematopoietic system: rarely – thrombocytopenia; rarely – eozinofilija, reversible after drug withdrawal.

From the digestive system: often – increase in liver transaminases (usually transient nature).

Allergic reactions: rarely – angioedema, skin reactions.

Local reactions: Often – the formation of small subcutaneous hematoma at the injection site; In some cases the appearance of dense knots (Ne oznachayushikh inkapsulirovaniye gyeparina), which disappear in a few days; rarely – skin necrosis, usually at the site of administration. Development of necrosis typically precedes Purpura or infiltration or painful spot jeritematoznoe, that may or may not be accompanied by common symptoms (in such cases, treatment should be stopped forthwith Fraxiparine).

Other: rarely – priapism, reversible hyperkalemia (associated with the ability of heparins suppress aldosterone secretion, especially in patients at risk).

Contraindications

-thrombocytopenia in applying nadroparina history;

— signs of bleeding or increased risk of bleeding, associated with the violation of hemostasis (except for DIC-syndrome, not caused by heparin);

-organic disease with a tendency to bleeding (eg, acute gastric ulcer or duodenal ulcer);

— injury or operational intervention in the brain and spinal cord or eyes;

is intracranial hemorrhage;

— acute septic endocardit;

- Severe renal insufficiency (CC <30 ml / min) patients, receiving Fraksiparin for treatment of thromboembolism, unstable angina and myocardial infarction without zubza Q;

— childhood and adolescence (to 18 years);

-hypersensitivity to nadroparinu or any other components of the drug.

FROM caution You should assign Fraksiparin in situations, associated with an increased risk of bleeding: hepatic failure, in renal failure, in severe hypertension, with a history of peptic ulcers or other conditions with increased risk of bleeding, If there is a violation of the circulatory system in the choroid and retina, in the postoperative period after operations on the brain and spinal cord or eyes, in patients weighing less than 40 kg, the duration of therapy, exceeding the recommended (10 days), in the case of non-compliance with recommended treatment conditions (especially increase the duration and dose for course use), in combination with drugs, increase the risk of bleeding.

Pregnancy and lactation

At present, there are only limited data on the penetration of nadroparina through the placental barrier in humans. Therefore, the use of Fraxiparina during pregnancy is not recommended, except in cases, the potential benefit to the mother outweighs the risk to the fetus.

There are currently only limited data to allocate nadroparina with breast milk. In this regard, use nadroparina lactation (breast-feeding) not recommended.

IN experimental studies animals not detected tertogennogo nadroparina calcium.

Cautions

Particular attention should be paid to specific instructions for use for each medicinal product, relating to the class of low molecular weight heparins, tk. they can be used in various metering units (U or mg). Because of this, it is unacceptable to the alternation of Fraxiparina with other NMG in long-term care. You must also pay attention to, What kind of drug is used – Fraksiparin or Fraksiparin Fort, tk. This affects the dosing regimen.

Graduated syringes are intended for dose selection depending on the body weight of the patient.

Fraksiparin is not intended to be in the/m introduction.

Because when you apply heparins there is possibility of developing trombozitopenia (heparin-induced thrombocytopenia), throughout the course of treatment should monitor the level of platelets Fraxiparine. Reported rare cases of thrombocytopenia, sometimes severe, that might be associated with arterial or venous thrombosis, that it is important to consider in the following cases: for thrombocytopenia; with a substantial reduction in the level of platelets (on 30-50% compared to normal rates); When negative dynamics by thrombosis, about which patient gets treatment; at DIC. In these cases treatment Fraxiparine should stop.

Thrombocytopenia is immunoallergicheskuju nature and is usually between 5-m and-m 21 days of therapy, but can occur before, If the patient has a heparin-induced thrombocytopenia in history.

In the presence of heparin-induced thrombocytopenia in history (with the use of conventional or low molecular weight heparins) Fraksiparin can be assigned, if necessary,. However, in this situation, shows strict clinical monitoring and, least, daily measurement of the number of platelets. If trombozitopenia application Fraxiparina should immediately discontinue. If the background of heparins (normal or low) thrombocytopenia occurs, You should consider the possibility of appointing anticoagulants other groups. If other drugs are not available, You may use a different low molecular weight heparin. This should be done daily to monitor the number of platelets in the blood. If signs of initial object continue to occur after you replace trombozitopenia drug, You should stop treatment as early as possible.

It must be remembered, that control platelet aggregation, based on in vitro tests, is of limited significance in the diagnosis of heparin-induced thrombocytopenia.

In elderly patients before therapy Fraxiparine need to evaluate kidney function.

Heparins can suppress aldosterone secretion, that can lead to giperkaliemii, especially in patients with elevated levels of potassium in the blood or in patients at risk of giperkaliemii (for patients with diabetes, chronic renal failure, metabolic azidoze, or in case of simultaneous use of medicines, that can cause giperkaliemia, When conducting long-term therapy). In patients with an increased risk of giperkaliemii should monitor the level of potassium in the blood.

The risk of spinal/epidural hematoma is increased in persons with established jepidural'nymi catheters or with concomitant use of other drugs, affecting hemostasis (NSAIDs, antiagregantы, other anticoagulants). Risk, probably, also incremented when a traumatic or repeated epidural or spinal puncture. Question about combined application of nejroaksial'noj blockade and anticoagulants should be addressed individually, After evaluating the efficiency ratios/risk. Patients, who already receive anticoagulants, should be the necessity of spinal or epidural anesthesia. Patients, that you want to jelektivnoe surgery using spinal or epidural anesthesia, should be the necessity of introduction of anticoagulants. If the patient is performed lumbar puncture or spinal or epidural anesthesia, should observe a sufficient time interval between the introduction of the Fraxiparina and the introduction or removal of spinal/epidural catheter or needle. Careful monitoring of the patient in order to identify the signs and symptoms of neurological disorders. When violations are detected in the neurological patient need urgent relevant therapy.

The prevention or treatment of venous thromboembolism, as well as in the prevention of blood clotting in the extracorporeal circulation in gemodialise not recommended joint appointment with such drugs as Fraxiparina acetylsalicylic acid, other salicylates, NSAID and antiplatelet agents, tk. This can increase the risk of bleeding.

Fraksiparin should be cautious appoint patients, receiving oral anticoagulants, CORTICOSTEROIDS for system application and dekstrana. When appointing oral anticoagulants in patients, receiving Fraksiparin, its use should be to continue to stabilize the measure prothrombin time to the required value.

Effects on ability to drive vehicles and management mechanisms

No data on the impact of Fraxiparina on the ability to drive a car or other mechanisms.

Overdose

Symptoms: the main sign of overdose is bleeding; you need to keep track of the number of platelets and other blood coagulation parameters.

Treatment: slight bleeding does not require special therapy (It is usually enough to reduce the dose or delay subsequent introduction). Protamine sulfate has a strong neutralizing action vis-à-vis the antikoaguljantnym effects of heparin, However, in some cases anti-HA activity may partially recover. Application of protamine sulfate required only in severe cases. It should be taken into account, what 0.6 ml protamine sulfate will neutralize approximately 950 anti-HA ME nadroparina. Dose of protamine sulfate is calculated taking into account the time, Since the introduction of heparin, with a possible decrease in doses of antidote.

Drug Interactions

Risk of giperkaliemii increases when applying Fraxiparina in patients, receiving potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins (low molecular weight or nefrackzionirovanne), Cyclosporine and Tacrolimus, trimethoprim.

Fraksiparin may potentiate the action of drugs, affecting hemostasis, such as acetylsalicylic acid or other NSAIDS, Vitamin k antagonists, fibrinolitiki and dextran.

Platelet aggregation inhibitors (In addition to acetylsalicylic acid as pain and antipyretic drug, ie. in a dose of 500 mg; NSAIDs): abciksimab, acetylsalicylic acid as a antiagreganta (ie. dose 50-300 mg) When cardiac and neurological testimony, beraprost, Clopidogrel, move eptifibatid, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, away from heating devices at a temperature of no higher than 30° c; Do not freeze. Shelf life – 3 year.