Fraxiparin Forte (Fraxiparine Forte)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceNadroparin calciumNadroparin calcium
Dosage form: & nbsp

Solution for subcutaneous administration

Composition:

Component name

Quantity per 1 ml

Nadroparin calcium

19000 ME anti-Ha-factor activity

Calcium hydroxide solution 1% (or dilute hydrochloric acid 8%)

sufficient amount to pH 4.5-7.5

Water for injections

up to 1.0 ml

The content of calcium nadroparin in various forms of release:

Syringes for 0.6 ml - 11400 ME anti-Ha-factor activity.

Syringes on 0,8 ml - 15200 ME of anti-Ha-factor activity.

Syringes of 1.0 ml - 19000 ME anti-Ha-factor activity.

Description:

Transparent or slightly opalescent, colorless or slightly colored solution.

Pharmacotherapeutic group:Anticoagulant means of direct action
ATX: & nbsp

B.01   Anticoagulants

Pharmacodynamics:

Nadroparin calcium is characterized by a higher activity with respect to the coagulation factor Xa in comparison with the activity with respect to the coagulation factor IIa. He has both immediate and prolonged anticoagulant activity.

Compared with unfractionated heparin, adenoparin calcium has less influence on the function of platelets and on their aggregation and has little effect on primary hemostasis.

In preventive doses does not cause a marked decrease in activated partial thrombin time (APTTV).

At course treatment during the period of maximum activity, the APTT can be extended to a value 1.4 times higher than the standard one. This prolongation reflects the residual anticoagulant effect of calcium supra-paryl.


Mechanism of action

Nadroparin calcium is a low molecular weight heparin (LMWH), obtained by depolymerization from standard heparin. It is a glycosaminoglycan with an average molecular weight of about 4,300 daltons.

Nadroparin calcium shows a high ability to bind to antithrombin III (ATIII). This binding leads to an accelerated inhibition of the coagulation factor of Ha, which is responsible for the high anticoagulant potential of the calcium supraparin. Other mechanisms providing an anticoagulant effect of calcium suparaprin include the activation of a tissue factor pathway inhibitor (TFPI), the activation of fibrinolysis by direct release of a tissue activatorplasminogen from endothelial cells and modification of the rheological properties of blood (decrease in blood viscosity and increase in the permeability of platelet and granulocyte membranes).

Pharmacokinetics:

Pharmacokinetic properties are determined on the basis of a change in the anti-Xa factor activity of the plasma.

Suction. After subcutaneous administration, the maximum anti-Ha-factor activity (CmOh) is achieved in 3-5 hours (Tmax).

After intravenous administration, the maximum plasma concentration is reached within the first 10 minutes.

Distribution. After subcutaneous administration adenoparin calcium almost completely absorbed (about 88%).

With intravenous administration, the maximum anti-Ha-factor activity is achieved in less than 10 minutes, the half-life (T1/2) is about 2 hours.

Metabolism. Metabolism occurs mainly in the liver (desulphation, depolymerization).

Excretion. The half-life after subcutaneous administration is about 3.5 hours. However, anti-Ha-factor activity persists for at least 18 hours after the injection of calcium supraparin at a dose of 1900 anti-XA ME.


Special patient groups

Elderly patients

In elderly patients, in connection with a possible decrease in kidney function, elimination of calcium supraparin can be slowed down. Possible renal failure in this group of patients requires evaluation and appropriate dose adjustment.

Patients with impaired renal function

In clinical studies devoted to the study of the pharmacokinetics of calcium supra-paryrin with intravenous administration to patients with renal insufficiency of varying severity, a correlation was established between the clearance of calcium supra-paryl and the clearance of creatinine. When comparing the values ​​obtained with the indices in healthy volunteers, it was found that AUC (area under the pharmacokinetic curve "concentration-time") and T1/2 in patients with moderate renal insufficiency (creatinine clearance 36-43 ml / min) were increased by 52 and 39%, respectively, and plasma clearance of the supraparrin calcium was reduced to 63% of the normal values. In patients with severe renal insufficiency (creatinine clearance 10-20 ml / min) AUC and T1/2 were increased by 95% and 112%, respectively, and the plasma clearance of the supraparrin calcium was reduced to 50% of the normal values.In patients with severe renal dysfunction (creatinine clearance 3-6 ml / min) on hemodialysis, AUC and T1/2 were increased by 62 and 65%, respectively, and the plasma clearance of the supraparrin calcium was reduced to 67% of the normal values.

The results of the study showed that a small accumulation of calcium supraparin can be observed in patients with a moderate degree of moderate renal insufficiency (creatinine clearance is more than or equal to 30 ml / min and less than 50 ml / min), therefore, the dose of Fraxiparin Forte should be reduced by 25-33% in such patients receiving it for the purpose of treating thromboembolism. The drug Fraxiparin Forte is contraindicated in patients with severe renal insufficiency, in order to treat these conditions.

Indications:

The drug Fraxiparin Forte is prescribed to patients for:

  • Treatment of thrombosis and thromboembolism.

Contraindications:

- Hypersensitivity to nadaraparin calcium or any other component of the drug;

- Thrombocytopenia with the use of a calcium supra-paparin in the anamnesis;

- Signs of bleeding or an increased risk of bleeding due to hemostasis disorder, with the exception of DIC syndrome not caused by heparin;

- Organic damage to organs with a tendency to bleeding (eg, exacerbation of peptic ulcer of the stomach and duodenum);

- Trauma or surgery on the brain and spinal cord or on the eyes;

- Intracranial hemorrhage;

- Acute septic endocarditis;

- Severe renal insufficiency (creatinine clearance less than 30 ml / min) in patients receiving Fraxiparin Forte for the treatment of thromboembolism, unstable angina and myocardial infarction without Q wave;

- Children under 18 years of age (due to insufficient data).

Carefully:

The drug Fraxiparin Forte should be administered in the following situations with caution, due to an increased risk of bleeding:

  • With hepatic insufficiency;
  • With renal insufficiency;
  • With severe arterial hypertension;
  • With peptic ulcers in a history or other diseases with an increased risk of bleeding;
  • With circulatory disorders in the choroid and the retina of the eye;
  • In the postoperative period after operations on the brain and spinal cord or on the eyes;
  • Patients weighing less than 40 kg;
  • In case of treatment duration exceeding recommended (10 days);
  • In case of non-observance of the recommended treatment conditions (in particular, duration and establishment of a dose based on body weight for the course application);
  • When combined with drugs that increase the risk of bleeding (see section "Interactions with other drugs").

Pregnancy and lactation:

Fertility. There is no data on the effect of calcium supaparin on fertility.

Pregnancy. Experiments on animals did not show teratogenic or fetotoxic effects of calcium supraparin, however, at the present time there are only limited data concerning the penetration of calcium supra-paparin through the placenta in humans. Therefore, the use of the drug Fraksiparin Forte during pregnancy is not recommended, except when the potential benefit to the mother exceeds the risk to the fetus.

Lactation. At present, there are only limited data on the release of calcium supra-carragein in breast milk. In this regard, the use of calcium supra-paparin in the period of breastfeeding is not recommended.

Dosing and Administration:

For subcutaneous administration.

The drug Fraksiparin Forte is not intended for intramuscular administration.

When treating the drug Fraksiparin Forte, a clinical monitoring of the platelet count should be carried out.

When carrying out a spinal / epidural anesthesia / spinal puncture, you should also read the information provided in the "Special instructions" section.

Particular attention should be given to specific instructions for use for each drug belonging to the class of low molecular weight heparins (LMWH), various dosage units (ED or mg) can be used in them. Because of this, the alternation of the drug Fraksiparin Forte with other LMWH during long-term treatment is not permissible. Also it is necessary to pay attention to what kind of drug is used - Fraksiparin or Fraksiparin Forte, tk. this affects the dosing regimen.

Graduated syringes are designed to adjust the dose depending on the weight of the patient's body.

The technique of subcutaneous injection

Preferably, the drug is administered in the patient's "lying" position, in the subcutaneous tissue of the anterolateral or posterolateral surface of the abdominal wall, alternately from the right and left sides.Admission to the hip is permissible.

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

The needle should be inserted perpendicularly, and not at an angle, into a pre-formed skin fold, which must be kept between the thumb and forefinger until the end of the solution. Do not rub the injection site after injection.

Adults

In the treatment of thromboembolic conditions, oral anticoagulants should be given as early as possible, provided there are no contraindications to them. Treatment with Fraksiparin Forte should continue until the target values ​​of the international normalized relationship are reached.

Recommended dosing regimen: once a day, subcutaneously, the usual duration of the course is 10 days. The dose depends on the body weight of the patient and is listed below in the table, based on 171 anti-Ha IU / kg body weight.

Body mass patient (kg)

Once a day, the duration is 10 days

Volume, ml

Anti-Ha ME

<50

0.4

7600

50-59

0.5

9500

60-69

0.6

11400

70-79

0.7

13300

80-89

0.8

15200

>90

0.9

17100

Children under the age of 18

The drug Fraksiparin Forte is not recommended for use in children and adolescents, t. to date, there is insufficient data on efficacy and safety, to determine the dose in patients under 18 years of age.

Elderly patients

Older patients do not need a dosage adjustment, except for patients with impaired renal function. Before starting treatment with the drug Fraksiparin Forte, it is recommended that an evaluation of kidney function is performed.

Renal impairment

In patients with impaired renal function of moderate severity (creatinine clearance 30-50 ml / min) receiving Fraxiparin Forte for the treatment of thromboembolism, the dose should be reduced by 25%. The drug Fraksiparin Forte is contraindicated in patients with severe renal failure.

Patients with impaired hepatic function

There were no special studies for this group of patients.

Side effects:

The undesirable phenomena presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. Frequency of occurrence is defined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1 000 and <1/100), rarely (> 1/10 000 and <1/1 000), very rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration observations.

From the hematopoietic and lymphatic system

Often: bleeding of various localizations, more often in patients with other risk factors;

Rarely: thrombocytopenia (including heparin-induced thrombocytopenia), thrombocytosis;

Rarely: eosinophilia reversible after drug withdrawal.

From the immune system

Rarely: hypersensitivity reactions (including Quincke's edema and skin reactions), anaphylactoid reactions.

From the side of metabolism and nutrition

Rarely: reversible hyperkalemia associated with the effect of heparins suppressing the secretion of aldosterone, especially in patients at risk.

From the liver and biliary tract

Often: increased activity of "liver" transaminases, which is usually of a transient nature.

General disorders and disorders at the site of administration

Often: the formation of subcutaneous hematoma at the injection site. In some cases there is the appearance of tight knots, not meaning the encapsulation of heparin, which disappear after a few days;

Often: reactions at the injection site;

Rarely: Calcification at the injection site. Calcification is more common in patients with impaired calcium and phosphate metabolism, for example, in some cases with chronic kidney failure.

From the genitals and breast

Rarely: priapism.

From the skin and subcutaneous fat

Rarely: rash, hives, erythema, itching;

Rarely: necrosis of the skin, usually at the injection site.

Overdose:

Symptoms

The main sign of an overdose with subcutaneous injection is bleeding. It is necessary to monitor the number of platelets and other parameters of the blood coagulation system. Minor bleeding does not require special therapy, it is usually sufficient to reduce or delay the subsequent dose of Fraksiparin Forte.

Treatment

Protamine sulfate has a pronounced neutralizing effect with respect to anticoagulant effects of heparin, however some anti-Xa factor activity may persist. The use of protamine sulfate is necessary only in severe cases.

0.6 ml of protamine sulfate neutralizes about 950 anti-Xa ME of calcium supaparin. The dose of protamine sulfate is calculated taking into account the time elapsed after the administration of heparin, with a possible reduction in the dose of the antidote.

Interaction:

The development of hyperkalemia may depend on the simultaneous presence of several risk factors. Drugs that cause hyperkalemia: potassium salts,potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, non-steroidal anti-inflammatory drugs, heparins (low molecular or unfractionated), ciclosporin and tacrolimus, trimethoprim. The risk of hyperkalemia increases with a combination of the above mentioned drugs with the drug Fraksiparin Forte.

Joint use of the drug Fraksiparin Forte with drugs that affect hemostasis, such as acetylsalicylic acid, non-steroidal anti-inflammatory drugs (NSAIDs), indirect anticoagulants, fibrinolytics and dextran, leads to a mutual enhancement of the effect.

In addition, it should be taken into account that antiplatelet agents (except for acetylsalicylic acid as an analgesic and antipyretic drug, i.e., in a dose exceeding 500 mg): abciximab, acetylsalicylic acid in antiplatelet doses (50-300 mg) with cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban - increase the risk of bleeding.

The drug Fraxiparin Forte should be administered with caution to patients receiving indirect anticoagulants, systemic glucocorticosteroids and dextrans. In the appointment of indirect anticoagulants to patients receiving the drug Fraksiparin Forte, its use should continue until the INR is stabilized to the required value.

Special instructions:

Heparin-induced thrombocytopenia

Since the use of heparins, there is the possibility of developing thrombocytopenia (heparin-induced thrombocytopenia), during the entire course of treatment with the drug Fraksiparin Forte, the number of platelets must be monitored.

There have been reports of rare cases of thrombocytopenia, sometimes severe, that could be associated with arterial or venous thrombosis, which is important to consider in the following cases:

  • with thrombocytopenia;
  • with a significant decrease in platelet count (by 30-50% compared with the initial value);
  • with negative dynamics on the part of thrombosis, for which the patient is receiving treatment;
  • at a thrombosis, developed on a background of application of a preparation;
  • with ICE (disseminated intravascular coagulation) -syndrome.

In these cases, treatment with Fraksiparin Forte should be discontinued.

These effects of immunoallergic nature are usually observed between the 5th and 21st day of treatment, but may occur earlier if the patient has heparin-induced thrombocytopenia in the anamnesis.

In the presence of heparin-induced thrombocytopenia in the history (on the background of unfractionated or low-molecular-weight heparins), treatment with the drug Fraksiparin Forte, if necessary, can be prescribed. However, in this situation, strict clinical monitoring and, at a minimum, a daily measurement of the number of platelets are shown. When thrombocytopenia occurs, the use of Fraksiparin Forte should be stopped immediately.

If thrombocytopenia occurs against the background of heparins (unfractionated or low-molecular), then the use of anticoagulants of other groups should be considered. If other drugs are not available, then another low-molecular-weight heparin may be used. It should be observed daily the number of platelets in the blood. If signs of beginning thrombocytopenia continue to occur after the drug has been changed, treatment should be stopped as soon as possible.It should be remembered that the control of platelet aggregation, based on in vitro tests, is of limited importance in the diagnosis of heparin-induced thrombocytopenia.

Elderly patients

Before starting treatment with Fraksiparin Forte, the kidney function should be evaluated.

Renal insufficiency

The decision on the need to reduce the dosage in patients with mild renal failure patients (creatinine clearance of more than or equal to 30 ml / min and less than 50 ml / min) should take the attending physician, weighing the risk of bleeding on the one hand and on the other hand thromboembolism.

Hyperkalemia

Heparins may inhibit the secretion of aldosterone, which may cause hyperkalemia, especially in patients with an elevated blood concentration of potassium or patients with a risk of increasing the content of potassium in the blood (e.g., patients with diabetes mellitus, chronic renal insufficiency, metabolic acidosis or patients taking drugs , which can cause hyperkalemia (eg, ACE inhibitors, NSAIDs)). The risk of hyperkalemia increases with prolonged therapy, but is usually reversible upon cancellation.In patients at risk, the concentration of potassium in the blood should be monitored.

Spinal / epidural anesthesia / spinal puncture and concomitant medications

The risk of spinal / epidural hematomas increases in persons with established epidural catheters or concomitant use of other drugs that may affect hemostasis, such as NSAIDs, antiaggregants or other anticoagulants. The risk, apparently, also increases with traumatic or repeated epidural or spinal punctures. Thus, the question of the combined use of neuraxial blockade and anticoagulants should be addressed individually after assessing the benefit / risk ratio in the following situations:

  • in patients who are already receiving anticoagulants, the need for spinal or epidural anesthesia should be justified;
  • in patients who are planning an elective surgical intervention with spinal or epidural anesthesia, the need to introduce anticoagulants should be justified.

When conducting a lumbar puncture or spinal / epidural anesthesia should pass a minimum of 12 hours between the introduction of the drug Fraksiparin Forte to prevent or 24 hours of the treatment and the insertion or removal of spinal / epidural catheter or needle. In patients with renal insufficiency, an increase in these intervals can be considered.

Careful observation of the patient is necessary in order to identify signs and symptoms of neurological disorders. If violations are found in the neurological status of the patient, urgent appropriate therapy is required.

Salicylates, NSAIDs and antiplatelet agents

In the prevention or treatment of venous thromboembolism and for the prevention of blood clotting in the extracorporeal blood circulation system in hemodialysis is not suitable for the simultaneous administration of the preparation Fraksiparin Forte with drugs such as NSAIDs (including acetylsalicylic acid and other salicylates) and antiaggregants, tk. this may increase the risk of bleeding.

Allergy to latex

The base of the needle of the pre-filled syringe may contain a dry natural latex,which can cause an allergic reaction in patients with hypersensitivity to latex.

Necrosis of the skin

About the cases of skin necrosis were reported very rarely. Necrosis of the skin is usually preceded by purpura or an infiltrated or painful erythematous spot that may or may not be accompanied by general symptoms. In such cases, treatment with Fraksiparin Forte should be immediately withdrawn.

Effect on the ability to drive transp. cf. and fur:

There is no evidence of the effect of the drug Fraksiparin Forte on the ability to drive vehicles, mechanisms.

Form release / dosage:

Solution for subcutaneous administration 19000 ME anti-Xa / ml.

Packaging:

For 0.6 ml, 0.8 ml or 1.0 ml of the drug in a single-dose glass syringe with a protective casing, a tip with a stainless steel needle, a closed cap.

2 syringes are packed in a transparent blister of PVC / PE film.

For 1 or 5 blisters (2 or 10 syringes), together with instructions for medical use, put in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription
Registration number:П N012486 / 01
Date of registration:07.06.2010
The owner of the registration certificate:Aspen Pharma Trading LimitedAspen Pharma Trading Limited
Manufacturer: & nbsp
Representation: & nbspAspen Hells Ltd.Aspen Hells Ltd.
Information update date: & nbsp02.02.2015
Illustrated instructions
    Instructions
    Up