Fraxiparine 0.3 instructions for use. Fraxiparine, Solution for injection (syringes). When does a pregnant woman need Fraxiparine?

Fraxiparine®

Active substance

Nadroparin calcium*

ATX:

Pharmacological group

Nosological classification (ICD-10)

Composition and release form

in a blister there are 2 disposable syringes of 0.3 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 0.4 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 0.6 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 1 ml each; There are 1 or 5 blisters in a cardboard box.

Description of the dosage form

Transparent, slightly opalescent, colorless or light yellow solution.

Characteristic

Low molecular weight heparin (LMWH).

pharmachologic effect

pharmachologic effect- antithrombotic, anticoagulant .

Pharmacodynamics

Nadroparin calcium is characterized by higher anti-Xa factor compared to anti-IIa factor or antithrombotic activity. The ratio between the two activities for nadroparin is in the range of 2.5-4.

In prophylactic doses, nadroparin does not cause a significant decrease in activated partial thrombin time (aPTT).

During a course of 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 antithrombotic effect of nadroparin calcium.

Pharmacokinetics

Pharmacokinetic properties are determined based on changes in plasma anti-Xa factor activity. After subcutaneous administration, almost 100% of the drug is rapidly absorbed. Cmax in plasma is achieved between 3 and 4 hours if nadroparin calcium is used in a regimen of 2 injections per day. When using nadroparin calcium in the regimen of 1 injection per day, Cmax is achieved between 4 and 6 hours after administration. Metabolism occurs mainly in the liver (desulfation, depolymerization). After subcutaneous administration, half-life of anti-Xa factor activity of low molecular weight heparins is higher than in the case of unfractionated heparins and is 3-4 hours.

As for anti-factor IIa activity, when low molecular weight heparins are used, it disappears from the plasma faster than anti-factor Xa activity.

Excretion occurs primarily by the kidneys, in its original or slightly modified form.

At-risk groups

In elderly patients, since renal function is physiologically reduced, elimination slows down. This does not affect the dose and regimen of administration of the drug for prophylactic purposes as long as the renal function of these patients remains within acceptable limits, i.e. slightly damaged.

Before starting treatment with LMWH, renal function should be systematically assessed in elderly patients over 75 years of age using the Cockroft formula.

Mild to moderate renal failure (Cl >30 ml/min): in some cases it may be useful to monitor the level of anti-Xa factor activity in the blood to exclude the possibility of overdose during a course of drug use.

Hemodialysis: Low molecular weight heparin is injected into the arterial line of the dialysis loop in sufficiently high doses to prevent clotting in the loop. In principle, pharmacokinetic parameters do not change, except in the case of overdose, when the passage of the drug into the systemic circulation may lead to an increase in anti-Xa factor activity associated with end-phase renal failure.

Indications of the drug

Prevention of thrombus formation during surgical interventions, blood coagulation in the extracorporeal circulatory system during hemodialysis or hemofiltration, thromboembolic complications in patients with a high risk of thrombus formation (with acute respiratory and/or heart failure in the intensive care unit).

Treatment of thromboembolism, unstable angina and non-Q wave myocardial infarction.

Contraindications

History of hypersensitivity (including thrombocytopenia) to Fraxiparine or other LMWHs and/or heparin; signs of bleeding or increased risk of bleeding associated with impaired hemostasis, with the exception of disseminated intravascular coagulation not caused by heparin; organic lesions of organs with a tendency to bleeding (for example, acute gastric or duodenal ulcer); injuries or surgical interventions on the central nervous system; septic endocarditis.

Use during pregnancy and breastfeeding

Experiments on animals have not shown the teratogenic effect of nadroparin calcium; however, in the first trimester of pregnancy it is preferable to avoid prescribing Fraxiparine, both in a prophylactic dose and in the form of a course of treatment.

During the II and III trimesters of pregnancy, Fraxiparine can be used only in accordance with the doctor's recommendations for the prevention of venous thrombosis (when comparing the benefits to the mother with the risk to the fetus). Course treatment is not used during this period.

If the use of epidural anesthesia is considered, it is recommended, as far as possible, to withhold prophylactic heparin treatment at least 12 hours before anesthesia.

Since absorption of the drug in the gastrointestinal tract in newborns is, in principle, unlikely, treatment with Fraxiparine in nursing mothers is not contraindicated.

Side effects

The most common side effect is the formation of a subcutaneous hematoma at the injection site. In some cases, the appearance of dense nodules is observed, which does not indicate heparin encapsulation, which disappear after a few days.

Large doses of Fraxiparine can provoke bleeding of various localizations and mild thrombocytopenia (type I), which usually disappears with further therapy. A temporary moderate increase in the level of liver enzymes (ALT, AST) is possible.

Skin necrosis and allergic reactions occur rarely. Several cases of anaphylactic reactions and immune thrombocytopenia (type II) associated with arterial and/or venous thrombosis or thromboembolism have been reported.

Interaction

The development of hyperkalemia may depend on the simultaneous presence of several risk factors. Drugs that cause hyperkalemia: potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor blockers, NSAIDs, heparins (low molecular weight or unfractionated), cyclosporine and tacrolimus, trimethoprim. The risk of developing hyperkalemia increases when the above-mentioned drugs are combined with Fraxiparine.

The combined use of Fraxiparine with drugs that affect hemostasis, such as acetylsalicylic acid, NSAIDs, vitamin K antagonists, fibrinolytics and dextran, leads to a mutual enhancement of the effect.

In addition, it should be taken into account that platelet aggregation inhibitors (except for acetylsalicylic acid as an analgesic and antipyretic drug, i.e. in doses over 500 mg): NSAIDs, abciximab, acetylsalicylic acid in antiplatelet doses (50-300 mg) at Cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Directions for use and doses

SC (except for use during hemodialysis).

This form is intended for adults.

Cannot be administered intramuscularly!

1 ml of Fraxiparine is equivalent to approximately 9500 IU of the anti-Xa factor activity of nadroparine.

Technique of subcutaneous administration

It is preferable to inject the patient in a supine position into the subcutaneous tissue of the anterolateral or posterolateral abdominal girdle, alternately from the right and left sides.

The needle should be inserted perpendicularly, (not at an angle), into the pinched fold of skin, and held between the thumb and forefinger until the end of the solution. Graduated syringes are designed to select the dose depending on the patient’s body weight.

Prevention of thromboembolism in surgery

Frequency of application. 1 injection per day.

Dose used. The dose is determined by the individual level of risk, depending on the patient’s body weight and the type of operation.

Situations with moderate thrombogenic risk. In surgical operations that pose a moderate thrombogenic risk, as well as in patients without an increased risk of thromboembolism, effective prevention of thromboembolic disease is achieved by administering a dose of 2850 IU of anti-Xa factor activity per day (0.3 ml).

The initial injection should be administered 2 hours before surgery.

Situations with increased thrombogenic risk. Surgeries on the hip and knee: the dosage of nadroparin depends on the patient’s body weight. Administered once a day: 38 IU of anti-Xa factor activity/kg before surgery, i.e. 12 hours before the procedure, after the operation, i.e. starting 12 hours after the end of the procedure, then daily, until the third day after surgery, inclusive; 57 IU of anti-Xa factor activity/kg, starting from the fourth day after surgery.

Other situations. In cases where the thromboembolic risk associated with the type of operation (especially in oncological operations) and/or with the individual characteristics of the patient (especially with a history of thromboembolic disease) appears to be increased, a dose of 2850 IU of anti-Xa factor activity nadroparin (0.3 ml).

Duration of treatment. Treatment with LMWH, in combination with the technique of traditional elastic compression of the lower extremities, should continue until the patient’s motor function is completely restored.

In general surgery, treatment with LMWH should last less than 10 days, unless there is a particular risk of venous thromboembolism associated with the individual characteristics of the patient (see "Special Instructions").

If the risk of thromboembolic complications is present after the recommended period of treatment, it is necessary to continue preventive treatment, primarily with oral anticoagulants.

However, the clinical benefit of long-term treatment with low molecular weight heparins or vitamin K antagonists has not been assessed to date.

Prevention of blood coagulation in the extracorporeal circulation system during hemodialysis: intravascularly(into the arterial shunt of the dialysis loop).

In patients receiving repeated hemodialysis sessions, prevention of coagulation in the extracorporeal purification loop is achieved by administering an initial dose of 65 IU/kg into the arterial line of the dialysis loop at the beginning of the session.

This dose, administered as a single intravascular bolus injection, is only suitable for dialysis sessions lasting no more than 4 hours. Subsequently, the dose can be adjusted depending on the individual response of the patient, which varies greatly.

The doses used in patients, depending on body weight, are as follows:

If necessary, the dose can be changed in accordance with each individual case and the technical conditions of dialysis. In patients with an increased risk of bleeding, dialysis sessions can be performed using half the dose of the drug.

Treatment of deep vein thrombosis (DVT)

Any suspicion must be immediately confirmed by the results of appropriate tests.

Frequency of application. 2 injections per day with an interval of 12 hours.

Dose used. The dose of each injection is 85 IU of anti-Xa factor activity/kg.

The dosage of LMWH has not been studied depending on the body weight of patients weighing more than 100 kg or less than 40 kg. In patients weighing more than 100 kg, the effectiveness of LMWH may be reduced. On the other hand, in patients weighing less than 40 kg, the risk of bleeding may increase. In such cases, special clinical monitoring is required.

For this indication, the dose used depending on the patient's body weight is 0.1 ml/10 kg body weight every 12 hours, as shown in the following table:

Duration of treatment. Treatment with LMWH should be quickly replaced with oral anticoagulants, unless the latter are contraindicated. The duration of treatment with LMWH should not exceed 10 days, including the period of transition to vitamin K antagonists (VKA), except in cases where difficulties arise in stabilizing the INR (see “Special Instructions”). Therefore, treatment with oral anticoagulants should be started as early as possible.

Treatment of unstable angina/myocardial infarction without Q wave change

Frequency of application. Nadroparin calcium is used in the form of two subcutaneous injections per day (with an interval of 12 hours), each at a dose of 86 IU of anti-Xa factor activity, in combination with aspirin (recommended doses 75-325 mg orally, after an introductory minimum dose of 160 mg ).

Dose used. The initial dose should be administered as an IV bolus at a dose of 86 IU anti-Xa/kg, then SC at the same dose.

Overdose

Accidental overdose with subcutaneous administration of large doses of low molecular weight heparins can cause bleeding.

In the case of oral administration - even a massive dose - of low molecular weight heparin (not observed so far), serious consequences cannot be expected, given the very low absorption of the drug.

Treatment: if bleeding is minor, delay the next dose.

In some cases, the use of protamine sulfate may be indicated, taking into account the following: its effectiveness is significantly lower than that described in connection with an overdose of unfractionated heparin; The benefit/risk ratio of protamine sulfate must be carefully assessed due to its side effects (especially anaphylactic shock).

If it is decided to use such treatment, neutralization is carried out by slow intravenous administration of protamine sulfate.

The effective dose of protamine sulfate depends on: the dose of heparin administered (100 anti-heparin units of protamine sulfate can be used to neutralize the activity of 100 IU of anti-Xa factor activity of LMWH); time elapsed after heparin administration, with a possible reduction in the dose of the antidote.

However, it is impossible to completely neutralize anti-Xa factor activity.

Moreover, the absorption kinetics of low molecular weight heparin may make this neutralization temporary and require fragmentation of the full calculated dose of protamine sulfate into several injections (2-4) distributed over the day.

special instructions

Although the concentrations of various low molecular weight heparin preparations are expressed in international units of anti-Factor Xa activity, their effectiveness is not limited by anti-Factor Xa activity. Replacing the dosage regimen of one LMWH with another is dangerous and unacceptable, because Each regimen has been tested in dedicated clinical trials. Therefore, special care is required and compliance with the specific instructions for use for each medicinal product.

Risk of bleeding. It is necessary to follow the recommended therapeutic regimens (dosage and duration of treatment). Otherwise, bleeding may occur, especially in patients at risk (elderly people, patients suffering from renal failure, etc.).

Serious bleeding has been observed: in elderly patients, especially due to weakening of kidney function with age; with renal failure; in patients weighing less than 40 kg; in case of treatment duration exceeding the recommended (10 days); in case of non-compliance with the recommended treatment conditions (especially the duration and dosage based on body weight for course use); when combined with drugs that increase the risk of bleeding.

In any case, special monitoring is required in elderly patients and patients suffering from renal failure, as well as when the drug is used for more than 10 days. To detect drug accumulation, it may be useful in some cases to measure anti-factor Xa activity.

Risk of heparin-induced thrombocytopenia (HIT). If a patient receiving treatment with LMWH (in course or prophylactic doses) experiences: negative dynamics of thrombosis for which the patient is being treated, phlebitis, pulmonary embolism, acute ischemia of the lower extremities, myocardial infarction or stroke, they should be considered as manifestation of heparin-induced thrombocytopenia (HIT), and immediately perform a platelet count analysis.

Use in children. Due to the lack of data, the use of LMWH in children is not recommended.

Kidney function. Before starting treatment with LMWH, it is necessary to monitor renal function, especially in elderly patients over the age of 75 years. Creatinine clearance is calculated using the Cockroft formula and based on the actual body weight of the patient: in men, creatinine Cl = (140-age) × body weight / (0.814 × serum creatinine), expressing age in years, body weight in kg, and serum creatinine in µmol /l (if creatinine is expressed in mg/ml, multiply by 8.8).

For women, this formula is supplemented by multiplying the result by 0.85.

Detection of severe renal failure (Cl creatinine about 30 ml/min) is a contraindication to the use of LMWH in course form (see “Contraindications”).

Laboratory control

Platelet count control

Heparin-induced thrombocytopenia

Due to the danger of developing HIT, platelet count control is necessary, regardless of the indication for use and the prescribed dose. The platelet count is carried out before the start of treatment or no later than during the first day after the start of treatment, and then 2 times a week during the entire course of treatment.

The diagnosis of HIT should be assumed if the platelet count<100000/мм 3 и/или наблюдается падение числа тромбоцитов на 30-50% по отношению к предыдущему анализу. Она развивается в основном между 5 и 21 днем после начала лечения гепарином (с максимальной частотой — около 10 дня).

However, it can manifest itself much earlier if the patient has a history of thrombocytopenia associated with heparin treatment, in very rare cases, and after 21 days. The collection of such anamnesis should be systematically carried out during an interview with the patient before treatment. In addition, the risk of HIT with repeated administration of heparin may persist for several years or even indefinitely (see “Contraindications”).

In any case, the occurrence of HIT is an emergency and requires consultation with a specialist. Any significant drop in platelet count (30-50% from the initial value) should be considered an alarm signal even before reaching critical values. If the platelet count drops, you must: immediately check the platelet count.

Withhold heparin if a fall is confirmed or detected during this monitoring, in the absence of other obvious causes.

Collect a blood sample in a citrate tube for platelet aggregation testing in vitro and immunological analysis. However, in such situations, immediate action does not depend on the results of these tests, since these tests are carried out by only a few specialized laboratories and, at best, the results can only be obtained after a few hours. Despite this, tests must be carried out to establish an accurate diagnosis of the complication, because with continued treatment with heparin, the risk of thrombosis is very high.

To prevent and treat thrombotic complications of HIT.

If a complication occurs, it is necessary to continue anticoagulant treatment, heparin should be replaced by another class of antithrombotic drugs: danaparoid sodium or hirudin, prescribed in prophylactic or therapeutic doses, depending on the situation.

Replacement with vitamin K antagonists can be carried out only after normalization of the platelet count, due to the risk of increasing the thrombotic effect.

Replacing heparin with a vitamin K antagonist. In this case, clinical and laboratory monitoring should be increased to monitor the effects of the vitamin K antagonist.

Because the full effect of the vitamin K antagonist is not immediately apparent, heparin should be continued at an equivalent dose for as long as necessary to achieve the required INR level for a given indication in two consecutive tests.

Control of anti-Xa factor activity. Because most clinical trials demonstrating the effectiveness of LMWH have been conducted at weight-based doses and without any specific laboratory controls, the value of this type of monitoring for assessing the effectiveness of LMWH has not been established. However, laboratory monitoring by determining anti-Factor Xa activity may be useful for the risk of bleeding in some clinical situations, often associated with the risk of overdose.

These situations may concern the indications for course use of LMWH, in connection with the doses used, in mild to moderate renal failure (Cl, calculated using the Cockroft formula, 30-60 ml/min): indeed, in contrast to unfractionated standard heparin, LMWH is excreted mainly kidneys, and impaired renal function can lead to relative overdose. As for severe renal failure, it is a contraindication to the use of LMWH in a course regimen (see “Contraindications”); with extreme body weight (low body weight or even exhaustion, obesity); for unexplained bleeding.

In order to identify possible cumulation after repeated administration, it is recommended to take blood from the patient, if possible, at maximum activity of the drug (in accordance with available data), i.e.:

approximately 4 hours after the third administration, if the drug is used in the form of two subcutaneous injections per day or approximately 4 hours after the second administration, if the drug is used in the form of one subcutaneous injection per day.

Repeated testing of anti-Factor Xa activity to measure serum heparin levels—every 2 or 3 days—should be considered on a case-by-case basis, depending on the results of the previous test, modifying the LMWH dosage if necessary.

For each LMWH and for each therapeutic regimen, the anti-Factor Xa activity generated is different.

In accordance with the indications and according to available data, the average anti-Xa factor activity (± standard deviation) observed in the fourth hour after administration of nadroparin at a dose of:

83 IU/kg in the form of two injections per day, was 1.01±0.18 IU

168 IU/kg in the form of one injection per day was 1.34±0.15 IU

The average value was observed during clinical trials to determine anti-Xa factor activity, conducted using the chromogenic (amidolytic) method.

Activated partial thromboplastin time (aPTT). Some LMWHs moderately prolong the aPTT. (No clinical significance).

Carrying out spinal/epidural anesthesia in case of prophylactic use of LMWH. When using LMWH, as well as other anticoagulants, during spinal or epidural anesthesia, rare cases of intraspinal hematoma leading to prolonged or persistent paralysis have been observed.

The risk of intraspinal hematoma appears to be higher with the use of an epidural catheter than with spinal anesthesia.

The risk of this rare complication may increase with prolonged use of an epidural catheter after surgery.

If preoperative treatment with LMWH is necessary (prolonged immobilization, trauma) and the benefits of spinal anesthesia have been carefully assessed, this technique can be used in a patient who received a preoperative LMWH injection if a period of at least 12 hours has passed between the heparin injection and the use of the spinal anesthetic Due to the risk of intraspinal hematoma, careful neurological monitoring is necessary.

In almost all cases, prophylactic treatment with LMWH can be started within 6-8 hours after application of the anesthetic or removal of the catheter, with neurological monitoring.

Particular caution is required in case of combination with other drugs that affect hemostasis (namely NSAIDs, acetylsalicylic acid).

Does not affect the ability to drive a car or operate machines.

Using the needle guard system: after administering the drug, use the safety system for the Fraxiparine syringe. Hold the used syringe by the protective housing in one hand and pull the holder with the other hand to release the latch and slide the needle protective cover until it clicks. The used needle is completely protected.

Manufacturer

Sanofi Winthrop Industrie, France.

Storage conditions of the drug

At a temperature not exceeding 30 °C.

Keep out of the reach of children.

Treatment of thromboembolism, unstable angina and non-Q wave myocardial infarction.

Release form of the drug Fraxiparine

solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.6 ml, blister 2, box (box) 1;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 1 ml, blister 2, box (box) 5;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.8 ml, blister 2, box (box) 5;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.8 ml, blister 2, box (box) 1;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.6 ml, blister 2, box (box) 5;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.3 ml, blister 2, box (box) 1;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.3 ml, blister 2, box (box) 5;
solution for subcutaneous administration 3800 IU; disposable syringe 0.4 ml, blister 2, box (box) 1;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 1 ml, blister 2, box (box) 1;
solution for subcutaneous administration 3800 IU; disposable syringe 0.4 ml, blister 2, box (box) 5;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.4 ml, blister 2, box (box) 1;
solution for subcutaneous administration 9500 IU (anti-Xa)/ml; disposable syringe 0.4 ml, blister 2, box (box) 5;

Compound
Solution for injections 1 syringe
nadroparin calcium ME anti-Xa 2850
excipients: calcium hydroxide solution - q.s. (or dilute hydrochloric acid) to pH 5.0–7.5; water for injection - q.s. up to 0.3 ml
in a blister there are 2 disposable syringes of 0.3 ml each; There are 1 or 5 blisters in a cardboard box.

Solution for injections 1 syringe
nadroparin calcium ME anti-Xa 3800
excipients: calcium hydroxide solution - q.s. (or dilute hydrochloric acid) to pH 5.0–7.5; water for injection - q.s. up to 0.4 ml
in a blister there are 2 disposable syringes of 0.4 ml each; There are 1 or 5 blisters in a cardboard box.

Solution for injections 1 syringe
nadroparin calcium, ME anti-Xa 5700
excipients: calcium hydroxide solution - q.s. (or dilute hydrochloric acid) to pH 5.0–7.5; water for injection - q.s. up to 0.6 ml

Solution for injections 1 syringe
nadroparin calcium, ME anti-Xa 7600
excipients: calcium hydroxide solution - q.s. (or dilute hydrochloric acid) to pH 5.0–7.5; water for injection - q.s. up to 0.8 ml
in a blister there are 2 disposable syringes of 0.6 ml each; There are 1 or 5 blisters in a cardboard box.

Solution for injections 1 syringe
nadroparin calcium, ME anti-Xa 9500
excipients: calcium hydroxide solution - q.s. (or dilute hydrochloric acid) to pH 5.0–7.5; water for injection - q.s. up to 1 ml
in a blister there are 2 disposable syringes of 1 ml each; There are 1 or 5 blisters in a cardboard box.

Pharmacodynamics of the drug Fraxiparine

Nadroparin calcium is characterized by higher anti-Xa factor compared to anti-IIa factor or antithrombotic activity. The ratio between the two activities for nadroparin is in the range of 2.5–4.

In prophylactic doses, nadroparin does not cause a significant decrease in activated partial thrombin time (aPTT).

Pharmacokinetics of the drug Fraxiparine

Pharmacokinetic properties are determined based on changes in plasma anti-Xa factor activity. After subcutaneous administration, almost 100% of the drug is rapidly absorbed. Cmax in plasma is achieved between 3 and 4 hours if nadroparin calcium is used in a regimen of 2 injections per day. When using nadroparin calcium in a regimen of 1 injection per day, Cmax is achieved between 4 and 6 hours after administration. Metabolism occurs mainly in the liver (desulfation, depolymerization). After subcutaneous administration, T1/2 of anti-Xa factor activity of low molecular weight heparins is higher than in the case of unfractionated heparins and is 3–4 hours.

As for anti-factor IIa activity, when low molecular weight heparins are used, it disappears from the plasma faster than anti-factor Xa activity.

Excretion occurs primarily by the kidneys, in its original or slightly modified form.

At-risk groups

Before starting treatment with LMWH, renal function should be systematically assessed in elderly patients over 75 years of age using the Cockroft formula.

Use of the drug Fraxiparine during pregnancy

If the use of epidural anesthesia is considered, it is recommended, as far as possible, to withhold prophylactic heparin treatment at least 12 hours before anesthesia.

Since absorption of the drug in the gastrointestinal tract in newborns is, in principle, unlikely, treatment with Fraxiparine in nursing mothers is not contraindicated.

Contraindications to the use of the drug Fraxiparine

Side effects of the drug Fraxiparine

Method of administration and dosage of the drug Fraxiparine

Injected into the subcutaneous tissue of the abdomen, into the thickness of the skin fold (the needle is positioned perpendicular to the skin fold). Maintain the fold throughout the entire insertion period. Prevention of thromboembolism in general surgery: 0.3 ml once a day. 0.3 ml is administered 2-4 hours before surgery. The course of treatment is at least 7 days. For therapeutic purposes: administered 2 times a day for 10 days at a dose of 225 IU/kg (100 IU/kg), which corresponds to: 45-55 kg - 0.4-0.5 ml, 55-70 kg - 0.5-0.6 ml, 70 -80 kg - 0.6-0.7 ml, 80-100 kg - 0.8 ml, more than 100 kg - 0.9 ml. In orthopedic surgery, the dose is selected depending on body weight. Administered once a day daily, in the following doses: for body weight less than 50 kg: in the preoperative period and for 3 days after surgery - 0.2 ml; in the postoperative period (starting from day 4) - 0.3 ml. For body weight from 51 to 70 kg: in the preoperative period and for 3 days after surgery - 0.3 ml; in the postoperative period (starting from day 4) - 0.4 ml. For body weight from 71 to 95 kg: in the preoperative period and for 3 days after surgery - 0.4 ml; in the postoperative period (starting from day 4) - 0.6 ml. After venography, it is administered every 12 hours for 10 days, the dose depends on body weight: with a weight of 45 kg - 0.4 ml; 55 kg - 0.5 ml; 70 kg - 0.6 ml; 80 kg - 0.7 ml; 90 kg - 0.8 ml; 100 kg or more - 0.9 ml. In the treatment of unstable angina and myocardial infarction without a Q wave, 0.6 ml (5700 IU antiXa) is administered 2 times a day.

Overdose of Fraxiparine

Accidental overdose with subcutaneous administration of large doses of low molecular weight heparins can cause bleeding.

In the case of oral administration - even a massive dose - of low molecular weight heparin (not observed so far), serious consequences cannot be expected, given the very low absorption of the drug.

Treatment: if bleeding is minor, delay the next dose.

If it is decided to use such treatment, neutralization is carried out by slow intravenous administration of protamine sulfate.

However, it is impossible to completely neutralize anti-Xa factor activity.

Interactions of the drug Fraxiparine with other drugs

The combined use of Fraxiparine with drugs that affect hemostasis, such as acetylsalicylic acid, NSAIDs, vitamin K antagonists, fibrinolytics and dextran, leads to a mutual enhancement of the effect.

In addition, it should be taken into account that platelet aggregation inhibitors (except for acetylsalicylic acid as an analgesic and antipyretic drug, i.e. at a dose of over 500 mg): NSAIDs, abciximab, acetylsalicylic acid in antiplatelet doses (50–300 mg) at Cardiological and neurological indications, beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban increase the risk of bleeding.

Special instructions when taking Fraxiparine

Risk of bleeding. It is necessary to follow the recommended therapeutic regimens (dosage and duration of treatment). Otherwise, bleeding may occur, especially in patients at risk (elderly people, patients suffering from renal failure, etc.).

Risk of heparin-induced thrombocytopenia (HIT). If a patient receiving treatment with LMWH (in course or prophylactic doses) experiences: negative dynamics of thrombosis for which the patient is being treated, phlebitis, pulmonary embolism, acute ischemia of the lower extremities, myocardial infarction or stroke, they should be considered as manifestation of heparin-induced thrombocytopenia (HIT), and immediately perform a platelet count analysis.

Use in children. Due to the lack of data, the use of LMWH in children is not recommended.

Kidney function. Before starting treatment with LMWH, it is necessary to monitor renal function, especially in elderly patients over the age of 75 years. Creatinine clearance is calculated using the Cockroft formula and based on the actual body weight of the patient: in men, creatinine Cl = (140-age) × body weight / (0.814 × serum creatinine), expressing age in years, body weight in kg, and serum creatinine in µmol /l (if creatinine is expressed in mg/ml, multiply by 8.8).

For women, this formula is supplemented by multiplying the result by 0.85.

Detection of severe renal failure (Cl creatinine about 30 ml/min) is a contraindication to the use of LMWH in course form (see “Contraindications”).

Laboratory control

Platelet count control

Heparin-induced thrombocytopenia

The diagnosis of HIT should be assumed if the platelet count<100000/мм3 и/или наблюдается падение числа тромбоцитов на 30–50% по отношению к предыдущему анализу. Она развивается в основном между 5 и 21 днем после начала лечения гепарином (с максимальной частотой - около 10 дня).

In any case, the occurrence of HIT is an emergency and requires consultation with a specialist. Any significant drop in platelet count (30–50% from the initial value) should be considered an alarm signal even before reaching critical values. If the platelet count drops, you must: immediately check the platelet count.

Withhold heparin if a fall is confirmed or detected during this monitoring, in the absence of other obvious causes.

Collect a blood sample in a citrate tube for in vitro platelet aggregation and immunological testing. However, in such situations, immediate action does not depend on the results of these tests, since these tests are carried out by only a few specialized laboratories and, at best, the results can only be obtained after a few hours. Despite this, tests must be carried out to establish an accurate diagnosis of the complication, because with continued treatment with heparin, the risk of thrombosis is very high.

To prevent and treat thrombotic complications of HIT.

Replacement with vitamin K antagonists can be carried out only after normalization of the platelet count, due to the risk of increasing the thrombotic effect.

Replace heparin with a vitamin K antagonist. In this case, clinical and laboratory monitoring should be increased to monitor the effects of the vitamin K antagonist.

Control of anti-Xa factor activity. Because most clinical trials demonstrating the effectiveness of LMWH have been conducted at weight-based doses and without any specific laboratory controls, the value of this type of monitoring for assessing the effectiveness of LMWH has not been established. However, laboratory monitoring by determining anti-Factor Xa activity may be useful for the risk of bleeding in some clinical situations, often associated with the risk of overdose.

These situations may concern the indications for course use of LMWH, in connection with the doses used, in mild to moderate renal failure (Cl, calculated using the Cockroft formula, 30–60 ml/min): indeed, in contrast to unfractionated standard heparin, LMWH is excreted mainly kidneys, and impaired renal function can lead to relative overdose. As for severe renal failure, it is a contraindication to the use of LMWH in a course regimen (see “Contraindications”); with extreme body weight (low body weight or even exhaustion, obesity); for unexplained bleeding.

Approximately 4 hours after the third administration, if the drug is used in the form of two subcutaneous injections per day, or approximately 4 hours after the second administration, if the drug is used in the form of one subcutaneous injection per day.

Repeated testing of anti-Factor Xa activity to measure serum heparin levels - every 2 or 3 days - should be considered on a case-by-case basis, depending on the results of the previous analysis, modifying the LMWH dosage if necessary.

For each LMWH and for each therapeutic regimen, the anti-Factor Xa activity generated is different.

83 IU/kg in the form of two injections per day, was 1.01±0.18 IU

168 IU/kg in the form of one injection per day was 1.34±0.15 IU

The average value was observed during clinical trials to determine anti-Xa factor activity, conducted using the chromogenic (amidolytic) method.

Activated partial thromboplastin time (aPTT). Some LMWHs moderately prolong the aPTT. (No clinical significance).

Carrying out spinal/epidural anesthesia in case of prophylactic use of LMWH. When using LMWH, as well as other anticoagulants, during spinal or epidural anesthesia, rare cases of intraspinal hematoma leading to prolonged or persistent paralysis have been observed.

The risk of intraspinal hematoma appears to be higher with the use of an epidural catheter than with spinal anesthesia.

The risk of this rare complication may increase with prolonged use of an epidural catheter after surgery.

In almost all cases, prophylactic treatment with LMWH can be started within 6–8 hours after application of the anesthetic or removal of the catheter, with neurological monitoring.

Particular caution is required in case of combination with other drugs that affect hemostasis (namely NSAIDs, acetylsalicylic acid).

Does not affect the ability to drive a car or operate machines.

Using the needle protection system: after administering the drug, use the safety system for the Fraxiparine syringe. Hold the used syringe by the protective housing in one hand and pull the holder with the other hand to release the latch and slide the needle protective cover until it clicks. The used needle is completely protected.

During pregnancy, there are situations when the doctor, after the next blood test, prescribes an additional drug to the woman - an anticoagulant. The tendency to form blood clots is dangerous for the life of the mother and child, so it is permissible to use drugs that are contraindicated during this period. Fraxiparine during pregnancy, despite the prohibition of official instructions, is prescribed to prevent hypercoagulation. Most hemostasiologists agree that the drug, when used correctly, does not harm the fetus.

Fraxiparine is a low molecular weight heparin that has an anticoagulant effect. In other words, it prevents the activation of the chain of reactions leading to blood clotting. With regular administration of this drug, the formation of blood clots is prevented.

The active component of Fraxiparine is calcium nadroparin. This substance is able to quickly and reliably form bonds with protein molecules in plasma. It is this mechanism that prevents blood clots from appearing. The administration of Fraxiparine, or calcium nadroparine, has a pronounced effect on the properties of the blood and practically does not cause adverse reactions. Like all heparins, it does not increase the risk of bleeding.

Thrombophilia is a blood clotting disorder with a risk of blood clots. This condition can lead to the death of the fetus inside the womb. Fraxiparine during pregnancy maintains normal blood supply to the unborn child and does not harm the health of the mother. Another advantage of this drug is that it does not pass through the placental barrier and does not affect the fetus.

Use during pregnancy

During pregnancy, Fraxiparine is prescribed for the treatment of conditions associated with increased blood clotting, as well as for their prevention. The duration of the course of therapy is selected individually: in some cases it is all 9 months. Long-term treatment may be required if the woman has previously had miscarriages due to blood clots. In such cases, even a one-day break in the administration of the medicinal solution can provoke fetal death.

It is impossible to say for sure how safe Fraxiparine is during pregnancy. The instructions contain information that its use is possible in the 2nd and 3rd trimesters. Hemostasiologists are confident that the drug is harmless to women and fetuses, but no clinical studies have been conducted in this category of people. That is, the question of the teratogenicity of Fraxiparine remains open. Nevertheless, the drug has been used for a very long time for the treatment and prevention of increased blood clotting in pregnant women, and the annotation for the drug has not been adjusted for several decades.

Fraxiparine is rarely prescribed to pregnant women. After receiving laboratory diagnostic data, the doctor determines the degree of risk of premature birth and intrauterine fetal death, and then decides on the need to use the drug. Its regular administration helps restore normal blood clotting and avoid such complications.

The 1st trimester is the most dangerous for taking any medications, including anticoagulants. They try to delay their use until the 16th week, when the placenta is formed. It can be used in the 2nd and 3rd trimesters if the pregnant woman has no other contraindications.

The longer the period, the higher the risk of complications due to increased blood clotting. The placenta grows during all 9 months, the number of large and small vessels in it constantly increases. Blood clots form most quickly in the capillaries, which leads to chronic and further intrauterine growth retardation.

In the 3rd trimester, the uterus and fetus reach their maximum size. The larger they become, the more they compress the inferior vena cava, which carries blood from the extremities to the heart. As a result, it stagnates, which leads to the development of blood clots. The most dangerous option is blockage of the pulmonary artery; this condition can lead to the death of the pregnant woman.

It becomes clear that there are vital indications for prescribing Fraxiparine. In all of the above cases, the risks from its use are less than the consequences of impaired blood clotting.

When planning pregnancy, Fraxiparine is also prescribed for increased blood clotting. Thrombosis is one of the reasons that prevents the fertilized egg from attaching to the wall of the uterus. That is, the administration of this drug promotes conception.

Mode of application

When prescribing Fraxiparine during pregnancy, it is important to know how to inject it. The manufacturer is concerned about ease of use: the drug is available in the form of a solution, poured into disposable syringes with a needle for injection under the skin. The volume of one dose may vary; in pharmacies you can find options: 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 1 ml.

During pregnancy, the minimum dosage most often prescribed is 0.3 ml, 1 time per day. The duration of the course of injections is selected individually, but it cannot be less than 10 days. The dosage increases if the woman has a large body weight.

The ideal option is when Fraxiparine is administered by a medical professional. But since many people are prescribed the drug for a long time, and sometimes for the entire 9 months, there is a need to master the procedure on their own. And yet, before switching to home treatment, you need a specialist to perform several injections. This way you will be able to see the correct technique and understand what the sensations may be when injecting the solution.

The solution is administered as follows:

1. Remove air from the syringe by turning it upside down.
2. Prepare a cotton swab soaked in alcohol.
3. Lie on your back and treat a small area of skin with alcohol, moving a few centimeters away from the navel.
4. On the treated area, grab the skin fold with two fingers.
5. Insert a needle into the top of the fold at an angle of 90° to the general surface of the skin.
6. Slowly press the plunger until all the solution has been injected.
7. Remove the needle and press cotton wool to the puncture site.

After the procedure, do not allow rubbing of the injection site. You need to change it daily, alternating sides (left, right). Immediately after removing the needle, a little blood may appear at the puncture site, and after a while there may be slight swelling. This is normal and should not be alarming.

Fraxiparine can be obtained free of charge during pregnancy. The drug is prescribed at the antenatal clinic at the place of residence. Its receipt is ensured by means of a birth certificate within the framework of the national project “Health” (Order of the Ministry of Health and Social Development of the Russian Federation of January 16, 2008 N 11N).

Contraindications

Fraxiparine is a potent drug, so its use is contraindicated in certain conditions and diseases. Before prescribing this medication, the doctor carefully examines the medical history and writes out a referral for laboratory diagnostics. The collected data helps assess the woman’s health status and identify possible risks.

Fraxiparine cannot be prescribed in the following cases:

with individual intolerance to nadroparin;
with a deficiency of blood clotting with bleeding;
if previous treatment with antiplatelet agents has not yielded a positive result.

Fraxiparine should be prescribed with caution to patients with disorders of the liver or kidneys, diseases of the gastrointestinal tract, or high blood pressure.

Side effects and consequences

Side effects from the administration of Fraxiparine sometimes manifest themselves in the form of skin reactions: the injection site itches and becomes covered with a rash. Allergies can manifest themselves with urticaria and Quincke's edema. Anaphylactic shock develops extremely rarely. In case of overdose, bleeding may occur.

Fraxiparine during pregnancy is always prescribed on the basis of serious indications; the consequences for the fetus have not been studied. But most doctors agree that if you follow the dosage, the risk of their occurrence is minimal.

1 syringe of Fraxiparine may contain 9500, 7600, 5700, 3800 or 2850 IU of anti-Xa nadroparin calcium .

Additional components: hydrochloric acid or solution calcium hydroxide , water.

Release form

The syringes contain a slightly opalescent, colorless, transparent solution for subcutaneous injection.

Two such disposable syringes in a blister, five or one blisters in a pack of paper.

pharmachologic effect

Anticoagulant And antithrombotic.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Combined use with , indirect anticoagulants, NSAIDs, fibrinolytics or mutually enhances the effects of drugs.

Terms of sale

On prescription.

Storage conditions

Do not freeze.
Store at temperatures up to 30 degrees.
Keep away from children.

Best before date

Three years.

special instructions

Fraxiparine should not be administered intramuscularly.

Does not affect the ability to drive a car.

Analogs

Level 4 ATX code matches:

Analogues of Fraxiparine: Atenativ, Heparin-Biolek, Heparin-Darnitsa, Heparin-Indar, Heparin-Novopharm, Heparin-Pharmex, Novoparin, Flenox, Enoxarin.

For children

Age under 18 years is a contraindication for prescribing the drug.

Fraxiparine during pregnancy (and lactation)

Nadroparin calcium penetrates the placenta and is excreted into breast milk. Therefore, it is not recommended to prescribe Fraxiparine injections during and during pregnancy, except in extreme cases.

Fraxiparine for IVF

It is prescribed to improve the rheological properties of blood, since the use of hormones causes the opposite effect, and to facilitate implantation.

Reviews about Fraxiparine

Patient reviews of the drug are quite different, but you should not rely on them if you are offered treatment with Fraxiparine. The validity of prescribing the drug, its effectiveness and all the risks associated with it can only be assessed by a specialist.

There are no bad reviews about Fraxiparine during pregnancy from those who have undergone treatment. As practice shows, the drug does not affect the health of children. In the Latin recipe, the name of the product sounds like Fraxiparini.

Fraxiparine price, where to buy

In Russia, the price of Fraxiparine No. 10 0.3 ml is 2177-4020 rubles (buying in Moscow will cost about the same amount). In Ukraine, the price of the drug in this form of release is 510 hryvnia. The price of analogues, also used during pregnancy, is almost always noticeably lower.

Online pharmacies in Russia Russia
Online pharmacies in Ukraine Ukraine

ZdravCity

Fraxiparine solution for subcutaneous treatment 9500 anti-Xa IU/ml syringe 0.6 ml (5700 IU) 10 pcs.

Fraxiparine solution for subcutaneous injection. 9500 anti-Ha IU/ml syringe 0.3 ml (2850 IU) 10 pcs.Aspen Notre Dame de Bondeville/Nanolek LLC

Fraxiparine solution for subcutaneous treatment 9500 anti-Xa IU/ml syringe 0.8 ml (7600 IU) 10 pcs.Aspen Notre Dame de Bondeville/Nanolek LLC

Composition and release form

in a blister there are 2 disposable syringes of 0.3 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 0.4 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 0.6 ml each; There are 1 or 5 blisters in a cardboard box.

in a blister there are 2 disposable syringes of 1 ml each; There are 1 or 5 blisters in a cardboard box.

Description of the dosage form

Transparent, slightly opalescent, colorless or light yellow solution.

Characteristic

Low molecular weight heparin (LMWH).

pharmachologic effect

pharmachologic effect- antithrombotic, anticoagulant.

Pharmacodynamics

Nadroparin calcium is characterized by higher anti-Xa factor compared to anti-IIa factor or antithrombotic activity. The ratio between the two activities for nadroparin is in the range of 2.5-4.

In prophylactic doses, nadroparin does not cause a significant decrease in activated partial thrombin time (aPTT).

Pharmacokinetics

As for anti-factor IIa activity, when low molecular weight heparins are used, it disappears from the plasma faster than anti-factor Xa activity.

Excretion occurs primarily by the kidneys, in its original or slightly modified form.

At-risk groups

Before starting treatment with LMWH, renal function should be systematically assessed in elderly patients over 75 years of age using the Cockroft formula.

Indications for the drug Fraxiparine

Treatment of thromboembolism, unstable angina and non-Q wave myocardial infarction.

Contraindications

History of hypersensitivity (including thrombocytopenia) to Fraxiparine or other LMWHs and/or heparin; signs of bleeding or increased risk of bleeding associated with impaired hemostasis, with the exception of disseminated intravascular coagulation syndrome not caused by heparin; organic lesions of organs with a tendency to bleeding (for example, acute gastric or duodenal ulcer); injuries or surgical interventions on the central nervous system; septic endocarditis.

Use during pregnancy and breastfeeding

If the use of epidural anesthesia is considered, it is recommended, as far as possible, to withhold prophylactic heparin treatment at least 12 hours before anesthesia.

Since absorption of the drug in the gastrointestinal tract in newborns is, in principle, unlikely, treatment with Fraxiparine in nursing mothers is not contraindicated.

Side effects

Interaction

The combined use of Fraxiparine with drugs that affect hemostasis, such as acetylsalicylic acid, NSAIDs, vitamin K antagonists, fibrinolytics and dextran, leads to a mutual enhancement of the effect.

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

Directions for use and doses

SC (except for use during hemodialysis).

This form is intended for adults.

Cannot be administered intramuscularly!

1 ml of Fraxiparine is equivalent to approximately 9500 IU of the anti-Xa factor activity of nadroparine.

Technique of subcutaneous administration

It is preferable to inject the patient in a supine position into the subcutaneous tissue of the anterolateral or posterolateral abdominal girdle, alternately from the right and left sides.

Prevention of thromboembolism in surgery

Frequency of application. 1 injection per day.

Dose used. The dose is determined by the individual level of risk, depending on the patient’s body weight and the type of operation.

The initial injection should be administered 2 hours before surgery.

If the risk of thromboembolic complications is present after the recommended period of treatment, it is necessary to continue preventive treatment, primarily with oral anticoagulants.

However, the clinical benefit of long-term treatment with low molecular weight heparins or vitamin K antagonists has not been assessed to date.

Prevention of blood coagulation in the extracorporeal circulation system during hemodialysis: intravascularly(into the arterial shunt of the dialysis loop).

The doses used in patients, depending on body weight, are as follows:

Treatment of deep vein thrombosis (DVT)

Any suspicion must be immediately confirmed by the results of appropriate tests.

Frequency of application. 2 injections per day with an interval of 12 hours.

Dose used. The dose of each injection is 85 IU of anti-Xa factor activity/kg.

For this indication, the dose used depending on the patient's body weight is 0.1 ml/10 kg body weight every 12 hours, as shown in the following table:

Patient's body weight, kg	Fraxiparine volume per administration, ml
40-49	0,4
50-59	0,5
60-69	0,6
70-79	0,7
80-89	0,8
90-99	0,9
≥100	1,0

Treatment of unstable angina/myocardial infarction without Q wave change

Dose used. The initial dose should be administered as an IV bolus at a dose of 86 IU anti-Xa/kg, then SC at the same dose.

Patient's body weight, kg	Injected volume of Fraxiparine
Patient's body weight, kg	Initial dose (iv, bolus), ml	SC injection every 12 hours, ml
<50	0,4	0,4
50-59	0,5	0,5
60-69	0,6	0,6
70-79	0,7	0,7
80-89	0,8	0,8
90-99	0,9	0,9
>100	1,0	1,0