Use of anticoagulants during pregnancy: Fraxiparine. Fraxiparine - instructions for use Fraxiparine therapeutic dose

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.

Fraxiparin 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.

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.

Release form of the drug Fraxiparin

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).

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 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

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.

Use of the drug Fraxiparine during pregnancy

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.

Contraindications to the use of the drug Fraxiparine

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.

Side effects of the drug Fraxiparine

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.

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 phlebography, 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.

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.

Interactions of the drug Fraxiparine with other drugs

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.

Special instructions when taking Fraxiparine

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/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).

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 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.

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.

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.

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 analysis, 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 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.

Low molecular weight heparins (LMWHs) are a class of anticoagulant drugs that are used to prevent and treat thromboembolic complications.

The range of applications is quite wide, combining surgical and therapeutic profiles, as well as emergency medicine.

Unlike its predecessor, Heparin, LMWHs have pronounced pharmacological activity, are safer and more controlled, and can be administered both subcutaneously and intravenously.

Today, there are several generations of these drugs on the market, which are constantly being supplemented with new drugs. In this article we will talk about, the price and quality of which fully satisfy the needs of doctors and patients.

Indications

The active ingredient of Fraxiparin is nadroparin calcium, which is indicated in the following clinical situations:

prevention of thrombosis in surgical patients;
treatment of pulmonary embolism;
treatment of thrombophlebitis of various origins;
prevention of blood clotting during hemodialysis;
in the treatment of acute coronary syndrome (heart attack).

It is important to note that Fraxiparine is used primarily in a hospital setting under the supervision of a physician. Before prescribing, a number of clinical and laboratory studies should be performed, in particular a coagulogram.

Contraindications

There is no medicine that is suitable for all patients.

Before use, you should carefully read the instructions and determine whether you have the following:

allergic reactions to nadroparin calcium or auxiliary components that are part of the solution;
thrombocytopenia;
active bleeding or increased risk of its development;
traumatic brain injury;
and lactation period;
heavy;
children under 18 years of age (relative contraindication).

Unlike Heparin, which has a natural antidote - Protamine sulfate, LMWHs do not have one.

If Fraxiparine is used incorrectly or if adverse reactions occur, its effect cannot be stopped.

Release form

Fraxiparine is available as a solution for subcutaneous or intravenous administration. Available in disposable sealed syringes with a protective cap, which are securely packed in 10 pieces per package.

Solution for subcutaneous administration Fraxiparine

It is usually administered subcutaneously; to do this, the syringe is removed from the sheath and the cap is removed. The injection site (peri-umbilical area) is treated three times with an antiseptic.

A fold of skin is formed with the fingers of the left hand, and the needle is inserted strictly perpendicular to the skin along its entire length. The syringe is removed and is not suitable for reuse.

Manufacturer

Fraxiparine is a branded drug of the American pharmaceutical corporation Aspen.

This company has been on the market for more than 160 years; according to 2017 data, it is one of the ten world leaders in the production of drugs, medical and laboratory equipment.

The French companies Sanofi-aventis and Glaxosmithkline present a wide variety of different dosages of nadroparin calcium, also under the trade name Fraxiparine.

In this case, the drug is a generic (we bought the right to manufacture from Aspen). Nadroparin-Pharmex, which is produced by the Pharmex group company, is available for sale in Ukraine.

Packing

Available in disposable syringes of 0.3, 0.4, 0.6 and 0.8 ml, 10 pieces in one package.

Dosage of the drug

0.3 ml

The dose depends on the concentration of the active substance - nadroparin calcium, measured in international units.

1 ml of Fraxiparine contains 9500 IU of the active component.

Thus, 0.3 ml will contain 2850 IU. This amount of the drug is indicated for patients whose weight does not exceed 45 kg.

0.4 ml

Contains 3800 IU of nadroparin calcium, indicated for patients weighing from 50 to 55 kg.

0.6 ml

Contains 5700 IU of active ingredient, suitable for patients from 60 to 69 kg.

Price

The price of Fraxiparine depends on the dose and manufacturer. It goes without saying that a branded drug is much more expensive than a generic drug.

Fraxiparine price depending on dosage:

Prices are average, presented for 2017. May vary by region and pharmacy.

Video on the topic

About the course of thrombophlebitis in the video:

Thus, Fraxiparine is an indispensable drug for the treatment and prevention of thrombosis. Advantages include the variety of available dosages, safety and reasonable cost.

In this article you can read the instructions for use of the drug Fraxiparine. Reviews of site visitors - consumers of this medicine, as well as the opinions of specialist doctors on the use of Fraxiparine in their practice are presented. We kindly ask you to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not stated by the manufacturer in the annotation. Fraxiparine analogues in the presence of existing structural analogues. Use for the treatment and prevention of thrombosis and thromboembolism in adults, children, as well as during pregnancy and lactation.

Fraxiparine- is a low molecular weight heparin (LMWH), obtained by depolymerization from standard heparin, is a glycosaminoglycan with an average molecular weight of 4300 daltons.

Shows a high ability to bind to the blood plasma protein antithrombin 3 (AT 3). This binding leads to accelerated inhibition of factor 10a, which is responsible for the high antithrombotic potential of nadroparin (the active substance of the drug Fraxiparine).

Other mechanisms mediating the antithrombotic effect of nadroparin include activation of tissue factor converting inhibitor (TFPI), activation of fibrinolysis through direct release of tissue plasminogen activator from endothelial cells, and modification of blood rheological properties (decreasing blood viscosity and increasing platelet and granulocyte membrane permeability).

Nadroparin calcium is characterized by higher anti-10a factor activity compared to anti-2a factor or antithrombotic activity and has both immediate and prolonged antithrombotic activity.

Compared with unfractionated heparin, nadroparin has a lesser effect on platelet function and aggregation and a less pronounced effect on primary hemostasis.

In prophylactic doses, Fraxiparine does not cause a significant decrease in aPTT.

During a course of treatment during the period of maximum activity, it is possible to increase the aPTT to a value 1.4 times higher than the standard one. This prolongation reflects the residual antithrombotic effect of nadroparin calcium.

Compound

Nadroparin calcium + excipients.

Pharmacokinetics

Pharmacokinetic properties are determined based on changes in plasma anti-10a factor activity.

Fraxiparine is absorbed almost completely (about 88%). When administered intravenously, maximum anti-10a activity is achieved in less than 10 minutes. Metabolized mainly in the liver by desulfation and depolymerization.

The results of the study showed that a slight accumulation of nadroparin may be observed in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min and< 60 мл/мин). Следовательно, дозу Фраксипарина следует уменьшить на 25% у пациентов, получающих Фраксипарин с целью лечения тромбоэмболии, нестабильной стенокардии/инфаркта миокарда без зубца Q. Пациентам с почечной недостаточностью тяжелой степени с целью лечения данных состояний Фраксипарин противопоказан.

In patients with mild or moderate renal failure, when using Fraxiparine for the purpose of preventing thromboembolism, the accumulation of nadroparine does not exceed that in patients with normal renal function taking Fraxiparine in therapeutic doses. When using Fraxiparine for the purpose of prevention, dose reduction in this category of patients is not required. In patients with severe renal failure receiving Fraxiparine in prophylactic doses, a dose reduction of 25% is necessary.

Low molecular weight heparin is injected into the arterial line of the dialysis loop in doses high enough to prevent clotting in the dialysis loop. Pharmacokinetic parameters do not fundamentally change, except in the case of overdose, when the passage of the drug into the systemic circulation can lead to an increase in anti-10a factor activity associated with the final phase of renal failure.

Indications

prevention of thromboembolic complications (during surgical and orthopedic interventions; in patients with a high risk of thrombus formation in acute respiratory and/or heart failure in ICU settings);
treatment of thromboembolism;
prevention of blood clotting during hemodialysis;
treatment of unstable angina and non-Q wave myocardial infarction.

Release forms

Solution for subcutaneous administration (injections in single-dose syringes) 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml and 1 ml (including Fraxiparine Forte).

There are no other forms of release, for example, tablets.

Instructions for use and dosage

How and where to inject Fraxiparine - injection technique

When administered subcutaneously, the drug is preferably administered with the patient lying down, into the subcutaneous tissue of the anterolateral or posterolateral surface of the abdomen, alternately from the right and left sides. Injection into the thigh is allowed.

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

The needle should be inserted perpendicularly, not at an angle, into the pinched fold of skin formed between the thumb and index finger. The fold should be maintained throughout the entire period of drug administration. Do not rub the injection site after injection.

For the prevention of thromboembolism in general surgical practice, the recommended dose of Fraxiparine is 0.3 ml (2850 anti-10a IU) subcutaneously. The drug is administered 2-4 hours before surgery, then once a day. Treatment is continued for at least 7 days or for the entire period of increased risk of thrombosis, until the patient is transferred to an outpatient regimen.

To prevent thromboembolism during orthopedic operations, Fraxiparine is administered subcutaneously at a dose set depending on the patient’s body weight at the rate of 38 anti-10a IU/kg, which can be increased to 50% on the 4th postoperative day. The initial dose is prescribed 12 hours before surgery, the 2nd dose - 12 hours after the end of the operation. Further, Fraxiparine continues to be used once a day throughout the entire period of increased risk of thrombosis until the patient is transferred to an outpatient regimen. The minimum duration of therapy is 10 days.

In the treatment of unstable angina and myocardial infarction without a Q wave, Fraxiparine is prescribed subcutaneously 2 times a day (every 12 hours). The duration of treatment is usually 6 days. In clinical studies, patients with unstable angina/non-Q wave myocardial infarction were prescribed Fraxiparine in combination with acetylsalicylic acid at a dose of 325 mg per day.

The initial dose is administered as a single intravenous bolus injection, followed by subsequent doses administered subcutaneously. The dose is set depending on body weight at the rate of 86 anti-10a IU/kg.

When treating thromboembolism, oral anticoagulants (in the absence of contraindications) should be prescribed as early as possible. Fraxiparine therapy is not stopped until the target prothrombin time is achieved. The drug is prescribed subcutaneously 2 times a day (every 12 hours), the usual course duration is 10 days. The dose depends on the patient’s body weight at the rate of 86 anti-10a IU/kg body weight.

Side effect

bleeding of various locations;
thrombocytopenia;
eosinophilia, reversible after discontinuation of the drug;
hypersensitivity reactions (Quincke's edema, skin reactions);
formation of a small subcutaneous hematoma at the injection site;
skin necrosis, usually at the injection site;
priapism;
reversible hyperkalemia (associated with the ability of heparins to suppress aldosterone secretion, especially in patients at risk).

Contraindications

thrombocytopenia with a history of nadroparin use;
signs of bleeding or increased risk of bleeding associated with impaired hemostasis (except for DIC 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 brain, spinal cord or eyes;
intracranial hemorrhage;
acute septic endocarditis;
severe renal failure (CK<30 мл/мин) у пациентов, получающих Фраксипарин для лечения тромбоэмболии, нестабильной стенокардии и инфаркта миокарда без зубца Q;
childhood and adolescence (up to 18 years);
hypersensitivity to nadroparin or any other components of the drug.

Fraxiparine should be prescribed with caution in situations associated with an increased risk of bleeding:

with liver failure;
with renal failure;
with severe arterial hypertension;
with a history of peptic ulcers or other diseases with an increased risk of bleeding;
for circulatory disorders in the choroid and retina of the eye;
in the postoperative period after operations on the brain, spinal cord or eyes;
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.

Use during pregnancy and breastfeeding

Animal studies have not shown teratogenic or fetotoxic effects of nadroparin calcium, however, there are currently only limited data regarding the penetration of nadroparin calcium across the placenta in humans. Therefore, the use of Fraxiparine during pregnancy is not recommended, unless the potential benefit to the mother outweighs the risk to the fetus.

Currently, there are only limited data regarding the excretion of nadroparin calcium into breast milk. In this regard, the use of nadroparin calcium during breastfeeding is not recommended.

Use in children

Contraindicated in children and adolescents (under 18 years of age).

special instructions

Particular attention should be paid to the specific instructions for use for each drug belonging to the LMWH class, because they may use different dosage units (IU or mg). Because of this, alternating Fraxiparine with other LMWHs during long-term treatment is unacceptable. It is also necessary to pay attention to which drug is used - Fraxiparine or Fraxiparine Forte, because this affects the dosage regimen.

Graduated syringes are designed to select the dose depending on the patient’s body weight.

Fraxiparine is not intended for intramuscular administration.

Heparin-induced thrombocytopenia

Since there is a possibility of developing thrombocytopenia (heparin-induced thrombocytopenia) when using heparins, the platelet count must be monitored during the entire course of treatment with Fraxiparine.

Rare cases of thrombocytopenia, sometimes severe, have been reported, which may be associated with arterial or venous thrombosis, which is important to consider in the following cases:

with thrombocytopenia;
with a significant decrease in platelet content (by 30-50% compared to the initial value);
with negative dynamics of thrombosis for which the patient is receiving treatment;
with thrombosis that developed during the use of the drug;
with DIC syndrome.

In these cases, treatment with Fraxiparine should be discontinued.

These effects of an immunoallergic nature are usually observed between 5 and 21 days of treatment, but may occur earlier if the patient has a history of heparin-induced thrombocytopenia.

If there is a history of heparin-induced thrombocytopenia (due to unfractionated or low molecular weight heparins), treatment with Fraxiparine may be prescribed if necessary. However, strict clinical monitoring and, at a minimum, daily platelet count measurement are indicated in this situation. If thrombocytopenia occurs, use of Fraxiparine should be stopped immediately.

If thrombocytopenia occurs against the background of heparins (unfractionated or low molecular weight), then the possibility of prescribing anticoagulants of other groups should be considered. If other drugs are not available, then another LMWH may be used. In this case, the number of platelets in the blood should be monitored daily. If signs of incipient thrombocytopenia continue to be observed after changing the drug, then treatment should be stopped as soon as possible. It must be remembered that monitoring of platelet aggregation based on in vitro tests is of limited value in the diagnosis of heparin-induced thrombocytopenia.

Hyperkalemia

Heparins may suppress aldosterone secretion, which may lead to hyperkalemia, especially in patients with elevated blood potassium concentrations or in patients at risk for elevated blood potassium levels (eg, patients with diabetes mellitus, chronic renal failure, metabolic acidosis, or patients taking medications that can cause hyperkalemia (including ACE inhibitors, NSAIDs)). The risk of hyperkalemia increases with long-term therapy but is usually reversible with discontinuation. In patients at risk, the concentration of potassium in the blood should be monitored.

Spinal/epidural anesthesia/lumbar puncture and related medications

The risk of spinal/epidural hematomas is increased in individuals with epidural catheters or concomitant use of other medications that may affect hemostasis, such as NSAIDs, antiplatelet agents, or other anticoagulants. The risk also appears to increase with traumatic or repeated epidural or spinal taps. Thus, the issue of the combined use of neuraxial blockade and anticoagulants should be decided individually after assessing the benefit/risk ratio in the following situations:

in patients already receiving anticoagulants, the need for spinal or epidural anesthesia must be justified;
in patients planning elective surgery using spinal or epidural anesthesia, the need for anticoagulants should be justified.

When performing a lumbar puncture or spinal/epidural anesthesia, a minimum of 12 hours must elapse between the administration of Fraxiparine for prophylaxis or 24 hours for treatment and the insertion or removal of a spinal/epidural catheter or needle. In patients with renal impairment, increasing these intervals may be considered. Careful monitoring of the patient is necessary to identify signs and symptoms of neurological disorders. If disturbances are detected in the patient’s neurological status, urgent appropriate therapy is required.

Salicylates, NSAIDs and antiplatelet agents

When preventing or treating venous thromboembolism, as well as when preventing blood coagulation in the extracorporeal circulatory system during hemodialysis, simultaneous use of the drug Fraxiparine with drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) (including acetylsalicylic acid and other salicylates) and antiplatelet agents is not recommended , because this may increase the risk of bleeding.

Impact on the ability to drive vehicles and operate machinery

There is no data on the effect of the drug Fraxiparine on the ability to drive vehicles and machinery.

Drug interactions

The combined use of the drug Fraxiparine with drugs that affect hemostasis, such as acetylsalicylic acid, 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 of over 500 mg): abciximab, acetylsalicylic acid in antiplatelet doses (50-300 mg) for cardiac and neurological indications , beraprost, clopidogrel, eptifibatide, iloprost, ticlopidine, tirofiban - increase the risk of bleeding.

The drug Fraxiparine should be prescribed with caution to patients receiving indirect anticoagulants, systemic corticosteroids and dextrans. When prescribing indirect anticoagulants to patients receiving Fraxiparine, its use should be continued until the MHO level stabilizes to the required value.

Analogues of the drug Fraxiparine

Structural analogues of the active substance:

Fraxiparine Forte.

Analogs by pharmacological group (anticoagulants):

Angiox;
Angioflux;
Antithrombin 3 human;
Anfiber;
Arixtra;
Acenocoumarol;
Warfarex;
Warfarin;
Viatromb;
Hemapaxan;
Heparin;
Calciparin;
Clexane;
Klivarin;
Xarelto;
Lavenum;
Lyoton 1000;
Marewan;
Pelentan;
Piyawit;
Pradaxa;
Seprotin;
Sinkumar;
Trombless;
Thrombophobe;
Troparin;
Phenilin;
Fragmin;
Tsibor 2500;
Cibor 3500;
Exanta SK;
Eliquis;
Emeran;
Enoxaparin sodium.

If there are no analogues of the drug for the active substance, you can follow the links below to the diseases for which the corresponding drug helps, and look at the available analogues for the therapeutic effect.

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).

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

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

Indications of the drug

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

Contraindications

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 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.

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.

special instructions

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/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).

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.

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.

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 test, 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 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.