ARIXTRA instructions for use, description of the drug ARIXTRA: contraindications, side effects, dosages, composition - solution for intravenous and subcutaneous administration in the drug directory

Release form and composition

Arixtra is available in the form of a solution for intravenous and subcutaneous or only subcutaneous administration: colorless, transparent or almost transparent liquid (0.5 ml in glass syringes, 5 syringes in plastic trays, 2 trays in a cardboard box).

Composition of the solution for 1 syringe:

active ingredient: fondaparinux sodium – 2.5 mg;
auxiliary components: sodium chloride, 0.01M hydrochloric acid solution/0.005M sodium hydroxide solution, water for injection.

Indications for use

Arixtra is used to treat the following diseases:

deep vein thrombosis in the acute stage;
acute symptomatic thrombosis of the superficial veins of the lower extremities in the absence of deep vein thrombosis;
acute coronary syndrome with non-ST segment elevation myocardial infarction or unstable angina (to prevent refractory ischemia, myocardial infarction or cardiovascular death);
acute coronary syndrome with ST-segment elevation myocardial infarction (to prevent reinfarction and death in persons receiving thrombolytic therapy or patients who did not initially receive reperfusion treatment);
pulmonary embolism.

For the purpose of prevention, the drug is used in the following cases:

venous thromboembolic complications in persons who undergo abdominal surgery and have risks of such complications;
venous thromboembolic complications in patients undergoing “major” surgical orthopedic operations on the lower extremities (hip replacement, knee replacement, hip fracture, including long-term prophylaxis in the postoperative period);
venous thromboembolic complications in non-surgical patients in the presence of risk factors for such complications with limited mobility in the acute period of the disease.

Arixtra

Places of subcutaneous injection

there should be alternately left and right anterolateral surfaces of the anterior abdominal wall. To avoid loss of the drug, do not remove air bubbles from the syringe. The needle should be inserted the full length perpendicularly into the fold of skin, sandwiched between the thumb and forefinger; the skin fold is not unclenched during the entire insertion.

Arixtra is intended for use only under the supervision of a physician. The patient is allowed to independently perform subcutaneous injections only if the doctor deems it necessary, with mandatory follow-up with a doctor and only after appropriate training in the technique of performing subcutaneous injections.

With intravenous administration

(first dose only
in patients with ST-segment elevation myocardial infarction
) the drug is administered directly into the catheter or using mini-containers with 0.9% sodium chloride solution (25 or 50 ml), in which the drug is pre-diluted. To avoid loss of the drug, do not remove air bubbles from the syringe before injection. After injection, flush the catheter with sufficient saline to ensure delivery of the full dose of the drug. When administered using mini-containers, the infusion should be carried out over 1-2 minutes.

Adults

Prevention of venous thromboembolic complications

Orthopedic and abdominal surgery:

The recommended dose of Arixtra is 2.5 mg subcutaneously once a day after surgery.

The initial dose is administered no earlier than 6 hours after completion of the operation, provided there is satisfactory hemostasis.

The course of treatment continues during the period of increased risk of developing venous thromboembolic complications, usually until the patient is transferred to an outpatient regimen, for at least 5-9 days.

Experience has shown that for patients undergoing surgery for a hip fracture,

the duration of the period of increased risk of developing venous thromboembolic complications exceeds 9 days. For such patients, a decision must be made to extend the prophylactic use of Arixtra for up to 24 days.

Non-surgical patients with risk factors for thromboembolic complications:

The recommended dose of Arixtra is 2.5 mg subcutaneously 1 time/day. The duration of treatment in this case ranges from 6 to 14 days.

Treatment of deep vein thrombosis and pulmonary embolism

The recommended dose of Arixtra for subcutaneous administration 1 time/day is for patients weighing less than 50 kg

- 5 mg;
for patients weighing 50-100 kg
– 7.5 mg;
for patients weighing more than 100 kg
- 10 mg.

Treatment should continue for at least 5 days and stop no earlier than a complete transfer to adequate therapy with oral anticoagulants is possible, i.e. when MHO values reach 2 to 3. It is also necessary to add vitamin K antagonists to treatment as soon as possible, usually no later than 72 hours. Typically, the duration of the course of Arixtra is from 5 to 9 days.

Treatment of unstable angina/non-ST segment elevation myocardial infarction

The recommended dose is 2.5 mg subcutaneously 1 time/day. Treatment should begin as soon as possible after diagnosis and continue for 8 days or until the patient is discharged if it occurs earlier than 8 days.

If a patient is scheduled to undergo PCI while being treated with fondaparinux sodium, unfractionated heparin (UFH) should be administered during PCI, according to standard practice at the institution; In this case, it is necessary to take into account the risk of hemorrhagic complications that the patient has, and the fact that the level of this risk is affected, among other things. and time since the last dose of fondaparinux sodium.

The time to restart Arixtra after catheter removal should be determined based on the patient's clinical condition. In clinical studies, treatment with fondaparinux was resumed no earlier than 2 hours after catheter removal.

In patients undergoing coronary artery bypass grafting (CABG), if possible, fondaparinux sodium should not be administered within 24 hours before surgery; Fondaparinux should be resumed 48 hours after CABG.

Treatment of myocardial infarction with ST segment elevation

The recommended dose is 2.5 mg 1 time/day. The first dose is administered intravenously, all subsequent doses are administered subcutaneously. Treatment should begin as soon as possible after diagnosis and continue for 8 days or until the patient is discharged if it occurs earlier than 8 days.

If a patient is scheduled to undergo non-primary PCI while being treated with fondaparinux sodium, UFH should be administered during PCI, according to standard practice in that medical institution; In this case, it is necessary to take into account the risk of hemorrhagic complications that the patient has, and the fact that the level of this risk is affected, among other things. and time since the last dose of fondaparinux sodium.

In patients undergoing CABG, if possible, fondaparinux sodium should not be administered within 24 hours before surgery; Fondaparinux should be resumed 48 hours after CABG.

Treatment of superficial vein thrombosis

The recommended dose of Arixtra is 2.5 mg subcutaneously 1 time/day. Treatment should begin as soon as possible after diagnosis (without concomitant deep vein thrombosis) and continue for 45 days.

Special patient groups

Children

The pharmacokinetic parameters of fondaparinux were characterized in a pharmacokinetic analysis based on blood sampling data from 24 children. The administration of 0.1 mg/kg/body weight subcutaneously once a day in children is based on similar fondaparinux exposure observed in adults when administered at recommended doses for the treatment of deep vein thrombosis and pulmonary embolism.

Elderly patients (over 75 years old)

Arixtra should be used with caution in elderly patients, since renal function may decrease with age. In elderly patients undergoing surgery, the timing of the first dose of Arixtra must be strictly observed.

Patients weighing less than 50 kg

Patients weighing less than 50 kg are at risk of bleeding. In such patients undergoing surgery, the timing of the first dose of Arixtra must be strictly observed.

Patients with impaired renal function

Prevention of venous thromboembolism

For patients with CC more than 30 ml/min

no dose adjustment is required.

In patients with CC from 20 to 30 ml/min

, as well as in those patients for whom the benefits of using fondaparinux sodium outweigh the risks of its use, the recommended dosage of the drug is 1.5 mg 1 time / day or 2.5 mg every other day (i.e., approximately every 48 hours).

In patients undergoing surgery, the timing of the first dose of Arixtra must be strictly observed.

Treatment of deep vein thrombosis and pulmonary embolism

For patients with
CC 30 ml/min or more,
no dose adjustment of Arixtra is required.

Patients with CC less than 30 ml/min

Fondaparinux sodium should not be prescribed.

Treatment of unstable angina and myocardial infarction without/with ST segment elevation

The use of Arixtra is not recommended for use in patients with creatinine clearance less than 20 ml/min.

.
No dose adjustment is required in patients with CC 20 ml/min or more
.

Treatment of superficial vein thrombosis

For patients with CC more than 30 ml/min

no dose adjustment is required.

In patients with CC from 30 to 50 ml/min

Arixtra can be used with caution.

Patients with CC less than 30 ml/min

Fondaparinux sodium should not be prescribed.

Patients with liver dysfunction

For patients with mild to moderate liver dysfunction

No dose adjustment of Arixtra is required.

Arixtra should be administered with caution to patients with severe hepatic impairment

Instructions for use of the drug

Technique of subcutaneous administration

1. You should take a “sitting” or “lying” position. Choose a place in the lower abdomen, at least 5 cm below the navel.

It is preferable to inject the drug into the right and left sides of the anterior abdominal wall alternately (this will help reduce discomfort at the injection site). Injection into the thigh is allowed.

2. Remove the protective cap by first twisting and then pulling it in a straight line away from the body of the syringe. Note: Do not touch the needle after removing the cap and do not allow the exposed needle to come into contact with any surfaces. Air bubbles may appear; they should not be removed from the syringe before injection.

3. Hold the syringe tightly. The needle should be inserted perpendicularly, and not at an angle, its entire length into the pinched fold of skin, which must be held with the thumb and forefinger until the solution is injected. Then carefully remove the needle. Do not rub the injection site after injection.

4. After performing the injection, a protection system is installed on the used syringe: holding the used syringe in one hand by the protective housing, with the other hand, pull the holder to release the latch and slide the housing to protect the needle until an audible click indicates the fitting of the protective housing.

The syringe can then be disposed of according to normal medical waste disposal procedures.

Contraindications

Absolute:

severe renal failure (creatinine clearance less than 20 ml/min);
acute bacterial endocarditis;
clinically significant active bleeding;
hypersensitivity to any of the components of the drug.

Reception is not recommended:

performing a primary PCI (percutaneous coronary intervention) procedure in individuals with ST-segment elevation myocardial infarction (immediately before and during the procedure);
conducting non-primary PCI in individuals with non-elevation and ST-segment elevation myocardial infarction.

Relative (the drug Arixtra is used with caution):

exacerbation of peptic ulcer of the duodenum and stomach;
severe liver dysfunction;
recent intracranial hemorrhage;
acquired or congenital disorders of the blood coagulation system (in the form of bleeding);
recent surgery on the spinal cord or brain;
recent ophthalmic surgery;
moderate renal failure (creatinine clearance less than 50 ml/min);
the patient's body weight is less than 50 kg (due to a high risk of bleeding);
elderly age over 75 years (due to a high risk of bleeding);
simultaneous use with drugs that increase the risk of bleeding.

The use of the drug during pregnancy is allowed only if the expected benefit to the mother significantly outweighs the potential risk to the fetus.

During lactation (breastfeeding), the use of Arixtra is not recommended.

Special instructions for the use of Arixtra

The drug should not be used for intramuscular administration. Percutaneous coronary intervention and the risk of guiding catheter thrombosis. ST- segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention, the use of Arixtra before and during the procedure is not recommended. For the treatment of patients with unstable angina/non- ST segment elevation myocardial infarction and ST -segment elevation myocardial infarction who are undergoing non-primary percutaneous coronary intervention, the use of Arixtra as an independent anticoagulant during the intervention period is not recommended. According to current recommendations, unfractionated heparin should be used. Data regarding the use of unfractionated heparin during non-primary percutaneous coronary intervention in patients treated with Arixtra are limited. In those patients who underwent non-primary percutaneous coronary intervention 6 to 24 hours after the last dose of fondaparinux, the mean unfractionated heparin dose was 8000 IU and the incidence of major bleeding was 2% (2/98). In patients who underwent non-primary percutaneous coronary intervention less than 6 hours after the last dose of fondaparinux, the mean unfractionated heparin dose was 5000 IU and the incidence of major bleeding was 4.1% (2/49). Clinical studies have demonstrated a low but increased risk of guiding catheter thrombosis in patients treated with fondaparinux alone as an anticoagulant during percutaneous coronary intervention compared with controls. ST -segment elevation myocardial infarction was 1.0% compared with 0.3% (fondaparinux versus enoxaparin) and in primary coronary intervention in patients with non-ST-segment elevation myocardial infarction ST - 1.2% versus 0% (fondaparinux versus control). Bleeding. Arixtra, like other anticoagulants, should be used with caution in patients with an increased risk of bleeding, such as congenital or acquired disorders of the blood coagulation system in the form of bleeding, peptic ulcer of the stomach or intestines in the acute phase, recent intracranial hemorrhage, in the near future after brain or spinal cord surgery or ophthalmic surgery. Prevention and treatment of venous thromboembolism. Drugs that increase the risk of bleeding should not be used concomitantly with Arixtra, with the exception of vitamin K antagonists used to treat venous thromboembolism. If such combined use is necessary, it should be done under close supervision. Prevention of venous thromboembolism after surgery (time of administration of the first dose of Arixtra). It is necessary to strictly adhere to the time of administration of the first dose of Arixtra, which must be administered no earlier than 6 hours after completion of the operation and only after hemostasis has been achieved. Prescribing Arixtra earlier than 6 hours may be associated with an increased risk of severe bleeding. High-risk groups include patients over 75 years of age, with body weight ≤50 kg, and moderate renal failure (creatinine clearance ≤50 ml/min). Unstable angina/myocardial infarction without ST segment elevation and myocardial infarction with ST segment elevation. Arixtra should be used with caution in the treatment of patients concomitantly receiving other drugs that increase the risk of bleeding (such as GP IIb/IIIa receptor antagonists or thrombolytics). Epidural/lumbar puncture. When using Arixtra simultaneously with epidural anesthesia or lumbar puncture, there is a risk of epidural or subdural spinal hematomas, which can cause prolonged or persistent paralysis. The risk of these rare events increases with the use of indwelling epidural catheters after surgery or the simultaneous administration of other drugs that affect hemostasis. Elderly patients. The risk of bleeding in elderly patients is higher than in other patients. Because renal function generally declines with age, the elimination of fondaparinux may be reduced in elderly patients, thereby increasing drug exposure. Therefore, Arixtra should be used with caution in elderly patients (see APPLICATION). Insufficient body weight. Patients weighing ≤50 kg are at high risk of bleeding. Elimination of fondaparinux decreases with decreasing body weight. Arixtra should be used with caution in such patients (see APPLICATION). Renal dysfunction . Fondaparinux elimination time decreases with increasing severity of renal impairment and is associated with an increased risk of bleeding. Patients with renal failure, especially those with creatinine clearance ≤30 ml/min, are at increased risk of both significant bleeding and venous thromboembolism. Unstable angina/myocardial infarction without ST segment elevation and myocardial infarction with ST segment elevation. Clinical data regarding the use of fondaparinux for the treatment of unstable angina and non- ST- ST- segment elevation myocardial infarction in patients with creatinine clearance in the range of 20-30 ml/min. Therefore, the possibility of use is assessed from the point of view of the benefit/risk ratio. Arixtra is not recommended for use in patients with creatinine clearance ≤20 ml/min. Severe liver failure. In patients with an increased prothrombin time, Arixtra should be used with caution, given the increased risk of bleeding due to insufficient coagulation factors in patients with severe hepatic impairment. Heparin-induced thrombocytopenia . Fondaparinux does not bind to platelet factor IV and does not cross-react with plasma from patients with heparin-induced thrombocytopenia. Arixtra should be used with caution in patients with a history of heparin-induced thrombocytopenia. The efficacy and safety of Arixtra for the treatment of patients with heparin-induced thrombocytopenia type II have not been studied. There have been isolated reports of the development of heparin-induced thrombocytopenia in patients treated with fondaparinux. The connection between Arixtra therapy and the occurrence of heparin-induced thrombocytopenia has not yet been established. Allergy to latex. The protective cap on the needle of a pre-filled syringe contains rubber made from natural latex, which can cause allergic reactions if you are hypersensitive to latex. During pregnancy and breastfeeding. Clinical experience regarding the use of the drug during pregnancy and lactation is currently limited, therefore Arixtra should not be prescribed during this period, unless the expected benefit to the mother outweighs the potential risk to the fetus. Arixtra is excreted into the milk of rats, but it is not known whether the drug passes into women's breast milk. During treatment with the drug, breastfeeding should be stopped. Impact on the ability to drive vehicles and perform work that requires increased attention. No studies have been conducted to study the effect of the drug.

Directions for use and dosage

Arixtra is administered subcutaneously (SC) or intravenously (IV) under the supervision of a physician.

Subcutaneous injections are performed alternately into the left and right anterolateral surface of the anterior abdominal wall. The needle is inserted to its full length into a fold of skin, which is pinched with the thumb and forefinger and not released during insertion.

For intravenous administration, Arixtra solution is injected into a catheter or mini-containers of 25 or 50 ml with 0.9% sodium chloride solution are used, in which the drug is pre-diluted. After injection, the catheter should be flushed with a sufficient amount of isotonic sodium chloride solution to ensure delivery of the full dose of the drug. If mini-containers are used for administration, the infusion duration should be 1-2 minutes.

Recommended doses and duration of treatment with Arixtra in adult patients:

deep vein thrombosis and pulmonary embolism: 5 mg subcutaneously (patients weighing less than 50 kg), 7.5 mg (patients weighing 50-100 kg) or 10 mg (patients weighing more than 100 kg) once a day. No later than 72 hours from the start of treatment, vitamin K antagonists should be added to therapy. Duration of treatment is 5-9 days;
Thrombosis of superficial veins: s/c 2.5 mg once a day. Treatment begins as early as possible and continues for 45 days;
unstable angina or myocardial infarction without ST segment elevation: subcutaneously 2.5 mg once daily. Treatment begins as early as possible and continues for 8 days, and in the case of earlier discharge of the patient - until discharge. When undergoing PCI while being treated with Arixtra, the patient should also be administered unfractionated heparin. During CABG (coronary artery bypass grafting), it is not advisable to administer fondaparinux sodium within 24 hours before surgery; resume administration of the drug two days after CABG;
myocardial infarction with ST segment elevation: 2.5 mg once a day. The first dose should be administered intravenously, all subsequent doses should be administered subcutaneously. Treatment begins as early as possible and continues for 8 days, and in the case of earlier discharge of the patient - until discharge. When undergoing PCI while being treated with Arixtra, the patient should also be administered unfractionated heparin. In case of CABG, it is not advisable to administer fondaparinux sodium within 24 hours before surgery; resume administration of the drug two days after CABG;
prevention of venous thromboembolic complications: subcutaneously 2.5 mg once a day after surgery. The first dose of the drug is administered no earlier than 6 hours after the end of the operation, as well as under the condition of independent hemostasis. The duration of treatment is at least 5-9 days. In patients with a hip fracture, therapy can be continued for up to 24 days after surgery. In non-surgical patients with risk factors for thromboembolic complications, the duration of use of the drug is 6-14 days.

Special studies on the use of Arixtra in children and adolescents under 17 years of age have not been conducted.

Fondaparinux sodium is prescribed to children for the treatment of pulmonary embolism and deep vein thrombosis in doses similar to those used in adult patients - subcutaneously 0.1 mg/kg/body weight once a day.

Pharmacological properties of the drug Arixtra

Pharmacodynamics . Fondaparinux sodium (α-d-glucopyranoside, methyl O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-d-glucopyranosyl-(1→4)-O-β-d-glucopyranosyl-(1 →4)-O-2-deoxy-3,3-di-O-sulfo-2-(sulfoamino)-α-d-glucopyranosyl-(1→4)-O-2-O-sulfo-(-L- Idopyranuronosyl-(1→4)-2-deoxy-2-(sulfoamino), 6-(hydrosulfate), decane sodium salt) is a synthetic selective inhibitor of activated factor X (Xa).The antithrombotic activity of fondaparinux is the result of selective inhibition of factor Xa mediated by antithrombin III (AT III). By selectively binding to AT III, fondaparinux potentiates (approximately 300-fold) the initial neutralization of factor Xa by antithrombin III. Neutralization of factor Xa interrupts the coagulation chain and inhibits both thrombin formation and thrombus formation. Fondaparinux does not inactivate thrombin (activated factor IIa) and has no effect on platelets.At a dose of 2.5 mg, Arixtra 2.5 mg/0.5 ml does not affect the results of conventional coagulation tests such as activated partial thromboplastin time (aPTT), activated clotting time or prothrombin plasma time/international normalized ratio (INR), bleeding time and fibrinolytic activity. However, there have been isolated reports of an increase in aPTT when using 2.5 mg of the drug. Fondaparinux does not cross-react with the blood serum of patients with heparin-induced thrombocytopenia. Pharmacokinetics . Suction. After subcutaneous administration, fondaparinux is rapidly absorbed (absolute bioavailability - 100%). With a single subcutaneous administration of 2.5 mg of fondaparinux to young healthy volunteers, the maximum plasma concentration (on average 0.34 mg/l) was achieved 2 hours after drug administration. Plasma concentrations of half the maximum are achieved 25 minutes after administration. In healthy elderly individuals, the pharmacokinetics of fondaparinux is linear in the dose range of 2–8 mg s.c. When administered once a day, a steady-state equilibrium concentration in the blood plasma is achieved after 3-4 days with an increase of 1.3 times in the maximum concentration and AUC. After a single intravenous bolus administration of the drug to healthy elderly volunteers, the pharmacokinetic profile of fondaparinux is linear within therapeutic doses. The average (CV%) pharmacokinetic parameters of fondaparinux at steady state in patients who underwent hip surgery and received fondaparinux at a dose of 2.5 mg/day were: maximum plasma concentration - 0.39 mg/l (31%), the time to achieve it is 2.8 hours (18%), the minimum concentration is 0.14 mg/l (56%). In elderly patients who underwent surgery for a femoral fracture, the equilibrium concentrations of fondaparinux were: maximum - 0.50 mg/l (32%), minimum - 0.19 mg/l (58%). Distribution. In healthy volunteers, after subcutaneous and intravenous administration, fondaparinux is distributed in such a way that most of it is in the blood and only a small amount is in the extravascular fluid. The volume of distribution of fondaparinux is (7–11 L). In vitro, fondaparinux binds to a high degree (at least 94%) and specifically binds to the AT III protein. The binding of fondaparinux to other plasma proteins, including platelet factor IV and red blood cells, is insignificant. Metabolism. in vivo metabolism of fondaparinux has not been studied because in patients with normal renal function, most of the administered dose is excreted unchanged in the urine. Excretion. Fondaparinux is excreted primarily unchanged by the kidneys; in healthy individuals, 64–77% of a single dose is excreted in the urine within 72 hours. The half-life is approximately 17 hours in young healthy individuals and approximately 21 hours in healthy elderly individuals. In patients with normal renal function, the average clearance of fondaparinux is 7.82 ml/min. Special groups of patients. Renal dysfunction . Fondaparinux is eliminated more slowly in patients with renal impairment because the drug is eliminated primarily unchanged by the kidneys. In patients receiving prophylactic treatment after hip fracture surgery or hip replacement, the total clearance of fondaparinux is approximately 25% lower in patients with mild renal impairment (creatinine clearance 50–80 ml/min), approximately 40% lower in patients with moderate renal impairment (creatinine clearance 30–50 ml/min) and 55% lower in patients with severe renal failure (creatinine clearance ≤30 ml/min) compared with individuals with normal renal function. Accordingly, the final half-life was 29 hours in moderate and 72 hours in severe renal impairment. A similar relationship between fondaparinux clearance and the severity of renal failure was noted in the treatment of patients with deep vein thrombosis. Prevention of venous thromboembolism . A population pharmacokinetic model was developed from studies of patients treated with fondaparinux for major lower extremity orthopedic surgery, including patients with creatinine clearance ≤23.5 mL/min. Pharmacokinetic modeling using this model showed that the predicted mean fondaparinux level in patients with a creatinine clearance of 20–30 ml/min using 1.5 mg once daily or 2.5 mg every other day was similar to that in patients with renal impairment. mild to moderate insufficiency (creatinine clearance 30–80 mg/min), using 2.5 mg fondaparinux once daily. Liver dysfunction . Based on the pharmacokinetics of the drug, unbound fondaparinux concentrations are expected to remain unchanged in patients with mild to moderate hepatic impairment and therefore no dose adjustment is necessary. Following a single subcutaneous administration of fondaparinux to patients with moderate hepatic impairment (Child-Pugh class B), fondaparinux Cmax and AUC decreased by 22% and 39%, respectively, compared with patients without renal impairment. The lower plasma concentration of fondaparinux is explained by a decrease in the degree of binding to AT III, since patients with liver failure have lower plasma concentrations of AT III. Thus, the result of this is an increase in the renal clearance of fondaparinux. The pharmacokinetics of fondaparinux have not been studied in patients with severe hepatic impairment. Children . Fondaparinux has not been studied in children. Elderly patients . Elimination of fondaparinux is reduced in patients over 75 years of age. In studies of fondaparinux 2.5 mg prophylactically following surgery for hip fracture or hip replacement, the total clearance of fondaparinux was approximately 25% lower in patients over 75 years of age compared to patients under 65 years of age. A similar relationship between fondaparinux clearance and age was noted in the treatment of patients with deep vein thrombosis. Floor . The pharmacokinetics of the drug does not differ depending on gender. Race . Pharmacokinetic studies have not been conducted in representatives of different races. However, the results of studies involving healthy representatives of the Mongoloid race did not demonstrate differences in the pharmacokinetic profile compared with healthy representatives of the Caucasian race. There were no differences in the clearance of the drug from the blood plasma of patients of the Negroid and Caucasian races who underwent orthopedic surgery. Body mass. In patients weighing ≤50 kg, the total clearance of fondaparinux is reduced by 30%. The clearance of fondaparinux increases with increasing body weight (9% for every 10 kg of body weight).

Side effects

nervous system: sometimes – headaches; rarely - drowsiness, dizziness, anxiety, loss or confusion;
digestive system: sometimes – vomiting and nausea; rarely - gastritis, diarrhea or constipation, dyspepsia, abdominal pain;
liver and biliary tract: sometimes - increased concentrations of liver enzymes in the blood, abnormal results of liver tests; rarely - increased bilirubin concentration;
cardiovascular system: rarely – decreased blood pressure;
hematopoietic system: often – purpura, various bleedings, anemia; sometimes - thrombocythemia, bleeding disorder, thrombocytopenia, platelet abnormality;
respiratory system: rarely – cough, shortness of breath;
metabolism: rarely – hypokalemia;
skin and subcutaneous fat: sometimes – itching, rash, discharge from the wound;
other reactions: often - swelling; sometimes – fever; rarely - pain in the chest and lower extremities, facial flushing, allergic reactions, postoperative wound infection, fatigue, syncope, reactions at the injection site.

special instructions

Arixtra should not be administered intramuscularly.

Medicines that increase the likelihood of bleeding should not be used concomitantly with fondaparinux sodium. An exception is vitamin K antagonists, which are used in the treatment of pulmonary embolism and venous thrombosis. If it is necessary to use such combinations, therapy is carried out under the strict supervision of a physician.

With simultaneous lumbar puncture or epidural/spinal anesthesia and the use of Arixtra, spinal or epidural hematomas may occur, sometimes leading to prolonged or permanent paralysis. The risk of such rare events increases with the simultaneous administration of other drugs that affect hemostasis and with the postoperative use of indwelling epidural catheters.

Studies on the effect of Arixtra on the speed of psychomotor reactions and concentration have not been conducted.

Drug interactions

When used simultaneously with antiplatelet agents (acetylsalicylic acid), cardiac glycosides (digoxin), oral anticoagulants (warfarin) and non-steroidal anti-inflammatory drugs (piroxicam), the pharmacodynamics or pharmacokinetics of fondaparinux sodium did not change. The drug also did not affect the pharmacodynamic and pharmacokinetic parameters of the listed drugs.

It is not recommended to mix Arixtra solution in the same syringe with other drugs.

Interactions of the drug Arixtra

fondaparinux does not inhibit cytochrome P450 enzymes (CYP 1A2, CYP 2A6, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 and CYP 3A4) in vitro . Therefore, Arixtra should not be expected to interact with other drugs at the level of inhibition of CYP-mediated metabolism in vivo . Since the binding of fondaparinux to plasma proteins, with the exception of AT III, is insignificant, interaction with other drugs that are metabolized to plasma proteins should not be expected. Drugs that increase the risk of bleeding should not be used concomitantly with Arixtra, with the exception of vitamin K antagonists used to treat venous thromboembolism. If such combined use is necessary, it should be done under close supervision. As a result of clinical studies of fondaparinux, it has been proven that its combined use with oral anticoagulants (warfarin), antiplatelet agents (acetylsalicylic acid), NSAIDs (piroxicam) and cardiac glycosides (digoxin) does not significantly affect the pharmacokinetics and pharmacodynamics of fondaparinux. In addition, the drug does not affect the activity of warfarin, bleeding time during treatment with acetylsalicylic acid or piroxicam, or the pharmacokinetics or pharmacodynamics of digoxin at steady state. Arixtra should not be mixed with other drugs, since no compatibility studies have been conducted.