Instructions for use ARIXTRA

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).

Arixtra instructions for use

Suction.

After subcutaneous administration, fondaparinux sodium is completely and quickly absorbed (absolute bioavailability 100%). With a single subcutaneous administration of 2.5 mg of fondaparinux sodium to young healthy volunteers, Cmax in blood plasma (average Cmax - 0.34 mg/l) was achieved 2 hours after dosing. Plasma concentrations equal to half the above Cmax were achieved 25 minutes after administration.

In healthy elderly subjects, the pharmacokinetics of fondaparinux sodium is linear over the dose range of 2–8 mg SC. With a single dose per day, Css in blood plasma is achieved after 3–4 days with a 1.3-fold increase in Cmax and AUC values.

The average pharmacokinetic parameters of fondaparinux sodium in the equilibrium state in patients who underwent substitution surgery on the hip joint and received the drug Arixtra subcutaneously at a dose of 2.5 mg per day were: Cmax - 0.39 mg/l (31%), Tmax - 2 .8 h (18%) and Cmin - 0.14 mg/l (56%). In elderly patients who underwent surgery for a hip fracture, Css of fondaparinux sodium were: Cmax - 0.5 mg/l (32%), Cmin - 0.19 mg/l (58%).

In patients with symptoms of deep vein thrombosis and pulmonary embolism receiving fondaparinux sodium 5 mg (body weight less than 50 kg), 7.5 mg (body weight 50 to 100 kg) and 10 mg (body weight more than 100 kg ) s/c 1 time per day; Similar values ​​of maximum and minimum Css in plasma were recorded when doses were selected in accordance with body weight in all weight categories. The maximum Css of the drug in blood plasma ranged from 1.2 to 1.26 mg/l. The mean trough plasma Css in these patients ranged from 0.46 to 0.62 mg/L.

Distribution.

In healthy volunteers, fondaparinux sodium, when administered intravenously or subcutaneously, is mainly distributed in the blood and only to a small extent in the interstitial fluid, since the apparent Vd in the equilibrium and unstable states was 7–11 L.
In vitro,
fondaparinux sodium binds highly (at least 94%) and specifically to antithrombin III (AT III). Binding of fondaparinux sodium to other plasma proteins, incl. with platelet factor IV, or red blood cells, slightly.

Metabolism.
in vivo
metabolism of fondaparinux sodium has not been studied because most of the administered dose is excreted unchanged in the urine in patients with normal renal function.

Excretion.

Fondaparinux sodium is excreted unchanged by the kidneys. In healthy individuals, 64–77% of one dose of the drug administered subcutaneously or intravenously is excreted in the urine within 72 hours. T1/2 is about 17 hours in young healthy individuals and about 21 hours in elderly healthy individuals. In patients with normal renal function, the average clearance of fondaparinux sodium is 7.82 ml/min.

Special groups of patients

Patients with impaired renal function.

Elimination of fondaparinux sodium occurs more slowly in patients with renal failure, because it is mainly excreted unchanged by the kidneys. In patients receiving prophylactic treatment after surgery for hip fracture or hip replacement, the total clearance of fondaparinux sodium is 25% lower than in patients with mild renal impairment (Cl creatinine 50–80 ml/min); 40% lower in patients with moderate renal impairment (Cl creatinine 30–50 ml/min) and 55% lower in patients with severe renal impairment (Cl creatinine less than 30 ml/min) compared with values ​​in patients with normal renal function . The corresponding final T1/2 is 29 hours for moderate and 72 hours for severe renal failure. A similar relationship between the clearance of fondaparinux sodium and the severity of renal failure was observed in the treatment of patients with deep vein thrombosis.

Prevention of venous thromboembolic complications.

The pharmacokinetic model used data from patients with creatinine Cl less than 23.5 ml/min who underwent lower extremity surgery and received fondaparinux sodium. As a result of pharmacokinetic modeling, it was shown that the use of fondaparinux sodium in patients with creatinine Cl from 20 to 30 ml/min at a dosage of 1.5 mg/day or 2.5 mg every other day corresponds to that in patients with mild to moderate impairment of function kidneys (Cl creatinine 30–80 ml/min), receiving 2.5 mg/day.

Due to the limited data currently available, Arixtra should not be used in patients with severe renal impairment.

Patients with impaired liver function.

Free fondaparinux sodium plasma concentrations are believed to be unchanged in mild to moderate hepatic impairment and no dosage adjustment is necessary based on pharmacokinetics. After a single subcutaneous administration of fondaparinux sodium to patients with moderate hepatic impairment (Child-Pugh functional class B), Cmax and AUC decreased by 22–39% compared with data from patients with normal liver function. The decrease in plasma concentrations of fondaparinux sodium is explained by decreased binding to AT III due to reduced plasma levels of this enzyme in patients with impaired liver function, resulting in increased renal excretion of fondaparinux sodium. The pharmacokinetics of fondaparinux sodium in severe hepatic impairment have not been studied.

Children.

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

Elderly patients.

Elimination of fondaparinux sodium slows down in patients over 75 years of age. In a study of fondaparinux sodium 2.5 mg administered prophylactically following hip fracture or hip replacement surgery, the total clearance of fondaparinux sodium was approximately 25% less in patients over 75 years of age compared with patients aged 75 years or older. under 65 years of age. A similar relationship between fondaparinux sodium clearance and age was observed in the treatment of patients with deep vein thrombosis.

Floor.

When dose was adjusted for body weight, no differences were found between sexes.

Race.

No planned studies of pharmacokinetic differences have been conducted. However, trials conducted in healthy subjects of Asian origin (Japan) did not reveal differences in the pharmacokinetic profile compared with that in healthy Caucasian subjects. Similarly, no differences in clearance of fondaparinux sodium were observed between Caucasian and Black patients undergoing orthopedic surgery.

Body mass.

In patients weighing less than 50 kg, the total clearance of fondaparinux sodium is reduced by approximately 30%.

Indications for use of the drug Arixtra

Prevention of venous thromboembolic complications in patients after major orthopedic surgery on the lower extremities, such as hip fracture surgery including prolonged prophylaxis), knee or hip replacement. Prevention of venous thromboembolism in patients at risk of thromboembolic complications after abdominal surgery. Prevention of venous thromboembolism in patients at risk of such complications due to prolonged limitation of mobility during the acute phase of the disease. ST segment elevation myocardial infarction to prevent death, myocardial infarction and refractory ischemia. ST- segment elevation myocardial infarction to prevent death and recurrent myocardial infarction in patients treated with thrombolytics or not initially receiving other forms of reperfusion therapy. Treatment of acute deep vein thrombosis. Treatment of pulmonary embolism.

Use of the drug Arixtra

The drug is intended for subcutaneous or intravenous injection. Do not use IM. Subcutaneous injection. Arixtra is used as a deep subcutaneous injection, with the patient in a supine position. The injection site should be alternately the left and right anterolateral or left and right posterolateral abdominal walls. To avoid loss of the drug, do not remove the air bubble from the pre-filled syringe before injection. The needle should be inserted the full length perpendicularly into the fold of skin sandwiched between the thumb and index finger; During insertion, the skin fold must be kept clamped. Arixtra is used only as prescribed by a doctor. The subcutaneous injection is administered in the same way as with a classic syringe. IV injection (only the first dose in the treatment of patients with ST-segment elevation myocardial infarction) Administered IV through the existing IV system directly without dilution or diluted in a small volume (25 or 50 ml) 0.9% r- ra sodium chloride. To avoid loss of the drug, do not remove the air bubble from the pre-filled syringe before injection. After injection, the system or catheter should be thoroughly rinsed with 0.9% sodium chloride solution to ensure that the product is completely injected. When diluting Arixtra with 0.9% sodium chloride solution, the administration should be carried out over 1–2 minutes. Before using the solution for injection, it is necessary to visually check for the absence of suspended particles and changes in coloration. Arixtra pre-filled syringes are designed with an automatic needle protection system to prevent damage after drug injection. Any unused product or material should be disposed of according to legal regulations. Prevention of venous thromboembolism Orthopedic and abdominal interventions. The recommended dose of Arixtra for adult patients is 2.5 mg once a day after surgery in the form of subcutaneous injection. The initial dose is administered no earlier than 6 hours after completion of the operation, provided that hemostasis is achieved. Treatment should be carried out until the risk of thromboembolism decreases, usually before the patient is transferred to outpatient treatment, at least 5–9 days after surgery. Experience shows that patients undergoing surgery for a hip fracture for more than 9 days are at risk of deep vein thrombosis. In such patients, additional prophylactic use of Arixtra is recommended for up to 24 days. Patients at risk of thromboembolic complications due to prolonged limitation of mobility. The recommended dose of Arixtra is 2.5 mg once a day as a subcutaneous injection. Duration of treatment is 6–14 days. Unstable angina/myocardial infarction without ST segment elevation. The recommended dose of Arixtra is 2.5 mg once a day as a subcutaneous injection. Treatment should begin as soon as possible after diagnosing the disease and continue for up to 8 days. In patients requiring percutaneous coronary intervention while being treated with Arixtra, unfractionated heparin should be used during such procedure, taking into account the potential risk of bleeding in the patient, including the time since the last dose of fondaparinux (see SPECIAL INSTRUCTIONS). The time for resuming subcutaneous use of Arixtra after catheter removal should be determined based on the clinical condition of the patient. In a clinical study of unstable angina/non- ST , resumption of treatment with Arixtra was started no earlier than 2 hours after catheter removal. In patients who have undergone coronary artery bypass surgery, Arixtra should, if possible, not be prescribed within 24 hours before surgery and can be prescribed 48 hours after surgery. Myocardial infarction with ST segment elevation. The recommended dose of Arixtra is 2.5 mg once a day. The first dose of Arixtra is administered intravenously, subsequent doses by subcutaneous injection. Therapy should begin as soon as possible after diagnosis and continue until 8 days or until discharge. In patients undergoing non-primary percutaneous coronary intervention while being treated with Arixtra, unfractionated heparin should be used during such procedure, taking into account the patient's potential risk of bleeding, including the time since the last dose of fondaparinux (see SPECIAL INSTRUCTIONS). The time for resuming subcutaneous use of Arixtra after catheter removal should be determined based on the clinical condition of the patient. In a clinical study of unstable angina/ ST- , treatment with Arixtra was resumed no earlier than 3 hours after catheter removal. In patients who have undergone coronary artery bypass grafting, Arixtra should, if possible, not be prescribed within 24 hours before surgery and can be resumed 48 hours after surgery. Acute deep vein thrombosis and pulmonary embolism. Recommended doses of Arixtra for subcutaneous administration once a day:

• 5 mg - for patients with body weight ≤50 kg;
• 7.5 mg - for patients weighing 50–100 kg;
• 10 mg - for patients weighing 100 kg.

The duration of treatment should be at least 5 days and it can be stopped no earlier than it is possible to use adequate therapy with oral anticoagulants (international normalized ratio value - 2-3). It is also necessary to add vitamin K antagonists to treatment as soon as possible, usually no later than 72 hours. The usual duration of treatment with Arixtra is 5–9 days. Special patient groups Children The safety and effectiveness of Arixtra in children have not been established. Elderly patients (over 75 years of age) Arixtra should be used with caution in elderly patients, since renal function decreases with age. In elderly patients undergoing surgery, it is necessary to strictly adhere to the timing of the first dose of Arixtra (see SPECIAL INSTRUCTIONS). Patients weighing ≤50 kg Patients weighing ≤50 kg have an increased risk of bleeding. Elimination of fondaparinux decreases with body weight. In such patients, the drug is used with caution; during surgery, it is necessary to strictly adhere to the time of administration of the first dose of Arixtra (see SPECIAL INSTRUCTIONS). Renal failure Prevention of venous thromboembolism. There is no need for dose adjustment in patients with creatinine clearance ≥30 ml/min. For patients with a creatinine clearance of 20–30 ml/min, as prescribed by a doctor, it is recommended to use the drug at a dose of 1.5 mg/day or 2.5 mg every other day (the interval between doses should be 48 hours). Arixtra is not recommended for use in patients with creatinine clearance ≤20 ml/min. When performing surgery, it is necessary to strictly adhere to the time of administration of the first dose of the drug. Treatment of venous thromboembolism. There is no need for dose adjustment in patients with creatinine clearance ≥30 ml/min. Arixtra should not be used in patients with creatinine clearance ≤30 ml/min. Unstable angina/myocardial infarction without ST segment elevation and myocardial infarction with ST segment elevation . Arixtra should not be used in patients with creatinine clearance ≤20 ml/min. There is no need for dose adjustment in patients with creatinine clearance ≥20 ml/min. Impaired liver function There is no need to adjust the dose in patients with mild to moderate hepatic impairment; in patients with severe hepatic impairment, Arixtra should be used with caution (see SPECIAL INSTRUCTIONS).

Instructions for use ARIXTRA

For adults

for
the prevention of venous thromboembolic complications in orthopedic and abdominal surgery,
the recommended dose of Arixtra is 2.5 mg 1 time / day after subcutaneous 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 should continue 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 shows that for patients undergoing surgery for a hip fracture, the period of increased risk of developing venous thromboembolic complications exceeds 9 days. For such patients, a decision should be made to extend the prophylactic use of Arixtra to 24 days.

For patients at high risk of thromboembolic complications

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

For the treatment of acute deep vein thrombosis and acute pulmonary embolism

The recommended dose of Arixtra for subcutaneous administration 1 time/day is 5 mg for
patients weighing less than 50 kg
;
7.5 mg - for patients weighing 50-100 kg
;
10 mg - for patients weighing more than 100 kg
. Therapy should continue for at least 5 days and stop no earlier than switching to adequate therapy with oral anticoagulants (INR values ​​from 2 to 3) is possible. 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 Arixtra course is from 5 to 9 days.

For the treatment of acute 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.

To minimize the risk of bleeding, elective percutaneous coronary intervention (PCI) should be performed no earlier than 24 hours after the last dose of fondaparinux, if possible. If PCI is performed less than 6 hours after the last dose of Arixtra, the dose of unfractionated heparins (if applicable) should be reduced. The timing of resumption of Arixtra administration after catheter removal should be determined based on the clinical condition of the patient. 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 should not be prescribed for 24 hours before surgery and 48 hours after CABG.

For the treatment of ST-segment elevation myocardial infarction

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.

To minimize the risk of bleeding, elective PCI should be performed, if possible, no earlier than 24 hours after the last dose of fondaparinux. If PCI is performed less than 6 hours after the last dose of Arixtra, the dose of unfractionated heparins (if applicable) should be reduced. The timing of resumption of Arixtra administration after catheter removal should be determined based on the clinical condition of the patient. In clinical studies, treatment with fondaparinux was resumed no earlier than 2 hours after catheter removal. In patients undergoing CABG, if possible, fondaparinux should not be administered for 24 hours before surgery and 48 hours after CABG.

Efficacy and safety of Arixtra in children under 17 years of age

has not yet been installed.

Arixtra should be used with caution in elderly patients (over 75 years of age)

, because With age, kidney function may decline. In elderly patients undergoing surgery, the timing of the first dose of Arixtra must be strictly observed.

Arixtra should not be prescribed to patients with severely impaired renal function (creatinine clearance <30 ml/min).

For
patients with mild or moderate renal impairment (creatinine clearance > 30 ml/min),
no dose adjustment of Arixtra is required. In such patients undergoing surgery, the timing of the first dose of Arixtra must be strictly observed.

For patients with liver dysfunction

No dose adjustment of Arixtra is required.

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

Rules for administering the drug

The sites of subcutaneous injection should be alternately the left and right anterolateral and left and right posterolateral abdominal walls. To avoid loss of the drug, do not remove air bubbles from a pre-filled syringe before injection. The needle should be inserted the full length perpendicularly into the fold of skin sandwiched between the thumb and index finger; 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 self-administer subcutaneous injection only if the doctor deems it necessary, with mandatory follow-up with a doctor and only after appropriate training in the technique of subcutaneous injection.

Only the first dose is administered IV in patients with ST-segment elevation myocardial infarction into the catheter directly or diluted in small volumes of saline (25 or 50 ml). To avoid loss of the drug, do not remove air bubbles from a pre-filled 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.

Side effects of Arixtra

The following side effects are classified by organs and systems and by frequency of occurrence: very often (1/10), often (1/100, ≤1/10), infrequently (1/1000, ≤1/100), rarely (1/100). 10,000, ≤1/1000), isolated cases (≤1/10,000).

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.

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.

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 3 hours after catheter removal.

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.

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.