Nardin injection solution 4000 anti-Xa IU syringe 0.4 ml No. 10

Instructions Nardin solution for injection 4000 anti-Xa IU syringe 0.4 ml No. 10

Composition

active ingredient: enoxaparin sodium;

1 ml of solution contains enoxaparin sodium with anti-Xa activity of 10,000 IU, which is equivalent to enoxaparin sodium 100 mg;

2000 anti-Xa IU/0.2 ml, equivalent to enoxaparin sodium 20 mg;

4000 anti-Xa IU/0.4 ml, equivalent to enoxaparin sodium 40 mg;

6000 anti-Xa IU/0.6 ml, equivalent to enoxaparin sodium 60 mg;

8000 anti-Xa IU/0.8 ml, equivalent to enoxaparin sodium 80 mg;

10,000 anti-Xa IU/1.0 ml, equivalent to enoxaparin sodium 100 mg;

excipient: water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: colorless or light yellow transparent solution.

Pharmacotherapeutic group

Antithrombotic agents. Heparin group. Enoxaparin.

ATX code B01A B05.

Pharmacological properties

Pharmacodynamics.

Enoxaparin is a low molecular weight heparin (LMWH) that does not have the antithrombotic and anticoagulant activities of standard heparin. It has a higher anti-Xa activity than anti-IIa (or antithrombin) activity (their ratio is 3.6).

When used in prophylactic doses, enoxaparin has no significant effect on APTT (activated partial thromboplastin time).

When using therapeutic doses of the drug, the APTT may be prolonged and exceed the control time of maximum activity by 1.5–2.2 times. This prolongation reflects residual antithrombin activity.

Treatment of acute ST-segment elevation myocardial infarction in combination with a thrombolytic agent in patients undergoing subsequent coronary angioplasty, as well as in patients who do not undergo this procedure.

In a large multicenter clinical trial, 20,479 patients with acute ST-segment elevation myocardial infarction after receiving fibrinolytic therapy were randomly assigned to receive either enoxaparin as a bolus intravenous injection of 3000 anti-Xa IU, followed immediately by a subcutaneous dose of 100 anti-Xa IU/kg, and then subcutaneous injections of 100 anti-Xa IU/kg every 12 hours, or intravenous unfractionated heparin as a bolus injection of 60 IU/kg (maximum 4000 IU/kg) followed by a continuous infusion at a dose adjusted depending on the activated partial thromboplastin time. Subcutaneous injections of enoxaparin were administered until discharge from the hospital or for no more than 8 days (in 75% of cases – at least 6 days). Half of the patients who received heparin, the drug was administered for at least 48 hours (in 89.5% of cases ≥ 36 hours). All patients also received acetylsalicylic acid for at least 30 days. The dose of enoxaparin for patients ≥ 75 years of age was adjusted: 0.75 mg/kg (75 anti-Xa IU/kg) as a subcutaneous injection every 12 hours without an initial bolus intravenous injection.

In the study, 4716 (23%) patients underwent coronary angioplasty while receiving antithrombotic therapy with masked study drugs. Patients received no additional doses if less than 8 hours had passed since the last subcutaneous injection of enoxaparin before balloon inflation, or received a bolus intravenous injection of enoxaparin at a dose of 0.3 mg/kg (30 anti-Xa IU/kg) if more than 8 hours had passed since the last subcutaneous injection of enoxaparin before balloon inflation.

Enoxaparin significantly reduced the incidence of events corresponding to the primary endpoints [combined endpoint of recurrent myocardial infarction and all-cause mortality during the 30-day follow-up period after inclusion in the study: 9.9% in the enoxaparin group compared with 12% in the unfractionated heparin group (relative risk reduction - 17%; p < 0.001)]. The incidence of recurrent myocardial infarction was significantly lower in the enoxaparin group (3.4% compared with 5%, p < 0.001, relative risk reduction - 31%). Mortality was lower in the enoxaparin group, but the difference between the groups was not statistically significant (6.9% compared with 7.5%, p = 0.11).

The advantage of enoxaparin in terms of the primary endpoint was unconditional regardless of subgroup (age, gender, location of myocardial infarction, diabetes or history of myocardial infarction, type of thrombolytic agent prescribed, and time interval between the appearance of the first clinical signs and the start of treatment).

Enoxaparin demonstrated a significant advantage over unfractionated heparin on the primary efficacy endpoint in both patients who underwent coronary angioplasty within 30 days of study entry (10.8% vs. 13.9%, 23% relative risk reduction) and patients who did not undergo coronary angioplasty (9.7% vs. 11.4%, 15% relative risk reduction).

Analysis of the combined criteria used to determine clinical benefit showed a statistically significant advantage (p < 0.0001) of enoxaparin over unfractionated heparin: a relative risk reduction of 14% in favor of enoxaparin (11% versus 12.8%) for the combined criteria of death, recurrent myocardial infarction, and major bleeding (TIMI criteria) up to day 30, and 17% (10.1% versus 12.2%) for the combined criteria of death, recurrent myocardial infarction, and intracranial hemorrhage up to day 30.

Pharmacokinetics.

The pharmacokinetic parameters of the drug are assessed by changes over time in anti-Xa and anti-IIa activity in blood plasma when used in the recommended dose ranges.

Bioavailability: Enoxaparin is rapidly and almost completely (almost 100%) absorbed after subcutaneous administration. Peak plasma activity is observed between 3 and 4 hours after administration.

This maximum activity (expressed in anti-Xa IU) is 0.18±0.04 (after administration of 2000 anti-Xa IU), 0.43±0.11 (after administration of 4000 anti-Xa IU) and 1.01±0.14 (after administration of 10000 anti-Xa IU).

After a bolus intravenous injection of 30 mg (0.3 ml; 3000 anti-Xa IU) followed by subcutaneous injections of 1 mg/kg (100 anti-Xa IU/kg) every 12 hours, the initial maximum anti-Xa concentration is 1.16 IU/ml (n = 16) and the mean area under the pharmacokinetic curve corresponds to 88% of the steady-state level. Steady-state is reached by the second day of treatment.

In the recommended dose range, the pharmacokinetics of enoxaparin are linear. Intra- and inter-patient differences are quite small. After repeated subcutaneous administration of 40 mg (0.4 ml; 4000 anti-Xa IU) once daily to healthy volunteers, steady state was reached on the 2nd day, with mean enoxaparin activity being approximately 15% higher than that observed with a single dose. Steady-state levels of enoxaparin activity are fairly predictable with single doses. After repeated subcutaneous administration of 1 mg/kg (100 anti-Xa IU/kg) twice daily, steady state was reached between days 3 and 4, with mean AUC 65% higher than that observed with a single dose, and maximum and minimum anti-Xa activity of 1.2 and 0.52 anti-Xa IU/ml, respectively. Given the pharmacokinetics of enoxaparin sodium, this difference in steady state is also expected for the therapeutic dose range.

Anti-Xa activity in plasma after subcutaneous administration is almost 10 times lower than anti-IIa activity. The mean maximum anti-Xa activity is observed approximately 3-4 hours after subcutaneous injection, reaching 0.13 anti-Xa IU/ml after repeated administration of a dose of 1 mg/kg (100 anti-Xa IU/kg) twice daily.

Distribution: The volume of distribution of enoxaparin sodium for anti-Xa activity is approximately 5 liters and almost corresponds to the volume of circulating blood.

Metabolism: Enoxaparin is metabolized primarily in the liver (by desulfation and depolymerization).

Elimination: After subcutaneous injection, the half-life of anti-Xa activity for low molecular weight heparins is longer than that for unfractionated heparins.

The elimination of enoxaparin is monophasic, with a half-life of approximately 4 hours after a single subcutaneous injection and almost 7 hours after repeated doses. Low molecular weight heparins are characterized by a more rapid decline in anti-IIa activity in plasma compared with anti-Xa activity.

Enoxaparin and its metabolites are excreted in the urine (unsaturable mechanism) and also in the bile.

Renal clearance of substances with anti-Xa activity is 10% of the administered dose, and total renal excretion of active and inactive metabolites is 40% of the dose.

High-risk groups

Elderly patients. Since this age group has a physiological decline in renal function, elimination is slower. This does not require a change in dosage or administration regimen for prophylactic treatment. It is very important to systematically monitor renal function in patients over 75 years of age using the Cockcroft formula before starting treatment with LMWH.

Patients with mild to moderate renal impairment (creatinine clearance >30 ml/min).

In some cases, monitoring of anti-Xa activity may be useful to rule out the possibility of overdose if enoxaparin is used in therapeutic doses.

Indication

The medicine is indicated for use in adults:

• for the prevention of venous thromboembolic complications in surgical patients at moderate and high risk, especially in patients undergoing orthopedic or general surgical interventions, including surgical interventions for oncological diseases;
• for the prevention of venous thromboembolic complications in therapeutic patients with acute illnesses (such as acute heart failure, respiratory failure, severe infections or rheumatic diseases) and reduced mobility who are at increased risk of venous thromboembolism;
• for the prevention of blood clots in extracorporeal circulation during hemodialysis;
• in acute coronary syndrome:
• for the treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI), in combination with oral acetylsalicylic acid;
• for the treatment of acute ST-segment elevation myocardial infarction (STEMI), including in patients who are scheduled for medical treatment or subsequent percutaneous coronary intervention (PCI).

Contraindication

Enoxaparin sodium is contraindicated for use in patients with the following conditions:

• hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins;
• history of immune-mediated heparin-induced thrombocytopenia (HIT) within the last 100 days with circulating antibodies (see also section "Special warnings and precautions for use");
• Active clinically significant bleeding and conditions with a high risk of bleeding, including recent hemorrhagic stroke, gastrointestinal ulcer, presence of a malignant neoplasm with a high risk of bleeding, recent brain, spinal cord or eye surgery, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or serious malformations of intraspinal or intracerebral vessels;
• spinal or epidural anesthesia or locoregional anesthesia if enoxaparin sodium has been used for treatment within the previous 24 hours (see section "Special warnings and precautions for use").

Interaction with other medicinal products and other types of interactions

Concomitant use with the following drugs is not recommended.

Medicinal products affecting haemostasis (see section 4.4). It is recommended that certain medicinal products affecting haemostasis be discontinued prior to initiation of treatment with enoxaparin sodium, unless absolutely necessary. If this combination is indicated, enoxaparin sodium should be used with close clinical and laboratory monitoring.

Such drugs include:

• salicylates for systemic use, acetylsalicylic acid in anti-inflammatory doses and non-steroidal anti-inflammatory drugs (NSAIDs), including ketorolac;
• other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and anticoagulants (see section "Method of administration and dosage").

Drugs that require caution when used concurrently.

• Other drugs that affect hemostasis, such as:
• platelet aggregation inhibitors, including acetylsalicylic acid used in an antiplatelet dose (cardioprotection), clopidogrel, ticlopidine and glycoprotein IIb/IIIa antagonists, indicated for acute coronary syndrome - risk of bleeding;
• dextran 40;
• glucocorticoids for systemic use.
• Medicinal products that increase serum potassium levels may be administered concomitantly with enoxaparin sodium with careful clinical and laboratory monitoring (see sections 4.4 and 4.8).

Application features

Enoxaparin sodium should not be used interchangeably (unit for unit) with other low molecular weight heparins (LMWHs). These drugs differ in their manufacturing processes, molecular weights, specific anti-Xa and anti-IIa activities, units of activity, dosage, and clinical efficacy and safety. This results in differences in pharmacokinetics and biological activity (e.g. antithrombin activity, platelet interaction).

In this regard, it is necessary to study the instructions for medical use of each medicinal product and follow them.

History of heparin-induced thrombocytopenia (HIT) (> 100 days).

Enoxaparin sodium is contraindicated in patients with a history of immune-mediated HIT within the past 100 days in the presence of circulating antibodies (see section 4.3). Circulating antibodies may persist for several years.

Enoxaparin sodium should be used with extreme caution in patients with a history (> 100 days) of immune-mediated HIT without circulating antibodies. The decision to use enoxaparin sodium in such cases should be made only after a careful benefit/risk assessment and after consideration of alternative non-heparin treatments (e.g. danaparoid sodium or lepirudin).

Monitoring platelet count.

Also, when using LMWH, there is a risk of antibody-mediated HIT, which usually develops between the 5th and 21st days after the start of treatment with enoxaparin sodium.

The risk of HIT is higher in patients who have undergone surgery and is observed mainly after cardiac surgery and in patients with cancer.

If clinical symptoms suggestive of HIT are present (any new episode of arterial and/or venous thromboembolism, any painful skin lesion at the injection site, any allergic or anaphylactoid reaction during treatment), platelet counts should be determined. Patients should be made aware that they may experience such symptoms and should inform their physician if they experience them.

In clinical practice, in the event of a confirmed significant decrease in platelet levels (30-50% of the initial value), enoxaparin sodium should be immediately discontinued and the patient transferred to another alternative non-heparin treatment.

Hemorrhagic phenomena.

As with other anticoagulants, bleeding/hemorrhage at any site may occur. In case of bleeding, the source should be investigated and appropriate treatment initiated.

Enoxaparin sodium, like any other anticoagulant drug, should be used with caution in conditions that increase the likelihood of bleeding, such as:

• hemostasis disorders;
• history of peptic ulcer;
• recent ischemic stroke;
• severe arterial hypertension;
• recent development of diabetic retinopathy;
• surgery on the nervous system or eyes;
• simultaneous use of drugs that affect hemostasis (see section "Interaction with other drugs and other types of interactions").

Laboratory tests.

Enoxaparin sodium in doses used for the prevention of venous thromboembolism has no significant effect on bleeding time, general coagulation parameters, and does not affect platelet aggregation and fibrinogen binding to platelets.

When using the drug in higher doses, the activated partial thromboplastin time (APTT) and activated clotting time (ACT) may increase. Since there is no linear relationship between the increase in APTT and ACTT and the increase in the antithrombotic activity of enoxaparin sodium, these indicators are unreliable and cannot be used to monitor the activity of enoxaparin sodium.

Use of the drug during spinal/epidural anesthesia or lumbar puncture.

Spinal/epidural anesthesia or lumbar puncture should not be performed within 24 hours after the use of enoxaparin sodium in therapeutic doses (see also section "Contraindications").

Cases of neuraxial hematomas have been reported with the concomitant use of enoxaparin sodium and spinal/epidural anesthesia or spinal puncture procedures, resulting in long-term or irreversible paralysis. These cases are rare with enoxaparin sodium 4000 IU (40 mg) once daily or lower doses. The risk of such events is higher with the use of postoperative indwelling epidural catheters, with the concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs, with traumatic or repeated epidural or spinal procedures, or in patients with a history of spinal surgery or spinal deformity.

To reduce the potential risk of bleeding associated with the concomitant use of enoxaparin sodium and epidural or spinal anesthesia/analgesia or spinal puncture, the pharmacokinetic profile of enoxaparin sodium should be considered (see section 5.2). It is best to insert or remove an epidural catheter or perform a lumbar puncture when the anticoagulant effect of enoxaparin sodium is low, but the exact time to achieve a sufficiently low anticoagulant effect in each individual patient is unknown. It should also be considered that the elimination of enoxaparin sodium is longer in patients with creatinine clearance of 15-30 ml/min (see section 5.2).

If the physician decides to use anticoagulant therapy during epidural or spinal anesthesia/analgesia or lumbar puncture, the patient should be closely monitored for any signs of neurological disorders, such as midline back pain, sensory and motor disorders (numbness or weakness in the lower extremities), bowel and/or bladder dysfunction. Patients should be instructed to report any of the above symptoms to their physician immediately. If a spinal hematoma is suspected, appropriate diagnostic and treatment measures should be initiated immediately, including consideration of spinal cord decompression, even if such treatment may not prevent adverse neurological sequelae.

Percutaneous coronary revascularization procedures. To minimize the risk of bleeding after instrumental vascular procedures in the treatment of unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI) and acute ST-segment elevation myocardial infarction (STEMI), the recommended intervals between doses of enoxaparin sodium should be strictly observed. It is important to achieve hemostasis at the puncture site after percutaneous coronary intervention (PCI). If a device is used to close the vessel puncture site, the introducer can be removed immediately after the procedure. If the manual vessel compression method is used, the introducer should be removed 6 hours after the last intravenous or subcutaneous injection of enoxaparin sodium. If treatment with enoxaparin sodium is to be continued, the next scheduled dose should be administered no earlier than 6-8 hours after removal of the introducer. The catheter site should be monitored for signs of bleeding or hematoma formation.

Acute infective endocarditis. The use of heparin in patients with acute infective endocarditis is generally not recommended due to the risk of cerebral haemorrhage. If such use is considered absolutely necessary, the decision should be made only after careful individual benefit/risk assessment.

Mechanical prosthetic heart valves. The use of enoxaparin sodium for thromboprophylaxis in patients with mechanical prosthetic heart valves has not been adequately studied. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves receiving enoxaparin sodium for thromboprophylaxis. The presence of factors that may contribute to additional risk, including underlying disease, and the paucity of clinical data limit the assessment of such cases. In some of these cases, which occurred in pregnant women, thrombosis resulted in maternal and fetal death.

Pregnant women with mechanical prosthetic heart valves. The use of enoxaparin sodium for thromboprophylaxis in pregnant women with mechanical prosthetic heart valves has not been adequately studied. In a clinical trial in which pregnant women with mechanical prosthetic heart valves received enoxaparin sodium (100 IU/kg (1 mg/kg) twice daily) to reduce the risk of thromboembolism, 2 of 8 women developed blood clots that resulted in valve occlusion and maternal and fetal death. There have been isolated postmarketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves receiving enoxaparin sodium for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at increased risk of thromboembolism.

Elderly patients. When using the drug in the prophylactic dose range in elderly patients, no increased tendency to bleed was observed. Elderly patients (especially patients over 80 years of age) are at increased risk of hemorrhagic complications when using the drug in therapeutic doses. For patients over 75 years of age treated with the drug for ST-segment elevation myocardial infarction (STEMI), careful clinical monitoring is recommended, and a dose reduction may also be appropriate (see sections “Method of administration and dosage” and “Pharmacokinetics”).

Renal impairment: In patients with renal impairment, there is an increase in exposure to enoxaparin sodium, which increases the risk of bleeding. In such patients, careful clinical monitoring is recommended, and biological monitoring by determining anti-Xa activity may also be appropriate (see sections 4.2 and 4.3).

Enoxaparin sodium is not recommended for use in patients with end-stage renal disease (creatinine clearance < 15 ml/min) due to the lack of adequate data in this population, except for the prevention of thrombus formation in the extracorporeal circulation during hemodialysis.

For patients with severe renal impairment (creatinine clearance 15-30 ml/min), due to a significant increase in enoxaparin sodium exposure, dose adjustment of the drug is recommended for both therapeutic and prophylactic use (see section "Method of administration and dosage").

No dose adjustment is required for patients with moderate (creatinine clearance 30-50 ml/min) and mild (creatinine clearance 50-80 ml/min) renal impairment.

Hepatic impairment: Enoxaparin sodium should be used with caution in patients with hepatic impairment due to an increased risk of bleeding. Dose adjustment based on monitoring of anti-Xa activity levels is unreliable in patients with cirrhosis and is not recommended (see Pharmacokinetics).

Obese patients. Obese patients are at increased risk of thromboembolism. The safety and efficacy of prophylactic doses of the drug in obese patients (BMI > 30 kg/m²) have not been adequately studied, and there is currently no consensus on the appropriateness of dose adjustment in this category of patients. These patients should be closely monitored for possible symptoms of thromboembolism.

Hyperkalemia: Heparins may inhibit adrenal aldosterone secretion, leading to hyperkalemia (see section 4.8), especially in patients with diabetes mellitus, chronic renal failure, pre-existing metabolic acidosis and in patients receiving medicinal products that may increase potassium levels (see section 4.5). Plasma potassium levels should be monitored periodically, especially in patients at increased risk of hyperkalemia.

Traceability: Low molecular weight heparins are biological medicinal products. To improve their traceability, it is recommended that healthcare professionals record the trade name and batch number of the administered product in the patient's record.

Use during pregnancy or breastfeeding

Pregnancy: There is no evidence that enoxaparin crosses the placental barrier in humans during the second and third trimesters of pregnancy. Information regarding the first trimester is currently unavailable.

In animal studies, no signs of fetotoxicity or teratogenicity of the drug were detected. Data obtained in animal experiments showed that the penetration of enoxaparin across the placenta is minimal.

Enoxaparin sodium should be prescribed to pregnant women only if the doctor determines a clear need for such treatment.

Pregnant women receiving enoxaparin sodium should be closely observed for signs of bleeding or excessive anticoagulant effect and should be informed of the risk of hemorrhagic events. Overall, available data indicate that there is no evidence of an increased risk of bleeding, thrombocytopenia, or osteoporosis in these patients compared with non-pregnant women, except for the risk observed in pregnant women with prosthetic heart valves (see section "Special warnings and precautions for use").

If epidural anesthesia is planned, it is recommended to discontinue enoxaparin sodium treatment before performing it (see section "Special warnings and precautions for use").

Breastfeeding. It is not known whether enoxaparin is excreted in human milk. In lactating rats, the excretion of enoxaparin or its metabolites into milk is very low.

Absorption of enoxaparin sodium when taken orally is unlikely, so it can be used during breastfeeding.

Fertility: Clinical data on the effect of enoxaparin sodium on fertility are currently unavailable. Animal studies have not demonstrated any effect of the drug on fertility.

The ability to influence the reaction speed when driving or working with other mechanisms

The effect of enoxaparin sodium on the ability to drive vehicles and operate other mechanisms is absent or negligible.

Method of administration and doses

Dosage.

Prevention of venous thromboembolic complications in moderate- and high-risk surgical patients. Individual thromboembolic risk in patients can be assessed using a validated risk stratification model (scale).

• For patients at moderate risk of thromboembolic complications, the recommended dose of enoxaparin sodium is 2000 IU (20 mg) once daily administered by subcutaneous (sc) injection. Preoperative initial administration (2 hours before surgery) of enoxaparin sodium at a dose of 2000 IU (20 mg) has been shown to be effective and safe in moderate-risk surgical procedures.

In moderate-risk patients, prophylactic treatment with enoxaparin sodium should be continued for a period of at least 7-10 days, regardless of the state of recovery (e.g. mobility). Prophylaxis should be continued until the patient no longer has significantly reduced mobility.

• For patients at high risk of thromboembolic complications, the recommended dose of enoxaparin sodium is 4000 IU (40 mg) once daily, preferably administered 12 hours before surgery by subcutaneous (sc) injection. If there is a need to start prophylactic use of enoxaparin sodium more than 12 hours before surgery (e.g., a high-risk patient awaiting delayed orthopedic surgery), the last injection should be administered no later than 12 hours before surgery and prophylactic use should be resumed 12 hours after surgery.
• For patients undergoing major orthopedic surgery, long-term thromboprophylaxis is recommended for up to 5 weeks.
• For patients at high risk of venous thromboembolism (VTE) undergoing abdominal or pelvic surgery for cancer, long-term thromboprophylaxis is recommended for up to 4 weeks.

Prevention of venous thromboembolism in therapeutic patients. The recommended dose of enoxaparin sodium is 4000 IU (40 mg) once daily, administered by subcutaneous injection.

• Prophylactic treatment with enoxaparin sodium should last for at least 6-14 days, depending on the state of recovery (e.g. mobility). The benefit of such treatment for a period longer than 14 days is currently undetermined.

Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Enoxaparin sodium should be administered subcutaneously as a 150 IU/kg (1.5 mg/kg) injection once daily or as a 100 IU/kg (1 mg/kg) injection twice daily.

The dosage regimen should be selected by the physician based on the results of an individual assessment, which should include an assessment of the risk of thromboembolic complications and the risk of hemorrhagic complications. A dosage regimen of 150 IU/kg (1.5 mg/kg) once daily should be used in uncomplicated patients with a low risk of recurrent VTE. A dosage regimen of 100 IU/kg (1 mg/kg) twice daily should be used in all other patients, such as those with obesity, symptomatic PE, cancer, recurrent VTE, or proximal vein thrombosis (iliac vein).

Enoxaparin sodium is used for an average of 10 days. If necessary, oral anticoagulants should be initiated (see “Switching from enoxaparin sodium to oral anticoagulants” at the end of this section).

Prevention of thromboembolism during hemodialysis. The recommended dose of enoxaparin sodium is 100 IU/kg (1 mg/kg). In patients at high risk of hemorrhagic complications, the dose should be reduced to 50 IU/kg (0.5 mg/kg) in the presence of dual vascular access or to 75 IU/kg (0.75 mg/kg) in the presence of a single vascular access.

During hemodialysis, enoxaparin sodium should be administered into the arterial part of the circuit at the beginning of the dialysis session. This dose is usually sufficient for dialysis for 4 hours. However, if fibrin rings occur, for example when the session lasts longer than usual, an additional dose of 50 IU to 100 IU/kg (0.5 to 1 mg/kg) may be administered.

There are no data on the use of enoxaparin sodium in patients for prophylaxis or treatment and during hemodialysis sessions.

Acute coronary syndrome: treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI) and acute ST segment elevation myocardial infarction (STEMI).

• For the treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 100 IU/kg (1 mg/kg) administered every 12 hours by subcutaneous injection and administered in combination with antiplatelet therapy. Treatment should be administered for at least 2 days and continued until the patient is clinically stabilized. The usual duration of treatment is 2 to 8 days.
• For all patients without complications, oral acetylsalicylic acid is recommended in an initial loading dose of 150-300 mg (patients who have not yet received acetylsalicylic acid) and a maintenance dose of 75-325 mg/day long-term, regardless of the treatment strategy.
• For the treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) bolus of 3000 IU (30 mg) plus a dose of 100 IU/kg (1 mg/kg) subcutaneously followed by 100 IU/kg (1 mg/kg) subcutaneously every 12 hours (maximum 10,000 IU (100 mg) for each of the first two subcutaneous doses). Appropriate antiplatelet therapy, such as oral acetylsalicylic acid (75-325 mg once daily), should be administered concurrently unless contraindicated. The recommended duration of treatment is 8 days or until the patient is discharged from the hospital, whichever comes first. When used with thrombolytic therapy (fibrin-specific or non-fibrin-specific), enoxaparin sodium should be administered 15 minutes before the start of fibrinolytic therapy and 30 minutes after.