Novoparin ® injection solution 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 diseases (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 treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), except in cases of PE, which may require thrombolytic therapy or surgery; for the prevention of thrombus formation in the 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).
Composition
The active substance is enoxaparin sodium (1 ml of solution contains enoxaparin sodium with anti-factor Xa activity of 10,000 IU, equivalent to enoxaparin sodium 100 mg; 6,000 anti-factor Xa IU / 0.6 ml, equivalent to enoxaparin sodium 60 mg).
The excipient is water for injection.
Contraindication
Enoxaparin sodium is contraindicated for use in patients with the following conditions:
Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other LMWH; history of immune-mediated heparin thrombocytopenia (HIT) within the last 100 days in the presence of circulating antibodies; active clinically significant bleeding and conditions with a high risk of bleeding, including recent hemorrhagic stroke, gastrointestinal ulcer, the presence of a malignant neoplasm with a high risk of bleeding, recent surgery on the brain, spinal cord or eyes, known or suspected esophageal varices, arteriovenous malformations, vascular aneurysms or serious malformations of the intraspinal or intracerebral vessels; spinal or epidural anesthesia or locoregional anesthesia, if enoxaparin sodium was used for treatment within the previous 24 hours.
Method of application
Prevention of venous thromboembolic complications in surgical patients at moderate and high risk
Individual thromboembolic risk in patients can be assessed using a validated risk stratification model (scale).
For patients at moderate risk of thromboembolic events, the recommended dose of enoxaparin sodium is 2000 IU (20 mg) once daily, administered by subcutaneous (s/c) 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 events, the recommended dose of enoxaparin sodium is 4000 IU (40 mg) once daily, preferably administered 12 hours before surgery by subcutaneous (s/c) injection. If it is necessary to start prophylactic use of enoxaparin sodium more than 12 hours before surgery (for example, 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 - 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 - up to 4 weeks.
Prevention of venous thromboembolic complications 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 be administered for a period of at least 6-14 days, depending on the state of recovery (e.g., mobility). The benefit of such treatment for a period of more than 14 days has not yet been determined.
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 is selected by the physician, taking into account the results of an individual assessment, which should include an assessment of the risk of thromboembolic events and the risk of hemorrhagic events. The 150 IU/kg (1.5 mg/kg) once daily dosing regimen should be used in uncomplicated patients with a low risk of recurrent VTE. The 100 IU/kg (1 mg/kg) twice daily dosing regimen should be used in all other patients, such as patients 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 started.
Prevention of blood clots during hemodialysis
The recommended dose of enoxaparin sodium is 100 IU/kg (1 mg/kg). In patients at high risk of hemorrhagic events, 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 to conduct 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 one mg/kg) can 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 a minimum of two 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) SC followed by 100 IU/kg (1 mg/kg) SC every 12 hours (maximum 10,000 IU (100 mg) for each of the first two SC 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 between 15 minutes before the start of fibrinolytic therapy and 30 minutes after the start of fibrinolytic therapy.
In patients undergoing PCI, if the last dose of enoxaparin sodium was administered subcutaneously less than 8 hours before balloon inflation, additional doses are no longer required. If the last subcutaneous administration of the drug was more than 8 hours before balloon inflation, an intravenous bolus of 30 IU/kg (0.3 mg/kg) of enoxaparin sodium should be administered.
Application features
Pregnant women
There is no evidence in humans that enoxaparin crosses the placental barrier during the second and third trimesters of pregnancy. Information regarding the first trimester is not yet available. Enoxaparin sodium should be administered to pregnant women only if the physician clearly determines that such treatment is necessary. Pregnant women receiving enoxaparin sodium should be closely observed for signs of bleeding or excessive anticoagulant effect, and such patients should be informed of the risk of hemorrhagic events. Overall, the available data indicate that there is no evidence of an increased risk of bleeding, thrombocytopenia, or osteoporosis in such patients compared with this risk in non-pregnant women, except for the risk observed in pregnant women with prosthetic heart valves.
If epidural anesthesia is planned, it is recommended to cancel enoxaparin sodium treatment before performing it.
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 after oral administration is unlikely, so it can be used during breastfeeding.
There are no clinical data on the effect of enoxaparin sodium on fertility. Animal studies have not shown any effect of the drug on fertility.
Children
The safety and efficacy of enoxaparin sodium in pediatric patients have not yet been established.
Drivers
The effect of enoxaparin sodium on the ability to drive vehicles and operate other mechanisms is absent or insignificant.
Unintentional overdose of enoxaparin sodium as a result of intravenous, extracorporeal or subcutaneous administration may lead to hemorrhagic complications. After taking even fairly high doses, absorption of enoxaparin sodium is unlikely.
Treatment
The anticoagulant effects of the drug can be largely neutralized by slow intravenous administration of protamine. The dose of protamine depends on the dose of enoxaparin sodium administered:
1 mg of protamine neutralizes the anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium if enoxaparin sodium was administered within the previous 8 hours; protamine infusion at a dose of 0.5 mg for every 100 IU (1 mg) of enoxaparin sodium may be used if enoxaparin sodium was administered more than 8 hours before protamine administration or if a second dose of protamine is considered necessary; 12 hours after enoxaparin sodium administration, protamine administration may not be necessary.
However, even with high doses of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum by approximately 60%).
Side effects
In clinical trials, the most frequently reported adverse reactions were haemorrhagic events, thrombocytopenia and thrombocytosis.
Interaction
Subcutaneous injection - do not mix with other medications.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C, out of the reach of children. Do not freeze.
Shelf life - 3 years.
