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    Active Ingredient
    Enoxaparin (as sodium) 2000 IU, 4000 IU, 6000 IU, 8000 IU, 10000IU

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Pre-filled Syringe (solution for injection)

    2, 6, 10, 20, 50 X 2,000 IU (20 mg)/0.2 ml

    partial basket chart

    Pre-filled Syringe (solution for injection)

    2, 6, 10, 20, 30, 50 X 4,000 IU (40 mg)/0.4 ml

    partial basket chart

    Pre-filled Syringe (solution for injection)

    2, 6, 10, 12, 24, 30 X 6,000 IU (60 mg)/0.6 ml

    partial basket chart

    Pre-filled Syringe (solution for injection)

    2, 6, 10, 12, 24, 30 X 8,000 IU (80 mg)/0.8 ml

    partial basket chart

    Pre-filled Syringe (solution for injection)

    2, 6, 10, 12, 24, 30 X 10,000 IU (100 mg)/1 ml

    partial basket chart

    Dosage

    Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients:
    Individual thromboembolic risk for patients can be estimated using validated risk stratification model.
    In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 2,000 IU (20 mg) once daily by subcutaneous (SC) injection. Preoperative initiation (2 hours before surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.
    In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-10 days whatever the recovery status (e.g. mobility). Prophylaxis should be continued until the patient no longer has significantly reduced mobility.
    In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily given by SC injection preferably started 12 hours before surgery.If there is a need for earlier than 12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient waiting for a defered orthopaedic surgery), the last injection should be administered no later than 12 hours prior to surgery and resumed 12 hours after surgery.
    For patients who undergo major orthopaedic surgery an extended thromboprophylaxis up to 5 weeks is recommended.
    For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or pelvic surgery for cancer an extended thromboprophylaxis:  up to 4 weeks is recommended.
    Prophylaxis of venous thromboembolism in medical patients: The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection. Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status (e.g. mobility). The benefit is not established for a treatment longer than 14 days.
    Treatment of DVT and PE: Enoxaparin sodium can be administered SC either as a once daily injection of 150 IU/kg (1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg).
    The regimen should be selected by the physician based on an individual assessment including evaluation of the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg (1.5 mg/kg) administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose regimen of 100 IU/kg (1 mg/kg) administered twice daily should be used in all other patients such as those with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena iliaca) thrombosis.
    Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy should be initiated when appropriate.
    Prevention of thrombus formation during haemodialysis:
    The recommended dose is 100 IU/kg (1 mg/kg) of enoxaparin sodium.
    For patients with a high risk of haemorrhage, the dose should be reduced to 50 IU/kg (0.5 mg/kg) for double vascular access or 75 IU/kg (0.75 mg/kg) for single vascular access.
    During haemodialysis, enoxaparin sodium should be introduced into the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a 4-hour session; however, if fibrin rings are found, for example after a longer than normal session, a further dose of 50 IU to 100 IU/kg (0.5 to 1 mg/kg) may be given.
    No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during haemodialysis sessions.
    Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEMI: For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 100 IU/kg (1 mg/kg) every 12 hours by SC injection administered in combination with antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8 days.
    Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75– 325 mg/day long-term regardless of treatment strategy.
    For treatment of acute STEMI: the recommended dose of enoxaparin sodium is a single intravenous (IV) bolus of 3,000 IU (30 mg) plus a 100 IU/kg (1 mg/kg) SC dose followed by 100 IU/kg (1 mg/kg) administered 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 mg to 325 mg once daily) should be administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic (fibrin specific or non-fibrin specific), enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy.
    For dosage in patients ≥ 75 years of age, see “Elderly”.
    For patients managed with PCI, if the last dose of enoxaparin sodium SC was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 30 IU/kg (0.3 mg/kg) enoxaparin sodium should be administered.
    Elderly: For all indications except STEMI, no dose reduction is necessary in the elderly patients, unless kidney function is impaired.
    For treatment of acute STEMI in elderly patients ≥75 years of age, an initial IV bolus must not be used. Initiate dosing with 75 IU/kg (0.75 mg/kg) SC every 12 hours (maximum 7,500 IU (75 mg) for each of the first two SC doses only, followed by 75 IU/kg (0.75 mg/kg) SC dosing for the remaining doses).
    See prescribing information for full details.
    Method of administration: The drug should not be administered by the intramuscular route.
    See prescribing information for full details.


    Indications

    Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular those undergoing orthopaedic or general surgery including cancer surgery.
    Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at increased risk of venous thromboembolism.
    Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), excluding PE likely to require thrombolytic therapy or surgery.Prevention of thrombus formation in extra corporeal circulation during haemodialysis.
    Acute coronary syndrome:
    – Treatment of unstable angina and Non ST-segment elevation myocardial infarction (NSTEMI), in combination with oral acetylsalicylic acid.
    – Treatment of acute ST-segment elevation myocardial infarction (STEMI) including patients to be managed medically or with subsequent percutaneous coronary intervention (PCI).


    Contra-Indications

    Enoxaparin sodium is contraindicated in patients with:
    Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins (LMWH) or to any of the excipients.
    History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies.
    Active clinically significant bleeding and conditions with a high risk of hemorrhage, including recent haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.
    Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for treatment in the previous 24 hours.


    Special Precautions

    Enoxaparin sodium cannot be used interchangeably (unit for unit) with other LMWHs.
    History of HIT (>100 days): Use of enoxaparin sodium in patients with a history of immune mediated HIT within the past 100 days or in the presence of circulating antibodies is contraindicated. Circulating antibodies may persist several years.
    Enoxaparin sodium is to be used with extreme caution in patients with a history (>100 days) of heparin-induced thrombocytopenia without circulating antibodies. The decision to use enoxaparin sodium in such a case must be made only after a careful benefit risk assessment and after non-heparin alternative treatments are considered (e.g. danaparoid sodium or lepirudin).
    Monitoring of platelet counts: The risk of antibody-mediated HIT also exists with LMWHs. Should thrombocytopenia occur, it usually appears between the 5th and the 21st day following the beginning of enoxaparin sodium treatment.
    The risk of HIT is higher in postoperative patients and mainly after cardiac surgery and in patients with cancer.
    Haemorrhage: As with other anticoagulants, bleeding may occur at any site. If bleeding occurs, the origin of the haemorrhage should be investigated and appropriate treatment instituted.
    Enoxaparin sodium, as with any other anticoagulant therapy, should be used with caution in conditions with increased potential for bleeding, such as:
    – impaired haemostasis,
    – history of peptic ulcer,
    – recent ischemic stroke,
    – severe arterial hypertension,
    – recent diabetic retinopathy,
    – neuro- or ophthalmologic surgery,
    – concomitant use of medications affecting haemostasis.
    At doses used for prophylaxis of venous thromboembolism, enoxaparin sodium does not influence bleeding time and global blood coagulation tests significantly, nor does it affect platelet aggregation or binding of fibrinogen to platelets.
    Spinal/Epidural anaesthesia or lumbar puncture: Spinal/epidural anaesthesia or lumbar puncture must not be performed within 24 hours of administration of enoxaparin sodium at therapeutic doses.
    Skin necrosis/cutaneous vasculitis: Skin necrosis and cutaneous vasculitis have been reported with LMWHs and should lead to prompt treatment discontinuation.
    Percutaneous coronary revascularization procedures: To minimize the risk of bleeding following the vascular instrumentation during the treatment of unstable angina, NSTEMI and acute STEMI, adhere precisely to the intervals recommended between enoxaparin sodium injection doses. It is important to achieve haemostasis at the puncture site after PCI. In case a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If the treatment with enoxaparin sodium is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or hematoma formation.
    Acute infective endocarditis: Use of heparin is usually not recommended in patients with acute infective endocarditis due to the risk of cerebral haemorrhage. If such use is considered absolutely necessary, the decision must be made only after a careful individual benefit risk assessment.
    Mechanical prosthetic heart valves: The use of enoxaparin sodium has not been adequately studied for thromboprophylaxis in patients with mechanical prosthetic heart valves. Isolated cases of prosthetic heart valve thrombosis have been reported in patients with mechanical prosthetic heart valves who have received enoxaparin sodium for thromboprophylaxis. Confounding factors, including underlying disease and insufficient clinical data, limit the evaluation of these cases. Some of these cases were pregnant women in whom thrombosis led to maternal and foetal 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 study of pregnant women with mechanical prosthetic heart valves given enoxaparin sodium (100 IU/kg (1 mg/kg ) twice daily) to reduce the risk of thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and foetal death. There have been isolated post-marketing reports of valve thrombosis in pregnant women with mechanical prosthetic heart valves while receiving enoxaparin sodium for thromboprophylaxis. Pregnant women with mechanical prosthetic heart valves may be at higher risk for thromboembolism.
    Low weight: An increase in exposure of enoxaparin sodium with prophylactic dosages (non-weight adjusted) has been observed in low-weight women (<45 kg) and low-weight men (<57 kg), which may lead to a higher risk of bleeding. Therefore, careful clinical monitoring is advised in these patients.
    Obese Patients: Obese patients are at higher risk for thromboembolism. The safety and efficacy of prophylactic doses in obese patients (BMI >30 kg/m²) has not been fully determined and there is no consensus for dose adjustment. These patients should be observed carefully for signs and symptoms of thromboembolism.
    See prescribing information for full details.


    Side Effects

    Most common: Haemorrhage, haemorrhagic anaemia*, thrombocytopenia, thrombocytosis, Allergic reaction, Headache, Hepatic enzyme increases (mainly transaminases > 3 times the upper limit of normality), Urticaria, pruritus, erythema.
    See prescribing information for full details.


    Drug interactions

    Concomitant use not recommended:
    Medicinal products affecting haemostasis: It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products such as:
    – Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including ketorolac,
    – Other thrombolytics (e.g. alteplase, reteplase, streptokinase, tenecteplase, urokinase) and anticoagulants.
    Concomitant use with caution: The following medicinal products may be administered with caution concomitantly with enoxaparin sodium:
    Other medicinal products affecting haemostasis such as:
    – Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose (cardioprotection), clopidogrel, ticlopidine, and glycoprotein IIb/IIIa antagonists indicated in acute coronary syndrome due to the risk of bleeding,
    – Dextran 40,
    – Systemic glucocorticoids.
    Medicinal products increasing potassium levels: Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin sodium under careful clinical and laboratory monitoring.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third trimester of pregnancy. There is no information available concerning the first trimester.
    LactationIt is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is unlikely. This drug can be used during breastfeeding.
    See prescribing information for full details.


    Overdose

    Signs and symptoms: Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin sodium will be absorbed.
    Management: The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium injection, protamine administration may not be required. However, even with high doses of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the prescribing information for protamine salts).
    See prescribing information for full details.


    Important notes

    Storage: Store below 25°C. Do not freeze.


    Manufacturer
    Rovi Contract Manufacturing, Spain
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