Enoxaparin

Anticoagulant (LMWH)
Mechanism of Action ㅡ Enoxaparin is a type of low molecular weight heparin (LMWHs) with a mean molecular weight of 4000 to 5000. It has an immediate onset of action when given in the intravenous form. It binds to and potentiates antithrombin III, a serine protease inhibitor, to form a complex that irreversibly inactivates factor Xa. Enoxaparin has less activity against factor IIa (thrombin) compared to unfractionated heparin.
Trade name ㅡ Clexane 20, 40, 60, 80 mg

• Treatment of venous thromboembolism in pregnancy
• For Adult (body-weight up to 50 kg): 40 mg twice daily, dose based on early pregnancy body-weight.
• For Adult (body-weight 50–69 kg): 60 mg twice daily, dose based on early pregnancy body-weight.
• For Adult (body-weight 70–89 kg): 80 mg twice daily, dose based on early pregnancy body-weight.
• For Adult (body-weight 90 kg and above): 100 mg twice daily, dose based on early pregnancy body-weight.
• Prophylaxis of deep-vein thrombosis, especially in surgical patients—moderate risk; By subcutaneous injection, For Adult: 20 mg for 1 dose, dose to be given approximately 2 hours before surgery, then 20 mg every 24 hours.
• Prophylaxis of deep-vein thrombosis, especially surgical patients—high risk (e.g. orthopaedic surgery); By subcutaneous injection: 40 mg for 1 dose, dose to be given 12 hours before surgery, then 40 mg every 24 hours.
• Prophylaxis of deep-vein thrombosis in medical patients; By subcutaneous injection: 40 mg every 24 hours.
• Treatment of deep-vein thrombosis in uncomplicated patients with low risk of recurrence, Treatment of pulmonary embolism in uncomplicated patients with low risk of recurrence: 1.5 mg/kg every 24 hours until adequate oral anticoagulation established.
• Treatment of deep-vein thrombosis in patients with risk factors such as obesity, cancer, recurrent VTE, or proximal thrombosis, Treatment of pulmonary embolism in patients with risk factors such as obesity, symptomatic pulmonary embolism, cancer, or recurrent VTE: 1 mg/kg every 12 hours until adequate oral anticoagulation established.
• Treatment of acute ST-segment elevation myocardial infarction (patients not undergoing percutaneous coronary intervention)
• Initially by intravenous injection, For Adult 18–74 years: Initially 30 mg, followed by (by subcutaneous injection) 1 mg/kg for 1 dose, then (by subcutaneous injection) 1 mg/kg every 12 hours (max. per dose 100 mg) for up to 8 days, maximum dose applies for the first two subcutaneous doses only.
• By subcutaneous injection, For Adult 75 years and over: 750 micrograms/kg every 12 hours (max. per dose 75 mg), maximum dose applies for the first two doses only.
• Treatment of acute ST-segment elevation myocardial infarction (patients undergoing percutaneous coronary intervention)
• Initially by intravenous injection, For Adult 18–74 years: Initially 30 mg, followed by (by subcutaneous injection) 1 mg/kg for 1 dose, then (by subcutaneous injection) 1 mg/kg every 12 hours (max. per dose 100 mg) for up to 8 days, maximum dose applies for the first two subcutaneous doses only, then (by intravenous injection) 300 micrograms/kg for 1 dose, dose to be given at the time of procedure if the last subcutaneous dose was given more than 8 hours previously.
• Initially by subcutaneous injection, For Adult 75 years and over: 750 micrograms/kg every 12 hours (max. per dose 75 mg), maximum dose applies for the first two doses only, then (by intravenous injection) 300 micrograms/kg for 1 dose, dose to be given at the time of procedure if the last subcutaneous dose was given more than 8 hours previously.
• Unstable angina, Non-ST-segment-elevation myocardial infarction; By subcutaneous injection, For Adult: 1 mg/kg every 12 hours usually for 2–8 days (minimum 2 days).
• Prevention of clotting in extracorporeal circuits; To the device as a flush: consult product literature.

Dose equivalence and conversion: 1 mg equivalent to 100 units.
Unlicensed use: Treatment of venous thromboembolism in pregnancy.

• Hepatic impairment, Manufacturer advises caution — No information available.
• Renal impairment
• Risk of bleeding increased; use of unfractionated heparin may be preferable.
• Manufacturer advises avoid if creatinine clearance less than 15 mL/minute.
• Manufacturer advises reduce dose if creatinine clearance 15–30 mL/minute — Consult product literature for details.

• For all Heparins. Acute bacterial endocarditis; after major trauma; Avoid injections containing benzyl alcohol in neonates; epidural anaesthesia with treatment doses; hemophilia or other hemorrhagic disorders; peptic ulcer; recent cerebral hemorrhage; recent surgery to eye; recent surgery to nervous system; spinal anaesthesia with treatment doses; thrombocytopenia (including history of heparin-induced thrombocytopenia)
• Cautions
• For all Heparins, Elderly; severe hypertension
• For Enoxaparin sodium, Low body-weight (increased risk of bleeding)

• For all Heparins. Common or very common: Hemorrhage; heparin-induced thrombocytopenia; skin reactions; thrombocytopenia; thrombocytosis
• Uncommon
• CNS hemorrhage
• Rare or very rare
• Alopecia; hyperkalaemia; osteoporosis (following long term use); priapism
• Frequency not known. Hypoaldosteronism
• Side-effects, further information
• Hemorrhage. If hemorrhage occurs it is usually sufficient to withdraw unfractionated or low molecular weight heparin, but if rapid reversal of the effects of the heparin is required, protamine sulfate is a specific antidote (but only partially reverses the effects of low molecular weight heparins).
• Heparin-induced thrombocytopenia. Clinically important heparin-induced thrombocytopenia is immune-mediated and can be complicated by thrombosis. Signs of heparin-induced thrombocytopenia include a 30% reduction of platelet count, thrombosis, or skin allergy. If heparin-induced thrombocytopenia is strongly suspected or confirmed, the heparin should be stopped and an alternative anticoagulant, such as danaparoid, should be given. Ensure platelet counts return to normal range in those who require warfarin.
• Hyperkalemia. Inhibition of aldosterone secretion by unfractionated or low molecular weight heparin can result in hyperkalemia; patients with diabetes mellitus, chronic renal failure, acidosis, raised plasma potassium or those taking potassium-sparing drugs seem to be more susceptible. The risk appears to increase with duration of therapy.

• For all Heparins
• Heparin-induced thrombocytopenia. Platelet counts should be measured just before treatment with unfractionated or low molecular weight heparin, and regular monitoring of platelet counts may be required if given for longer than 4 days. See the British Society for Hematology’s Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol 2012; 159: 528–540.
• Hyperkalemia. Plasma-potassium concentration should be measured in patients at risk of hyperkalemia before starting the heparin and monitored regularly thereafter, particularly if treatment is to be continued for longer than 7 days.
• For Enoxaparin sodium. Routine monitoring of anti-Factor Xa activity is not usually required during treatment with enoxaparin, but may be necessary in patients at increased risk of bleeding (e.g. in renal impairment and those who are underweight or overweight).

• When administered in conjunction with a thrombolytic, manufacturer advises enoxaparin should be given between 15 minutes before and 30 minutes after the start of thrombolytic therapy.

• Lexicomp: www.lexicomp.com 
• Aamani Jupalli and Arshad Muhammad Iqbal (2019). Enoxaparin. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/books/NBK539865