see also:

• anticoagulants

• enoxaparin (Clexane) is a low molecular weight (LMW) heparin which is usually given bd or daily s/c in the prevention or Rx of deep venous thrombosis (DVT) or pulmonary embolism (PE) or in Mx of acute coronary syndromes, but can also be given as an initial iv bolus.
• It has several actions on the coagulation pathway through binding to antithrombin III. The antithrombotic activity is related to inhibition of thrombin generation and inhibition of two main coagulation factors: factor Xa and thrombin. It also induces a sustained release of the tissue factor pathway inhibitor in vivo.
• both regular unfractionated and LMW heparin can inactivate factor Xa.
• regular unfractionated heparin also inactivates thrombin (IIa) because it binds both antithrombin III and thrombin at the same time.
• in contrast, LMW heparins such as enoxaparin, increase the action of antithrombin III on factor Xa, but because of their small size, they do not bind antithrombin III and thrombin at the same time, hence they have a relatively minor effect on activated partial thromboplastin time (APTT).

• after injection by the SC route, it is rapidly and completely absorbed. The absolute bioavailability is over 90%.
• The maximum plasma activity is observed after three hours and is, on average, 1.6 microgram/mL after the SC injection of a 20 mg dose and 3.8 microgram/mL after the injection of a 40 mg dose. The anti-Xa activity, measured like that of UFH, gives values of approximately 0.16 and 0.38 IU/mL, respectively.
• The elimination of enoxaparin (based on anti-Xa activity levels) is characterised by a half-life of approximately 4.4 hours for a dose of 40 mg. At higher doses of 73.8 mg to 132.6 mg, a study has shown that anti-Xa activity levels exhibit a first phase elimination half-life of approximately five hours and a second stage elimination half-life of approximately nine hours. Following a 40 mg dose, anti-Xa activity may persist in the plasma for 24 hours.
• The anti-Xa activity generated by Clexane does not cross the placental barrier during the second trimester of pregnancy.
• Metabolic breakdown of Clexane is slight and takes place mainly in the liver
• A linear relationship between anti-Xa plasma clearance and creatinine clearance at steady state has been observed.
• kinetic profile is not different in elderly subjects compared to younger subjects when renal function is normal.

• allergy to enoxaparin or heparin or other LMW heparins
• acute bacterial endocarditis.
• high risk of uncontrolled haemorrhage including major bleeding disorders, focal lesions, haemorrhagic stroke, active peptic ulcer or ulcerative colitis.
• thrombocytopenia associated with a positive in vitro test for antiplatelet antibody in the presence of enoxaparin

• LMW heparin products are not clinically interchangeable
  • The biological activity of different low molecular weight heparins cannot be expressed in a test allowing for a simple dose comparison.
• Not to be administered by the intramuscular route.
• Risk of haemorrhage
• use with care in patients with the following conditions: hepatic insufficiency, a bleeding diathesis, uncontrolled arterial hypertension, a history of gastrointestinal ulceration, impaired haemostasis, recent ischaemic stroke, diabetic retinopathy, recent neurosurgery or ophthalmological surgery and haemorrhage.
• Heparin induced thrombocytopenia.
• Spinal/ epidural anaesthesia
• Thrombocytopenia.
• Prosthetic heart valves
  • There have been no adequate studies to assess the safe and effective use of enoxaparin in preventing thromboembolism in patients with prosthetic heart valves.
• Percutaneous coronary revascularisation procedures
• low weight adults (women < 45kg, men < 57kg) are at higher risk of bleeding with non-weight adjusted prophylactic doses.
• Monitoring of platelet count - heparin-induced thrombocytopaenia usually occurs between day 5 and day 21 of Rx.
  • discontinue if it drops > 30-50% of pre-Rx count.
• Impaired renal function.
  • adjust dose if severe renal impairment (creatinine clearance < 30 mL/minute), otherwise watch with care in mild-mod. renal impairment.
• Elderly patients (especially 80 years or older) may be at an increased risk for bleeding complications with the therapeutic dosage ranges, reduce dose if renal impairment.
• pregnancy (cat C)
• lactation - breast milk concentrations are similar to maternal plasma in rats. No human data.
• children - no usage data available.

• bleeding
  • overdosage can be partly reversed with protamine
    • if enoxaparin was administered in the previous eight hours, 1 mg or 100 antiheparin units of protamine neutralises the anti-IIa activity generated by 1 mg (100 IU anti-Xa activity) of enoxaparin
    • An infusion of protamine 0.5 mg per 1 mg of enoxaparin may be administered if enoxaparin was administered greater than eight hours previously, or if it has been determined that a second dose of protamine is required.
    • Protamine administration may not be required 12 hours after the enoxaparin injection.
• heparin-induced thrombocytopenia - usually occurs between day 5 and 21 of Rx
• asymptomatic & reversible abnormal LFTs
• nausea, diarrhoea, confusion, peripheral oedema, fever have all been commonly reported in clinical trials.

• other anticoagulants
  • It is recommended that agents which affect haemostasis should be discontinued prior to Clexane therapy unless strictly indicated.

• injection should be made preferably when the patient is reclining.
• administer by deep SC injection.
• alternate between the left and right anterolateral abdominal wall using a different site for each injection.
• do not expel the air bubble from the syringe before the injection to avoid the loss of drug.
• Clexane contains no antimicrobial agent and should be used only once and then discarded.

The needles on prefilled syringes of Clexane are covered in a silicon coating, to enable ease of penetration. Do not wipe the needle or allow Clexane solution to crystallise on the needle prior to use, as this will damage the silicon coating. A `dart' injection technique should be used to administer Clexane. Do not rub the injection site after administration.

• if indicated, 40mg s/c daily appears to be as effective in preventing PE and extension of thrombus as 1.5mg/kg ¹⁾

• high risk of DVT: 40mg s/c daily (20mg s/c daily if severe renal impairment)
• moderate risk of DVT: 20mg s/c daily
• Rx for 7-10 days (if post-op) or 14 days (if medical immobilisation) or until risk has diminished such as ambulating well, but consider 30 days after THR.

• 1.5mg/kg s/c once daily or 1mg/kg s/c bd
• In high risk patients, e.g. the obese or patients with baseline iliac vein thrombosis or cancer, a dose of 1 mg/kg bodyweight administered twice daily may be more beneficial.
• warfarin Rx should be initiated when appropriate (usually within 72 hours of commencing enoxaparin initiation).
• enoxaparin should be continued for a minimum of five days and until a therapeutic oral anticoagulant effect has been achieved (INR 2.0 to 3.0).

• should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive aspirin as soon as they are identified as having STEMI (unless contraindicated). The recommended duration of enoxaparin Rx is 8 days or until hospital discharge, whichever comes first.
• age < 75yrs:
  • single IV bolus of 30 mg plus a 1 mg/kg SC dose, followed by 1 mg/kg administered SC every 12 hours (maximum 100 mg for the first two doses only, followed by 1 mg/kg dosing for the remaining doses).
• age > 75 yrs:
  • 0.75mg/kg administered SC every 12 hours (max. 75mg for 1st two doses) WITHOUT the initial iv bolus

• Prefilled syringes in doses of 20mg, 40mg, 60mg, 80mg, 100mg, 120mg, and 150mg.