ADMINISTRATION ROUTES:
SC
ALTERNATIVE NAMES:
Clexane
ICU INDICATIONS:
- Therapeutic anticoagulation
- Venous thrombus prophylaxis
PRESENTATION AND ADMINISTRATION:
SC:
Pre-mixed syringes 20 mg/0.2 mL, 40 mg/0.4 mL, 100 mg/mL
Do not remove air bubble from pre-mixed syringe prior to injection
Inject at 90 degrees to the skin on the lower abdomen. Alternate between the left and right anterolateral abdominal wall
Do not rub injection site after administration
DOSAGE:
SC:
Venous thrombosis prophylaxis:
40 mg OD SC
For adults weighing ≥ 130 kg
60 mg OD SC
Prophylactic enoxaparin should always be administered at night (usually 6pm). Most invasive procedures occur during daylight hours so administering enoxaparin at night reduces the risk of procedural bleeding
Therapeutic dose:
1 mg/kg BD or 1.5 mg/kg OD SC
Enoxaparin dosing in extremes of body weight:
The dose of enoxaparin does not need to be adjusted in the morbidly obese (BMI >35, or greater than 150kg), or those with a BMI <20 (underweight). These patients should be dosed on a mg/kg basis in the same way as patients of normal bodyweight, with adjustment for renal impairment if needed. There is evidence that twice daily dosing is safer for patients with BMI >35 or weight >150 kg.
People at extremes of bodyweight (BMI <20 or >35) should have their anti-Xa level checked after 48 hours of dosing of enoxaparin, and the dose adjusted accordingly (see Laboratory Tests section below)
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment:
Venous thrombosis prophylaxis:
GFR (ml/min) | DOSE |
---|---|
<30 | 20 mg OD |
≥30 | 40 mg OD |
Therapeutic dose:
GFR (ml/min) | DOSE |
---|---|
<30 | 0.66 mg/kg BD |
30-60 | 0.8 mg/kg BD |
>60 | dose as in normal renal function |
Dose in renal replacement therapy:
Use systemic heparinisation in these patients in ICU
DOSAGE IN PAEDIATRICS:
Venous thrombosis prophylaxis: Most children do not require enoxaparin prophylaxis unless deemed high risk of venous thrombosis. For those that do, dosage differs by age.
< 2 months old:
0.75 mg/kg BD SC
2 months - 18 years old:
0.5 mg/kg BD SC
Therapeutic dose:
1 mg/kg BD SC
CLINICAL PHARMACOLOGY:
Low molecular weight heparin
CONTRAINDICATIONS:
- Hypersensitivity to enoxaparin
- Active bleeding
- Presence of an external ventricular drain
Patients with traumatic brain injury should always be discussed with the neurosurgical team before commencing any anticoagulation, including enoxaparin
WARNINGS:
Bleeding Risk:
Every patient being considered for enoxaparin therapy should be assessed for their risk of bleeding. This assessment should be documented in the clinical notes. Risk of bleeding with enoxaparin is increased in the following groups:
- Older age (> 65 years)
- BMI < 20
- Renal impairment
- Require a prolonged period of treatment
- Take concomitant clopidogrel (8-fold increased risk of major bleeding), aspirin or NSAID (3-4 fold increased risk)
- Have had previous upper GI bleeding
- Have moderate hypertension (BP 140-180 systolic, 90-110 diastolic, even if on treatment)
- Have multiple medical co- morbidities (especially diabetes, previous CVA or heart failure)
- Have undiagnosed iron deficiency anaemia (in non-menstruating women)
PRECAUTIONS:
General:
Many ICU procedures require reversal of anticoagulation. As enoxaparin is a not readily reversed, therapeutic systemic heparinisation may be a more appropriate choice for many ICU patients as it has a shorter half-life and is more easily reversed
Laboratory Tests:
Routine anti-Xa monitoring is not recommended. Prothrombin Time (PT) and Activated Partial Thromboplasin Time (aPTT) are insensitive measures of enoxaparin activity so are not recommended to assess enoxaparin efficacy. Measuring peak Anti-Xa levels is recommended for patients on therapeutic doses of enoxaparin in the following situations:
- Moderate renal impairment (eGFR < 60 mL/min)
- Weight < 50 kg
- Morbid obesity (BMI > 35)
- Pregnancy
- Receiving treatment dose enoxaparin for longer than 14 days
- Patients with changing renal function
- Any other factors from the 'increased bleeding risk' list above
When to monitor anti-Xa:
Blood for anti-Xa levels should be sent in a sodium citrate (light blue) tube.
PEAK: Peak anti-Xa concentration yields the best correlation with clinical effect and risk of bleeding. Peak levels should be taken 4 hours after the last dose of enoxaparin. Anti-Xa monitoring should only occur when enoxaparin is at steady state after about 48 hours (5 half lives). Levels should not be measured prior to this as they are uninterpretable. Patients receiving enoxaparin for less than 48 hours do not need anti Xa monitoring.
TROUGH: Trough measurements are not routinely recommended as correlation between bleeding risk and trough anti-Xa has not been clearly established. The only exception for trough measurement is patients with severe renal impairment (eGFR <30 mL/min) to whom enoxaparin has been administered. These patients should also have peak anti-Xa levels measured. For twice daily dosing, the trough sample should be taken 12 hours after a dose, immediately preceding the next dose. The acceptable trough level should be ≤ 0.5 IU/ mL. If the trough level is > 0.5 IU/mL, the patient should be changed to once daily dosing of enoxaparin. For once daily dosing, the sample should be taken 20 hours after a dose, and should be ≤ 0.4 IU/mL
Therapeutic range:
Therapeutic peak anti-Xa range for treatment dose enoxaparin is 0.5−1.2 IU/mL (BD dosing), or 1−2 IU/mL (OD dosing). In patients who are not bleeding and have stable renal function, the dose should be adjusted using the following nomogram:
Enoxaparin Dose Adjustment for ONCE DAILY DOSING
Peak Anti-Xa Level (IU/mL) | Withhold Next Dose | Dose Change | Next Peak Anti-Xa Level |
---|---|---|---|
< 0.5 | No | Increase by 50% | 48 hours |
0.51 - 0.99 | No | Increase by 25% | 48 hours |
1 - 2 | No | No | 1 week |
2.1 - 3 | No | Decrease by 30% | 48 hours |
>3 | Yes. Check every 6 hours until Anti-Xa <0.5 | Decrease by 50% | 48 hours after next dose. Consider change to heparin |
Enoxaparin Dose Adjustment for TWICE DAILY DOSING
Peak Anti-Xa Level (IU/mL) | Withhold Next Dose | Dose Change | Next Peak Anti-Xa Level |
---|---|---|---|
< 0.25 | No | Increase by 50% | 48 hours |
0.25 - 0.49 | No | Increase by 25% | 48 hours |
0.5 - 1.2 | No | No | 1 week |
1.21 - 1.5 | No | Decrease by 25% | 48 hours |
1.51 - 2 | For 3 hours | Decrease by 30% | 48 hours after next dose |
> 2 | Yes. Check every 6 hours until Anti-Xa <0.5 | Decrease by 50% | 48 hours after next dose. Consider change to heparin |
If reversal of the anticoagulant effects of enoxaparin are required due to the need for an emergent procedure or significant bleeding occurs, partial reversal (60-75%) can be achieved by administering protamine. The dose required is dependent on the dose and time the enoxaparin was administered:
- If < 8 hours have passed since enoxaparin administration, give 1 mg protamine for every 1 mg of enoxaparin given
- If ≥ 8 hours have passed since enoxaparin administration, give 0.5 mg protamine for every 1 mg of enoxaparin given
See protamine monograph for more information
Drug/Laboratory Test Interactions:
None noted
IMPORTANT DRUG INTERACTIONS IN ICU:
Increased risk of bleeding when combined with other anti-platelet and anticoagulant agents
ADVERSE REACTIONS:
Body as a Whole:
Bleeding, anaphylaxis, fever
Cardiovascular System:
Peripheral oedema
Haematological System:
Anaemia, thrombocytopaenia, HITTS
Gastrointestinal System:
GI upset, deranged liver function tests
Local:
Haematoma (at injection site), skin necrosis