From the Guidelines
Enoxaparin dosing should be adjusted based on creatinine clearance (CrCl) to prevent bleeding complications in patients with renal impairment, with a recommended dose reduction to 1 mg/kg SC once daily for patients with CrCl <30 mL/min, as suggested by the 2014 AHA/ACC guideline 1.
Enoxaparin Dosing Adjustment
When considering enoxaparin therapy, it is crucial to assess renal function, as the drug is primarily eliminated by the kidneys.
- For patients with normal renal function (CrCl ≥30 mL/min), standard dosing applies: 1 mg/kg twice daily or 1.5 mg/kg once daily for treatment indications, and 40 mg once daily for prophylaxis.
- For patients with impaired renal function (CrCl <30 mL/min), the dose should be reduced to 1 mg/kg SC once daily, as recommended by the 2014 AHA/ACC guideline 1 and supported by the 2012 American College of Chest Physicians evidence-based clinical practice guidelines 1.
Rationale for Dose Adjustment
The dose adjustment is necessary because enoxaparin is primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation, increasing bleeding risk.
- Regular monitoring of anti-Xa levels may be helpful in patients with renal impairment to ensure appropriate anticoagulation while minimizing bleeding risk, as suggested by the 2012 American College of Chest Physicians evidence-based clinical practice guidelines 1.
- Additionally, assess patients for other bleeding risk factors when using enoxaparin in the setting of renal dysfunction.
Clinical Considerations
In patients with severe renal impairment (CrCl <15 mL/min), enoxaparin is generally not recommended, and unfractionated heparin may be preferred, as suggested by the 2012 American College of Chest Physicians evidence-based clinical practice guidelines 1.
- The 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care also support the use of enoxaparin in patients with impaired renal function, with a recommended dose reduction to 1 mg/kg SC once daily for patients with CrCl <30 mL/min 1.
From the Research
Enoxaparin and CrCl
- Enoxaparin sodium has predictable pharmacokinetics, but reliance on renal function for excretion may lead to accumulation in patients with moderate renal impairment 2
- Moderate renal impairment is defined as creatinine clearance (CrCl) of 30 to 50 mL/min, and normal renal function is defined as CrCl greater than 80 mL/min 2
- Studies have shown an increased risk of major bleeding in patients with moderate renal impairment who receive enoxaparin 2, 3
Dose Adjustment
- A pharmacokinetic program was created to adjust enoxaparin doses based on anti-Xa levels in patients with renal impairment 3
- The program provided a loading dose of 1 mg/kg enoxaparin, with subsequent doses adjusted based on CrCl 3
- A dose-adjustment ratio was used to adjust doses in patients whose levels were outside the therapeutic range 3
Renal Function and Enoxaparin
- Renal function plays an important role in the clearance of low molecular weight heparins like enoxaparin 4, 5
- Studies have shown a linear correlation between creatinine clearance and anti-Xa concentrations 5
- Enoxaparin dose should be adjusted based on body weight, serum creatinine, and gender to reach a target anticoagulation level in patients with decreased renal function 6
Safety and Efficacy
- Enoxaparin can be safely administered once a day to patients with renal impairment and a CrCl of less than 30 mL/min 4
- A study found no adverse events in patients with renal impairment who received enoxaparin 4
- However, another study found an increased risk of major bleeding in patients with moderate renal impairment who received enoxaparin 2