What is the recommended approach for switching a patient with a history of atrial fibrillation, deep vein thrombosis (DVT), or pulmonary embolism (PE) and impaired renal function from Apixaban (Apixaban) to Enoxaparin (Low Molecular Weight Heparin, LMWH)?

Switching from Apixaban to Enoxaparin

Discontinue apixaban and begin enoxaparin at the usual time of the next scheduled apixaban dose, without any bridging or overlap period. 1

Timing of the Switch

• Stop apixaban completely and start enoxaparin at the time when the next apixaban dose would have been due. 1
• No washout period or bridging anticoagulation is required between stopping apixaban and starting enoxaparin. 1
• The FDA-approved prescribing information explicitly states to "discontinue apixaban and begin taking the new anticoagulant other than warfarin at the usual time of the next dose of apixaban." 1

Enoxaparin Dosing by Indication

For DVT/PE Treatment

• Standard dosing: 1 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg once daily. 2
• This dosing applies to both acute treatment and extended therapy in most patients. 2

For Cancer-Associated VTE

• Preferred regimen: 1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg once daily for the first 6 months. 2
• The American College of Cardiology specifically recommends enoxaparin as the preferred agent for cancer-associated thrombosis. 2

For Atrial Fibrillation (Bridging Context)

• If bridging is deemed necessary for high-risk AF patients, use standard therapeutic dosing as above. 2
• However, bridging with LMWH is associated with increased bleeding risk and should be reserved only for patients at very high risk of recurrent VTE (e.g., within 3 months of acute VTE). 2

Special Populations Requiring Dose Adjustment

Severe Renal Impairment (CrCl <30 mL/min)

• Enoxaparin is the preferred anticoagulant when apixaban must be discontinued due to severe renal dysfunction. 2
• Consider reducing the enoxaparin dose by approximately 20% in patients with CrCl <30 mL/min, particularly for treatment dosing. 2
• Monitor anti-Xa activity in patients with severe renal impairment to guide dosing. 2

Obesity (BMI ≥40 or Class 3)

• For VTE treatment: Continue weight-based dosing (1 mg/kg every 12 hours) without dose capping in most cases. 2
• Consider measuring anti-Xa activity in patients with BMI >40, particularly if body weight exceeds 140 kg. 2
• For enoxaparin specifically, consider reducing the dose by approximately 20% in patients with BMI >40 to avoid overdosing. 2
• Alternatively, consider twice-daily dosing rather than once-daily to improve pharmacokinetics in severe obesity. 2

Underweight Patients (BMI <18.5 or weight <60 kg)

• Use standard weight-based dosing without adjustment. 2
• Monitor closely for bleeding risk, as underweight patients may have higher bleeding rates. 2

Common Clinical Scenarios

Switching Due to Inability to Take Oral Medications

• Start enoxaparin 1 mg/kg every 12 hours or 1.5 mg/kg once daily at the time of the next scheduled apixaban dose. 1
• This scenario commonly occurs with acute illness, surgery, or gastrointestinal issues preventing oral intake. 2

Switching Due to Worsening Renal Function

• When CrCl falls below 15 mL/min, apixaban is contraindicated and enoxaparin becomes the preferred alternative. 2
• For CrCl 15-30 mL/min, either agent can be used, but if switching to enoxaparin, use dose-reduced regimens with anti-Xa monitoring. 2

Pre-Operative Transition

• If switching from apixaban to enoxaparin for perioperative management, apixaban should be stopped 48 hours before high-bleeding-risk procedures or 24 hours before low-bleeding-risk procedures. 1
• Enoxaparin can then be started at therapeutic doses if continued anticoagulation is required, or at prophylactic doses (40 mg once daily) for standard VTE prophylaxis. 2

Critical Pitfalls to Avoid

• Do not overlap apixaban and enoxaparin. The FDA labeling is explicit that you should discontinue one and start the other at the scheduled time—no bridging is needed. 1
• Do not use prophylactic-dose enoxaparin (40 mg daily) when switching from therapeutic-dose apixaban for active VTE or AF. Match the intensity of anticoagulation to the clinical indication. 2
• Do not forget to adjust enoxaparin dosing for severe renal impairment (CrCl <30 mL/min). Unlike apixaban, which is contraindicated below CrCl 15 mL/min, enoxaparin can be used but requires dose reduction and monitoring. 2
• Do not assume once-daily dosing is always appropriate. For acute VTE treatment, twice-daily dosing (1 mg/kg every 12 hours) is generally preferred over once-daily dosing, particularly in obesity. 2

Monitoring Considerations

• Anti-Xa monitoring is recommended in specific populations: severe renal impairment (CrCl <30 mL/min), severe obesity (BMI >40 or weight >140 kg), pregnancy, and extremes of age. 2
• Target anti-Xa levels for therapeutic dosing: 0.6-1.0 IU/mL for twice-daily dosing (measured 4 hours post-dose) or 1.0-2.0 IU/mL for once-daily dosing. 2
• Routine anti-Xa monitoring is not required in patients with normal renal function and normal body weight. 2