When should a patient with Deep Vein Thrombosis (DVT) on apixaban (eliquis) be switched to enoxaparin (low molecular weight heparin, LMWH)?

When to Switch from Apixaban to Enoxaparin for DVT

Switch from apixaban to enoxaparin primarily in three clinical scenarios: cancer-associated DVT (especially gastrointestinal/genitourinary malignancies), severe renal impairment (CrCl <15-30 mL/min), or inability to take oral medications. 1, 2

Primary Indications for Switching to Enoxaparin

Cancer-Associated DVT

• Enoxaparin 1 mg/kg subcutaneously every 12 hours (or 1.5 mg/kg once daily) is preferred for the first 6 months in cancer-associated DVT, as recommended by the American College of Cardiology 2
• The 2022 International Clinical Practice Guidelines specifically recommend LMWH as first-line for initial treatment of established VTE in cancer patients when creatinine clearance is ≥30 mL/min 1
• Patients with gastric or gastroesophageal tumors are at particularly high risk for hemorrhage with DOACs and should preferentially receive LMWH 1
• In the event of VTE recurrence on apixaban in cancer patients, switching to LMWH is one of three recommended options 1

Severe Renal Impairment

• Switch to enoxaparin when CrCl falls below 15-30 mL/min, as apixaban is contraindicated or should be used with extreme caution in this range 2, 1
• Enoxaparin dosing for severe renal impairment (CrCl <30 mL/min): 1 mg/kg subcutaneously every 24 hours for VTE treatment 1
• Monitor anti-Xa levels in patients with severe renal impairment receiving enoxaparin, targeting peak levels of 0.5-1.5 IU/mL measured 4-6 hours after the third or fourth dose 1, 3
• While enoxaparin also accumulates in renal failure, dose adjustment protocols exist and monitoring is available, unlike with apixaban 4, 5

Inability to Take Oral Medications

• Enoxaparin 1 mg/kg every 12 hours or 1.5 mg/kg once daily should be used when patients cannot take oral medications due to nausea, vomiting, NPO status for procedures, or gastrointestinal dysfunction 2
• Continue enoxaparin until oral therapy becomes feasible 2

Clinical Scenarios Where Apixaban Should Be Continued

Standard DVT Without Contraindications

• Apixaban remains the preferred agent for uncomplicated DVT in patients without cancer, with normal renal function (CrCl >30 mL/min), and ability to take oral medications 2, 1
• Apixaban demonstrated lower or similar rates of recurrent VTE compared with dalteparin in the ADAM VTE and Caravaggio trials 1

Moderate Renal Impairment

• For CrCl 15-30 mL/min, apixaban can be used with caution at standard initial dosing, though consider 2.5 mg twice daily for extended therapy 2
• Insufficient data exist for safe apixaban dosing in hemodialysis patients, making enoxaparin the safer choice 1

Important Caveats and Pitfalls

Avoid Concurrent Administration

• Never administer enoxaparin and apixaban concurrently, as this significantly increases bleeding risk 6
• When switching from apixaban to enoxaparin, discontinue apixaban and wait approximately 12 hours before initiating enoxaparin 6

Duration Considerations

• Cancer patients should continue anticoagulation for at least 6 months, often indefinitely while cancer remains active 2, 1
• After 6 months on enoxaparin in cancer patients, the dose may be reduced from 200 IU/kg daily to 150 IU/kg daily (for dalteparin) or 75-80% of initial LMWH dose 1

Monitoring Requirements

• Therapeutic monitoring is generally not required for enoxaparin except in severe renal impairment (CrCl <30 mL/min), obesity (BMI >40), low body weight (<50 kg), or elderly patients (≥70 years) 1
• Peak anti-Xa levels should be measured 4-6 hours after dosing, only after 3-4 doses have been administered 1

Special Population Warnings

• Avoid tinzaparin in patients aged ≥70 years with renal insufficiency due to increased mortality demonstrated in randomized trials 1
• Use caution with all LMWHs when CrCl <50 mL/min, as evidence suggests increased bleeding risk even with moderate renal impairment 1