What is the recommended initial dose of Fragmin (dalteparin) when converting from Apixaban (apixaban) 2.5 mg twice daily?

Converting from Apixaban 2.5 mg Twice Daily to Dalteparin (Fragmin)

There is no established direct conversion protocol from apixaban to dalteparin in clinical guidelines; however, based on standard anticoagulation bridging principles, dalteparin should be initiated at treatment doses (200 units/kg subcutaneously once daily for VTE, or 100 units/kg subcutaneously every 12 hours) after allowing appropriate washout time from the last apixaban dose. 1

Timing of Conversion

• Wait for apixaban clearance before initiating dalteparin. Given apixaban's half-life of approximately 12 hours, the drug is substantially cleared after 24-48 hours in patients with normal renal function 1

• In patients with renal impairment (CrCl 15-50 mL/min), extend the washout period as apixaban clearance is prolonged, with 27% renal excretion 1

• For urgent situations requiring immediate anticoagulation, dalteparin can be started 12-24 hours after the last apixaban dose, accepting some overlap risk 1

Dalteparin Dosing Regimens

For Venous Thromboembolism Treatment:

• Initial therapy: 200 units/kg subcutaneously once daily for the first 30 days, then reduce to 150 units/kg once daily for extended treatment 1
• Alternative regimen: 100 units/kg subcutaneously every 12 hours can be used throughout the treatment course 1

For Cancer-Associated VTE:

• Preferred regimen: 200 units/kg subcutaneously once daily for 30 days, followed by 150 units/kg once daily for extended therapy 1
• This is the NCCN-recommended approach for cancer patients requiring LMWH 1

For Atrial Fibrillation (Bridging):

• Treatment-dose dalteparin: 100 units/kg subcutaneously every 12 hours until therapeutic anticoagulation with another agent is established 1

Important Clinical Considerations

Why the Patient is on Apixaban 2.5 mg:

• The 2.5 mg twice daily dose indicates dose reduction criteria were met: either ≥2 of the following: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL (CrCl 15-50 mL/min) 1
• These same factors affect dalteparin dosing and bleeding risk, requiring careful monitoring 1

Renal Function Impact:

• Dalteparin is renally cleared (66% renal excretion) and accumulates in renal impairment 2
• In patients with CrCl <30 mL/min, consider dose reduction or anti-Xa monitoring to prevent accumulation, though specific dose adjustments are not well-established 1, 2
• The fact that apixaban was dose-reduced suggests underlying renal impairment may be present, warranting baseline creatinine clearance calculation before dalteparin initiation 1

Monitoring Requirements:

• Anti-Xa levels may be considered in high-risk patients (renal impairment, extremes of body weight, elderly) to ensure appropriate anticoagulation without excessive drug accumulation 2
• Peak anti-Xa levels (4 hours post-dose) of 0.6-1.0 IU/mL for twice-daily dosing or 1.0-2.0 IU/mL for once-daily dosing are therapeutic targets 2

Common Pitfalls to Avoid

• Do not use prophylactic dalteparin doses (5,000 units subcutaneously daily) when converting from therapeutic apixaban—this provides inadequate anticoagulation 1

• Do not overlap apixaban and dalteparin except in urgent situations, as this significantly increases bleeding risk without established benefit 1

• Do not assume the patient needs only prophylactic anticoagulation because they were on low-dose apixaban—the 2.5 mg dose is still therapeutic for stroke prevention in atrial fibrillation or VTE secondary prophylaxis 1, 3

• Reassess the indication for anticoagulation during conversion—if the patient was on apixaban 2.5 mg for extended VTE secondary prophylaxis after completing initial treatment, consider whether full treatment-dose dalteparin is necessary or if the clinical scenario has changed 3

Special Populations:

Cancer patients: LMWH (dalteparin) is preferred over DOACs for cancer-associated VTE, making this conversion clinically appropriate 1, 4

Elderly patients (≥80 years): Both increased bleeding risk and thromboembolic risk require careful dose selection and monitoring 1

Low body weight (≤60 kg): Weight-based dalteparin dosing is advantageous but may require dose capping at maximum 18,000 units daily to prevent over-anticoagulation 1