What is the difference between Fragmin (dalteparin) and Clexane (enoxaparin)?

Difference Between Fragmin (Dalteparin) and Clexane (Enoxaparin)

Both Fragmin (dalteparin) and Clexane (enoxaparin) are low-molecular-weight heparins that are clinically effective for VTE prophylaxis and treatment, but they differ significantly in their pharmacokinetic properties, FDA-approved indications, dosing requirements, and behavior in renal insufficiency—making them NOT interchangeable despite being commonly substituted in practice. 1

Key Pharmacological Differences

Manufacturing and Molecular Structure

• Dalteparin (Fragmin) is produced through nitrous acid depolymerization of unfractionated heparin 1
• Enoxaparin (Clexane/Lovenox) is manufactured by benzylation followed by alkaline depolymerization 1
• These different production methods result in distinct molecular weight distributions, anti-Xa/anti-IIa ratios, and pharmacokinetic profiles 1

Pharmacokinetic Properties

• Enoxaparin demonstrates superior bioavailability: When normalized to the same injected dose (1,000 IU anti-Xa), enoxaparin generates 2.28 times greater plasma anti-Xa activity than dalteparin (p < 0.001) 2
• Enoxaparin has longer half-life: 4.1 hours versus 2.8 hours for dalteparin 2
• Enoxaparin has slower clearance: apparent total body clearance is 13.8-16.7 ml/min for enoxaparin compared to 33.3 ml/min for dalteparin (p < 0.001) 2
• Enoxaparin has greater renal excretion: 6.4-8.7% of the dose is recovered in urine versus only 3.4% for dalteparin 2

FDA-Approved Indications

Enoxaparin (Clexane/Lovenox)

• Approved for BOTH prophylaxis AND immediate treatment of VTE 1
• Approved for acute coronary syndromes 1
• Broader FDA approval makes it more versatile in clinical practice 1

Dalteparin (Fragmin)

• Approved for VTE prophylaxis 1
• Approved for extended treatment of symptomatic VTE specifically in patients with cancer (the only LMWH with this indication) 1
• NOT FDA-approved for immediate VTE treatment in non-cancer patients, though used off-label based on clinical trial data 1

Critical Differences in Renal Insufficiency

Enoxaparin Requires Dose Adjustment

• For severe renal insufficiency (CrCl <30 mL/min): FDA-approved dose reduction to 30 mg subcutaneously once daily for prophylaxis and 1 mg/kg subcutaneously every 24 hours for treatment 1
• Enoxaparin accumulation increases bleeding risk 2- to 3-fold in severe renal impairment when standard doses are used 1
• Renal clearance is reduced by 31% with moderate impairment and 44% with severe impairment 1

Dalteparin May Be Safer in Renal Dysfunction

• Dalteparin appears to be cleared by non-saturable mechanisms, making it less affected by renal impairment 3
• Mean anti-Xa activity remains similar between patients with severe renal impairment and those with normal renal function 1, 4
• No specific FDA dose adjustment recommendations exist for dalteparin in renal insufficiency 1
• This makes dalteparin potentially preferable when renal function is compromised 1, 3

Dosing Regimens

Standard Prophylactic Dosing

• Enoxaparin: 40 mg subcutaneously once daily 5, 6
• Dalteparin: 5,000 units subcutaneously once daily 5, 7
• Both provide equivalent efficacy for DVT prophylaxis in general surgical and medical patients 1, 5

Treatment Dosing

• Enoxaparin: 1 mg/kg subcutaneously every 12 hours OR 1.5 mg/kg once daily 1
• Dalteparin: 200 units/kg subcutaneously once daily initially, then reduced to 150 units/kg daily after 1 month for extended therapy 1

Clinical Efficacy Comparisons

Equivalence in Most Populations

• Direct comparison studies show no significant difference in VTE prevention or treatment efficacy between dalteparin and enoxaparin in trauma patients (DVT: 3.2% vs 3.3%, p=1.00; PE: 1.8% vs 1.2%, p=0.74) 8
• Both are equally effective compared to unfractionated heparin for DVT prophylaxis 1, 7
• No difference in major bleeding rates between the two agents 3, 8

Cancer Patients: Dalteparin Has Strongest Evidence

• Dalteparin is the ONLY LMWH with FDA approval for extended VTE treatment in cancer patients 1
• The CLOT trial demonstrated dalteparin superiority over warfarin (recurrent VTE: 8.0% vs 15.8%; HR 0.48, p=0.002) with 12-month safety data 1
• Enoxaparin evidence in cancer is limited to smaller studies 1
• For cancer-associated VTE, dalteparin receives Category 1 recommendation 1

Acute Coronary Syndromes: Enoxaparin Superior

• Enoxaparin demonstrated superiority over unfractionated heparin in the ESSENCE trial (primary endpoint reduced from 19.6% to 16.6% at 14 days; OR 0.80, CI 0.67-0.98) 1
• Dalteparin showed benefit over placebo in FRISC but no significant difference versus unfractionated heparin in FRIC 1
• Enoxaparin is preferred for acute coronary syndromes based on stronger evidence 1

Practical Clinical Considerations

Cost Differences

• Switching from enoxaparin to dalteparin resulted in $107,778 annual cost savings in one trauma center with 277 patients 8
• Dalteparin may offer significant institutional cost advantages without compromising efficacy 8

Monitoring Requirements

• Neither agent requires routine laboratory monitoring in most patients 1
• Both facilitate outpatient treatment due to predictable dose-response 1, 7
• Anti-Xa monitoring may be considered in extreme body weights or renal impairment 9

Neuraxial Anesthesia Timing

• For dalteparin prophylactic doses: wait minimum 12 hours after last dose before neuraxial procedure; may restart 4 hours after catheter removal 4
• Enoxaparin has similar timing requirements, though specific guidelines vary 4

Common Pitfalls to Avoid

• DO NOT assume LMWHs are interchangeable—they have different molecular weights, half-lives, FDA indications, and renal handling 1
• DO NOT use standard enoxaparin doses in severe renal insufficiency (CrCl <30 mL/min) without dose reduction—this dramatically increases bleeding risk 1, 5
• DO NOT use dalteparin in elderly patients (≥70 years) with renal insufficiency due to potentially increased mortality risk 9
• DO NOT substitute one LMWH for another without verifying FDA approval for the specific indication 1
• DO NOT administer either agent intravenously—subcutaneous administration is the only appropriate route 5

Algorithm for Selecting Between Dalteparin and Enoxaparin

For VTE prophylaxis in general medical/surgical patients:

• Either agent is appropriate; choose based on cost and institutional preference 1, 5, 8

For severe renal insufficiency (CrCl <30 mL/min):

• Prefer dalteparin (no dose adjustment needed) OR dose-reduced enoxaparin (30 mg daily) OR switch to unfractionated heparin 1, 5

For cancer-associated VTE treatment:

• Prefer dalteparin (Category 1 recommendation, FDA-approved, strongest evidence) 1

For acute coronary syndromes:

• Prefer enoxaparin (superior evidence versus unfractionated heparin) 1

For immediate VTE treatment in non-cancer patients:

• Prefer enoxaparin (FDA-approved for this indication) 1

For obese patients (BMI >40 kg/m²) or very low weight (<50 kg):

• Consider weight-based dosing; limited data exist for both agents 1, 4