What is the dosage and administration of Fragmin (dalteparin) for preventing and treating deep vein thrombosis?

Fragmin (Dalteparin) Dosage and Administration

VTE Prophylaxis in Surgical Patients

For cancer patients undergoing major abdominal surgery, dalteparin 5000 IU subcutaneously once daily is the recommended dose, started 12-2 hours preoperatively and continued for at least 7-10 days postoperatively. 1

Standard Prophylactic Dosing

• High-risk abdominal surgery (including cancer): Dalteparin 5000 IU subcutaneously once daily for 5-10 days 2
• Lower-risk abdominal surgery: Dalteparin 2500 IU subcutaneously once daily 2
• Hip replacement surgery: Dalteparin 5000 IU once daily, with first dose either 12 hours before surgery or 4 hours after surgery, continued for 4-8 days 2

Evidence for Dose Selection

• In cancer patients undergoing major abdominal surgery, dalteparin 5000 IU once daily was significantly more effective than 2500 IU once daily, reducing postoperative VTE from 15.1% to 9.3% (p=0.001), with no significant difference in bleeding complications (4.6% vs 3.6%) 1, 2
• Dalteparin 5000 IU once daily showed comparable benefit-to-risk ratio to fondaparinux 2.5 mg in high-risk abdominal surgery patients 1

Extended Duration Prophylaxis

For cancer patients undergoing major abdominopelvic surgery, extend prophylaxis to 28 days postoperatively rather than stopping at 7-10 days. 1

• Extended prophylaxis (28 days vs 7 days) reduced VTE from 16.3% to 7.3% in cancer patients undergoing major abdominal surgery 1
• The absolute risk reduction is modest (approximately 1% symptomatic VTE), requiring treatment of 91 patients to prevent one event 1

VTE Prophylaxis in Medical Patients

For acutely ill medical patients with severely restricted mobility, dalteparin 5000 IU subcutaneously once daily for 14 days is recommended. 2

• Eligible patients include those with congestive heart failure (NYHA Class III or IV), acute respiratory failure, acute infection, or acute rheumatic disorders requiring bed rest 2
• Dalteparin significantly reduced thromboembolic reactions through Day 21 compared to placebo, with sustained effect through Day 90 2

Treatment of Established DVT

For treatment of acute deep vein thrombosis, dalteparin 200 IU/kg subcutaneously once daily is the recommended therapeutic dose. 3, 4

Therapeutic Dosing Regimen

• Standard treatment dose: 200 IU anti-Xa/kg subcutaneously once daily 3, 4
• Alternative regimen: 100 IU/kg twice daily (though once-daily dosing is preferred for convenience) 5, 6
• Continue until oral anticoagulation achieves therapeutic INR (2-3) on two consecutive days 3

Evidence for Treatment Efficacy

• Once-daily dalteparin 200 IU/kg showed equivalent efficacy to continuous intravenous unfractionated heparin for initial DVT treatment, with similar improvements in Marder score and no major bleeding events 3
• Treatment can be initiated immediately upon clinical suspicion of DVT without waiting for phlebographic confirmation 3

Special Population Considerations

Renal Impairment

Dalteparin should be avoided or used with extreme caution in patients with severe renal impairment (creatinine clearance <30 mL/min) due to risk of drug accumulation and life-threatening hemorrhage. 7

• Unlike unfractionated heparin, dalteparin is primarily cleared renally and can accumulate dangerously in renal failure 7
• If dalteparin must be used in severe renal impairment, close monitoring of anti-factor Xa activity is mandatory 7
• Consider switching to unfractionated heparin in patients with significant renal dysfunction, as UFH monitoring is better established and dosage adjustments are more rapid 7

Cancer Patients Requiring Extended Treatment

For cancer-associated VTE, dalteparin is the only FDA-approved LMWH for extended therapy and should be continued for at least 6 months, or indefinitely while cancer remains active. 1

• Dalteparin 200 IU/kg once daily for the first month, then consider dose reduction to 150 IU/kg for months 2-6 1
• This is the only LMWH with specific FDA approval for extended cancer-associated VTE treatment 1

Administration Timing Considerations

Surgical Prophylaxis Timing

• Preoperative dosing: Administer 12-2 hours before surgery 1
• Postoperative dosing: If starting after surgery, administer 4 hours postoperatively 2
• Both timing strategies show equivalent efficacy 2

Chronopharmacological Considerations

• Evening administration (8 PM) produces higher APTT, thrombin time, and tissue factor pathway inhibitor levels compared to morning administration (8 AM), though anti-Xa activity remains similar 4
• This suggests potential optimization of clinical efficacy with evening dosing for once-daily therapeutic regimens 4

Monitoring Requirements

Routine laboratory monitoring is not required for prophylactic doses of dalteparin, unlike unfractionated heparin. 5, 6

• Dalteparin has predictable dose-response and does not alter standard coagulation tests at prophylactic doses 6
• Anti-factor Xa monitoring is only necessary in patients with severe renal impairment or extreme body weights 7
• Platelet count monitoring for heparin-induced thrombocytopenia follows standard protocols 5

Common Pitfalls and Caveats

• Underdosing in cancer surgery: Using 2500 IU instead of 5000 IU in high-risk cancer patients results in significantly higher VTE rates (14.9% vs 8.5%) 1, 2
• Premature discontinuation: Stopping prophylaxis at hospital discharge rather than continuing for 7-10 days (or 28 days in cancer patients) misses the peak VTE risk period 1
• Renal failure oversight: Failing to assess renal function before initiating dalteparin can lead to life-threatening hemorrhage due to drug accumulation 7
• Inadequate duration in medical patients: Stopping prophylaxis before 14 days in acutely ill medical patients may not provide sustained protection through the high-risk period 2