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Dalteparin (Fragmin ® ). Akash Bhakta B.S. Biological Sciences University of California, Irvine Trauma Research Associates Program January 2011. Classification/Clinical Uses. Classifications: Anticoagulant – Low Molecular Weight Heparin Clinical Uses
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Dalteparin (Fragmin®) Akash Bhakta B.S. Biological Sciences University of California, Irvine Trauma Research Associates Program January 2011
Classification/Clinical Uses Classifications: Anticoagulant – Low Molecular Weight Heparin Clinical Uses Prophylaxis of deep vein thrombosis in patients undergoing abdominal surgery Prophylaxis of deep vein thrombosis in patients undergoing hip replacement surgery Prophylaxis of deep vein thrombosis in critically ill patients. Prophylaxis of ischemic complications from unstable angina and non-Q wave myocardial infarction Treatment of venous thromboembolism in cancer patients to prevent reoccurrence
Pharmacodynamics/Mechanism of Action Dalteparin and other Low Molecular Weight Heparins bind to factor X and Antithrombin promoting antithrombin’s activity at blocking key reactions in the clotting cascade
Dosing For Adults: 5000 int. units for adults with high risk of DVT Special Populations: Renal Insufficiency: Monitor anti-Xa levels to determine appropriate dose Obesity: Monitor anti-Xa levels to determine appropriate dose
Pharmacokinetics Delivery: Subcutaneous Time to Peak: 2-4 hrs Bioavailability: 87% Half-life: 3-5 hours Elimination: Renal Reference (red) group refers to ICU patients without edema. Note: dosage in this study was 2500 IU dalteparin
Blood Thinning Agents Antiplatelet drugs Anticoagulant drugs Cox Inhibitor Vitamin K Inhibitors Aspirin Warfarin (Coumadin) Adenosine diphosphate inhibitor Acenocoumarol Clopidogrel (Plavix) Phenprocoumon Prasugrel Phenindione Ticlopidine Heparin Phosphodiesterase inhibitor Heparin Cilostazol Low Molecular Weight Heparins Glycoprotein inhibitor Ardeparin Abciximab Certoparin Eptifibatide Enoxaparin (Lovenox) Tirofiban Dalteparin (Fragmin) Adenosine reuptake inhibitors Tinzaparin Dipyridamole Nadroparin
Follow up question If LMWH’s are more effective and safer in preventing DVT’s compared to coumadin, why is coumadin still commonly prescribed in both inpatient and outpatient settings?
Future Drugs -Factor Xa inhibitors Fondaparinux and Idraparinux -Chemically related to LMWH. -Idraparinux has shown to have a significantly long half-life possibly needing the dosage only once a week.
Future Drugs -Direct Thrombin Inhibitors Pradaxa -Oral medication -Same efficacy as LMWH and Coumadin in surgery patients
Future Drugs -Direct Factor Xa Inhibitor Rivaroxaban (Xarelto) - Oral Medication - Found to be more effective than enoxaparin in preventing VTE in knee and hip replacement patients
References • Clinical Pharmacist: Dalteparin • Coagulation Cascade (Image). Coagulation. Wikipedia.org • Connolly S.J., Ezekowitz M.D., et al. “Dabigatran Versus Warfarin in Patients with Atrial Fibrilation.” N Engl J Med, 2009, 261(12):1139-51 • Eriksson B.I., Dahl, O.E., et al. “Oral Dabigatran Etexilate Versus Subcutaneous Enoxaprin for Prevention of Venous Thromboembolism after Total Knee Replacement: The RE-MODEL Randomized Trial”. J Throm Haemost, 2007 5(11):2178-2185 • Eriksson, B. I., Bauer, K. A., et al. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N. Engl J Med. 2001, 345(18):1298-1304 • Geerts WH, Jay RM, Code KI, et al. A comparison of low-does heparin with • low-molecular-weight heparin as prophylaxis against venous thromboembolism • after major trauma. N Engl J Med. 1996;335:701–707. • Hull, R., Raskob, G., et al., A Comparison of Subcutaneous Low-Molecular-Weight Heparin with Warfarin Sodium for Prophylaxis against Deep-Vein Thrombosis after Hip or Knee Implantation. N Engl J Med 1993; 329:1370-1376
References • Lexi-Complete: Dalteparin Sodium • Lexi-Complete: Warfarin • Lexi-Complete: Heparin • Lexi-Complete: Clopidogrel • Lexi-Complete: Aspirin • Ray, Sarah. “Rivaroxaban: the next oral anticoagulant?” www.pharmacist.com • Ray, Sarah. “Promising data for rivaroxaban, apixaban from ASH” www.pharmacist.com • Rommers, M. K., Van Der Lely, N., et al. Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study. Critical Care 2006, 10:R93 • Samana, M. M., Gerotziafas, G. T., Comparative Pharmacokinetics of LMWH’s. Semin Thromb Hemost 2000; 26(1): 031-038