Cardinal Health

Preventing Venous Thromboembolism: A Healthcare Professional Guide to Intervention 18 Examples heparin sodium/ DBL™ enoxaparin/ Clexane™, dalteparin/ Fragmin™. fondaparinux/ Arixtra™ rivaroxaban/ Xarelto™ dabigatran etexilate/ Pradaxa™ apixabnan/ Eliquis(R) Warfarin Coumadin™ Marevan™ Origin Porcine or bovine origin Porcine origin No animal- source components No animal- source components No animal- source components No animal- source components No animal- source components Absorption Binds with plasma, platelet & endothelial proteins Variable dose effect response and decreased bioavailability Rapidly taken up by endothelial cells with remainder bound to plasma proteins 100% absorbed from subcutaneous injections. Binds with single factor giving a predictable response Rapidly absorbed via the gut Stomach and Small Intestine Throughout GI tract Complete absorption in the GI tract Bioavailability Approximately 15% > 85% Approximately 100% 80-100% 65% 50% Nearly 100% Plasma half-life 1-2 hrs 4-6 hrs 17 hrs 5-9 hrs 7-9 hrs 12 hrs 5-7 days 11-13hrs (elderly) 12-14hrs (elderly) Primary Mechanism(s) of action Larger UFH molecules Bind with antithrombin which in turn inhibits thrombin (factor IIa) and factor Xa Primary anticoagulant activity is inhibition of factor Xa Binds with antithrombin which inactivates factor Xa, this leads to inhibition of thrombin (factor IIa) and clot formation Highly selective factor Xa inhibitor with oral bioavailability Inhibition of thrombin (factor IIa) Highly selective factor Xa inhibitor Interferes with vitamin K metabolism in the liver, preventing synthesis of clotting factors II, VII, IX and X as well as protein C and protein S Smaller heparin molecules - Inactivate factor Xa Inactivates thrombin (factor IIa) to lesser extent than UFH Therapeutic Effect Peak action 2-6hrs after subcutaneous injection Maximum anti-Factor Xa and anti- thrombin (anti-Factor IIa) activities occur 3-5hrs after post dose Immediate onset of action; Within 30 min. Maximum inhibition of factor Xa in 2-4hrs Within 30mins. Maximum inhibition of thrombin 0.5-2hrs post dose 3-4 hours 36 to 72hrs Peak plasma concentration 3hrs post dose Antidote/ Reversal Agents Protamine Sulfate Up to 60% with Protamine Sulfate Recombinant activated factor VIIa may have some reversal effect None Praxbind ® (idarucizumab) Rapid, specific reversal agent None Vitamin K or fresh frozen plasma. Prothrombin complex concentrate Monitoring May monitor No routine monitoring usually required No routine monitoring No routine monitoring No routine monitoring No routine monitoring No routine monitoring Prothrombin time (goal to maintain International Normalised Ratio (INR) between 2- 2.5 FBC platelet counts, stool occult blood tests and for symptoms of bleeding. aPTT (indirect measurement) if necessary anti-Xa assays May monitor anti-Factor Xa concentration in patients with renal dysfunction May use prothrombin time or chromogenic anti-factor Xa assay May use ecarin clotting time or aPTT (less sensitive) if required Metabolism Elimination Metabolised mainly in the liver Metabolised by liver Majority of dose is eliminated unchanged in urine with normal renal function 2/3 metabolised in liver 20% excreted via biliary system, 80% excreted by kidneys unchanged Multiple routes Metabolised by liver Renal clearance Renal excretion 1/3 eliminated unchanged Renal excretion VTE Prevention. Pharmaceutical. The differences between these agents? 32-38