Use of Newer Anticoagulants in Patients With Chronic Kidney Disease

Bob L. Lobo

Disclosures

Am J Health Syst Pharm. 2007;64(19):2017-2026. 

In This Article

VTE Prophylaxis and Treatment

Newer anticoagulants with labeling approved by the Food and Drug Administration (FDA) for VTE prophylaxis, treatment, or both include the low-molecular-weight heparins (LMWHs) and the factor Xa inhibitor fondaparinux (Arixtra, GlaxoSmithKline).[1,19,20] Three LMWHs are currently available for VTE prophylaxis, treatment, or both: enoxaparin (Lovenox, Sanofi-Aventis), dalteparin (Fragmin, Pfizer), and tinzaparin (Innohep, Pharmion).[21,22,23] These agents may be subcutaneously administered without monitoring the activated partial thromboplastin time (aPTT) and may be used instead of unfractionated heparin for most clinical indications.[24,25]

Fondaparinux is currently the only factor Xa inhibitor commercially available in the United States.[20] A synthetic pentasaccharide with a high affinity for antithrombin, fondaparinux acts by accelerating selective inhibition of factor Xa, thereby inhibiting thrombin generation.[1] Fondaparinux is administered subcutaneously and has FDA-approved labeling for both the prophylaxis and treatment of VTE. In clinical trials, fondaparinux has been shown to be at least as effective as LMWHs for the prevention and treatment of VTE.[19] Another factor Xa inhibitor, idraparinux, is under investigation for the prevention and treatment of VTE.[20,26] Both fondaparinux and idraparinux are eliminated primarily by renal clearance, but because idraparinux has a longer half-life (80 hours) than does fondaparinux 17-21 hours), it may be less suitable for use in patients with renal impairment.[20,26]

Direct thrombin inhibitors (DTIs) are another class of anticoagulants that have been investigated for the prevention and treatment of VTE.[20,26] Desirudin (Iprivask, Aventis Pharmaceuticals), administered subcutaneously, is currently the only DTI with labeling approved by FDA for the prevention of VTE in patients undergoing total hip replacement, but it is not commercially available in the United States.[20,27] Lepirudin (Refludan, Bayer HealthCare Pharmaceuticals), another DTI, is structurally similar to desirudin but is administered intravenously, with FDA-approved labeling for the prevention of further thromboembolic complications in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease.[1,28] Argatroban, a small-molecule DTI, is administered intravenously and has FDA-approved indications for the prophylaxis or treatment of thrombosis in patients with HIT.[29]

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