Use of Newer Anticoagulants in Patients With Chronic Kidney Disease

Bob L. Lobo


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

In This Article

Drug Dosing Considerations in Renal Failure

Drug dosing in patients with CKD may require that adjustments be made to the usual loading or maintenance dose of a drug.[15] Although most drugs can and should be given at their normal loading dose to patients with CKD, the initial dose of some drugs (e.g., lepirudin) must be reduced. Once therapy has been initiated, drug dosages may then need to be adjusted in patients with CKD by expanding the dosing interval, reducing the dose, or using both measures. These general strategies for dosage adjustment have been incorporated into current manufacturer recommendations for the use of newer anticoagulants in patients with severe renal impairment ( Table 2 ).

It is important to recognize that patients with CKD have an increased risk of bleeding independent of treatment with anticoagulation therapy.[16] The uremic state itself is associated with an increased tendency toward bleeding. Causes of uremic bleeding appear to be multifactorial and are incompletely understood. However, platelet abnormalities and alterations in platelet-vessel wall interactions are thought to be primary mechanisms involved in its pathogenesis.

Estimated GFR is the primary measure used in current strategies for dosage adjustment of newer anticoagulants in patients with CKD. However, other factors may also play an important role in establishing an appropriate dosing regimen for these patients.[15,17] Both renal and nonrenal processes may contribute to the reduced drug clearance observed in patients with CKD.[18] Drug elimination by the kidneys may be altered due to changes in renal tubular secretion and reabsorption and to changes in GFR.[15] Protein binding is also often altered in the uremic state, which may affect the volume of distribution of many drugs.[17] The kidneys are estimated to have nearly 15% of the metabolic function of the liver.[15] Altered renal and hepatic metabolism occurs during the uremic state. The potential for drug-drug interactions may also be increased by the frequent existence of comorbidities and the tendency for polypharmacy in this subpopulation.[15] Thus, strategies for adjusting the dosages of newer anticoagulants that solely use formulas that estimate GFR should be considered only the first step for drug dosing in patients with CKD.


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