Dosing of Enoxaparin in Renal Impairment.

OBJECTIVE: To review enoxaparin treatment dosing, pharmacokinetics, and clinical outcomes data in patients with renal impairment and to examine the current two-tiered dosing regimen approved by the Food and Drug Administration (FDA).

DATA SOURCES: A literature search of PubMed (1990-2016) was performed using the search terms low-molecular-weight heparin, unfractionated heparin, bleeding, enoxaparin, renal impairment, pharmacokinetics, and hemodialysis.

STUDY SELECTION AND DATA EXTRACTION: All studies assessing the pharmacokinetic properties of enoxaparin in patients with renal impairment were evaluated. In addition, all retrospective and prospective studies assessing the safety and efficacy of enoxaparin treatment in this population were evaluated.

DATA SYNTHESIS: Five pharmacokinetic studies evaluated changes in the pharmacokinetics of enoxaparin in patients with renal impairment. In these studies, enoxaparin clearance was reduced by 17% to 44% in patients with mild and moderate renal impairment. Six retrospective studies evaluated the safety of enoxaparin in patients with renal impairment. In one study, patients with moderate renal impairment were at increased risk of bleeding when using the current FDA-approved two-tiered scheme (odds ratio, 4.7; 95% confidence interval, 1.7-13.0; P = 0.002). Another study demonstrated that individualized enoxaparin dosing, when compared to FDA-approved dosing, resulted in a decreased risk of bleeding. Two retrospective studies evaluated efficacy. One of these studies compared reduced-dose enoxaparin with unfractionated heparin; there was a trend toward lower incidences of thromboembolism and 30-day mortality with reduced-dose enoxaparin. Hospital length of stay also decreased with reduced-dosed enoxaparin.

CONCLUSIONS: This paper highlights the differences in the pharmacokinetic properties and safety and efficacy outcomes in multiple degrees of renal impairment when using treatment-dose enoxaparin. Given the literature highlighted in this review, a more multitiered enoxaparin renal dosing strategy-perhaps shifting from the current two-tier approach to at least three or four tiers-should be considered.