Clinical experience with prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment or renal failure requiring renal replacement therapy

Ann Pharmacother. 2015 Mar;49(3):270-7. doi: 10.1177/1060028014563325. Epub 2014 Dec 16.

Abstract

Background: Fondaparinux has an increased bleeding risk in patients with a CrCl ≤ 50 mL/min and is contraindicated if CrCl < 30 mL/min. Data regarding dosing and anti-Xa monitoring are lacking in this population.

Objective: To describe dosing, monitoring, and safety outcomes of prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment, including renal replacement therapy (RRT).

Methods: Retrospective analysis from October 2006 to November 2012 of patients ≥ 18 years old who received fondaparinux for ≥ 72 hours with ≥ 1 dose in an intensive care unit and a CrCl ≤ 50 mL/min or RRT during therapy. Participants were divided into 4 cohorts: moderate impairment (CrCl = 30-50 mL/min), severe impairment (CrCl < 30 mL/min), hemodialysis (HD), or continuous venovenous hemofiltration (CVVH). Outcomes included the incidence of clinically significant bleeding and thromboembolic events. Fondaparinux dose, dosing frequency, and anti-Xa level monitoring are described. Pharmacokinetic modeling was performed to assess drug accumulation.

Results: In all, 95 patients met inclusion criteria: 64 (67.4%) with moderate impairment, 10 (10.5%) with severe impairment, 5 (5.3%) with HD, and 16 (16.8%) with CVVH. The median defined daily doses in the moderate, severe, HD, and CVVH cohorts were 2.5, 2.5, 0.9, and 1.9 mg. Anti-Xa monitoring occurred in 19 (20%) patients, although few concentrations were peaks. Clinically significant bleeding occurred in 4 (4.2%) patients. A pharmacokinetic model demonstrated drug accumulation.

Conclusions: Empirical dose adjustments may be prudent in critically ill patients with renal dysfunction; however, the optimal fondaparinux dosage in this population remains unknown. Peak anti-Xa concentrations may help guide therapy.

Keywords: anti-Xa monitoring; dialysis; fondaparinux; heparin-induced thrombocytopenia; major bleeding; renal impairment.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Chemoprevention
  • Critical Illness / therapy*
  • Female
  • Fondaparinux
  • Hemofiltration
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Heparin, Low-Molecular-Weight / blood
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Polysaccharides / therapeutic use*
  • Renal Dialysis
  • Renal Insufficiency / blood
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / epidemiology
  • Renal Insufficiency / surgery*
  • Renal Replacement Therapy*
  • Retrospective Studies
  • Severity of Illness Index
  • Young Adult

Substances

  • Anticoagulants
  • Heparin, Low-Molecular-Weight
  • Polysaccharides
  • Fondaparinux