Argatroban Anticoagulation in Renal Dysfunction: A Literature Analysis

Abstract

Background/Aims: Argatroban, a hepatically metabolized direct thrombin inhibitor, is approved for use in heparin-induced thrombocytopenia (HIT; several countries) and in antithrombin-deficient patients undergoing hemodialysis (Japan). This literature analysis aimed to determine the effects of renal function on argatroban pharmacokinetics, pharmacodynamics, and its therapeutic dose in HIT and to evaluate argatroban dosing and safety during renal replacement therapy (RRT) and in adults with renal dysfunction undergoing surgical or invasive procedures. Methods: A literature search identified 34 publications (12 prospective studies, 4 retrospective studies, 18 anecdotal reports) that together described 644 argatroban-treated patients (446 with HIT, 82 with antithrombin deficiency) with varying degrees of renal function. Pertinent data were extracted and summarized. Results: In pharmacokinetic studies (40 patients, overall), renal dysfunction exerted little or no clinically significant effects on argatroban pharmacokinetic parameters. For argatroban therapy in HIT, evidence existed that an initial 2 µg/kg/min dose was sometimes excessive; patients with hepatic dysfunction, irrespective of renal function, required reduced initial doses; lesser doses were required in combined hepatic and renal dysfunction than hepatic dysfunction, and for each 30 ml/min decrease in patient creatinine clearance, the therapeutic dose decreased ∼0.1–0.6 µg/kg/min. Argatroban was well tolerated and enabled RRT with little or no thrombotic or hemorrhagic complications. Experiences with argatroban in renally impaired patients undergoing procedures besides RRT were limited. Conclusion: Current literature suggests that argatroban is well tolerated and provides adequate anticoagulation in patients with renal dysfunction or failure, including individuals with HIT or antithrombin deficiency where anticoagulant options are limited.

Clinical Experience with Argatroban for Heparin-Induced Thrombocytopenia in a Large Teaching Hospital

“…A recent review of argatroban in 644 patients with differing degrees of renal function noted that for each 30 mL/min decrease in CrCl, the therapeutic dose decreased by about 0.1 to 0.6 µg/kg per minute. 34 Several reports, each describing a small number of patients, have reported the use of argatroban in patients requiring renal replacement therapy. [16][17][18][19]21,26,31,[35][36][37][38][39][40][41][42] Dialytic clearance of argatroban with high-flux membranes has been suggested to be clinically insignificant, with systemic clearance increased by about 20%.…”

Management of Heparin-Induced Thrombocytopenia in Uremic Patients with Hemodialysis

“…The empirical dose of the drug is estimated to 0.7μg/kg/min in patients with a normal liver function and 0.2μg/kg/min in those with hepatic dysfunction or a risk of bleeding. Future studies should be done on how to apply the drug on non-session days (Hursting & Murray et al, 2008).…”

Venous Thromboembolism in Neonates, Children and Patients with Chronic Renal Disease – Special Considerations

“…In patients with renal failure it has been suggest lower dosing requirements with dose reduction of approximately 0.1 to 0.6 μg/kg/min for each 30 ml/min decrease in the creatinine clearance. (Hursting, 2008;Arpino, 2004) …”