Argatroban anticoagulation in renal dysfunction: a literature analysis.
OBJECTIVE
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 microg/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 approximately 0.1-0.6 microg/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.


CONCLUSIONS
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 Science Consulting, Austin, Tex 78746, USA. mhursting@sprintmail.com
Marcie J
MJ
Hursting
Patrick T
PT
Murray
D000925:Anticoagulants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives; D015897:Comorbidity; D006801:Humans; D010875:Pipecolic Acids / Q000008:administration & dosage*; D015995:Prevalence; D051437:Renal Insufficiency / Q000150:complications* / Q000453:epidemiology*; D013449:Sulfonamides; D013927:Thrombosis / Q000453:epidemiology* / Q000517:prevention & control*; D016896:Treatment Outcome
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban