Argatroban dosing in patients with heparin-induced thrombocytopenia.
OBJECTIVE
To retrospectively evaluate clinical experiences with argatroban dosing, particularly incremental dosage adjustments, during a clinical trial of argatroban anticoagulation in heparin-induced thrombocytopenia (HIT).


METHODS
Records of 304 patients with HIT administered argatroban during a prospective study were reviewed to determine each dose, incremental dosage adjustment, and duration of therapy. Dosing information (stratified by patient initial dose) and incremental adjustments (overall, and stratified by dose from which adjustment occurred) were summarized. The relationship between median incremental adjustments and adverse outcomes, including bleeding, was investigated.


RESULTS
Two hundred seventy-one (89%) patients received initial doses of 1.9-2.1 micro g/kg/min (group B). Twenty-six (9%) patients were started at a lower dose. Group B's median (5-95th percentile) final dose was 1.6 (0.25-4.0) micro g/kg/min. During a median of 6 days of argatroban therapy, patients underwent a median of 3.0 dosage adjustments using a median and mode incremental adjustment of 0.5 micro g/kg/min (5-95th percentile, 0.1-2.0 micro g/kg/min). Fifty-two (17%) patients required no dosage adjustment. Incremental adjustments decreased with decreasing current dose (e.g., median 0.25 micro g/kg/min from doses of 0.26-0.75 micro g/kg/min). Outcomes were similar between patients with no adjustment or with median incremental adjustments of </=0.4, 0.41-0.75, or >0.75 micro g/kg/min.


CONCLUSIONS
Based on this clinical experience, together with the established linear pharmacokinetics and pharmacodynamics of argatroban, appropriate dosage increments may be proposed for argatroban-treated patients with HIT. Incremental adjustments of 0.5 micro g/kg/min are reasonable for most patients. Smaller adjustments (e.g., 0.25 micro g/kg/min) should be used when modifying lower doses, such as those recommended for use in hepatically impaired patients.
Verme-Gibboney
Catherine N
CN
GlaxoSmithKline, Philadelphia, PA, USA.
Hursting
Marcie J
MJ
D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007262:Infusions, Intravenous; D010875:Pipecolic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D012189:Retrospective Studies; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control; D016896:Treatment Outcome
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; D013917:Thrombin; C031942:argatroban