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Senior Medical Information Specialist, GlaxoSmithKline, Philadelphia, PA
Director, Clinical Science Consulting, Potomac, MD
Reprints: Marcie J Hursting PhD, Clinical Science Consulting, 11329 Berger Terrace, Potomac, MD 20854-2017, FAX 301/765-8175, E-mail mhursting{at}sprintmail.com
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 µg/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) µg/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 µg/kg/min
(5–95th percentile, 0.1–2.0 µg/kg/min). Fifty-two (17%)
patients required no dosage adjustment. Incremental adjustments decreased with
decreasing current dose (e.g., median 0.25 µg/kg/min from doses of
0.26–0.75 µg/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 µg/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 µg/kg/min are reasonable for most patients. Smaller adjustments (e.g., 0.25 µg/kg/min) should be used when modifying lower doses, such as those recommended for use in hepatically impaired patients.
Key Words: argatroban, dosage adjustment, heparin-induced thrombocytopenia
Published Online, May 21, 2003. www.theannals.com, DOI 10.1345/aph.1C443
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