Clinical Experience with Argatroban: DISCUSSION part 2
Argatroban has been studied in renal dysfunction; however, the effect of renal insufficiency on dosing remains unclear. Guzzi and others reviewed the effect of renal function on argatroban therapy in 260 patients with no hepatic impairment. Their classification consisted of normal or mild impairment of renal function (ClCr > 60 mL/min; n = 144), moderate impairment (CrCl 30-60 mL/min; n = 80), and severe impairment (CrCl < 30 mL/min; n = 36). Among these 3 groups, there were no significant differences in argatroban dose during therapy (mean 1.9 ± 1.1 Hg/kg per minute), duration of therapy (7 ± 6 days), aPTT (63 ± 17 s), or incidence of major bleeding. 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 Hg/kg per minute.
Several reports, each describing a small number of patients, have reported the use of argatroban in patients requiring renal replacement therapy Dialytic clearance of argatroban with high-flux membranes has been suggested to be clinically insignificant, with systemic clearance increased by about 20%. Many authors have reported using doses less than 0.5 Hg/kg per minute to achieve aPTT of 40-80 s, but some of the patients were critically ill, with acute changes in liver function or recent cardiovascular surgery, or they may have had volume overload, with subsequent hepatic congestion. These conflicting reports create confusion for clinicians who are attempting to initiate argatroban in patients with renal impairment. In the study reported here, renal dysfunction (including hemodialysis) did not appear to affect dosage, as the mean dose used during therapy was 2.01 Hg/kg per minute.
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This study was limited by its retrospective design, the small sample size, and potential confounding factors. One of the most important limitations of a chart review is incomplete or inaccurate documentation of pertinent information. For example, the adjustments to argatroban dose were based on the patient’s weight as entered by the nurse into the Guardian intravenous pump (Baxter Canada); however, this value may have been slightly different from the weight used at the time argatroban was initiated (i.e., the weight may have been rounded up or down or the patient’s weight may have changed in the interim). This discrepancy may explain the slight variation between adjustments reported in patients’ charts and those specified in the argatroban nomogram used by the former Calgary Health Region.
Conclusions
The results of this retrospective analysis, in conjunction with the literature, suggest that 2 Hg/kg per minute is an appropriate argatroban dose for patients without hepatic impairment or congestion. In acute and chronic hepatic dysfunction, a dose of 0.5 Hg/kg per minute is acceptable. A review of the evidence suggests that critically ill patients and patients with acute cardiac disease may be started on a lower dose (0.5-1 Hg/kg per minute), depending on the clinical scenario. In this study, there were no patients with renal impairment who required a reduction in dose, although evidence from other studies suggests that dose reductions may be needed. Clinical judgement plays a vital role in determining the initial dosing of argatroban. Depending on the aPTT result, an adjustment of 0.5 to 1 Hg/kg per minute is appropriate for most patients. For patients with reduced drug clearance, an adjustment of 0.1 or 0.2 Hg/kg per minute may be more appropriate. Viagra Soft Tabs
