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Reuters Health Information (2006-06-09): Reduced dose argatroban safe, effective with liver dysfunction


Reduced dose argatroban safe, effective with liver dysfunction

Last Updated: 2006-06-09 12:40:09 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Results of a study support the current recommendation for reduced argatroban dosing in the setting of hepatic impairment.

"Argatroban was safe and effective for the treatment of heparin-induced thrombocytopenia in patients with liver disease," Dr. Robert L. Levine from the University of Texas School of Medicine at Houston, who led the study, told Reuters Health. "This has never been shown before."

Argatroban is a direct thrombin inhibitor primarily metabolized in the liver and eliminated in the feces through biliary excretion. In patients without hepatic impairment, the initial recommended dose of argatroban is 2 �g/kg/min.

Dr. Levine and colleagues report in the May issue of Chest that they retrospectively studied the impact of hepatic and hepatic/renal dysfunction on argatroban dosing and anticoagulation responses in 82 patients with heparin-induced thrombocytopenia and compared their clinical outcomes with those of 34 historical controls with hepatic impairment who did not receive direct thrombin inhibitor therapy.

As expected, hepatic dysfunction affected argatroban dosing.

"Dosing of argatroban should start at 0.5 ug/kg/min in this group and then be titrated up or down as needed to maintain the PTT in the therapeutic range (1.5-3x control), as previously recommended," Dr. Levine told Reuters Health. "This is a conservative starting point and will work for most patients."

"In patients with liver disease, especially elevated bilirubin (>1.5 mg/dL), combined with renal dysfunction (creatinine >1.3), this is still a good starting place, but these patients, and patients with multi-system failure, may require very low doses of argatroban," he added.

Chest 2006;129:1167-1175.

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