Thursday June 1, 2006
Argatroban Therapy in Hepatic Dysfunction
Argatroban is a second line anti-coagulation as well as remained one of the drug of choice in patients affected with Heparin-induced thrombocytopenia (HIT). Argatroban improve outcomes in patients with HIT, by reducing new thrombosis 1 . Also reported its safety with no increase risk of bleeding 2 .
Argatroban is primarily metabolized in the liver and its dosing need to be adjusted in hepatic dysfunction. Dr. Levine and coll. from Texas has reported in this month of chest after retrospectively analysing data of 82 argatroban patients and 34 historical control therapy patients with hepatic impairments (all HIT patients) 5. Their results concluded following points:
1. In hepatic impairment 0.5 µg/kg/min is a reasonable, conservative initial dosage of argatroban.
2. serum bilirubin level appears to be a better indicator than ALT or AST of argatroban dosing requirements and argatroban should be initiated at a dose of 0.5 µg/kg/min if a patient’s serum total bilirubin level is 1.5 mg/dL.
3. Conservatic dose should be the starting point if combined hepatic/renal dysfunction is present.
4. As steady-state anticoagulation will be delayed in many patients with hepatic dysfunction, check the aPTT atleast 4 to 5 h after drug initiation or dose change.
5. Argatroban should be stopped for a more extended period in hepatic dysfuntion if an invasive procedure is planned.
Related: Sample Argatroban Protocol For HIT (from The George Washington University Hospital )
References: click to get abstract/article
1. Argatroban Anticoagulation in Patients With Heparin-Induced Thrombocytopenia - Arch Intern Med. 2003;163:1849-1856
2. Argatroban Anticoagulant Therapy in Patients With Heparin-Induced Thrombocytopenia - Circulation. 2001;103:1838
3. The Pharmacokinetics and Pharmacodynamics of Argatroban: Effects of Age, Gender, and Hepatic or Renal Dysfunction - Pharmacotherapy 2000;20,318-329
4. Argatroban Dosing in Patients with Heparin-Induced Thrombocytopenia The Annals of Pharmacotherapy: Vol. 37, No. 7, pp. 970-975.
5. Argatroban Therapy in Heparin-Induced Thrombocytopenia With Hepatic Dysfunction Chest. 2006;129:1167-1175