Argatroban monitoring

Hepaticaiiy impaired patients For patients with moderate hepatic impairment, an initial dose of 0.5 mcg/kg/min is recommended, based on the approximate 4-fold decrease in argatroban clearance relative to those with normal hepatic function. Monitor the aPTT closely and adjust the dosage as clinically indicated. 

The concomitant use of argatroban and warfarin results in prolongation of the PT and INR beyond that produced by warfarin alone. Alternative approaches for monitoring concurrent argatroban and warfarin therapy are described in Administration and Dosage. 

Argatroban is a small molecule thrombin inhibitor that is FDA-approved for use in patients with HIT with or without thrombosis and coronary angioplasty in patients with HIT. It, too, has a short half-life, is given by continuous intravenous infusion, and is monitored by aPTT. Its clearance is not affected by renal disease but is dependent on liver function dose reduction is required in patients with liver disease. Patients on argatroban will demonstrate elevated INRs, rendering the transition to warfarin difficult (ie, the INR will reflect contributions from both warfarin and argatroban). (INR is discussed in detail in the discussion of warfarin administration.) A nomogram is supplied by the manufacturer to assist in this transition. 

Anticoagulation with argatroban is easily controlled with minimal inter-patient differences, but monitoring is recommended for safety use. aPTT and ACT are correlated predictably with doses up to 40 jjig/kg/min infusion. This therefore allows the flexible use of aPTT and/or ACT depending on the clinical setting (45). 

Ahmad S, Ahsan A, Iqbal O, et al. Pharmacokinetics and pharmacodynamics of argatroban as studied by HPLC and functional methods implications in the monitoring and dosage-optimizations in cardiovascular patients. Clin Appl Thromb Hemost 1998 4 243-249. 

Argatroban is a synthetic arginine derivative that is a competitive inhibitor of the action of thrombin on fibrinogen. It is given parenterally and monitored by the APTT test. It has a short half-life, It is nonantigenic, It is approved for use in HIT and has undergone trials for PCI in some patients Gable I) (24). 

Iqbal O, Ahmad S, Lewis BE, et al. Monitoring of argatroban in ARG310 study potential recommendations for its use in... 

Argatroban has been approved in the USA and Canada for the prophylaxis and treatment of thrombosis in patients with heparin-induced thrombocytopenia, and in Japan and Korea for various thrombotic disorders. Its effects can be monitored using the activated partial thromboplastin time for low doses and the activated clotting time for high doses. Its pharmacology, clinical pharmacology, and uses have been reviewed (7-14). 

Argatroban 2 mcg/kg/min continuous IV infusion Obtain baseline PT and aPTT monitor aPTT 2 hours after initiation, and adjust dose to achieve therapeutic aPTT Reduce initial dose to 0.5 mcg/kg/min for those with hepatic impairment. Will cause significant elevation in PT/INR concurrent warfarin therapy requires special management. 

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