Argatroban

Arelix Arenavirus h6-Arene A-Rest Arfonad Argand diagram Argatroban [74863-84-6] Argemomne [6901-16-2] Argentite... 

Argatroban [74863-84-6] ((2R,4R)-4-methyl-l-[A/ -)(3 methyl l,2,3,4-tetrahydto-8-quiaoIiaesulfonyl)-L-atgiayl]-2-piperidiaecatboxyhc acid monohydrate) is a potent inhibitor of thrombin formation and activity (49). This agent has been studied in vitro and ia a few animal models. Its toxicity and activity ia humans ate unknown. 

Two small molecule DTIs are argatroban (Novastan, MW 527 Da) and the oral thrombin inhibitor, ximelagatran (Exanta, MW 474 Da) Ximelagatran is an inactive pro-drug after absorption, it is metabolized to the active DTI, melagatran [MW 430 Da]. Concerns regarding hepatotoxicity have prevented (xi)melagatran... 

Figure 24.4 The decision-analytic model shows the three strategies that were examined by Arnold and researchers [22] to evaluate the financial implications of the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset), compared with delayed treatment, of heparin-induced thrombocytopenia (HIT) with or without thrombosis.

Arnold R, Kim R, Zhou Y, Tang B. Budgetary impact of heparin-induced thrombocytopenia with thrombosis and treatment with the direct thrombin inhibitor Argatroban (P401E). ASHP 39th Midyear Clinical Meeting. Orlando, FL, 2004. 

Arnold R, Kim R, Tang B. The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia the effect of early versus delayed treatment. Cardiol Rev 2005 14 7-13. 

The argatroban package insert advises overlapping with warfarin aiming for an INR >4. Once achieved, check package insert for direction... 

Synthetic heterocyclic and modified amino acid derivatives have been grouped in a class of thrombin inhibitors called peptidomimetics. An example of such a compound is argatroban, with a molecular mass of 532 Da. It blocks thrombin s active catalytic site by binding to the adjacent apolar binding site. This selective reversible inhibitor of thrombin has a K of 19 nM and blocks thrombin s role in coagulation and fibrinolysis (62). 

Direct thrombin inhibitors such as hirudin, Hirulog, the peptide aldehyde efegatran, and peptidomimetic compound argatroban have undergone clinical trials. Their application in the prevention and treatment of deep vein thrombosis contin-... 

Amprenavir, indinavir, nelfinavir, ritonavir, saquinavir Allopurinol Argatroban Aspirin Amoxicilhn Captopril, enalapril... 

Argatroban has two indications (1) prevention or treatment of thrombosis in patients with HIT and (2) as an anticoagulant in patients with HIT, or at risk of HIT, who are undergoing PCI. The recommended dose for the treatment of HIT is 2 mcg/kg/min by continuous IV infusion. The first aPTT should be obtained 2 hours after initiation. The dose can be adjusted as clinically indicated (maximum 10 mcg/kg/min) until the aPTT is 1.5 to 3 times control. 

Argatroban, as supplied, is a concentrated drug (100 mg/mL) that must be diluted 100-fold prior to infusion. Do not mix with other drugs prior to dilution. 

Initial dosage in HIT or heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) Before administering argatroban, discontinue heparin therapy and obtain a baseline activated partial thromboplastin time (aPTT). The recommended initial dose of argatroban for adults without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion (see table). 

Standard Infusion Rates for 2 mcg/kg/min Dose of Argatroban (1 mg/mL Final Concentration) ... 

Recommended Doses and Infusion Rates of Argatroban for Patients Und<... 

Continued anticoaguiation after PCi - If a patient requires anticoagulation after the procedure, argatroban may be continued at a lower infusion dose. 

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. 

Coadministration of warfarin and argatroban at doses up to 2 mcg/kg/min -Use of argatroban with warfarin results in prolongation of INR beyond that produced by warfarin alone. The relationship between INR obtained on combined therapy and INR obtained on warfarin alone is dependent on the dose of argatroban and the thromboplastin reagent used. The INR value on warfarin alone (INRy, ) can be calculated from the INR value on combination... 

---