Reversal of Argatroban

Argatroban has a gentle dose-response relationship that offers a wide margin of safety during dose titration (Fig. 3). However, as with any anticoagulant, bleeding is a major safety concern. Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing argatroban or decreasing its infusion dose. Anticoagulant parameters generally return to baseline within 2-4 h after discontinuation of argatroban (Swan et al., 2000; Swan and Hursting, 2000). This reversal takes longer (at least 6 h and up to more than 20 h) in patients with hepatic impairment.

Argatroban has no specific antidote. If life-threatening bleeding occurs and excessive plasma argatroban levels are suspected, argatroban should be discontinued immediately, and the patient should be provided symptomatic and supportive

Plasma Argatroban (ng/mL)

Plasma Argatroban (ng/mL)

Infusion dose (^g/kg/min)

FIGURE 3 Relationship at steady state between argatroban dose, plasma argatroban concentration, and anticoagulant effect (aPTT). Mean (SEM) steady-state plasma argatroban concentrations and aPTT values are for healthy subjects (n = 9) administered iv argatroban at doses between 1.25 and 10 mg/kg/min. Abbreviation: aPTT, activated partial thromboplastin time. Source: Data from Swan et al., 2000.

Infusion dose (^g/kg/min)

FIGURE 3 Relationship at steady state between argatroban dose, plasma argatroban concentration, and anticoagulant effect (aPTT). Mean (SEM) steady-state plasma argatroban concentrations and aPTT values are for healthy subjects (n = 9) administered iv argatroban at doses between 1.25 and 10 mg/kg/min. Abbreviation: aPTT, activated partial thromboplastin time. Source: Data from Swan et al., 2000.

therapy. Clearance of argatroban by high-flux dialysis membranes is clinically insignificant (de Denus and Spinler 2003; Dager and White, 2003; Murray et al., 2004; Tang et al., 2005). Recombinant factor VIIa has been used to treat argatroban-treated patients with severe bleeding (Malherbe et al., 2004; Alsoufi et al., 2004), although this approach remains to be rigorously evaluated. Fresh frozen plasma has been used successfully following accidental overdose (Yee and Kuter, 2006).

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