Info

Abbreviations: aPTT, activated partial thromboplastin time; iv, intravenous.

Abbreviations: aPTT, activated partial thromboplastin time; iv, intravenous.

APPENDIX 8. DOSING SCHEDULES FOR ARGATROBAN TREATMENT OF PATIENTS WITH HIT (APPROVED INDICATIONS)

Clinical use

Bolusa

IV infusiona

Monitoring and adjusting therapy

Prophylaxis or treatment of thrombosisb,c

Percutaneous coronary intervention

350 mg/kg (given over 3-5 min)

2 mg/kg/min (For hepatically impaired patients, reduce initial dose.d Patients with renal insufficiency require no initial dosage adjustment.)

25 mg/kg/min

Dose adjusted (not to exceed 10 mg/kg/min) to achieve steady state aPTT 1.5-3.0 times the baseline value (not to exceed 100 s)e,f,g

Infusion dose adjusted (15-40 mg/kg/min) to achieve an ACT 300-450 s; additional bolus doses of 150 mg/kg may be given as neededj,k

Note: See chapter 15 for references cited below. aBased on patient's body weight.

bIncludes patients with active HIT who have isolated thrombocytopenia or associated thrombosis, as well as patients with a documented history of HIT who are no longer thrombocytopenic but require anticoagulation. c Argatroban is approved in the United States as an anticoagulant for prophylaxis or treatment of thrombosis in patients with HIT, and is also available for use in Austria, Canada, Denmark, Iceland, Germany, Netherlands, Norway, and Sweden as an anticoagulant in HIT.

dFor patients with moderate hepatic impairment, an initial dose of 0.5 mg/kg/min is recommended. A conservative, reduced initial dose may also be prudent for patients with heart failure, multiple organ system failure, severe anasarca, or postcardiac surgery, that is, conditions associated with increased hepatic congestion or fluid overload, and possibly decreased argatroban clearance (de Denus and Spinler, 2003; Reichert et al., 2003; Baghdasarian et al., 2004; Levine et al., 2006; Czyz et al., 2006; Koster et al., 2006). eThe aPTT should be checked at least 2 h after the initiation of argatroban or any dosage change. fFor patients in studies ARG-911 and ARG-915, the mean ±SEM dose of argatroban was 1.9 ±0.1 mg/kg/min. gFor transferring a patient to warfarin anticoagulant therapy: After substantial resolution of thrombocytopenia, initiate warfarin therapy using the expected daily dose of warfarin (do not use a loading dose) while maintaining argatroban infusion. At least 5 days of warfarin therapy are required to lower functional prothrombin concentrations to a therapeutic, steady state level. For monitoring the conversion to warfarin during coadministration of argatroban at doses up to 2 mg/kg/min, see text and Fig. 15.6.

hArgatroban is approved in the U.S. as an anticoagulant in patients with or at risk for HIT undergoing PCI. Argatroban has not been evaluated in hepatically impaired patients undergoing PCI. These recommendations do not consider the combination use of argatroban with glycoprotein IIb/IIIa antagonists, wherein lower doses of argatroban (e.g., 250-300 mg/kg bolus followed by infusion of 15 mg/kg/min) have been shown to provide effective anticoagulation with an acceptable bleeding risk (Jang et al., 2004).

Includes percutaneous transluminal coronary angioplasty (balloon angioplasty), stent implantation, and atherectomy; oral aspirin 325 mg should be given 2-24 h prior to PCI.

'The ACT should be checked 5-10 min following the initial bolus dose and after any additional bolus dose or change in the infusion rate. In studies ARG-216, ARG-310, and ARG-311, the majority of patients required only one bolus dose during the interventional procedure, and the mean ± SEM dose of argatroban was 23.1 ± 0.7 mg/kg/min.

kAfter the procedure, the sheaths should be removed no sooner than 2 h after discontinuing argatroban and when the ACT is <160 s.

Abbreviations: ACT, activated clotting time; aPTT, activated partial thromboplastin time; HIT, heparin-induced thrombocytopenia; iv, intravenous; PCI, percutaneous coronary intervention.

0 0

Post a comment