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Preparation for IV administrationArgatroban, as supplied, is a concentrated drug (100 mg/mL), which must be diluted 100-fold prior to infusion.[2] Argatroban should not be mixed with other drugs prior to dilution in a suitable intravenous fluid.Argatroban should be diluted in 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer's Injection, to a final concentration of 1 mg/mL, using 250 mg (2.5 mL) per 250 mL of diluent or 500 mg (5 mL) per 500 mL of diluent.[2] The constituted solution must be mixed by repeated inversion of the diluent bag for 1 minute. Upon preparation, the solution may show slight but brief haziness due to the formation of microprecipitates that rapidly dissolve upon mixing. The pH of the intravenous solution prepared as recommended is 3.2 to 7.5.[2] Dosing for heparin-induced thrombocytopenia (HIT/HITTS)Initial dosage: Before administering Argatroban, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial dose of Argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion. See Table 1 for standard infusion rates, Table 2 for a dosing checklist, and Figure 1 for summary of recommended dosing.Table 1. Recommended Doses and Infusion Rates for 2 mcg/kg/min Dose of Argatroban for Patients With HIT/HITTS (Without Hepatic Impairment) (1 mg/mL Final Concentration)
Table 2. Dosing Checklist for Argatroban
Table 3. Recommended Doses and Infusion Rates of Argatroban for Patients Undergoing PCI (Without Hepatic Impairment) (1 mg/mL Final Concentration)
Figure 1. Recommended Dosing for Argatroban[2]
Monitoring and adjusting Argatroban for heparin-induced thrombocytopenia (HIT/HITTS)In general, therapy with Argatroban is monitored using the aPTT. Steady-state anticoagulant effects (including the aPTT) typically occur within 1 to 3 hours following initiation of Argatroban. Dose adjustment may be required to attain the target aPTT. Check the aPTT 2 hours after initiation of therapy to confirm the patient has attained the desired therapeutic range.[2]Dosing for HIT patients undergoing PCIPCI in HIT/HITTS patients:Initial dosage: An infusion of Argatroban should be started at 25 mcg/kg/min and a bolus of 350 mcg/kg administered via a large-bore IV line over 3 to 5 minutes (see Table 3). ACT should be checked 5 to 10 minutes after the bolus dose is completed. The procedure may proceed if the ACT is greater than 300 seconds. See Table 3 for dosing recommendations and infusion rates. Dosage adjustment: If the ACT is less than 300 seconds, an additional IV bolus dose of 150 mcg/kg should be administered, the infusion dose increased to 30 mcg/kg/min, and the ACT checked 5 to 10 minutes later (see Table 3). Once a therapeutic ACT (between 300 and 450 seconds) has been achieved, this infusion dose should be continued for the duration of the procedure. In case of dissection, impending abrupt closure, thrombus formation during the procedure, or inability to achieve or maintain an ACT over 300 seconds, additional bolus doses of 150 mcg/kg may be administered and the infusion dose increased to 40 mcg/kg/min. The ACT should be checked after each additional bolus or change in the rate of infusion. Monitoring therapy for HIT patients undergoing PCI: Therapy with Argatroban is monitored using ACT. ACTs should be obtained before dosing, 5 to 10 minutes after bolus dosing and after change in the infusion rate, as well as at the end of the PCI procedure. Additional ACTs should be drawn about every 20 to 30 minutes during a prolonged procedure. Continued anticoagulation after PCI: If a patient requires anticoagulation after the procedure, Argatroban may be continued, but at a lower infusion dose [see Dosage and administration, Dosing for heparin-induced thrombocytopenia (HIT/HITTS)]. If the patient has HIT or HITTS, therapy with Argatroban should be continued until platelet counts have recovered substantially (i.e., 100,000/mcL or to pre-HIT/HITTS baseline value). Dosing in special populations — hepatic impairment: For patients with HIT with hepatic impairment, the initial dose of Argatroban should be reduced. Reversal of anticoagulant effect may take longer in patients with hepatic impairment. 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 clearance of Argatroban relative to those with normal hepatic function. The aPTT should be monitored closely, and the dosage should be adjusted as clinically indicated (see Precautions and Special populations: hepatic impairment). Hepatic impairment in HIT/HITTS patients undergoing PCI: Use of high doses of Argatroban in PCI patients with clinically significant hepatic disease or AST/ALT levels greater than 3 times the upper level of normal should be avoided. Such patients were not studied in PCI trials. Renal impairment: No dosage adjustment is necessary in patients with renal impairment (see Precautions and Special populations: renal impairment). |
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