From the Guidelines
Argatroban should be dosed at 2 mcg/kg per minute by continuous intravenous infusion, adjusted to maintain the activated partial thromboplastin time at 1.5 to 3 times baseline (but not >100 s). This dosing recommendation is based on the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, which suggests that argatroban, a direct thrombin inhibitor, is indicated for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia, including those undergoing PCI 1. Some key points to consider when dosing argatroban include:
- Steady state plasma concentrations are achieved in 1 to 3 hours after intravenous administration
- Argatroban can be used in patients with renal insufficiency due to its hepatic metabolism
- The dose should be adjusted based on activated partial thromboplastin time (aPTT) measurements, aiming for an aPTT of 1.5-3 times the baseline value, not exceeding 100 seconds
- aPTT should be checked 2 hours after initiation and after any dose adjustment, with dose adjustments made as needed to achieve the target aPTT. It is also important to note that argatroban works by directly inhibiting thrombin, preventing fibrin formation and platelet aggregation, making it valuable for patients who cannot receive heparin due to heparin-induced thrombocytopenia, as stated in the 2014 guideline 1.
From the FDA Drug Label
2 DOSAGE & ADMINISTRATION
Each 125 mL glass vial contains 125 mg of argatroban (1mg/mL); and, as supplied, is ready for intravenous infusion. 2. 1 Dosing in Patients With Heparin-Induced Thrombocytopenia 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 2. 2 Dosing in Patients Undergoing Percutaneous Coronary Interventions Initial Dosage: Initiate an infusion of Argatroban Injection at 25 mcg/kg/min and administer a bolus of 350 mcg/kg via a large bore intravenous line over 3 to 5 minutes
The recommended initial dose of Argatroban for adult patients without hepatic impairment is:
- 2 mcg/kg/min for patients with heparin-induced thrombocytopenia, administered as a continuous infusion.
- 25 mcg/kg/min with a bolus of 350 mcg/kg for patients undergoing percutaneous coronary interventions. 2
From the Research
Argatroban Dosing
- The US FDA-recommended argatroban dose in heparin-induced thrombocytopenia (HIT) is 2 microg/kg/min, reduced in patients with hepatic impairment and in pediatric patients, adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline (not >100 seconds) 3.
- Contemporary experiences indicate that reduced doses are also needed in patients with conditions associated with hepatic hypoperfusion, e.g. heart failure, yet are unnecessary for renal dysfunction, adult age, sex, race/ethnicity or obesity 3.
- Argatroban 0.5-1.2 microg/kg/min typically supports therapeutic aPTTs 3.
- The FDA-recommended dose during percutaneous coronary intervention (PCI) is 25 microg/kg/min (350 microg/kg initial bolus), adjusted to achieve activated clotting times (ACTs) of 300-450 sec 3.
Special Populations
- For patients with hepatic impairment, the initial dose is 0.5 microg/kg/min 4, 5.
- For patients with renal impairment, current dosing recommendations are adequate, and no initial dose adjustment is needed 4, 6.
- For patients undergoing renal replacement therapy, argatroban provides effective anticoagulation with an acceptably low bleeding risk, and current dosing recommendations are adequate 4.
Monitoring
- Argatroban anticoagulation is monitored using activated partial thromboplastin time (aPTT) values, with a target range of 1.5-3.0 times baseline 3, 5.
- Most aPTT reagents are similarly sensitive to argatroban, and reagent choice is unlikely to significantly affect argatroban monitoring in patients with heparin-induced thrombocytopenia 7.