Argatroban

BEFORE STARTING: discontinue heparin therapy and obtain a baseline aPTT; allow about 1-2 hours after stopping heparin for its effect on the aPTT to decrease. All parenteral anticoagulants should be discontinued before administration. MONITORING: target steady-state aPTT is 1.5-3.0 times the initial baseline value but not exceeding 100 seconds; steady state is typically reached within 1-3 hours. Check the aPTT two hours after starting the infusion, then at least once per day. DOSE MODIFICATION (from the 2 microgram/kg/min standard start): if aPTT is less than 1.5 times baseline, increase by 0.5 microgram/kg/min and recheck at 2 hours; if 1.5-3.0 times baseline (not exceeding 100 s), no change, recheck at 2 hours and then at least once daily after two consecutive in-range results; if greater than 3.0 times baseline or greater than 100 s, stop the infusion until the aPTT is 1.5-3.0 times baseline (typically within 2 hours) then resume at half the previous infusion rate and recheck at 2 hours. For patients started at 0.5 microgram/kg/min the corresponding increment is 0.1 microgram/kg/min with rechecks at 4 hours. REDUCED STARTING RATE OF 0.5 microgram/kg/min: moderate hepatic impairment (Child-Pugh Class B); HIT type II after cardiac surgery; and critically ill / ICU patients with (multiple) organ system failure — maximum 10 microgram/kg/min, adjusted to the target aPTT range, with a further reduced maintenance dose recommended in severe multiple organ failure and increased monitoring frequency. ELDERLY: the standard adult initial dosage recommendations apply. STANDARD INFUSION RATES at 1 mg/ml for 2 microgram/kg/min — 50 kg: 6 ml/hr; 60 kg: 7; 70 kg: 8; 80 kg: 10; 90 kg: 11; 100 kg: 12; 110 kg: 13; 120 kg: 14; 130 kg: 16; 140 kg: 17 ml/hr. For 0.5 microgram/kg/min the corresponding rates are 1.5, 1.8, 2.1, 2.4, 2.7, 3.0, 3.3, 3.6, 3.9 and 4.2 ml/hr. EXCIPIENTS: contains ethanol (at the maximum daily dose of 10 microgram/kg/min a 70 kg adult is exposed to 57.6 mg/kg ethanol, raising blood alcohol by about 9.6 mg/100 ml), sorbitol (avoid in hereditary fructose intolerance) and 177 mg sodium per 50 ml vial. There is no specific antidote. PAEDIATRIC: limited data from a prospective study in 18 children (neonates to 16 years old) — the safe and effective dose and the effective target aPTT or ACT range have not been clearly established, and the UK SPC states that no recommendation on a posology can be made. PCI: the UK SPC section covering HIT type II patients undergoing percutaneous coronary intervention was TRUNCATED in the fetched bundle. For reference only, the US argatroban prescribing information (openFDA, NOT UK labelling) states for PCI: initiate an infusion at 25 mcg/kg/min with a bolus of 350 mcg/kg via a large-bore intravenous line over 3 to 5 minutes, check the ACT 5 to 10 minutes after the bolus and proceed if the ACT is greater than 300 seconds; if the ACT is less than 300 seconds give a further 150 mcg/kg bolus and increase the infusion to 30 mcg/kg/min; if the ACT is greater than 450 seconds reduce the infusion to 15 mcg/kg/min; target ACT 300-450 seconds; additional 150 mcg/kg boluses with an infusion increase to 40 mcg/kg/min may be used for dissection, impending abrupt closure or thrombus formation. Verify against the UK SPC before use.