Anticoagulant · Direct thrombin inhibitor

Argatroban

Reviewed by Alex G, BSN, RN, CEN, CCRN, CMC, NREMT-P · From the Reference tab of the app

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Indications

Prevention or treatment of thrombosis in suspected or confirmed HIT
PCI in patients with or at risk of HIT
HIT with kidney failure or CRRT, since the kidneys play no part in its clearance
Circuit anticoagulation for CRRT or ECMO when heparin cannot be used (off-label)

Dosing

Argatroban drip card and mL/h converterStart: 2 mcg/kg/min; 0.5 mcg/kg/min with moderate or severe liver impairment (label); 0.5–1.2 with heart failure, multiorgan failure or after cardiac surgery (ACCP 2012)

Mechanism of action

Argatroban is a small synthetic direct thrombin inhibitor built on L-arginine. It binds reversibly to thrombin's catalytic site (Ki about 40 nM), its guanidino group sitting in the arginine-specific S1 pocket, and needs no antithrombin, so it inhibits free and clot-bound thrombin alike. That blocks fibrin formation, activation of factors V, VIII, XIII and protein C, and thrombin-induced platelet aggregation. It spares trypsin, Xa, plasmin and kallikrein and is not recognized by HIT antibodies.

Pharmacology

Hematologic: dose-dependent rise in aPTT, ACT, PT/INR and thrombin time, reaching steady state in 1–3 h
Hematologic: raises the INR more than other thrombin inhibitors, so warfarin overlap follows special INR rules
Hepatic: clearance falls in liver dysfunction and with congestion or low flow (heart failure, shock, after cardiac surgery), so these patients start lower

Pharmacokinetics

Onset	Immediate IV; check the aPTT 2 h after each change
Duration	aPTT back to baseline 2–4 h after stopping; longer in liver failure
Half-life	39–51 min; about 3 h (181 min) in hepatic impairment
Distribution	Vd 174 mL/kg, mainly extracellular fluid
Protein binding	54% (34% α1-acid glycoprotein, 20% albumin)
Metabolism	Liver: CYP3A4/5 hydroxylation and aromatization of the tetrahydroquinoline ring; the main metabolite is 3–5 times weaker
Clearance	5.1 mL/kg/min; 1.9 in hepatic impairment, where the label starts at a quarter of the usual rate
Elimination	Feces via bile about 65%, urine about 22% (16% unchanged); no kidney adjustment
Dialysis	About 20% removed in 4 h of hemodialysis, too little to change dosing

Chemistry

Synthetic L-arginine derivative carrying a 3-methyl-tetrahydroquinoline sulfonyl group and a 4-methylpiperidine carboxylic acid; MW 508.6 (526.7 as the monohydrate)
Three chiral centers are fixed; the fourth, C-21 on the tetrahydroquinoline, is a 65:35 R:S mixture given as is
Zwitterion at pH 7.4 (protonated guanidino group, ionized carboxyl), modestly lipophilic (XLogP 1.3); limited water solubility explains the propylene glycol and ethanol vehicle and the brief haze on dilution
The 250 mg/2.5 mL concentrate is diluted 100-fold to 1 mg/mL in NS, D5W or LR; ready-to-use 1 mg/mL also exists. Diluted drug keeps 24 h at room temperature, 96 h protected from light

Adverse effects and cautions

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Sources

FDA label: Argatroban, Fresenius Kabi (2025)
PubChem: argatroban
Garcia, ACCP Parenteral Anticoagulants (Chest 2012)

For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.