Direct Thrombin Inhibitor (Parenterally Administered Anticoagulant) Pregnancy: There are no adequate data in pregnant women and animal studies are insufficient with respect to reproductive toxicity. The increased bleeding risk may constitute a risk in pregnancy, and the product contains ethanol (a 70 kg patient on the maximum recommended daily dose of 10 microgram/kg/min would receive approximately 4 g ethanol per day). Use during pregnancy only if treatment is clearly necessary. Lactation: it is unknown whether argatroban or its metabolites are excreted in human milk, and animal studies show radioactivity reaching higher levels in milk than in maternal blood — decide whether to discontinue breast-feeding or to discontinue/abstain from therapy.

Argatroban Monohydrate

Brand names: Exembol, Novastan

Argatroban monohydrate is the hydrated salt form of the intravenous direct thrombin inhibitor argatroban, used for anticoagulation in patients with heparin-induced thrombocytopenia requiring a non-heparin parenteral anticoagulant.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 2 microgram/kg/min by continuous intravenous infusion — initial dosage in adult patients without hepatic impairment in heparin-induced thrombocytopenia (HIT) type II

Route: Continuous intravenous infusion (Exembol 1 mg/ml ready-to-use solution for infusion, 50 mg/50 ml); recommended for use with a syringe driver to control the rate of administration

Frequency: Continuous infusion, titrated against the aPTT

Max: Maximum recommended dose 10 microgram/kg/min. Maximum recommended duration of treatment 14 days, although there is limited clinical experience of administration for longer periods.

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 SPC states that no recommendation on a posology can be made. PCI: the SPC section covering HIT type II patients undergoing percutaneous coronary intervention was TRUNCATED in the fetched bundle and no US label was fetched for this id — the PCI regimen is NOT recorded here and the clinician must read section 4.2 of the SPC in full. NAMING: this id is the monohydrate salt name; the fetched SPC (Exembol) expresses dosing as argatroban — confirm salt/base equivalence is not an issue for this product.

Dose adjustments

Renal

The standard initial adult dosage recommendations apply to patients with renal impairment. Limited data are available in haemodialysis: therapy could be initiated with an initial bolus of 250 microgram/kg followed by a continuous infusion of 2 microgram/kg/min, with the infusion stopped 1 hour before the end of the procedure and a target ACT range of 170-230 seconds (measured using the Haemotec device); no bolus dose is required in patients already being treated. Clearance by high-flux membranes during haemodialysis and continuous venovenous haemofiltration was clinically insignificant.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Uncontrolled bleeding
Hypersensitivity to argatroban or to any of the excipients
Severe hepatic impairment

Side effects

Bleeding complications are the main adverse events — in HIT type II trials major bleeds occurred in 31/568 (5.5%) and minor bleeds in 221/568 (38.9%); major bleeding was almost three times more frequent when the aPTT exceeded 3 times baseline
Anaemia; also coagulopathy, thrombocytopenia and leukopenia
Nausea (and vomiting, constipation, diarrhoea, gastrointestinal haemorrhage, melaena)
Purpura, rash and increased sweating
Infection including urinary tract infection
Abnormal hepatic function, hyperbilirubinaemia, and raised AST, ALT, alkaline phosphatase and LDH

Interactions

Section 4.5 of the SPC was truncated in the fetched bundle — the entries below come from SPC section 4.4 and should be verified against SPC section 4.5
Heparin and other parenteral anticoagulants — all parenteral anticoagulants should be discontinued before administration; when starting after heparin, allow about 1-2 hours for heparin's effect on the aPTT to decrease
Oral anticoagulants — concomitant use may prolong the PT (INR) beyond that produced by oral anticoagulants alone; see SPC section 4.2 for alternative approaches to monitoring concurrent therapy

Clinical monograph

How it works

It reversibly inhibits the active site of both free and clot-bound thrombin, blocking fibrin generation, thrombin-mediated platelet aggregation and clotting-factor activation without needing antithrombin.

Prescribing in practice

Because it is hepatically cleared, dose reduction is essential in hepatic impairment, and as there is no reversal agent, bleeding risk is managed by careful infusion titration.
It elevates the INR, so conversion to an oral vitamin K antagonist follows a defined overlap protocol to prevent a gap in anticoagulation.
Infusion rate is titrated against the APTT to a defined therapeutic target.

Monitoring

Use APTT to titrate the infusion, alongside platelet count, haemoglobin and clinical surveillance for bleeding, with dose moderation in liver disease.

Counselling the patient

It is a continuous anticoagulant infusion managed in hospital.
Tell staff promptly about any signs of bleeding or new bruising.
Regular clotting tests guide adjustments to the infusion.

Evidence & guidelines

Direct thrombin inhibition with argatroban is supported by UK haematology guidance for the treatment of heparin-induced thrombocytopenia.

Reference: BSH Guidelines on diagnosis and management of HIT (2012 updated 2019); BCSH argatroban guidelines; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

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