argatroban monohydrate: clinical use

Prescribing considerations

• Initiate under a clinician experienced in coagulation disorders.
• Assess baseline bleeding risk, hepatic function, platelet count and coagulation status.
• Use particular caution after lumbar puncture, spinal anaesthesia or major surgery, and with severe hypertension, diabetic retinopathy, bleeding disorders or gastrointestinal ulceration.
• Argatroban prolongs PT/INR as well as aPTT; account for this during conversion to coumarin anticoagulation.
• Paediatric efficacy and safety are not established.

Contraindications and cautions

• Uncontrolled bleeding
• Hypersensitivity to argatroban or any excipient
• Severe hepatic impairment
• Hereditary fructose intolerance because the selected formulation contains sorbitol

Monitoring

• Activated partial thromboplastin time and clinical anticoagulant response
• Signs of overt or occult bleeding, including unexplained hypotension or falling haematocrit
• Platelet count and thrombotic complications related to HIT
• Hepatic function
• PT/INR interpretation during concurrent coumarin anticoagulation

Clinical pharmacology

Argatroban is a synthetic, reversible direct inhibitor of free and clot-associated thrombin. It acts independently of antithrombin, is principally cleared through hepatic and biliary pathways, and no specific antidote is available.

Formulation and product differences

• The selected product is a multidose concentrate that must be diluted before intravenous infusion.
• It contains ethanol and sorbitol; these excipients are clinically relevant in pregnancy, hepatic impairment and hereditary fructose intolerance.
• Use only the compatible infusion fluids specified in the SmPC and do not mix with other medicines.
• Discard solutions that remain cloudy or contain insoluble precipitate after correct mixing.

Solution for infusion

Route: Intravenous

Strengths: 1 mg/mL