Lepirudin

Lepirudin is a recombinant form of hirudin, a natural peptide anticoagulant produced by the medicinal leech. It is a direct thrombin inhibitor that binds with high affinity to thrombin, blocking the conversion of fibrinogen to fibrin and inhibiting thrombin-mediated platelet activation. Lepirudin inhibits both circulating and clot-bound thrombin and functions independently of antithrombin or heparin cofactors.

Indications for lepirudin include anticoagulation in patients with heparin-induced thrombocytopenia (HIT) when heparin cannot be used, and during certain procedures that require anticoagulation in HIT patients, such as some cardiovascular interventions.

Administration and dosing are via intravenous infusion; there is no oral formulation. Dosing is adjusted for renal function, since lepirudin is predominantly cleared by the kidneys.

Pharmacokinetics and monitoring: lepirudin is mainly excreted renally, with a half-life longer in individuals with renal impairment. Anticoagulant effects are monitored during use with tests such as activated partial thromboplastin time (aPTT) or activated clotting time (ACT) to guide dosing.

Safety and reversibility: the principal adverse effect is bleeding, which risk rises with higher doses and reduced renal function. Hypersensitivity reactions, including rare anaphylaxis, have been reported due to antibody formation. There is no specific reversal agent for lepirudin; management of overdose or significant bleeding involves stopping the infusion and providing supportive care, with clearance dependent on renal function.

Status: lepirudin is marketed in some regions under the brand name Refludan. It has largely been supplanted by other direct thrombin inhibitors, such as argatroban and bivalirudin, in many clinical settings.