Lepirudin (
Refludan), Berlex Laboratories, USA and Canada; Pharmion, all other countries), a recombinant derivative of the naturally occurring leech
anticoagulant hirudin, was the first
direct thrombin inhibitor to be approved by the European Agency for the Evaluation of Medicinal Products and the US Food and Drug Administration for the treatment of
heparin-induced
thrombocytopenia. Since its introduction into Europe and the USA, it has been studied in over 7000 patients requiring anticoagulation in conditions including
acute coronary syndromes,
percutaneous coronary intervention,
cardiopulmonary bypass and
heparin-induced
thrombocytopenia. Three European clinical trials, designated
Heparin-Associated
Thrombocytopenia (HAT)-1, -2 and -3, demonstrated the efficacy and safety of
lepirudin in the prevention and treatment of
thrombosis in patients with antibody-confirmed
heparin-induced
thrombocytopenia. A postmarketing, observational study, termed the
Drug-Monitoring Program, evaluated
lepirudin in over 1000 patients with
heparin-induced
thrombocytopenia in the setting of routine clinical practice. In the
Drug-Monitoring Program, adverse events were substantially reduced compared with clinical trials, while clinical efficacy was maintained; suggesting that insight gained through clinical experience was translated into improved safety. Here,
pharmacotherapy using
lepirudin is reviewed, with particular reference to clinical studies in
heparin-induced
thrombocytopenia, and some recommendations based on this extensive clinical experience with
lepirudin are provided. Although only approved for the treatment of
heparin-induced
thrombocytopenia, the use of
lepirudin in
acute coronary syndromes,
percutaneous coronary intervention,
vascular surgery and
coronary artery bypass grafting is also discussed. The review concludes with a discussion of pharmacokinetic and clinical data supporting the potential for subcutaneous administration of
lepirudin.