indication

For the treatment of heparin-induced thrombocytopenia

pharmacology

Lepirudin is used to break up clots and to reduce thrombocytopenia. It binds to thrombin and prevents thrombus or clot formation. It is a highly potent, selective, and essentially irreversible inhibitor of thrombin and clot-bond thrombin. Lepirudin requires no cofactor for its anticoagulant action. Lepirudin is a recombinant form of hirudin, an endogenous anticoagulant found in medicinal leeches.

mechanism of action

Lepirudin forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen and initiate the clotting cascade. The inhibition of thrombin prevents the blood clotting cascade.

toxicity

In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased.

biotransformation

Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, con-clusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.

absorption

Bioavailability is 100% following injection.

half life

Approximately 1.3 hours

route of elimination

Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) and other fragments of the parent drug.

drug interactions

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the anticoagulant, Lepirudin. Monitor for increased bleeding during concomitant thearpy.