Lepirudin

Summary

Lepirudin (Refludan) was a recombinant hirudin-based direct thrombin inhibitor approved for anticoagulation in patients with heparin-induced thrombocytopenia (HIT). It was administered intravenously and monitored via aPTT. The manufacturer voluntarily withdrew it from the global market in 2012 due to commercial reasons, and it has been replaced by alternative agents such as argatroban and bivalirudin.

Mechanism of Action

Lepirudin is a recombinant form of hirudin that directly and irreversibly binds to both the catalytic site and the fibrinogen-binding site (exosite 1) of thrombin, inhibiting its activity regardless of whether thrombin is free or clot-bound. This prevents thrombin-mediated conversion of fibrinogen to fibrin, platelet activation, and other downstream coagulation effects.

Routes of Administration

Goals & Uses

• Alternative anticoagulation in heparin-allergic patientsHematologyModerate
• Prevention of thromboembolic complications in HIT with thrombosisHematology / ThrombosisHigh
• Anticoagulation in heparin-induced thrombocytopenia (HIT)Hematology / ThrombosisHigh

Contraindications

• Hypersensitivity to hirudins or lepirudinAllergy / ImmunologyHigh
• Active major bleedingHemorrhagic RiskHigh
• Severe renal impairmentOrganHighKidney function concerns
• Bacterial endocarditisInfectious / CardiovascularModerate
• Recent major surgery or organ biopsySurgicalHigh

Adverse Effects

• Injection site reactionsLocalUncommon
• Anaphylaxis / hypersensitivity reactionsImmunologyUncommon
• FeverSystemicUncommonElevated body temperature
• Anti-hirudin antibody formationImmunologyCommon
• Bleeding (hemorrhage)HematologyCommon
• Renal function changesRenalUncommon

Drug Interactions

• Warfarin and other vitamin K antagonistsHigh
• Thrombolytics (e.g., alteplase, streptokinase)High
• NSAIDsModerateMay increase renal risk in susceptible patients
• Antiplatelet agents (e.g., aspirin, clopidogrel, GPIIb/IIIa inhibitors)Moderate

Population Constraints

• PregnancyReproductive SafetyRelative
• Renal impairmentOrgan ImpairmentAbsolute
• Pediatric patientsAgeRelative
• Patients with prior lepirudin exposureImmunologyRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionWithdrawnApproved: Anticoagulation in adult patients with heparin-induced thrombocytopenia (HIT)Marketing authorization surrendered; product withdrawn from European markets around 2012.
• United StatesWithdrawnApproved: Anticoagulation in adult patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic diseaseFDA approved in 1998; voluntarily withdrawn by Bayer in 2012 for commercial reasons. No longer available.
• United KingdomWithdrawnApproved: Anticoagulation in heparin-induced thrombocytopeniaNo longer available in the UK following global withdrawal in 2012.

Approved by the FDA in 1998 for HIT management. Voluntarily withdrawn from the US and global markets by Bayer in 2012; no longer commercially available. Argatroban is now preferred for HIT in many jurisdictions.

Evidence & Sources

No sources recorded yet.