lepirudin; hirudin (Refludan)

Introduction

Tradename: Refludan. One of the hirudins hirulog (from leeches).

Indications

heparin-induced thrombocytopenia

Contraindications

• hypersensitivity to hirudins
• relative contraindications
  • recent puncture of large vessel or organ biopsy
  • anomaly of vessels
  • stroke, intracerebral surgery
  • severe uncontrolled hypertension
  • bacterial endocarditis
  • advanced renal failure
  • hemorrhagic diathesis
  • recent major surgery
  • recent major bleeding (intracranial, intraocular, gastrointestinal, pulmonary)

Dosage

• 0.4 mg/kg IV up to 440 mg bolus over 20 sec, then 0.15 mg/kg/hr IV up to 16.5 mg/hr for 2-10 days
• ref says this dose too high omit bolus, then 0.08 mg/kg per hour

Injection: 16,000 antithrombin units/mg.

Dosage adjustment in renal failure

Table

creatinine (mg/dL)	% of standard dose
1.6-2.0	50%
2.1-3.0	30%
3.1-6.0	15%
> 6.0	stop
creatinine clearance	dose
30-60 mL/min	0.040 mg/kg per hour
< 30 mL/min	0.013 mg/kg per hour

Adverse effects

• anemia
• hematuria
• excessive bleeding
  • wounds & puncture sites
  • epistaxis
  • no increase in GI or rectal bleeding

Overdose

• activated prothrombin concentrate complex 50-100 units/kg IV
• hemofiltration through a polyfulfone membrane

• drug adverse effects of antithrombotic agent(s)

Drug interactions

• increased risk of intracranial hemorrhage when administered with thrombolytic agents
• concurrent use of warfarin increases risk of bleeding

• drug interaction(s) of oral anticoagulants with selective serotonin reuptake inhibitor (SSRI)
• drug interaction(s) of aspirin, P2Y12 inhibitors & anticoagulants

Laboratory

• hirudin in plasma

Mechanism of action

• direct thrombin inhibitor
  • one molecule of lepirudin binds to molecule of thrombin blocking thrombogenic activity of thrombin
• allegedly, they do not work (one opinion)

More general terms

• peptide
• thrombin inhibitor