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lepirudin; hirudin (Refludan)
Tradename: Refludan. One of the hirudins hirulog (from leeches).
Indications: heparin-induced thrombocytopenia
Contraindications:
1) hypersensitivity to hirudins
2) relative contraindications
a) recent puncture of large vessel or organ biopsy
b) anomaly of vessels
c) stroke, intracerebral surgery
d) severe uncontrolled hypertension
e) bacterial endocarditis
f) advanced renal failure
g) hemorrhagic diathesis
h) recent major surgery
i) recent major bleeding (intracranial, intraocular, gastrointestinal, pulmonary)
Dosage:
1) 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
2) ref [2] says this dose too high omit bolus, then 0.08 mg/kg per hour [2]
Injection: 16,000 antithrombin units/mg.
Dosage adjustment in renal failure:
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 [2]
30-60 mL/min 0.040 mg/kg per hour
< 30 mL/min 0.013 mg/kg per hour
Adverse effects:
1) anemia
2) hematuria
3) excessive bleeding
a) wounds & puncture sites
b) epistaxis
c) no increase in GI or rectal bleeding
Overdose
- activated prothrombin concentrate complex 50-100 units/kg IV
- hemofiltration through a polyfulfone membrane [3]
Drug interactions:
1) increased risk of intracranial hemorrhage when administered with thrombolytic agents
2) concurrent use of warfarin increases risk of bleeding
Laboratory:
- hirudin in plasma
Mechanism of action:
1) direct thrombin inhibitor
-> one molecule of lepirudin binds to molecule of thrombin blocking thrombogenic activity of thrombin
2) allegedly, they do not work (one opinion)
Interactions
drug interactions
drug adverse effects of antithrombotic agent(s)
General
peptide
thrombin inhibitor
Properties
SIZE: MW = 6.98 kD
entity length = 65 aa
INHIBITS: thrombin
MISC-INFO: elimination route KIDNEY
1/2life 10 HOURS
protein-binding <10%
References
- Hoescht Marion Roussel
- Tschudi M et al
Dosing lepirudin in patients with heparin-induced
thrombocytopenia and normal or impaired renal function:
A single-center experience with 68 patients.
Blood 2009 Mar 12; 113:2402.
PMID: 19059879
- Medical Knowledge Self Assessment Program (MKSAP) 16,
American College of Physicians, Philadelphia 2012