Dosing and uses of Refludan (lepirudin)
Adult dosage forms and strengths
powder for injection
- 50mg/vial
Heparin-induced Thrombocytopenia
Discontinued by manufacturer (5/17/2012)
0.4 mg/kg (not to exceed 44 mg) IV over 15-20 sec initially, THEn
0.15 mg/kg/hr (not to exceed 16.5 mg/hr) IV for 2-10 day
Dose Adjustment
Maintain aPTT ratio 1.5-2.5; monitor 4 hr after initial dose, then qDay
If aPTT high: Stop infusion for 2 hr, then restart infusion at 50% dose (no bolus)
If aPTT low: Increase dose in steps of 20%
Renal Impairment
Initial 0.2 mg/kg (not to exceed 22 mg) IV over 15-20 sec, THEn
CrCl 45-60 mL/min: 0.075 mg/kg/hr
CrCl 30-44 mL/min: 0.045 mg/kg/hr
CrCl 15-29 mL/min: 0.0225 mg/kg/hr
CrCl <15 mL/min: Contraindicated
Pediatric dosage forms and strengths
Safety and efficacy not established
Refludan (lepirudin) adverse (side) effects
>10%
Injection site bleeding (14%)
Anemia (12%)
Hematoma (11%)
Bleeding (<11%)
Extrinsic allergic respiratory disease (10% or more)
1-10%
Hematuria (7%)
Liver function test abnormalities (5%)
Pericardial effusion (1%)
Pneumonia (5%)
Ventricular fibrillation (1%)
Epistaxis (4%)
Fever (4%)
Heart failure (4%)
Gastrointestinal hemorrhage (4%)
Rectal hemorrhage (4%)
Cutaneous hypersensitivity (4%)
Increased transaminases (6%)
Hematuria (4%)
Sepsis (4%)
Renal failure (2%)
<1%
Cerebral ischemia
Confusion
Peripheral nerve facial nerve paralysis
Intracranial hemorrhage (rare)
Anaphylaxis (rare)
Warnings
Contraindications
Hypersensitivity to hirudins
Severe renal insufficiency (CrCl <15 mL/min)
Cautions
Formation of antihirudin antibodies (40%) may increase anticoagulant effect; monitor aPTT carefully
Cirrhosis may enhance anticoagulant effect
Patients with increased risk of bleeding
Cautiously administer after a thrombolytic episode (risk of intracranial bleeding)
Allergic reactions frequently reported in patients treated concomitantly with streptokinase
Pregnancy and lactation
Pregnancy category: B
Lactation: Not known if excreted in breast milk, not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Refludan (lepirudin)
Mechanism of action
Recombinant hirudin (leech anticoagulant), specific thrombin inhibitor; increases aPTt
Pharmacokinetics
Half-life: 1.3 hr
Distribution: Confined to extracellular fluids
Clearance: 164 mL/min
Excretion: Urine (48%)
Dialyzable: Yes
Administration
IV Incompatibilities
Do not mix with any other drug
IV Preparation
Reconstitute 50 mg vials with 1 mL SWI or NS, swirl gently to mix, should not take more than a few seconds
Bolus injection
- Transfer reconstituted vial contents (1 mL) into single-use syringe with at least 10 mL capacity
- Dilute with SWI, NS or D5W to total volume of 10 mL for a final concentration of 5 mg/mL
Infusion (makes 0.4 mg/mL or 0.2 mg/mL)
- Transfer 2 reconstituted vial contents to 250 mL or 500 mL of NS or D5W
IV Administration
Bolus: over 15-20 sec
See adult dosing for infusion rate
