Adult Dosing
Heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease
110kg:- Initially 0.4mg/kg by slow IV (over 15-20 seconds) bolus inj, follow by 0.15mg/kg/hr as a continuous IV infusion for 2-10 days or longer if clinically required
- >110kg:
- Max initial bolus dose 44 mg; max initial infusion dose 16.5 mg/hr
- Further adjustments made on the basis of aPTT but should not exceed infusion rate of 0.21 mg/kg/hr without checking for coagulation abnormalities
- Monitor aPTT at baseline, at 4 hrs, then qd or more frequently if renal impairment/serious hepatic injury or if risk factors for bleeding present
- Concomitant Use With Thrombolytic Therapy:
- Start 0.2 mg/kg IV bolus
- Then 0.1 mg/kg/hr IV as a continuous infusion
- Monitor aPTT at baseline, at 4 hrs, then qd or more frequently if renal impairment/ serious hepatic injury or if risk factors for bleeding present
Notes:
- Adjust dosage according to the aPTT ratio
- Target range for aPTT ratio during treatment should be 1.5-2.5. Do not start therapy if baseline aPTT is
2.5 - Preparation of a Refludan bolus injection requires dilution following reconstitution to obtain the final concentration of 5 mg/mL
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustment
Based on CrCl
- 45-60 mL/min: Start 0.2 mg/kg bolus, then 0.075 mg/kg/hr
- 30-44 mL/min: Start 0.2 mg/kg bolus, then 0.045 mg/kg/hr
- 15-29 mL/min: Start 0.2 mg/kg bolus, then 0.0225 mg/kg/hr
- <15 mL/min: Avoid use or stop infusion
- In HD/ARF/CrCl <15 mL/min: If aPTT ratio <1.5, then give 0.1 mg/kg bolus q48 hrs
Based on serum creatinine
- 1.6-2 mg/dL: Start 0.2 mg/kg bolus, then 0.075 mg/kg/hr
- 2.1-3 mg/dL: Start 0.2 mg/kg bolus, then 0.045 mg/kg/hr
- 3.1-6 mg/dL: Start 0.2 mg/kg bolus, then 0.0225 mg/kg/hr
- > 6 mg/dL: Avoid use or stop infusion
Hepatic Dose Adjustment
- Hepatic impairment: Dose adjustments not defined
- Hemorrhagic events may occur at any site. Monitor patient for signs of bleeding throughout therapy
- Monitor patients for an unexpected fall in hemoglobin, fall in blood pressure as these may occur in case of an hemorrhagic event
- Life-threatening intracranial bleeding may occur with co-administration of thrombolytic therapy
- Allergic and hypersensitivity reactions, including anaphylaxis have been reported; caution should be exercised in re-exposing patients
- Monitor creatinine at baseline; aPTT at baseline, then 4 hr after starting infusion, then once daily or more frequently if renal impairment/serious hepatic injury or if bleeding risk
Cautions: Use cautiously in
- Severe renal impairment (CrCl <15 mL/min)
- Hepatic cirrhosis
- Bleeding risk
- Tendency for bleeding
- Bacterial endocarditis
- Uncontrolled hypertension
- Recent intracerebral surgery
- Recent CVA
- Trauma
- Recent major bleeding
- Hemorrhagic diathesis
- Recent biopsy
- Recent active peptic ulcer
- Elderly patients
Pregnancy Category:B
Breastfeeding: Safety unknown. Limited information indicates that lepirudin doses 100 mg/day produce very low levels in milk and would not be expected to cause any adverse events in breastfed infants, especially if the infant is older than 2 months. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 10 February 2011). Manufacturer recommends discontinuation of breastfeeding, or postponing of treatment (taking into account the importance of the drug to the mother).
