IN THE MANAGEMENT OF THROMBOEMBOLISM IN PATIENTS WITH HEPARIN-INDUCED THROMBOCYTOPENIA & ARTERIAL THROMBO-EMBOLIC DISORDERS SUCH AS MYOCARDIAL INFARCTION, UNSTABLE ANGINA :
AN INITIAL DOSE OF 400 MICROGRAMS/KG (UPTO 110 KG WEIGHT) BY SLOW INTRAVENOUS INJECTION, FOLLOWED BY A MAINTENANCE DOSE OF 150 MICROGRAMS/KG PER HOUR BY CONTINUOUS INTRAVENOUS INFUSION, ADJUSTED ACCORDING TO RESPONSE, USUALLY FOR 2 TO 10 DAYS. RESPONSE SHOULD BE MONITORED ACCORDING TO THE ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT) RATIO TO ACHIEVE A TARGET OF 1.5 TO 2.5. IN GENERAL AN INFUSION RATE OF 210 MICROGRAMS/KG PER HOUR SHOULD NOT BE EXCEEDED.
DOSES OF LEPIRUDIN SHOULD BE REDUCED IN PATIENTS WITH RENAL IMPAIRMENT. THE INITIAL DOSE IS REDUCED TO 200 MICROGRAMS/KG, AND THE MAINTENANCE INFUSION RATE IS REDUCED ACCORDING TO CREATININE CLEARANCE (CC):
CC 45 TO 60 ML/MINUTE: INFUSION RATE 50% OF NORMAL RATE
CC 30 TO 44 ML/MINUTE: 30% OF NORMAL RATE
CC 15 TO 29 ML/MINUTE: 15% OF NORMAL RATE
CC BELOW 15 ML/MINUTE: INFUSION OF LEPIRUDIN SHOULD BE AVOIDED
IN HAEMODIALYSIS PATIENTS OR CASES OF ACUTE RENAL FAILURE INFUSION IS TO BE STOPPED & FURTHER INTRAVENOUS BOLUS DOSES OF 100 MICROGRAMS/KG MAY BE USED ON ALTERNATE DAYS, ACCORDING TO RESPONSE ONLY IF THE APTT RATIO FALLS BELOW THE LOWER THERAPEUTIC LIMIT OF 1.5.
USE IN PATIENTS SCHEDULED FOR A SWITCH TO ORAL ANTICOAGULATION:
THE DOSE OF REFLUDAN SHOULD FIRST BE GRADUALLY REDUCED IN ORDER TO REACH AN APTT RATIO JUST ABOVE 1.5 BEFORE INITIATING ORAL ANTICOAGULATION. COUMARIN DERIVATIVES SHOULD BE INITIATED ONLY WHEN PLATELET COUNTS ARE NORMALIZING. THE INTENDED MAINTENANCE DOSE SHOULD BE STARTED WITH NO LOADING DOSE. TO AVOID PROTHROMBOTIC EFFECTS WHEN INITIATING COUMARIN, CONTINUE PARENTERAL ANTICOAGULATION FOR 4 TO 5 DAYS. THE PARENTERAL AGENT CAN BE DISCONTINUED WHEN THE INR STABILIZES WITHIN THE DESIRED TARGET RANGE.