drotrecogin alfa

CLINICAL USE

Treatment of adult patients with severe sepsis with multiple organ failure

DOSE IN NORMAL RENAL FUNCTION

24 micrograms/kg/hour for 96 hours

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Approx 55 000

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :No data

%Excreted unchanged in urine &nbsp &nbsp : No data

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :8.2–31.2 litres

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :13 minutes/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unlikely to be dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Unlikely to be dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Unlikely to be dialysed. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp:Unlikely to be dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Heparin: avoid concomitant use with high dose heparin

Thrombolytic therapy: avoid for 3 days before administering drotrecoginOral anticoagulants, antiplatelets: avoid for 7 days before administering drotrecogin

ADMINISTRATION

Reconstition

Water for injection

Route

IV infusion

Rate of Administration

24 micrograms/kg/hour

Comments

Further dilute with sodium chloride 0.9% to a concentration of 100–200 mcg/mLMinimum volume: 20 mg in 50 mL. (UK Critical Care Group, Minimum Infusion Volumes for fluid restricted critically ill patients, 3rd Edition, 2006)

OTHER INFORMATION

No anticoagulation is required for haemofiltration as the drotrecogin acts as an anticoagulantCan be started 12 hours after major invasive procedures or surgeryClearance is reduced by 30% in renal impairment but no dose reduction is required Has a short half-life of 13 minutes and a β-half-life of 1.6 hours

Plasma clearance: Patients with sepsis: 41.8 L/hour —Healthy subjects: 28.1 L/hour —Haemodialysis patents: 30 L/hour —Peritoneal dialysis patients: 23 L/hour

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