irinotecan hydrochloride

CLINICAL USE

Treatment of metastatic colorectal cancer resistant to fluorouracil, or in conjunction with fluorouracil

DOSE IN NORMAL RENAL FUNCTION

Without 5-FU: 350 mg/m2 every 3 weeksWith 5-FU: 180 mg/m2 every 2 weeks

PHARMACOKINETICS

Molecular weight :677.2

%Protein binding :65

%Excreted unchanged in urine : 20

Volume of distribution (L/kg) :110–234 litres/m2

half-life – normal/ESRD (hrs) :14

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function and monitor closely

10 to 20 : Dose as in normal renal function and monitor closely

<10 : Reduce dose (50–80 mg/m2) and monitor closely. Increase as tolerated

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unlikely to be dialysed. Dose as in GFR <10 mL/min

CAV/VVHD :Unlikely to be dialysed. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis)

Antivirals: metabolism possibly inhibited by atazanavir (increased risk of toxicity)

ADMINISTRATION

Reconstition

–

Route

IV infusion

Rate of Administration

Over 30–90 minutes

Comments

Dilute in 250 mL sodium chloride 0.9% or glucose 5%

OTHER INFORMATION

Manufacturer advises avoiding use in renal impairment due to lack of dataMetabolism is primarily hepatic: where irinotecan is rapidly converted to active metabolite SN-38 by hepatic carboxylesterase enzymesExcretion is predominantly biliary: 64% excreted in faeces. The mean 24 hr urinary excretion of irinotecan and SN-38 (its active metabolite) was 19.9% and 0.25% respectivelyInfrequent reports of renal insufficiency due to inadequate hydrationTransient, mild to moderate increase in serum creatinine reported in 7.3% patients

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