ifosfamide

CLINICAL USE

Antineoplastic agent:Treatment of solid tumours, lymphomas and soft tissue sarcoma

DOSE IN NORMAL RENAL FUNCTION

Usual total dose for each course is either 8–12 g/m2, equally divided as single daily doses over 3–5 days, or 5–6 g/m2 (maximum 10 g) given as a 24 hour infusionOr according to local protocol

PHARMACOKINETICS

Molecular weight :261.1

%Protein binding :0

%Excreted unchanged in urine : 12–18

Volume of distribution (L/kg) :0.4–0.64

half-life – normal/ESRD (hrs) :4–8/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

>60 80% of normal dose30–60 80% of normal dose15–30 80% of normal dose<15 60% of normal dose

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Dialysed. Dose as in GFR<15 mL/min. Following dose, do not perform

CAPD : exchange for 12 hours

HD :Dialysed. Dose as in GFR<15 mL/min. Dose at minimum of 12 hours before next

HD : session

HDF/high flux :Dialysed. Dose as in GFR<15 mL/min. Dose at minimum of 12 hours before next HDF session

CAV/VVHD :Dialysed. Dose as in GFR=15–30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anticoagulants: possibly enhanced effect of coumarins

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

ADMINISTRATION

Reconstition

Reconstitute 1 g vial with 12.5 mL water for injection. Reconstitute 2 g vial with 25 mL water for injection. The resultant solution of 8% ifosfamide should NOT be injected directly into the vein

Route

IV injection: dilute to less than a 4% solution

IV infusion

: dilute as detailed below

Rate of Administration

IV infusion

: Infuse in glucose 5% or sodium —chloride 0.9% over 30–120 minutes, or Inject directly into a fast running —infusion, orMade up in 3 L of glucose 5% or —sodium chloride 0.9%; each litre should be given over 8 hours

Comments

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OTHER INFORMATION

Nephrotoxicity may occur with oliguria, raised uric acid, increased BUN and serum creatinine, and decreased creatinine clearanceIfosfamide is known to be more nephrotoxic than cyclophosphamide; hence greater caution is advisedSPC contraindicates the use of ifosfamide if serum creatinine >120 µmol/LIf patient is anuric and on dialysis, neither the ifosfamide nor its metabolites nor mesna should appear in the urinary tract. The use of mesna may therefore be unnecessary, although this would be a clinical decisionIf the patient is passing urine, mesna should be given to prevent urothelial toxicityIfosfamide is a prodrug – converted by hepatic microsomal enzymes to alkylating metabolites. Excretion is primarily renal. Approximately 80% of dose is excreted as parent compound.372 iFosFAMidEDoses from Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Can Treat Rev. 1995; 21: 33–64:GFR > 60 mL/min 80% of doseGFR = 45–60 mL/min 75% of doseGFR = 30–45 mL/min 70% of dose

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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