Etoposide

CLINICAL USE

Antineoplastic agent

DOSE IN NORMAL RENAL FUNCTION

IV: 60–120 mg/m2 daily according to local protocolOral: Twice the relevant IV dose should be given daily according to local protocol

PHARMACOKINETICS

Molecular weight :588.6

%Protein binding :74–94

%Excreted unchanged in urine : 29

Volume of distribution (L/kg) :0.17–0.5

half-life – normal/ESRD (hrs) :4–11/19

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

60 85% of dose45–60 80% of dose and see ‘Other Information’30–45 75% of dose and see ‘Other Information’< 30 50% of dose, based on clinical response and see ‘Other Information’

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR<30 mL/min

HD :Not dialysed. Dose as in GFR<30 mL/min

HDF/high flux :Not dialysed. Dose as in GFR<30 mL/min

CAV/VVHD :Unknown dialysability. Dose as in GFR<30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Anticoagulants: possibly enhanced anticoagulant effect with coumarins

Antipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosis

Ciclosporin: 50% reduction in etoposide clearance

ADMINISTRATION

Reconstition

5–10 mL of infusion fluid or water for injection

Route

Oral, IV

Rate of Administration

IV infusion

: 5 minutes – 3.5 hours

Comments

Dilute with sodium chloride 0.9% or glucose 5% to give a solution concentration as low as 100 mcg/mL of etoposide

OTHER INFORMATION

Avoid skin contact Liver metabolised, yielding inactive metabolites. Approximately 45% of an administered dose is excreted in the urine, 29% being excreted unchanged in 72 hrs. Up to 16% is recovered in the faecesOne study suggested that patients with serum creatinine >130 µmol/L require a 30% dose reduction. (Joel S, Clark P, Slevin M. Renal function and etoposide pharmacokinetics: is dose modification necessary? Am Soc Clin Oncol. 1991; 10: 103) This dose adjustment was calculated to result in equivalent total dose exposure in patients with reduced renal function. Patients with a raised bilirubin and/or decreased albumin may have an increase in free etoposide and hence greater myelosuppressionReaches high concentration in kidney: possible accumulation in renal impairmentPlasma clearance is reduced and volume of distribution increased in renal impairmentKintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Can Treat Rev. 1995; 21: 33–64. – provides dose modifications listed in ‘dose in renal impairment’Has been used without any problems in a haemodialysis patient, using a dose .290 EToPosidEthat increased gradually to 250 mg per treatment. (Holthius JJM, Van de Vyver FL, Van Oort WJ, et al. Pharmacokinetic evaluation of increased dosages of etoposide in a chronic haemodialysis patient. Cancer Treat Rep. 1985; 69(11): 1279–82.)Bristol-Myers Squibb advise giving 75% of dose if GFR is 15–50 mL/min.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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