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

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

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.