Mitoxantrone

CLINICAL USE

Metastatic breast cancerNon-Hodgkin’s lymphomaAdult acute non-lymphocytic leukaemia

DOSE IN NORMAL RENAL FUNCTION

Metastatic breast cancer, non-Hodgkin’s lymphoma and hepatoma: 14 mg/m2 every 21 days (12 mg/m2 or less if inadequate bone marrow reserves)Adult acute non-lymphocytic leukaemia: 12 mg/m2 for 5 consecutive daysOr according to local protocol

PHARMACOKINETICS

Molecular weight :517.4 (as hydrochloride)

%Protein binding :78

%Excreted unchanged in urine : 7

Volume of distribution (L/kg) :1000 L/m2

half-life – normal/ESRD (hrs) :5–18 days

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in normal renal function

HD :Not dialysed. Dose as in normal renal function

HDF/high flux :Not dialysed. Dose as in normal renal function

CAV/VVHD :Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsOther antineoplastic agents: enhanced myelosuppression – when used in combination reduce mitoxantrone dose by 2–4 mg/m2Cardiotoxic drugs: increased risk of cardiac toxicity

ADMINISTRATION

Reconstition

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Route

IV infusion

Rate of Administration

At least 3 minutes

Comments

Dilute to at least 50 mL in sodium chloride 0.9%, glucose 5% or sodium chloride 0.18% and glucose 4%

OTHER INFORMATION

Has been administered intraperitoneally at a dose of 28–38 mg/m2 every 3–4 weeks although some people advise a maximum dose of only 30 mg/m2 per month with a dwell time of 1–4 hours. (Alberts DS, Surwit EA, Peng YM, et al. Phase I clinical and pharmacokinetic study of mitoxantrone given to patients by intraperitoneal administration. Cancer Res. 1988, Oct 15; 48(20): 5874–7)Extensive metabolism in the liver. Excretion is predominantly via the bile and faeces. 5–10% of dose is excreted in the urine within 5 days.

See how to identify renal failure stages according to GFR calculation

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