Mitomycin

CLINICAL USE

Cytotoxic antibiotic used in a range of neoplastic conditions

DOSE IN NORMAL RENAL FUNCTION

IV: 4–10 mg/m2 or 0.06–0.15 mg/kg given every 1–6 weeks, depending on concurrent therapy and bone marrow recoveryFor instillation into bladder: 20–40 mg

PHARMACOKINETICS

Molecular weight :334.3

%Protein binding :No data

%Excreted unchanged in urine : 10

Volume of distribution (L/kg) :0.5

half-life – normal/ESRD (hrs) :50 minutes/–

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 : 75% of normal dose

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unknown dialysability. Dose as in GFR <10 mL/min

HD :Unknown dialysability. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

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

ADMINISTRATION

Reconstition

With water for injection or sodium chloride 0.9%; 5 mL for the 2 mg vial, at least 10 mL for the 10 mg vial and at least 20 mL for the 20 mg vial

Route

IV injection, intra-arterial, bladder instillation

Rate of Administration

Bolus injection over 3–5 minutes (1 mL/ min)Infusion over 15–30 minutes

Comments

–

OTHER INFORMATION

Prodrug, activated in vivo. Metabolism is predominantly in the liver. Rate of clearance is inversely proportional to the maximum serum concentration, due to saturation of the degradative pathways. Approximately 10% is excreted unchanged in the urine. Since metabolic pathways are saturated at low doses, the % dose excreted in the urine increases with increasing doseA syndrome of thrombotic microangiopathy resembling haemolytic-uraemic syndrome has been seen in patients receiving mitomycin, either alone or, more frequently, combined with other agents. Symptoms of haemolysis and renal failure may be accompanied by ATN and cardiovascular problems, pulmonary oedema and neurological symptomsPrincipal toxicity of mitomycin-C is bone marrow suppression. The nadir is usually around 4 weeks after treatment and toxicity is cumulative, with increasing risk after each course of treatment.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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