doxorubicin hydrochloride

CLINICAL USE

Antineoplastic agent:Acute leukaemias Lymphomas Sarcomas Various solid tumours

DOSE IN NORMAL RENAL FUNCTION

Varies according to local protocol

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :580

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :50–85

%Excreted unchanged in urine &nbsp &nbsp : <15

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :>20–30

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :30; (Liposomal: 55–75; Pegylated: 24–231)/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Unknown dialysability. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp: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

Ciclosporin: increased risk of neurotoxicity

ADMINISTRATION

Reconstition

Reconstitute with water for injection or sodium chloride 0.9%, 10 mg in 5 mL, 50 mg in 25 mL

Route

IV, intra-arterial, intravesical (bladder instillation)

Rate of Administration

Via the tubing of a fast running intravenous infusion of sodium chloride 0.9% or glucose 5%3–5 minutes for the injection 24 hours for continuous infusion

Comments

For bladder instillation, concentration of doxorubicin in bladder should be 50 mg per 50 mL. To avoid undue dilution in urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. This should limit urine production to approximately 50 mL per hour

OTHER INFORMATION

A cumulative dose of 450–550 mg/m 2 should only be exceeded with extreme caution. Above this level, the risk of irreversible congestive cardiac failure increases greatly. Patients with impaired hepatic function have prolonged and elevated plasma concentrations of both the drug and its metabolites. Dose reduction is requiredLiposomal preparations available: up to 90 mg in 250 mL glucose 5%; if greater than 90 mg dilute in 500 mL glucose 5%Mainly metabolised in the liver. Rapidly cleared from plasma and slowly excreted in the urine and bile (50% of drug recoverable in the bile or faeces in 7 days)

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