Procarbazine

CLINICAL USE

Antineoplastic agent:Main indication is Hodgkin’s disease

DOSE IN NORMAL RENAL FUNCTION

250–300 mg daily in divided doses; begin with small dosesMaintenance: 50–150 mg daily

PHARMACOKINETICS

Molecular weight :257.8 (as hydrochloride)

%Protein binding :No data

%Excreted unchanged in urine : 5

Volume of distribution (L/kg) :No data

half-life – normal/ESRD (hrs) :10 minutes/Increased

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : 50–100% of dose

10 to 20 : 50–100% of dose. Use with caution

<10 : 50–100% of dose. Use with caution

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

HD :Unlikely to be dialysed. 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 GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Alcohol: may produce a disulfiram reaction

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

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

After oral absorption, the drug appears to be rapidly and completely absorbed. Procarbazine is metabolised to an active alkylating agent by microsomal enzymes in the liver. After 24 hrs up to 70% of a dose is recovered in the urineNadir for bone-marrow depression is 4 weeks with recovery within 6 weeks For 48 hours after dose, wear protective clothing to handle urine. Increased toxicity reported in patients with renal impairment

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