Chlorambucil

CLINICAL USE

Alkylating agent:

Hodgkin’s disease

Non-Hodgkin’s lymphoma (NHL)

Chronic lymphocytic leukaemia (CLL)

Waldenström’s macroglobulinaemia (WM)

Ovarian carcinoma (OC)

Advanced breast cancer (ABC)

DOSE IN NORMAL RENAL FUNCTION

Hodgkin’s disease: 200 mcg/kg/day (4–8 wks)

NHL: 100–200 mcg/kg/day (4–8 wks) then reduce dose or give intermittently

CLL: initially 150 mcg/kg/day, then 4 weeks after 1st course ended 100 mcg/kg/day

WM = initially 6–12 mg daily, then reduce to 2–8 mg daily

OC = 200 mcg/kg/day

ABC = 200 mcg/kg/day for 6 wks (or 14–20 mg/day)

PHARMACOKINETICS

Molecular weight :304.2

%Protein binding :99

%Excreted unchanged in urine : <1

Volume of distribution (L/kg) :0.86

half-life – normal/ESRD (hrs) :1.5/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function. See ‘Other Information’

10 to 20 : Dose as in normal renal function. See ‘Other Information’

<10 : Dose as in normal renal function. See ‘Other Information’

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 :Unknown dialysability. Dose as in normal renal function

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

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Ciclosporin: ciclosporin concentration possibly reduced

Patients who receive phenylbutazone may require reduced doses of chlorambucil

ADMINISTRATION

Reconstition

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Route

Oral

Rate of Administration

–

Comments

–

OTHER INFORMATION

Chlorambucil is extensively metabolised in the liver via the hepatic microsomal enzyme oxidation system, principally to phenylacetic acid mustard, which is pharmacologically active

Chlorambucil is excreted in the urine, almost exclusively as metabolites

Monitor patients with renal impairment closely as they are at increased risk of myelosuppression associated with azotaemia

Oral absorption slowed and decreased by 10 to 20 % if ingested with food.

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