Chlorambucil
Chlorambucil.JPG

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

    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.



    See how to identify renal failure stages according to GFR calculation

    See how to diagnose irreversible renal disease

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