Mercaptopurine.txt

CLINICAL USE

Antineoplastic agent:Acute leukaemias Inflammatory bowel disease (unlicensed)

DOSE IN NORMAL RENAL FUNCTION

Usual dose is 2.5 mg/kg/day, but the dose and duration of administration depend on the nature and dosage of other cytotoxic agents given in conjunction

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :170.2

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :20

%Excreted unchanged in urine &nbsp &nbsp : 7

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :0.1–1.7

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :1–1.5/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Caution – reduce dose.

10 to 20 &nbsp &nbsp : Caution – reduce dose.

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Caution – reduce dose.

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Dialysed. Dose as in GFR

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min

HDF/high flux &nbsp :Dialysed. Dose as in GFR

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min

CAV/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAllopurinol: decreased rate of metabolism of mercaptopurine – reduce dose of mercaptopurine to a quarter of normal dose

Antibacterials: increased risk of haematological toxicity with co-trimoxazole and trimethoprim

Anticoagulants: possibly reduced anticoagulant effect of coumarins

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

Absorption of an oral dose is incomplete, averaging ~50%. This is largely due to first pass metabolism in the liver (less when given with food). There is enormous inter-individual variability in absorption, which can result in a 5-fold variations in AUCIt is extensively metabolised (by intracellular activation). At conventional doses clearance is primarily hepatic. Renal clearance may become important at high dosesThe active metabolites have a longer half- life than the parent drugWellcome UK recommend consideration be given to reducing the dose in patients with impaired hepatic or renal function, although no specific dosing guidelines are availableWith renal impairment, the following dosing intervals have been suggested: 24–36 hrs for CrCl of 50–80 mL/min, and 48 hrs for CrCl of 10–50 mL/min. (Summerhayes M, Daniels S (eds). Practical Chemotherapy – A Multidisciplinary guide. 1st ed. Abingdon: Radcliffe Medical Press Ltd. 2003. p. 384)A recent study on anti-cancer drug renal toxicity and elimination concluded that the dose of 6-mercaptopurine does not require modification in patients with decreased renal function (except in conjunction with allopurinol). This study also gives % excreted unchanged in urine as 21%.

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