Mercaptopurine is a purine antagonist which is converted intracellularly into its active nucleotides, including thioinosinic acid. The nucleotides inhibit several reactions which ultimately interferes with nucleic acid synthesis and prevents the formation of RNA and DNA.

Mercaptopurine is indicated for maintenance therapy of acute lymphatic (lymphocytic, lymphoblastic) leukemiaas part of a combination regimen. The response to this agent depends upon the particular subclassification of acute lymphatic leukemia and the age of the patient (pediatric or adult).

Mercaptopurine is not effective for prophylaxis or treatment of central nervous system leukemia. Mercaptopurine is not effective in acute myelogenous leukemia, chronic lymphatic leukemia, the lymphomas (including Hodgkins Disease), or solid tumors.

Crohn's disease:

• Adult: Initially 1-1.5 mg/kg daily, may increase to 125 mg daily.
• Child: Initially 1-1.5 mg/kg daily increased to a max of 75 mg daily

Acute lymphocytic leukemia:

• Adult: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.
• Child: Usual maintenance dose: Initially, 1.5-2.5 mg/kg daily as a single dose, usually used in combination with methotrexate. Dose may vary individually based on response and tolerance. Monitor blood counts at least once wkly. Withdraw treatment immedietely if there is a sharp drop in the white cell count or severe bone-marrow depression. May resume treatment slowly and carefully if white cell count remains constant for 2-3 days or rises. Reduce dose when used with allopurinol.

Administration

Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. Ensure adequate fluid intake.

Pregnancy and lactation. Prior resistance to mercaptopurine or thioguanine; severe liver disease; severe bone marrow suppression.

Hyperuricaemia, bone marrow toxicity, hypoplasia, anorexia, diarrhoea, leukopenia, thrombocytopenia, intestinal ulceration, crystalluria with haematuria, immunosuppression, interstitial pneumonitis. Cutaneous hyperpigmentation, alopecia.

Hepatic or renal dysfunction; monitor hepatic function periodically. Mercaptopurine is potentially carcinogenic. Thiopurine S-methyl transferase (TPMT) deficiency; porphyria.

Use in Special Populations

Renal Impairment: Dosage may need to be reduced.

Hepatic Impairment:

• Crohn's disease: Dosage may need to be reduced.
• Acute lymphocytic leukemia: Dosage may need to be reduced

Dosage adjustment in patients with thiopurine-S-methyl transferase (TPMT) deficiency to prevent life-threatening myelotoxicity.

For patients with homozygous TPMT deficiency: Substantial reduction is required.

For patients with heterozygous TPMT deficiency: Some may require reduction but most will tolerate the usual dosages.

Pregnancy & Lactation

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).