Mercaptopurine

Indications

Mercaptopurine is used for: Acute lymphatic leukaemia, Crohn's disease

Adult Dose

Acute Lymphatic Leukemia Induction: 2.5 mg/kg PO qDay; usually 100-200 mg PO qDay in average adult (other agents preferred) May increase by 5 mg/kg/day after 4 weeks Maintenance: 1.5-2.5 mg/kg PO qDay Reduce dose by 75% if concomitant allopurinol administration Crohn's disease Adult: Initially 1-1.5 mg/kg daily, may increase to 125 mg daily. Hepatic impairment: Dosage may need to be reduced.

Child Dose

Acute Lymphatic Leukemia Starting dose: 1.25-2.5 mg/kg (50-75 mg/m²) PO qDay Maintenance: 1.5-2.5 mg/kg PO qDay in combination with methotrexate

Renal Dose

Renal Impairment: Dosage may need to be reduced.

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.

Contra Indications

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

Precautions

Hepatic or renal dysfunction; monitor hepatic function periodically. Mercaptopurine is potentially carcinogenic. Thiopurine S-methyl transferase (TPMT) deficiency; porphyria. Lactation: not known if excreted in breast milk, do not nurse

Pregnancy-Lactation

Pregnancy Category: D Lactation: not known if excreted in breast milk, do not nurse

Interactions

Anticoagulant action of warfarin may be inhibited by mercaptopurine. Enhanced toxicity with myelosuppressive drugs. Potentially Fatal: Effects enhanced by allopurinol (reduce dose of mercaptopurine). Other hepatotoxic drugs (e.g. doxorubicin) potentiate toxicity.

Adverse Effects

Side effects of Mercaptopurine : >10% Elevated LFT's (15%) 1-10% Nausea (10%), Vomiting (10%), Stomatitis (3-10%), Thrombocytopenia (3-10%), Rash (1-3%), Diarrhea (1-3%), Dizziness (1-3%), Alopecia (1-3%), Leukopenia (1-3%) Frequency Not Defined Fatigue, Anorexia, Headache, Chills and fever, Chest pain, Mucositis, Upper respiratory infection, Cough, Ulceration of intestine, Ulcerative stomatitis, Myelosuppressionm, Decreased hematocrit, Hepatotoxicity, Decreased resistance to infections, Hyperuricemia, Nephrotoxicity, Increased risk of pancreatitis in pts with IBD, Hyperpigmentation of skin, Arthralgias, Eye discomfort, Tinnitus Potentially Fatal: Myelosuppression; hepatotoxicity, cholestatic jaundice.

Mechanism of Action

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.