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Mercaptopurine

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Mercaptopurine, 6-MP, Purixan

  • See Also
  1. Chemotherapy
  2. Antimetabolite Chemotherapy
  • Indications
  1. FDA Approved (in combination regimens)
    1. Acute Lymphoblastic Leukemia (ALL)
  2. Off-Label Use
    1. Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis)
    2. Cancer
      1. Acute promyelocytic Leukemia
      2. Autoimmune Hepatitis
      3. Lymphoblastic Lymphoma
  • Mechanism
  1. Mercaptopurine is a thiopurine derivative with antineoplastic and Immunosuppressant activity
  2. Mercaptopurine is a prodrug metabolized to active components by hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
    1. Metabolites inhibit interconversion between Nucleotides, inhibiting Purine and DNA synthesis
    2. Metabolites
      1. 6-thioGMP (6-thioguanosine-5'-phosphate)
      2. T-IMP (6-thioinosine monophosphate)
  3. Mercaptopurine is also a metabolized to deoxythioguanosine
    1. Deoxythioguanosine is a purine Nucleoside antimetabolite analog
    2. Incorporated into DNA in place of the Nucleoside Guanosine
    3. Interrupts DNA Replication
  4. Mercaptopurine is also metabolized to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase
    1. MMPR inhibits Purine synthesis
  • Medications
  1. Mercaptopurine tablets: 50 mg
  2. Mercaptopurine oral solution: 20 mg/ml
  • Dosing
  1. See other references for disease specific dosing protocols
  2. Consider concurrent Folic Acid supplementation
  3. Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis)
    1. Start (adult): 50 mg orally daily, then titrate to effect
    2. Adult and Child Dosing Range: 0.5 to 1.5 mg/kg orally daily
  4. Dose reduction indications (by >50%)
    1. Thiopurine methyltransferase (TPMT) Deficiency
    2. NUDT15 Gene Anomaly (Nudix Hydrolase 15 deficiency)
  • Adverse Effects
  1. Alopecia
  2. Carcinogenic
    1. Case reports of T-Cell Lymphoma development after Mercaptopurine
  3. Myelosuppression
  4. Hepatotoxicity
  5. Hyperuricemia
  6. Hypoglycemia
  7. Lymphoproliferative Disorder
  8. Pancreatitis
  9. Photosensitivity
  10. Portal Hypertension
  • Safety
  1. Avoid in Pregnancy (any trimester)
    1. Use reliable Contraception
  2. Avoid in Lactation
  3. Monitoring
    1. Complete Blood Count
    2. Liver Function Tests
    3. Renal Function tests
  • Drug Interactions
  1. Drugs that increase Mercaptopurine toxicity
    1. Allopurinol
    2. Trimethoprim Sulfamethoxazole
  • Resources
  1. Mercaptopurine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=15904472-4c32-4224-95d3-eb131a7ff9c8