II. 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

III. 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

IV. Medications

  1. Mercaptopurine tablets: 50 mg
  2. Mercaptopurine oral solution: 20 mg/ml

V. 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)

VI. 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

VII. 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

VIII. Drug Interactions

  1. Drugs that increase Mercaptopurine toxicity
    1. Allopurinol
    2. Trimethoprim Sulfamethoxazole

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Related Studies

Cost: Medications

mercaptopurine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MERCAPTOPURINE 50 MG TABLET Generic $0.85 each

Ontology: mercaptopurine (C0000618)

Definition (NCI) A thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis. (NCI04)
Definition (NCI_NCI-GLOSS) A drug used to treat acute lymphatic leukemia. It belongs to the family of drugs called antimetabolites.
Definition (MSH) An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.
Definition (PDQ) A thiopurine-derivative antimetabolite with antineoplastic and immunosuppressive activities. Produced through the metabolism of mercaptopurine by hypoxanthine-guanine phosphoribosyltransferase (HGPRT), mercaptopurine metabolites 6-thioguanosine-5'-phosphate (6-thioGMP) and 6-thioinosine (T-IMP) inhibit nucleotide interconversions and de novo purine synthesis, thereby blocking the formation of purine nucleotides and inhibiting DNA synthesis. This agent is also incorporated into DNA in the form of deoxythioguanosine, which results in the disruption of DNA replication. In addition, mercaptopurine is converted to 6-methylmercaptopurine ribonucleoside (MMPR) by 6-thiopurine methyltransferase; MMPRs are also potent inhibitors of de novo purine synthesis. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43436&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=43436&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C195" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Nucleic Acid, Nucleoside, or Nucleotide (T114)
MSH D015122
SnomedCT 1039008, 386835005
LNC LP15173-5, MTHU002562
English 6 Mercaptopurine, 6-Mercaptopurine, 6-Thiohypoxanthine, 6-Thiopurine, Mercaptopurine, 6 thiopurine, 6H-Purine-6-thione, 1,7-dihydro-, 1,7-Dihydro-6H-purine-6-thione, 3H-Purine-6-thiol, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Mercapto-6-purine, Purine-6-thiol (8CI), 1,7-Dihydro-6H-purine-6-thione Monohydrate, 6 Thiopurine, 6-Thioxopurine, 6MP, Mern, 6-Purinethiol, 6 Thiohypoxanthine, Mercapurin, MERCAPTOPURINE A 06, 6 mercaptopurine, 6-mercaptopurine (medication), 6-mercaptopurine, MERCAPTOPURINE, mercaptopurine, 6-Mercaptopurine [Chemical/Ingredient], 6-mp, 6-thiopurine, 6 MP, Purine, 6-mercapto-, 6-MP, 6MP - Mercaptopurine, Mercaptopurine (product), Mercaptopurine (substance), MP
Swedish 6-merkaptopurin
Czech 6-merkaptopurin, arabinosyl-6-merkaptopurin
Finnish 6-merkaptopuriini
Russian ARABINOZIL-6-MERKAPTOPURIN, 6-MERKAPTOPURIN, 6-МЕРКАПТОПУРИН, АРАБИНОЗИЛ-6-МЕРКАПТОПУРИН
German MERCAPTOPURIN A 06, 6-Mercaptopurin
Croatian 6-MERKAPTOPURIN
Polish 6-merkaptopuryna
Japanese メルカプトプリン, 6-メルカプトプリン
French Mercaptopurine, 6-Mercaptopurine
Spanish 6-mercaptopurina, mercaptopurina (producto), mercaptopurina (sustancia), mercaptopurina, 6-Mercaptopurina
Italian 6-Mercaptopurina
Portuguese 6-Mercaptopurina