Azathioprine

Aka: Azathioprine, Imuran, Azasan, AZA

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II. Indications

  1. Solid Organ Transplant
    1. Immunosuppression (maintenance prevention of rejection)
    2. Renal homograft maintenance
      1. FDA approved in adults (used off-label in children)
  2. Autoimmune Conditions
    1. Rheumatoid Arthritis (severe, refractory, FDA approved)
    2. Myasthenia Gravis
    3. Multiple Sclerosis
    4. Lupus Nephritis
    5. Behcet's Syndrome
    6. Acute Glomerulonephritis
    7. Inflammatory Bowel Disease (Crohns Disease, Ulcerative Colitis)

III. Contraindications

  1. TPMT or NUDT15 Deficiency
    1. Avoid in Homozygous patients (or significantly decrease Azathioprine dose)
    2. Homozygous patients are at risk of severe myelosuppression
      1. Thiopurine methyltransferase Deficiency (TPMT Deficiency)
      2. Nucleotide Diphosphatase Deficiency (NUDT15 Deficiency)

IV. Mechanism

  1. Azathioprine is a Purine Analog with cytotoxic and Immunosuppressant activity
    1. Purine Analogs, resembling adenine or guanine, and incorporate into DNA
    2. Result in DNA cross-linking and inhibition of synthesis and repair of DNA
  2. Azathioprine is a imidazolyl derivative of Mercaptopurine
    1. Metabolized to the Mercaptopurine (6-MP) by hepatic xanthine oxidase
    2. Mercaptopurine is further metabolized to metabolites that inhibit Nucleotide interconversion
    3. Inhibits Purine, DNA, RNA synthesis (as well as the related Protein synthesis), especially in Lymphocytes and Leukocytes

V. Medications

  1. Azathioprine IV solution
  2. Azathioprine (Imuran, Azasan, AZA) Tablets: 50 mg, 75 mg, 100 mg

VI. Dosing: Adults

  1. See other references for specific dosing
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring
  3. Rheumatoid Arthritis (severe, refractory)
    1. Start 1 mg/kg (up to 50 to 100 mg) orally daily or divided twice daily
    2. May increase to 1.5 mg/kg/day at 6 to 8 weeks if tolerated without toxicity
    3. May increase to 2.0 mg/kg/day after an additional 1 month
    4. Maximum: 2.5 mg/kg/day
    5. Maintain the lowest effective dose
  4. Kidney Transplant (renal homograft maintenance, dosing is also used off-label in children)
    1. Start: 3-5 mg/kg IV or oral daily
    2. Maintenance: 1 to 3 mg/kg/day
  5. Autoimmune Conditions (e.g. Myasthenia Gravis, Multiple Sclerosis, Lupus Nephritis, Inflammatory Bowel Disease)
    1. Typical dosing: 2 to 2.5 mg/kg/day (or 50 to 100 mg) orally daily
    2. Dosing Range: 1.5 to 3 mg/kg/day

VII. Adverse Effects (similar to Mercaptopurine)

  1. Bone Marrow suppression
    1. Mild to severe Leukopenia
    2. Anemia
    3. Thrombocytopenia
  2. Skin rash
  3. Drug Fever
  4. Secondary malignancy (black box warning)
    1. Post-transplant Lymphoma
    2. Hepatosplenic T-Cell Lymphoma (HSTCL)
    3. Skin Cancer
  5. Gastrointestinal
    1. Nausea and Vomiting
    2. Diarrhea
    3. Hepatic dysfunction (cholestasis, hepatitis)
    4. Drug-Induced Pancreatitis

VIII. Safety

  1. Considered safe in Lactation
  2. May be used in pregnancy if benefit outweighs risk
    1. Skeletal and visceral malformations have been found in animal studies
    2. Cytopenias have been observed in infants born to mothers taking Azathioprine
  3. Monitoring
    1. Complete Blood Count (CBC)
      1. Obtain baseline, weekly for 1 month, every 2 weeks for months 2-3, then monthly
    2. Liver Function Tests

IX. Pharmacoinetics

  1. Renal excretion

X. Drug Interactions

  1. See Cytochrome P-450 3A4
  2. See Purine Synthesis Inhibitor
  3. Allopurinol
    1. Allopurinol inhibits xanthine oxidase conversion of Azathioprine to Mercaptopurine (6-MP)
    2. May increase serum Azathioprine to toxic levels
    3. Decrease Azathioprine dose by 66 to 75% if concurrently taking Allopurinol
  4. Other drugs that increase Azathioprine toxicity
    1. ACE Inhibitors
    2. Febuxostat
    3. Methotrexate
  5. Azathioprine decreases other drug levels
    1. Anticoagulants
    2. Cyclosporine
    3. Neuromuscular Blockers

XI. Resources

  1. Azathioprine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=59f3219f-898f-4d05-a430-c2b3f5255af1
  2. Azathioprine (StatPearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK542190/

XII. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia

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Related Studies

Cost: Medications

azathioprine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
AZATHIOPRINE 100 MG TABLET Generic $4.40 each
AZATHIOPRINE 50 MG TABLET Generic $0.19 each
aza (on 12/30/2021 at Medicaid.Gov Survey of pharmacy drug pricing)
AZASITE 1% EYE DROPS $85.78 per ml
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

Ontology: Azathioprine (C0004482)

Definition (CHV) an immunosuppressive drug
Definition (CHV) an immunosuppressive drug
Definition (CHV) an immunosuppressive drug
Definition (CHV) an immunosuppressive drug
Definition (NCI) A purine analogue with cytotoxic and immunosuppressive activity. Azathioprine is a prodrug that is converted by hepatic xanthine oxidase to its active metabolite 6-mercaptopurine (6-MP). 6-MP is further metabolized by hypoxanthine-guanine phosphoribosyltransferase (HGPRT) into 6-thioguanosine-5'-phosphate (6-thio-GMP) and 6-thioinosine monophosphate (6-thio-IMP), both inhibit nucleotide conversions and de novo purine synthesis. This leads to inhibition of DNA, RNA, and protein synthesis. As a result, cell proliferation may be inhibited, particularly in lymphocytes and leukocytes.
Definition (MSH) An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
Definition (CSP) immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis; possible carcinogen.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D001379
SnomedCT 391800005, 327060009, 317390007, 111165009, 372574004
LNC LP18898-4, MTHU006794
English Azathioprine, Azothioprine, 1H-Purine, 6-((1-methyl-4-nitro-1H-imidazol-5-yl)thio)-, Azathioprine [gastrointestinal], Azathioprine [gi], Azathioprine [immunosuppress], 6-[(1-Methyl-4-nitro-1H-imidazol-5-yl)thio]-1H-purine, azathioprine, Azathioprine [immunosuppressant], AZTP, azathioprine (medication), AZATHIOPRINE, Azathioprine [Chemical/Ingredient], atps, ATP, azothioprine, azaTHIOprine, AzaTHIOprine, Azathioprine - chemical (substance), Azathioprine [immunosuppressant] (product), Azathioprine - chemical, Azathioprine [gastrointestinal] (product), AZT - Azathioprine, Azathioprine (product), Azathioprine (substance), Azathioprine [gastrointestinal] (substance), AZA
Swedish Azatioprin
Czech azathioprin
Finnish Atsatiopriini
Italian Azotioprina, Azatioprina
Russian IMURAN, AZATIOPRIN, АЗАТИОПРИН, ИМУРАН
Japanese イムラン, アザチオプリン
Polish Azatiopryna
Spanish azatioprina (gastrointestinal) (producto), azatioprina (gastrointestinal), azatioprina (producto), azatioprina (sustancia), azatioprina, Azatioprina
French Azathioprine
German Azathioprin
Portuguese Azatioprina
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Imuran (C0699279)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D001379
English Immuran, imuran, immuran, Imuran
French Imuran
German Imuran, Immuran
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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