II. Indications
-
Solid Organ Transplant
- Immunosuppression (maintenance prevention of rejection)
- Renal homograft maintenance
- FDA approved in adults (used off-label in children)
- Autoimmune Conditions
III. Contraindications
- TPMT or NUDT15 Deficiency
- Avoid in Homozygous patients (or significantly decrease Azathioprine dose)
- Homozygous patients are at risk of severe myelosuppression
- Thiopurine methyltransferase Deficiency (TPMT Deficiency)
- Nucleotide Diphosphatase Deficiency (NUDT15 Deficiency)
IV. Mechanism
- Azathioprine is a Purine Analog with cytotoxic and Immunosuppressant activity
- Purine Analogs, resembling adenine or guanine, and incorporate into DNA
- Result in DNA cross-linking and inhibition of synthesis and repair of DNA
- Azathioprine is a imidazolyl derivative of Mercaptopurine
- Metabolized to the Mercaptopurine (6-MP) by hepatic xanthine oxidase
- Mercaptopurine is further metabolized to metabolites that inhibit Nucleotide interconversion
- Inhibits Purine, DNA, RNA synthesis (as well as the related Protein synthesis), especially in Lymphocytes and Leukocytes
V. Medications
- Azathioprine IV solution
- Azathioprine (Imuran, Azasan, AZA) Tablets: 50 mg, 75 mg, 100 mg
VI. Dosing: Adults
- See other references for specific dosing
- Prescribers are typically specialists knowledgeable about the risks and monitoring
-
Rheumatoid Arthritis (severe, refractory)
- Start 1 mg/kg (up to 50 to 100 mg) orally daily or divided twice daily
- May increase to 1.5 mg/kg/day at 6 to 8 weeks if tolerated without toxicity
- May increase to 2.0 mg/kg/day after an additional 1 month
- Maximum: 2.5 mg/kg/day
- Maintain the lowest effective dose
-
Kidney Transplant (renal homograft maintenance, dosing is also used off-label in children)
- Start: 3-5 mg/kg IV or oral daily
- Maintenance: 1 to 3 mg/kg/day
-
Autoimmune Conditions (e.g. Myasthenia Gravis, Multiple Sclerosis, Lupus Nephritis, Inflammatory Bowel Disease)
- Typical dosing: 2 to 2.5 mg/kg/day (or 50 to 100 mg) orally daily
- Dosing Range: 1.5 to 3 mg/kg/day
VII. Adverse Effects (similar to Mercaptopurine)
-
Bone Marrow suppression
- Mild to severe Leukopenia
- Anemia
- Thrombocytopenia
- Skin rash
- Drug Fever
- Secondary malignancy (black box warning)
- Post-transplant Lymphoma
- Hepatosplenic T-Cell Lymphoma (HSTCL)
- Skin Cancer
- Gastrointestinal
- Nausea and Vomiting
- Diarrhea
- Hepatic dysfunction (cholestasis, hepatitis)
- Drug-Induced Pancreatitis
VIII. Safety
- Considered safe in Lactation
- May be used in pregnancy if benefit outweighs risk
- Skeletal and visceral malformations have been found in animal studies
- Cytopenias have been observed in infants born to mothers taking Azathioprine
- Monitoring
- Complete Blood Count (CBC)
- Obtain baseline, weekly for 1 month, every 2 weeks for months 2-3, then monthly
- Liver Function Tests
- Complete Blood Count (CBC)
IX. Pharmacoinetics
- Renal excretion
X. Drug Interactions
- See Cytochrome P-450 3A4
- See Purine Synthesis Inhibitor
-
Allopurinol
- Allopurinol inhibits xanthine oxidase conversion of Azathioprine to Mercaptopurine (6-MP)
- May increase serum Azathioprine to toxic levels
- Decrease Azathioprine dose by 66 to 75% if concurrently taking Allopurinol
- Other drugs that increase Azathioprine toxicity
- Azathioprine decreases other drug levels
XI. Resources
- Azathioprine (DailyMed)
- Azathioprine (StatPearls)
XII. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
Images: Related links to external sites (from Bing)
Related Studies
| 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 | |