Azathioprine
Mechanism :
Azathioprine is an immunosuppressive antimetabolite. It inhibits proliferation of both B and T lymphocytes.
Indication :
- As an adjunct for the prevention of rejection in renal homotransplantations, cardiac and hepatic transplants
- Connective tissue diseases and vasculitis
- Inflammatory bowel disease
- Juvenile Idiopathic Arthritis
- Lupus nephritis
- Autoimmune hepatitis
Contraindications :
Azathioprine should not be given to patients who have shown hypersensitivity to the drug. Patients previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a risk of neoplasia if treated with azathioprine.
Dosing :
TPMT genotyping or phenotyping can be used to identify patients with absent or reduced TPMT activity. Patients with low or absent TPMT activity are at an increased risk of developing severe, life threatening myelotoxicity from azathioprine.
Organ transplantation to prevent rejection:
Initially 3-5 mg/kg/day IV or oral on transplant day or rarely 3 days before transplant; maintenance 1-3 mg/kg/day IV or oral.
Autoimmune disease like lupus nephritis:
2 mg/kg/dose once daily with or without corticosteroids (low-dose).
Juvenile Idiopathic Arthritis and Inflammatory bowel disease:
Initially, 1 mg/kg/day IV/oral in a single or 12 hourly divided doses; may be increased 0.5 mg/kg/day after 6-8 week, followed by 0.5 mg/kg/day every 4 week; maximum dose: 2.5 mg/kg/day.
Myasthenia gravis, juvenile:
Oral: 1 to 3 mg/kg/dose once daily.
Adverse Effect :
Reversible bone marrow suppression, lymphoma, nausea, vomiting, diarrhea, fever, rash, dizziness, hepatitis and pancreatitis.
Interaction :
Allopurinol: Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of azathioprine.
Other Agents Affecting Myelopoiesis: May lead to exaggerated leukopenia, especially in renal transplant recipients.
Angiotensin Converting Enzyme Inhibitors: Severe leukopenia.
Live vaccines: Atypical, harmful reactions are seen.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | 75–100% |
| <10 | 50–100% |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Dialysed. Dose as in normal renal function |
| HD | Dialysed. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Dialysed. Dose as in normal renal function |
Hepatic Dose :
No dosage adjustments are recommended. Discontinue azathioprine if veno-occlusive disease occurs.