Makindo Medical Notes

Screen for Thiopurine methyltransferase deficiency an enzyme that metabolises azathioprine. Patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. inexplicable bruising or bleeding, infection

About: Always check the BNF link here

• Drug used to suppress the immune system by its effect on purine metabolism
• Used in autoinflammatory diseases and transplant medicine
• About 1 in 300 have very low levels of TPMT which increases toxicity

Mechanism

• Azathioprine is converted to 6-mercaptopurine
• Formation of 6-ThioGTP can cause cell apoptosis
• Effect mainly on T cell function. Blocks cell-mediated rejection

Indication/Dose

• Suppression of transplant rejection, Azathioprine 1-2.5 mg/kg daily adjusted according to response
• Autoimmune conditions, Azathioprine 1-3 mg/kg daily, adjusted according to response (consider withdrawal if no improvement within 3 months)
• Inflammatory bowel disease (normal TPMT level) TARGET dose is Azathioprine 2mg to 2.5 mg/kg OD PO.
• Drug should be started at half target dose for first week to minimise side effects. In patients with low TPMT levels take expert advice

Side effects

• Bone marrow suppression, Suppresses red cell and platelet production
• Hypersensitivity, malaise, dizziness, Arthralgia, Rash, alopecia
• Pancreatitis, liver and renal impairment
• IV dose is alkaline and very irritant and should be used only if the oral route not feasible

Dose range:You must check with BNF or drug datasheet

Cautions

• Monitor FBC weekly 4-8 weeks slowly to every 3 months
• Thiopurine methyltransferase deficiency increases azathioprine toxicity

Interactions

• Allopurinol and Azathioprine or Mercaptopurine is a potentially lethal combination
• Requires oxidation by Xanthine Oxidase before renal excretion
• Azathioprine toxicity with Allopurinol
• Azathioprine toxicity with ACE Inhibitors, Angiotensin receptor blockers, Trimethoprim, Rifampicin