TPMT

Cytosolic enzyme that metabolises thiopurines (azathioprine, mercaptopurine, thioguanine). TPMT deficiency (polymorphism) increases exposure to active metabolites and the risk of myelosuppression.

Drugs that inhibit TPMT (e.g. allopurinol) increase azathioprine toxicity; allopurinol + azathioprine is the classic interaction and requires azathioprine dose reduction.

The allopurinol + azathioprine (or mercaptopurine) combination requires a 50-75% thiopurine dose reduction; consider TPMT testing before starting.