💊 Azathioprine

Azathioprine is an immunosuppressant drug, classified as an antimetabolite. It is a prodrug of 6-mercaptopurine.

Azathioprine is metabolised to 6-mercaptopurine (6-MP), which then interferes with purine synthesis. This inhibits DNA and RNA synthesis, particularly in rapidly dividing cells like lymphocytes, thereby suppressing immune responses.

In the UK, it is widely used for organ transplant rejection prophylaxis, often in combination with other immunosuppressants. It is also indicated for severe rheumatoid arthritis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), and various other autoimmune conditions like SLE and autoimmune hepatitis.

Absolute contraindications include hypersensitivity to azathioprine or 6-mercaptopurine. It is also contraindicated in patients with severe bone marrow suppression. Caution is advised in patients with active infection or severe hepatic/renal impairment.

Common side effects include nausea, vomiting, and loss of appetite. Serious adverse effects include dose-dependent bone marrow suppression (leukopenia, thrombocytopenia, anaemia), hepatotoxicity, and an increased risk of infections and malignancies (e.g., skin cancers, lymphoma).

Baseline and regular monitoring of full blood count (FBC), liver function tests (LFTs), and renal function tests (U&Es) are essential. Thiopurine methyltransferase (TPMT) enzyme activity should be measured before starting treatment to identify patients at high risk of myelosuppression.

Always check for TPMT status before prescribing. Counsel patients on the increased risk of infection and to report any signs of illness, fever, or unexplained bruising/bleeding. Advise on sun protection due to increased skin cancer risk.

A cornerstone immunosuppressant, remember its prodrug nature and the critical role of TPMT genotyping. High yield for its significant bone marrow suppression and increased risk of infection and malignancy. Often used as a steroid-sparing agent.

SBAs frequently test the importance of TPMT testing before initiation to prevent severe myelosuppression. Questions may also focus on its broad immunosuppressive effects, leading to increased infection and malignancy risk, and its use across transplant and autoimmune conditions.