Azathioprin

Azathioprine is an immunosuppressive medication used in the treatment of autoimmune diseases and to prevent organ transplant rejection. It is a prodrug that is rapidly converted in the body to 6-mercaptopurine (6-MP), which is further metabolized into active thioguanine nucleotides that disrupt purine synthesis and DNA replication in immune cells, leading to decreased proliferation of B and T lymphocytes.

Common indications include inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, as well as maintenance immunosuppression after organ transplantation. It is also employed in various autoimmune conditions, including rheumatoid arthritis and certain vasculitides, usually as part of combination therapy.

Dosing is individualized and monitored. In autoimmune diseases, typical oral dosing ranges from about 1 to 3 mg/kg per day. For transplant recipients, higher doses are used in combination regimens. Response and tolerance guide adjustments, and long-term therapy requires regular laboratory monitoring.

Pharmacokinetics: azathioprine is taken by mouth and has variable bioavailability. It is rapidly converted to 6-MP, which is further metabolized into active and inactive metabolites. The immunosuppressive effect correlates with intracellular levels of thioguanine nucleotides and may take weeks to become evident.

Adverse effects include bone marrow suppression (anemia, leukopenia), hepatotoxicity (including cholestasis and rare fibrosis), pancreatitis, nausea, mucositis, and increased infection risk. Hypersensitivity reactions are possible but uncommon.

Monitoring and interactions: before starting therapy, assess baseline blood counts and liver function; consider TPMT activity testing due to risk of severe myelosuppression in some patients. Allopurinol can markedly increase azathioprine toxicity, necessitating dose adjustments. Live vaccines are generally avoided during immunosuppressive treatment. Contraindications include active infection, significant myelosuppression, and known hypersensitivity.