Azathioprine

Azathioprine is converted in the body into 6-mercaptopurine and then into thioguanine nucleotides, which slow the multiplication of white blood cells, particularly lymphocytes. The result is a steady, gradual reduction in immune activity rather than a quick effect; benefit in autoimmune disease often takes several weeks, sometimes up to three months, to appear. The UK SmPC covers its use with corticosteroids or other immunosuppressants to prevent rejection after kidney, heart and liver transplants. It is also licensed for severe rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis and polymyositis, autoimmune chronic active hepatitis, pemphigus vulgaris, polyarteritis nodosa, autoimmune haemolytic anaemia and chronic refractory immune thrombocytopenic purpura. In everyday practice it is widely prescribed for Crohn’s disease and ulcerative colitis, often as a steroid-sparing treatment.

Two strengths are listed. The 25 mg tablets come in packs of 30, 60, 90 or 120, and the 50 mg tablets in packs of 30, 60, 90, 120, 240 or 270. Because the dose is calculated from body weight, many people combine the two strengths to reach the right daily total. The tablets are film-coated and should be swallowed whole, not split or crushed, and anyone handling broken tablets should wash their hands afterwards.

For transplant patients the SmPC allows up to 5 mg per kg on the first day, followed by a maintenance dose usually between 1 and 4 mg per kg a day. In the other conditions the usual range is 1 to 3 mg per kg daily, adjusted to response and blood counts, then reduced to the lowest effective amount. Lower doses are considered for older people and for those with kidney or liver impairment. Taking the tablets with food can ease nausea. Before the first dose, a blood test for thiopurine methyltransferase (TPMT) activity is usually arranged, because people with low or absent TPMT are at high risk of severe bone marrow suppression on standard doses.

Azathioprine is a prescription-only medicine (POM). The original brand is Imuran, and generic tablets are produced by several manufacturers. Full blood counts are checked at least weekly for the first eight weeks, with liver tests at regular intervals, and then less often, at intervals of no more than three months, once the dose is stable. Treatment is generally started and supervised by a specialist team, often with shared care through the GP, and any decision to begin, change or stop it rests with the prescriber.

It must not be taken by anyone hypersensitive to azathioprine or mercaptopurine. Live vaccines, such as yellow fever, BCG or the oral typhoid vaccine, are avoided during treatment. Allopurinol, oxipurinol, thiopurinol and febuxostat block the breakdown of the drug; if allopurinol cannot be avoided, the azathioprine dose is cut to a quarter, and febuxostat is not recommended at all. Co-trimoxazole, trimethoprim, ACE inhibitors, cimetidine and indometacin can add to the effect on the bone marrow. Warfarin may become less effective, and ribavirin, methotrexate and infliximab need careful thought. Pregnancy and breastfeeding should be discussed with the specialist before and during treatment.

Infections, reduced white cells and platelets, and nausea are among the most frequent problems, especially early on. Seek medical advice quickly for fever, sore throat, mouth ulcers, unexplained bruising or bleeding, or yellowing of the skin. Pancreatitis, liver injury and hypersensitivity reactions with fever, rash and joint pain are less common. Long-term use raises the risk of skin cancer and lymphoma, so high-factor sunscreen and covering up in strong sunlight are advised. Shingles and other viral infections can be more severe; contact with chickenpox or shingles should be reported.