Azathioprine

Azathioprine has been used for decades. Once swallowed, it is converted to 6-mercaptopurine, which takes the place of a normal building block in DNA and so slows the multiplication of lymphocytes, the white cells behind transplant rejection and autoimmune attack. Benefit appears only after some weeks. Many people stay on it for years, and it often allows the dose of a steroid taken alongside to be reduced.

The UK SmPC has two families of use. Transplant recipients (kidney, heart or liver) take it to lower the chance that the graft is rejected. Among immune-mediated diseases it is 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 idiopathic thrombocytopenic purpura, and for moderate to severe inflammatory bowel disease. In each case it is brought in when steroids alone are not enough, or when a lower steroid dose is wanted.

The 25 mg tablet comes in packs of 30, 60, 90 and 120. For 50 mg the same four sizes apply, plus 240 and 270, and all of it is imported stock. The SmPC bases every dose on body weight, in milligrams per kilogram. For transplant patients the first-day dose can reach 5 mg/kg and long-term treatment is 1 to 4 mg/kg daily, often for life. For the other conditions the starting dose is generally 1 to 3 mg/kg daily; maintenance doses may be below 1 mg/kg daily, and the SmPC suggests reconsidering treatment if nothing has improved after three months, except in inflammatory bowel disease. In inflammatory bowel disease three to four months may pass before benefit shows, and at least a year of treatment is expected. Because the tablets are film-coated they should not be split, so a prescriber who wants an intermediate dose chooses another strength.

Before the first dose a prescriber may check TPMT activity, and NUDT15 where that is relevant, because low enzyme activity makes marrow suppression more likely. Blood counts are taken every week during the first eight weeks and then at intervals of no more than three months, and liver function is tested routinely. Tell the prescriber promptly about bruising or bleeding with no obvious cause, and about a sore throat, high temperature or any other hint of infection. Skin cancer becomes more likely after years of immunosuppression; hats, sleeves and a high-factor sunscreen are worthwhile. Live vaccines must be avoided. If pregnancy occurs or is planned, the doctor weighs the benefit to the mother against any risk, as the SmPC directs.

Allopurinol, oxipurinol and thiopurinol slow the clearance of azathioprine, which is why the dose is cut to a quarter, and febuxostat is not advised in combination. Warfarin may lose some of its effect with azathioprine, and co-trimoxazole, ACE inhibitors, cimetidine, indometacin and ribavirin also interact with it.

A low white cell count from marrow suppression is very common, as are infections in people who have had a transplant. Common effects include a fall in platelets and nausea. Anaemia, pancreatitis, allergic-type reactions and abnormal liver tests are less frequent, while hair loss and serious liver injury are rare.

In Britain azathioprine is available only on prescription. Several companies market licensed 25 mg and 50 mg tablets, and there is an oral suspension too. A hospital team will usually start treatment and then hand routine monitoring to the GP under a shared-care arrangement. The treating doctor chooses whether Azathioprine is right for the patient and keeps watch on progress, since blood tests and dose changes are as much a part of treatment as the tablets themselves.