Azathioprine Chemical formula
Synonyms: Atsatiopriini; Azathioprin; Azathioprinum; Azatioprin; Azatioprina; Azatioprinas; Azatiopryna; BW-57322; NSC-39084. 6-(1Methyl-4-nitroimidazol-5-ylthio)purine.
Cyrillic synonym: Азатиоприн.

💊 Chemical information

Chemical formula: C9H7N7O2S = 277.3.
CAS — 446-86-6.
ATC — L04AX01.
ATC Vet — QL04AX01.


In Chin., Eur., Int., Jpn, and US.

Ph. Eur. 6.2

(Azathioprine). A pale yellow powder. Practically insoluble in water and in alcohol; soluble in dilute solutions of alkali hydroxides; sparingly soluble in dilute mineral acids. Protect from light.

USP 31

(Azathioprine). A pale yellow, odourless powder. Insoluble in water; very slightly soluble in alcohol and in chloroform; sparingly soluble in dilute mineral acids; soluble in dilute solutions of alkali hydroxides. Store in airtight containers. Protect from light.

💊 Adverse Effects

Dose-related bone-marrow depression is common with use of azathioprine; this may be manifested as leucopenia or, less often, thrombocytopenia or anaemia, and rarely, as agranulocytosis, pancytopenia, or aplastic anaemia. Myelosuppression is generally reversible, and may occasionally be delayed. Macrocytic, including megaloblastic, anaemia has occurred. Patients with an inherited deficiency of the enzyme thiopurine methyltransferase (TPMT) may be at increased risk of myelotoxicity. Azathioprine has also been associated with the development of liver damage; it has been suggested that cholestatic symptoms may be due to the mercaptopurine moiety. Rarely, delayed and potentially fatal veno-occlusive liver disease has occurred. Other adverse effects associated with azathioprine include gastrointestinal disturbances, reversible alopecia, and symptoms including rashes, muscle and joint pains, fever, rigors, pneumonitis, pancreatitis, tachycardia, renal dysfunction, and hypotension, some or all of which may represent hypersensitivity reactions. Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely. Solutions for injection are irritant.
1. Lawson DH, et al. Adverse effects of azathioprine. Adverse Drug React Acute Poisoning Rev 1984; 3: 161–71.


Immunosuppression, including that with azathioprine, may be associated with an increased risk of certain neoplasms such as lymphomas and skin cancers in transplant recipients,1 in patients with inflammatory bowel disease,2,3 and in patients with rheumatoid arthritis.4-6 Partly because of lower doses of immunosuppressants used in inflammatory bowel disease, the risk of lymphoma in these patients appears to be less than that associated with transplant recipients;7 this risk appears to be far outweighed by the benefits of immunosuppressant therapy in inflammatory bowel disease. Rheumatic diseases may themselves be associated with an increased risk of malignancy that is independent of treatment, but one study5 concluded that there is a further risk related to the duration of exposure to immunosuppressive drugs, including azathioprine. A recent systematic review8 of the use of azathioprine for multiple sclerosis concluded that, when the balance between the benefits and harms were considered, azathioprine was a reasonable alternative to interferon beta in patients who frequently relapse and require corticosteroids. Other evidence in the literature suggested that the longterm risk of malignancy may be related to use for longer than 10 years and a cumulative dose above 600 g and the reviewers recommended that this dose should not be exceeded. Skin cancer may be a particular risk in immunosuppressed patients with a history of high sun exposure.7 A synergistic clastogenic effect has been noted with azathioprine and long-wave ultraviolet light.
1. Kinlen LJ, et al. Collaborative United Kingdom-Australasian study of cancer in patients treated with immunosuppressive drugs. BMJ 1979; 2: 1461–6
2. Kandiel A, et al. Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 2005; 54: 1121–5
3. Kwon JH, Farrell RJ. The risk of lymphoma in the treatment of inflammatory bowel disease with immunosuppressive agents. Crit Rev Oncol Hematol 2005; 56: 169–78.
4. Silman AJ, et al. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis 1988; 47: 988–92
5. Asten P, et al. Risk of developing certain malignancies is related to duration of immunosuppressive drug exposure in patients with rheumatic diseases. J Rheumatol 1999; 26: 1705–14
6. Patel P, et al. Azathioprine induced Hodgkin lymphoma: a case report and review of literature. Am J Clin Oncol 2005; 28: 427–8
7. Boyle J, et al. Cancer, warts, and sunshine in renal transplant patients: a case-control study. Lancet 1984; i: 702–5
8. Casetta I, et al. Azathioprine for multiple sclerosis. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2007 (accessed 24/01/08).

Effects on the blood.

Neutropenia in patients receiving mercaptopurine has been reported to correlate negatively with the concentration of the metabolite tioguanine nucleotide in erythrocytes,1 and it has been suggested that measurement of metabolite concentrations in erythrocytes,2 or activity of the enzyme thiopurine methyltransferase (TPMT),3-6 permits prediction of those individuals likely to experience severe bone-marrow toxicity with mercaptopurine and the related drugs tioguanine and azathioprine. However, not all studies have found such correlations,7and effects on the bone marrow with this class of drugs are probably multifactorial;8,9 low activity of other enzymes such as lymphocyte 5-nucleotidase,10 and other factors, may contribute to toxicity. A review9 of studies investigating TPMT activity in patients with Crohn’s disease concluded that measurement of TPMT activity on starting azathioprine has a role in identifying those at risk of severe myelosuppression. Lower TPMT activities correlate with low neutrophil counts in the initial 4 months of thiopurine therapy; identification of the heterozygote might allow for safer management (see Therapeutic Drug Monitoring, below). However, in those patients established on therapy, TPMT did not predict clinical response or toxicity. Pure red cell aplasia occurs rarely with use of azathioprine; reported cases have all been in renal transplant recipients. In one such case,11reduction of the dose and use of erythropoietin was ineffective; however, the patient recovered within weeks of stopping azathioprine.
1. Lennard L, et al. Childhood leukaemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. Br J Clin Pharmacol 1983; 16: 359–63
2. Maddocks JL, et al. Azathioprine and severe bone marrow depression. Lancet 1986; i: 156
3. Schütz E, et al. Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet 1993; 341: 436
4. Lennard L, et al. Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia. Arch Dis Child 1993; 69: 577–9
5. Jackson AP, et al. Thiopurine methyltransferase levels should be measured before commencing patients on azathioprine. Br J Dermatol 1997; 136: 133–4
6. Black AJ, et al. Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine. Ann Intern Med 1998; 129: 716–18
7. Boulieu R, et al. Intracellular thiopurine nucleotides and azathioprine myelotoxicity in organ transplant patients. Br J Clin Pharmacol 1997; 43: 116–18
8. Soria-Royer C, et al. Thiopurine-methyl-transferase activity to assess azathioprine myelotoxicity in renal transplant recipients. Lancet 1993; 341: 1593–4
9. Lennard L. TPMT in the treatment of Crohn’s disease with azathioprine. Gut 2002; 51: 143–6
10. Kerstens PJSM, et al. 5-Nucleotidase and azathioprine-related bone-marrow toxicity. Lancet 1993; 342: 1245–6
11. Agrawal A, et al. Azathioprine-induced pure red cell aplasia: case report and review. Transplant Proc 2004; 36: 2689–91.

Effects on the liver.

A review1 of drug-related hepatotoxicity noted that azathioprine has been associated with hepatocanalicular cholestasis, in which the interference with bile flow is combined with hepatocyte damage, and with several hepatic vascular disorders, including focal sinusoidal dilatation, peliosis, and veno-occlusive disease. A later review2 grouped reported cases into three syndromes: hypersensitivity, idiosyncratic cholestatic reaction, and presumed endothelial cell injury, with the imidazole and 6-mercaptopurine components of azathioprine playing different roles in pathogenesis.
1. Sherlock S. The spectrum of hepatotoxicity due to drugs. Lancet 1986; ii: 440–4
2. Romagnuolo J, et al. Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. Can J Gastroenterol 1998; 12: 479–83.


In 2 of 5 renal transplant recipients with acute allergic reactions associated with azathioprine, the symptoms (interstitial nephritis) were initially mistaken for acute rejection episodes.1 In another report,2 shock, fever, and acute renal insufficiency in a patient led to an initial mistaken diagnosis of sepsis, and it was recommended that a hypersensitivity reaction be considered as a cause if any of these symptoms occurred within 4 weeks of azathioprine ingestion. Other reported features of hypersensitivity include malaise, gastrointestinal disturbances, myalgia, arthralgia, fever, headache and raised liver enzymes.3,4Skin lesions have been reported, with maculopapular erythema occurring most frequently; purpura, urticaria, and erythema nodosum-like lesions have also been described.4,5 Skin biopsies often showed features of leucocytoclastic vasculitis.4 StevensJohnson syndrome has also been reported.5 In some cases, skin patch testing for azathioprine was negative;3,5 a drug-induced lymphocyte stimulation test (which evaluates the antigen specific reactivity of lymphocytes by measuring the proliferation of peripheral blood lymphocytes exposed to the suspected drug) has been proposed as a sensitive and reliable test for azathioprine hypersensitivity.5
1. Parnham AP, et al. Acute allergic reactions associated with azathioprine. Lancet 1996; 348: 542–3
2. Fields CL, et al. Hypersensitivity reaction to azathioprine. South Med J 1998; 91: 471–4
3. Hinrichs R, et al. Azathioprine hypersensitivity in a patient with peripheral demyelinating polyneuropathy. Br J Dermatol 2003; 148: 1076–7
4. Sinico RA, et al. Azathioprine hypersensitivity: report of two cases and review of the literature. J Nephrol 2003; 16: 272–6
5. Mori H, et al. Drug eruption caused by azathioprine: value of using the drug-induced lymphocytes stimulation test for diagnosis. J Dermatol 2004; 31: 731–6.

💊 Precautions

Regular monitoring of blood counts is required. Patients with renal or hepatic impairment require more frequent monitoring of blood counts and may need reduced doses; liver function tests should be performed in hepatic impairment. Consideration should be given to testing patients for thiopurine methyltransferase (TPMT) activity. Intra-uterine devices should be used with caution during immunosuppressive treatment as there is an increased risk of infection. Use of live vaccines should be avoided for the same reason. Azathioprine should generally be avoided in pregnancy (see below). For a recommendation that the cumulative dose of azathioprine should not exceed 600 g in patients with multiple sclerosis, see under Carcinogenicity, above.

Breast feeding.

Low concentrations of mercaptopurine have been found in human colostrum and breast milk of patients taking azathioprine.1 Breast feeding by these patients has not been recommended because of the potential risk of immunosuppression in the infant.1-3 However, there are reports1,2 of 3 breast-fed infants, whose mothers had been taking doses of 75 or 100 mg of azathioprine daily, in whom no evidence of immunosuppression was found. All 3 had normal blood counts, no increase in infections, and above average growth rate. In one case, the levels of mercaptopurine were determined at 2 days and after 2 weeks of breast feeding,1 and in the other 2 cases, no levels were determined.2 In a third report, 31 breast-milk samples were collected from 10 breast-feeding women (taking from 75 to 150 mg azathioprine daily);3 low concentrations of mercaptopurine were only detected in one case. The neonates were followed for up to 28 days, and showed no signs of immunosuppression, nor were mercaptopurine and tioguanine nucleotides detectable in their red blood cells. The authors concluded that breast feeding should not be withheld in infants of mothers receiving azathioprine. However, they cautioned that there were no data on the effect of thiopurine methyltransferase (TPMT) activity (see Therapeutic Drug Monitoring, below) on metabolite concentrations in breast milk, and expressed concern as to whether a TPMT-deficient infant, unable to inactivate mercaptopurine absorbed into the breast milk, will be exposed to significant blood levels of the drug. In a study of 4 mothers and their infants,4 all of whom had the wild-type TPMT genotype (with normal TPMT activity), infant exposure to azathioprine through breast milk was undetectable. The authors also cautioned that mothers taking higher doses or those with decreased TPMT activity might transfer more drug to the infant. It has been noted5 that many breast-fed infants would have already been exposed to potentially much higher concentrations of mercaptopurine in utero.
1. Coulam CB, et al. Breast-feeding after renal transplantation. Transplant Proc 1982; 14: 605–9
2. Grekas DM, et al. Immunosuppressive therapy and breast-feeding after renal transplantation. Nephron 1984; 37: 68
3. Sau A, et al. Azathioprine and breastfeeding—is it safe? Br J Obstet Gynaecol 2007; 114: 498–501
4. Gardiner SJ, et al. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol 2006; 62: 453–6
5. Moretti ME, et al. Breast-feeding during maternal use of azathioprine. Ann Pharmacother 2006; 40: 2269–72.


Azathioprine and/or its metabolites have been found in low concentrations in fetal blood after maternal use of azathioprine.1 Azathioprine is teratogenic in animals, and congenital abnormalities, chromosomal aberrations,2 fetal growth retardation,3,4 low birth-weight, and spontaneous abortion have been reported in the offspring of pregnant women taking azathioprine. Neonatal leucopenia and thrombocytopenia have also been reported after maternal exposure.5 Cohort studies have found an increased risk of congenital abnormalities, perinatal mortality, and preterm births after maternal or paternal exposure to azathioprine.6,7 However, adverse birth outcomes may be related to the underlying disease rather than use of azathioprine or mercaptopurine,8 and some consider its use in inactive inflammatory bowel disease to be safe;9 however, there is suggestion that those with active disease, especially Crohn’s disease, may have a higher incidence of spontaneous abortion, premature births, or still-births.9 Given the nature of the severe chronic conditions for which azathioprine is generally used, stopping therapy in patients who become pregnant may not be necessary or desirable, but it seems prudent to avoid its use where possible during pregnancy.
1. de Boer NKH, et al. Azathioprine use during pregnancy: unexpected intrauterine exposure to metabolites. Am J Gastroenterol 2006; 101: 1390–2
2. The Registration Committee of the European Dialysis and Transplant Association. Successful pregnancies in women treated by dialysis and kidney transplantation. Br J Obstet Gynaecol 1980; 87: 839–45
3. Pirson Y, et al. Retardation of fetal growth in patients receiving immunosuppressive therapy. N Engl J Med 1985; 313: 328
4. Hou S. Retardation of fetal growth in patients receiving immunosuppressive therapy. N Engl J Med 1985; 313: 328
5. Davison JM, et al. Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients. Br J Obstet Gynaecol 1985; 92: 233–9
6. Nørgård B, et al. Azathioprine, mercaptopurine and birth outcome: a population-based cohort study. Aliment Pharmacol Ther 2003; 17: 827–34
7. Nørgård B, et al. The risk of congenital abnormalities in children fathered by men treated with azathioprine or mercaptopurine before conception. Aliment Pharmacol Ther 2004; 19: 679–85
8. Langagergaard V, et al. Birth outcome in women treated with azathioprine or mercaptopurine during pregnancy: a Danish nationwide cohort study. Aliment Pharmacol Ther 2007; 25: 73–81
9. Alstead EM, et al. Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 1990; 99: 443–6.

💊 Interactions

The effects of azathioprine are enhanced by allopurinol and the dose of azathioprine should be reduced to onethird to one-quarter of the usual dose when allopurinol is given. A further dose reduction or alternative therapy should be considered in those patients with low or absent thiopurine methyltransferase (TPMT) activity.

Gastrointestinal drugs.

For mention of 5-aminosalicylates inhibiting the metabolism of thiopurines such as azathioprine, and increasing their toxicity, see Mercaptopurine.


The Institute for Safe Medication Practices in the USA reported a case in which a patient with a history of Crohn’s disease was prescribed azathioprine and mercaptopurine by separate practitioners. The patient developed profound myelosuppression, severe sepsis, and died. Many drug information software programs were found to not warn of this possible therapeutic duplication.1
1. Institute for Safe Medication Practices. Duplication with azathioprine and mercaptopurine (issued 29 June, 2006). Available at: 20060629_3.asp?ptr=y (accessed 15/01/08)

💊 Pharmacokinetics

Azathioprine is well absorbed from the gastrointestinal tract when given orally. After oral or intravenous doses it disappears rapidly from the circulation and is extensively metabolised to mercaptopurine. Both azathioprine and mercaptopurine are about 30% bound to plasma proteins. About 10% of a dose of azathioprine is reported to be split between the sulfur and the purine ring to give 1-methyl-4-nitro-5-thioimidazole. The proportion of different metabolites is reported to vary between patients. Metabolites and small amounts of unchanged azathioprine and mercaptopurine are eliminated in the urine. Azathioprine is distributed into breast milk in low concentrations.

Therapeutic drug monitoring.

Although plasma concentrations of 6-thiouric acid (the inactive product of mercaptopurine, and hence of azathioprine) can be readily measured in patients who have been receiving azathioprine, they are of little value in therapeutic drug monitoring.1 The active moieties are the tioguanine nucleotides (6-TGN) formed intracellularly, which appear to have extremely long half-lives,2 and mean erythrocyte concentrations of which appear to vary considerably between individuals.2 The formation of other inactive metabolites is catalysed by thiopurine methyltransferase (TPMT) and its activity is genetically determined, with a trimodal distribution in the general population; 0.3% have low activity of TPMT, 11% have intermediate activity, and 89% have normal or high activity. Patients with low or intermediate activity appear to shift metabolism toward production of 6-TGN. Because excess concentrations of 6-TGN have been associated with leucopenia, it has been suggested3 that:
patients with normal or high TPMT activity receive standard doses of azathioprine or mercaptopurine
those with intermediate TPMT activity have reduced doses
those with low activity not be treated with either drug However, these recommendations remain controversial.4
Haematological toxicity is not always explained by TPMT status, and other factors may be involved5 (see also Effects on the Blood, above). Some consider that TPMT deficiency is not a contra-indication to thiopurine therapy; an initial dose reduction to 10 to 15% of the standard azathioprine dose has been used in TPMT-deficient patients with inflammatory bowel disease.5There are a proportion of patients in whom TPMT activity is very high; these patients appear to respond less well to standard doses, and higher-than-standard doses have been recommended.6 While recommendations for pre-treatment measurement of TPMT status remain controversial,4,5 some consider the avoidance of potentially fatal toxicity a compelling argument for TPMT assessment before thiopurine therapy is started.6 However, TPMT units and normal ranges vary between laboratories depending on the methodology used,6 and TPMT genotype or phenotype testing is not a surrogate for monitoring of complete blood counts.4 Because low concentrations of erythrocyte 6-TGN have been associated with disease relapse in lymphomas and leukaemias, a small study7 of patients with inflammatory bowel disease attempted to define a therapeutic window of drug efficacy. Without monitoring TPMT genotype, treatment efficacy was found to correlate with erythrocyte 6-TGN levels. It was concluded that patients who remain symptomatic despite apparently therapeutic 6-TGN concentrations should be treated with adjunctive or alternative immunosuppression or surgery. However, a large study8did not confirm disease correlation with 6-TGN concentrations, and concluded that therapeutic drug monitoring of 6-TGN may be premature. It was noted that methodological differences, such as assay technique, existed between their study and others. As the role of routine monitoring of 6-TGN remains controversial,4,9,10it has been suggested that selective monitoring, such as in those with low or intermediate TPMT activity, be considered.3 Some consider the measurement of 6-TGN useful to assess treatment compliance, or in cases of malabsorption.4
1. Chan GLC, et al. Pharmacokinetics of 6-thiouric acid and 6mercaptopurine in renal allograft recipients after oral administration of azathioprine. Eur J Clin Pharmacol 1989; 36: 265–71
2. Chan GLC, et al. Azathioprine metabolism: pharmacokinetics of 6-mercaptopurine, 6-thiouric acid and 6-thioguanine nucleotides in renal transplant patients. J Clin Pharmacol 1990; 30: 358–63
3. Sandborn WJ. Rational dosing of azathioprine and 6-mercaptopurine. Gut 2001; 48: 591–2
4. Lichtenstein GR. Use of laboratory testing to guide 6-mercaptopurine/azathioprine therapy. Gastroenterology 2004; 127: 1558–64
5. Teml A, et al. Thiopurine treatment in inflammatory bowel disease: clinical pharmacology and implication of pharmacogenetically guided dosing. Clin Pharmacokinet 2007; 46: 187–208
6. Sanderson J, et al. Thiopurine methyltransferase: should it be measured before commencing thiopurine drug therapy? Ann Clin Biochem 2004; 41: 294–302
7. Cuffari C, et al. Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease. Gut 2001; 48: 642–6
8. Lowry PW, et al. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut 2001; 49: 665–70
9. Dubinsky MC. Monitoring of AZA/6-MP treatment in children with IBD is necessary. Inflamm Bowel Dis 2003; 9: 386–8
10. Griffiths AM. Monitoring of azathioprine/6-mercaptopurine treatment in children with IBD is not necessary. Inflamm Bowel Dis 2003; 9: 389–91.

💊 Uses and Administration

Azathioprine is an immunosuppressive antimetabolite with similar actions to those of mercaptopurine, to which it is converted in the body. Its effects may not be seen for several weeks after a dose. It is given orally, but where this is not feasible it may be given by slow intravenous injection or by infusion as azathioprine sodium. If given by infusion, the required dose should be diluted to a concentration of 0.25 to 2.5 mg/mL in sodium chloride 0.9% or glucose 5%, and infused over 30 to 60 minutes. Azathioprine is mainly used as an immunosuppressant for the prevention of rejection in organ and tissue transplantation. The dose for this purpose, given orally or intravenously, varies from 1 to 5 mg/kg daily and depends partly on the regimen used; the higher doses are used initially, adjusted according to clinical response and haematological tolerance. Azathioprine is also used in auto-immune diseases or conditions that are considered to have an auto-immune component, see below. The usual dose of azathioprine, given orally or intravenously, in these conditions is in the range of 1 to 3 mg/kg daily. If no improvement is seen after 12 weeks, therapy may be stopped. For doses in children, see Administration in Children, below. Use of azathioprine with a corticosteroid may have a corticosteroid-sparing effect. Blood counts should be carried out regularly during treatment and azathioprine withdrawn or the dosage reduced at the first indication of bone-marrow depression. Measurement of thiopurine methyltransferase (TPMT) activity may be used to identify patients at risk of haematological toxicity, although this cannot substitute for blood count monitoring.

Administration in children.

UK licensed product information for azathioprine allows for the same doses in children as those used in adults (see Uses and Administration, above), both in organ and tissue transplantation and for diseases with an autoimmune component. The BNFC recommends that children aged 1 month to 18 years be given a maintenance dose of 1 to 3 mg/kg once daily for suppression of transplant rejection; alternatively, the total daily dose may be given in 2 divided doses. Although unlicensed for severe ulcerative colitis and Crohn’s disease, the BNFC states that azathioprine may be given to children aged 2 to 18 years in an oral dose of 2 mg/kg (if necessary up to 3 mg/kg) once daily, reduced according to response to the lowest effective dose; alternatively, the total daily dose may be given in 2 divided doses.

Administration in hepatic or renal impairment.

UK licensed product information states that controlled studies have not supported the suggestion that toxicity of azathioprine might be enhanced in the presence of renal impairment. Nevertheless, doses used should be at the lower end of the normal range, and haematological response should be carefully monitored. US licensed product information also recommends low doses, while stating that relatively oliguric patients, especially those with tubular necrosis in the immediate post-cadaveric transplant period, may have delayed clearance of azathioprine and/or its metabolites. UK licensed product information states that the metabolism of azathioprine may be impaired in patients with hepatic dysfunction; regular blood counts and liver function tests should be performed and the dosage of azathioprine reduced if hepatic or haematological toxicity occurs.

Blood disorders.

Immunosuppressants such as azathioprine are occasionally tried in auto-immune haemolytic anaemia refractory to other treatment and may permit reduction of corticosteroid dosage. Similarly in patients with idiopathic thrombocytopenic purpura, immunosuppressants may be tried as a last resort. Azathioprine with a corticosteroid has been tried in the rare condition of acquired haemophilia.

Cogan’s syndrome.

Azathioprine has been used with corticosteroids for severe Cogan’s syndrome with large-vessel vasculitis.

Connective tissue and muscular disorders.

Azathioprine is one of many drugs tried for disease control in Behçet’s syndrome1 and SLE2. In polymyositis, combined therapy with azathioprine and a corticosteroid has been found to be better than a corticosteroid alone for maintenance long-term.3 However, there is also some evidence that methotrexate may be more effective in refractory polymyositis than azathioprine.4
1. Yazici H, et al. A controlled trial of azathioprine in Behçet’s syndrome. N Engl J Med 1990; 322: 281–5
2. Abu-Shakra M, Shoenfeld Y. Azathioprine therapy for patients with systemic lupus erythematosus. Lupus 2001; 10: 152–3
3. Bunch TW. Prednisone and azathioprine for polymyositis: longterm followup. Arthritis Rheum 1981; 24: 45–8
4. Joffe MM, et al. Drug therapy of the idiopathic inflammatory myopathies; predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Am J Med 1993; 94: 379–87.

Inflammatory bowel disease.

Azathioprine, or its metabolite mercaptopurine, is used to induce remission in chronically active inflammatory bowel disease, and to maintain remission, particularly in Crohn’s disease.1-3 They have a useful corticosteroid-sparing effect. Azathioprine may also be useful as a postoperative maintenance treatment in Crohn’s disease.4 In patients with ulcerative colitis, azathioprine may be an effective maintenance therapy for those who are refractory to or intolerant of mesalazine or sulfasalazine; it may also be useful for patients who require repeated courses of corticosteroids.5 Continuation of azathioprine therapy beyond 4 years has had conflicting results in terms of relapse rates and flare incidence. A randomised study in patients with Crohn’s disease and in clinical remission, having been treated with azathioprine for at least 42 months, found that relapse rates were higher in those patients continued on placebo compared with those continued on azathioprine.6 In another study of patients with corticosteroid-dependent Crohn’s disease, a breakthrough of symptoms during continuous therapy was common, particularly after 48 months on azathioprine.7 In an analysis of 1176 patients with inflammatory bowel disease, the authors concluded that stopping azathioprine therapy may be considered after 3 to 4 years in Crohn’s disease patients in complete remission and without corticosteroid requirements but that continuation appears beneficial in all other Crohn’s disease patients and for patients with ulcerative colitis.8 The onset of benefit from oral azathioprine may be delayed for several months. One study9 reported that a more rapid response could be achieved with an intravenous loading dose but a later study failed to confirm this.10
1. Sandborn W, et al. Azathioprine or 6-mercaptopurine for induction of remission in Crohn’s disease. Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 1998 (accessed 15/01/08)
2. Pearson DC, et al. Azathioprine for maintenance of remission in Crohn’s disease. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 1998 (accessed 15/01/08)
3. Fraser AG, et al. The efficacy of azathioprine for the treatment of inflammatory bowel disease: a 30 year review. Gut 2002; 50: 485–9
4. Myrelid P, et al. Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn’s disease. Scand J Gastroenterol 2006; 41: 1190–5
5. Timmer A, et al. Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2007 (accessed 15/01/08)
6. Lémann M, et al. A randomized, double-blind, controlled withdrawal trial in Crohn’s disease patients in long-term remission on azathioprine. Gastroenterology 2005; 128: 1812–18
7. Chebli JM, et al. Long-term results with azathioprine therapy in patients with corticosteroid-dependent Crohn’s disease: openlabel prospective study. J Gastroenterol Hepatol 2007; 22: 268–74
8. Holtmann MH, et al. Long-term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients. Dig Dis Sci 2006; 51: 1516–24
9. Sandborn WJ, et al. An intravenous loading dose of azathioprine decreases the time to response in patients with Crohn’s disease. Gastroenterology 1995; 109: 1808–17
10. Sandborn WJ, et al. Lack of effect of intravenous administration on time to respond to azathioprine for steroid-treated Crohn’s disease: North American Azathioprine Study Group. Gastroenterology 1999; 117: 527–35.


For mention of the use of azathioprine as a corticosteroid-sparing agent in the management of type 1 lepra reactions.

Liver disorders.

Azathioprine has been widely used with corticosteroids to produce and maintain remission of chronic active hepatitis; such combination therapy, which also permits a reduction in corticosteroid dosage, is generally thought to be more effective than azathioprine alone. Patients successfully maintained in remission for at least a year on azathioprine with a corticosteroid can subsequently be maintained on azathioprine (at a dose of 2 mg/kg daily) alone.1 Results in patients with primary biliary cirrhosis have been more equivocal, and initial studies did not indicate much benefit from azathioprine, although a later study did seem to indicate improved survival and disease retardation.2
1. Johnson PJ, et al. Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med 1995; 333: 958–63
2. Christensen E, et al. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis: final results of an international trial. Gastroenterology 1985; 89: 1084–91.

Lung disorders.

Although corticosteroids remain the mainstay of treatment for the various forms of diffuse parenchymal lung disease including cryptogenic fibrosing alveolitis (CFA), there is some evidence that combined therapy with azathioprine improves survival in the latter condition,1 and the British Thoracic Society now recommends that initial treatment of CFA should be with oral prednisolone plus azathioprine 2 to 3 mg/kg daily.2
1. Raghu G, et al. Azathioprine combined with prednisone in the treatment of idiopathic pulmonary fibrosis: a prospective double-blind, randomized, placebo-controlled clinical trial. Am Rev Respir Dis 1991; 144: 291–6
2. British Thoracic Society. The diagnosis, assessment and treatment of diffuse parenchymal lung disease in adults. Thorax 1999; 54 (suppl 1): S1–S30. Also available at: http:// DPLD/Guidelines/Parenchymaltext.pdf (accessed 17/07/08)

Neuromuscular disorders.

Azathioprine may be used for its corticosteroid-sparing properties in patients who require corticosteroid treatment for myasthenia gravis. It may also be of use when corticosteroids are contra-indicated or when response to corticosteroids alone is insufficient. Azathioprine is not usually used alone because it may be several months before any beneficial effect is seen. Some studies have also indicated modest benefit from azathioprine in patients with multiple sclerosis. It has been suggested that the benefits are too slight to justify the toxicity of the required doses, but it has also been pointed out that in terms of relapse reduction azathioprine appears as effective as newer treatments such as interferon beta. For a recommendation that the cumulative dose of azathioprine should not exceed 600 g, see under Carcinogenicity, above.

Ocular disorders.

For mention of the use of azathioprine in various disorders characterised by ocular lesions such as scleritis or uveitis.

Polymyalgia rheumatica.

Azathioprine may be used for its corticosteroid-sparing properties in patients who require corti costeroid treatment for polymyalgia rheumatica and in whom withdrawal is difficult.

Psoriatic arthritis.

Azathioprine may be useful for severe or progressive cases of psoriatic arthritis when the arthritis is not controlled by physical therapy and NSAIDs.

Rheumatoid arthritis.

Although azathioprine may be beneficial in rheumatoid arthritis in the short-term, its toxicity is significantly more severe than other disease-modifying antirheumatic drugs (DMARDs).1 It may, however, be useful in patients with severe disease unresponsive to other DMARDs especially in those with extra-articular manifestations such as vasculitis.2
1. Suarez-Almazor ME, et al. Azathioprine for treating rheumatoid arthritis. Available in The Cochrane Database of Systematic Reviews; Issu
4. Chichester: John Wiley; 2000 (accessed 15/01/08)
2. Heurkens AHM, et al. Prednisone plus azathioprine treatment in patients with rheumatoid arthritis complicated by vasculitis. Arch Intern Med 1991; 151: 2249–54.


Cytotoxic immunosuppressants such as azathioprine have been tried in patients with sarcoidosis who do not respond to or cannot tolerate corticosteroids.

Skin disorders.

Like other immunosuppressants, azathioprine has been tried in various refractory skin disorders, notably in pemphigus and pemphigoid1,2 (see below). Other conditions in which it has been tried include atopic eczema,3-8 nodular prurigo,9 chronic actinic dermatitis,3,6 pyoderma gangrenosum,4 erythema multiforme,4,10 pompholyx, and plaque psoriasis,6 as well as in the skin manifestations of systemic disorders such as dermatomyositis and lupus erythematosus.2 Guidelines for the use of azathioprine in dermatology have been developed.1 The recommended dose for azathioprine in dermatological disorders is 1 to 3 mg/kg daily, adjusted according to response. Treatment should be withdrawn if no response is seen within 3 months. Azathioprine should not be used in dermatology patients with very low or absent thiopurine methyltransferase (TPMT) activity (see Therapeutic Drug Monitoring, above), due to the danger of prolonged and severe myelosuppression (see Effects on the Blood, above). If azathioprine is given to patients with low TPMT activity, doses of 0.5 to 1 mg/kg daily should be used, with monitoring for myelosuppression. Patients with normal to high TPMT activity should be started on doses at the higher end of the range of 1 to 3 mg/kg daily; in those who do not respond, and have not experienced adverse effects, doses above this range may be considered for a trial period.
1. A ns te y AV, et al. British Association of Dermatologists Therapy, Guidelines and Audit Subcommittee. Guidelines for prescribing azathioprine in dermatology. Br J Dermatol 2004; 151: 1123–32. Also available at: guidelines/Azathioprine.pdf (accessed 15/01/08
2. Patel AA, et al. Azathioprine in dermatology: the past, the present, and the future. J Am Acad Dermatol 2006; 55: 369–89
3. Younger IR, et al. Azathioprine in dermatology. J Am Acad Dermatol 1991; 25: 281–6
4. Tan BB, et al. Azathioprine in dermatology: a survey of current practice in the UK. Br J Dermatol 1997; 136: 351–5
5. Lear JT, et al. A retrospective review of the use of azathioprine in severe atopic dermatitis. Br J Dermatol 1996; 135 (suppl 47): 38
6. Scerri L. Azathioprine in dermatological practice: an overview with special emphasis on its use in non-bullous inflammatory dermatoses. Adv Exp Med Biol 1999; 455: 343–8
7. Murphy L-A, Atherton D. A retrospective evaluation of azathioprine in severe childhood atopic eczema, using thiopurine methyltransferase levels to exclude patients at high risk of myelosuppression. Br J Dermatol 2002; 147: 308–15
8. Meggitt SJ, et al. Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial. Lancet 2006; 367: 839–46
9. Lear JT, et al. Nodular prurigo responsive to azathioprine. Br J Dermatol 1996; 134: 1151
10. Schofield JK, et al. Recurrent erythema multiforme: clinical features and treatment in a large series of patients. Br J Dermatol 1993; 128: 542–5.
PEMPHIGUS AND PEMPHIGOID. Corticosteroids are the main treatment for blistering in pemphigus and pemphigoid. Other immunosuppressants may be added to maintain disease control and allow a reduction in corticosteroid dosage, and azathioprine is commonly used in this way in pemphigus vulgaris.1 There is limited evidence to suggest that azathioprine may also be effective as monotherapy to induce remission in mild pemphigus.1 Azathioprine has been used similarly in bullous pemphigoid, but there is some disagreement about its efficacy,2 and guidelines suggest that it should only be considered if the corticosteroid cannot be reduced to an acceptable dose.3
1. Harman KE, et al. British Association of Dermatologists. Guidelines for the management of pemphigus vulgaris. Br J Dermatol 2003; 149: 926–37. Also available at: healthcare/guidelines/Pemphigus_Vulgaris.pdf (accessed 15/01/08
2. Walsh SRA, et al. Bullous pemphigoid: from bench to bedside. Drugs 2005; 65: 905–26
3. Wojnarowska F, et al. British Association of Dermatologists. Guidelines for the management of bullous pemphigoid. Br J Dermatol 2002; 147: 214–21. Also available at: healthcare/guidelines/Bullous_Pemphigoid.pdf (accessed 15/01/08)

Vasculitic syndromes.

Azathioprine has been tried in vasculitic syndromes, including giant cell arteritis, microscopic polyangiitis, Churg-Strauss syndrome, Takayasu’s arteritis, and Wegener’s granulomatosis. In general it is most useful in maintenance for its corticosteroid-sparing effect. Cyclophosphamide tends to be preferred where a more aggressive regimen is required, as in some combinations for induction of remission.

💊 Preparations

BP 2008: Azathioprine Tablets; USP 31: Azathioprine Oral Suspension; Azathioprine Sodium for Injection; Azathioprine Tablets.

Proprietary Preparations

Arg.: Imuran; Austral.: Azahexal; Azamun; Azapin; Imuran; Thioprine; Austria: Azaallen; Azaglax; Azarek†; Glaxoprin; Imurek; Belg.: Imuran; Braz.: Aseroprin†; Imunen; Imuran; Canad.: Imuran; Chile: Azafalk†; Imuran; Cz.: Azaprine; Immunoprin; Imuran; Denm.: Imurel; Fin.: Azamun; Imuprin†; Imurel; Fr.: Imurel; Ger.: Aza-Q; Azafalk; Azathiodura; Colinsan; Imurek; Zytrim; Gr.: Imuran†; Hong Kong: Azamun†; Imuran; Hung.: Imuran; India: Azoran; Imuran; Transimune; Indon.: Imuran; Irl.: Imuger; Imuran; Israel: Azopi; Imuran; Malaysia: Imuran; Mex.: Azatrilem; Imuran; Satedon†; Neth.: Imuran; Norw.: Imurel; NZ: Azamun; Imuran; Thioprine; Philipp.: Imuran; Pol.: Imuran; Port.: Imuran; Rus.: Imuran (Имуран)†; S.Afr.: Azamun; Azapress; Imuran; Zaprine; Singapore: Imuran; Spain: Imurel; Swed.: Imurel; Switz.: Azarek; Imurek; Thai.: Imuran; Turk.: Imuran; UK: Immunoprin†; Imuran; USA: Azasan; Imuran; Venez.: Azaprin. Multi-ingredient: Ger.: Azamedac.
Published October 13, 2018.