Azathioprine

Immunosuppressants, thiopurines

ATC code: L04AX01

Brand names: Imuran, Azasan

Updated 24 Sep 2026 · Methodology

Indications

Autoimmune hepatitis

First line

In autoimmune hepatitis, azathioprine is the mainstay of maintenance therapy. After glucocorticoid induction of remission, it is used as a steroid-sparing agent and continued long-term, often as monotherapy to sustain remission ( 2015, 2019). The indication is in the AEMPS ficha (autoimmune chronic active hepatitis). The effect develops over weeks to months. TPMT activity (and where possible NUDT15) must be tested before start, with monitoring of blood counts and liver tests for myelosuppression and hepatotoxicity.

Sources

ICD-10: K75.4 · ICD-11: DB96.0

Autoimmune conditions

Second line

In systemic lupus erythematosus, azathioprine is used as a steroid-sparing maintenance agent: an alternative to mycophenolate mofetil in mild-to-moderate lupus nephritis and when pregnancy is planned ( 2019), whereas mycophenolate mofetil is usually preferred for proliferative nephritis. In ANCA-associated vasculitis, azathioprine is an option for remission maintenance after induction (CYCAZAREM, Cochrane). Its role is support and alternative, not induction first-line. In reproductive-age patients it is one of the few immunosuppressants compatible with pregnancy (alongside tacrolimus and ciclosporin; hydroxychloroquine is separately recommended in SLE); the AEMPS ficha lists pregnancy as a relative contraindication, justified when benefit outweighs risk. TPMT activity (and where possible NUDT15) must be tested before start, with blood-count monitoring for myelosuppression; the increased risk of lymphoma and skin cancer persists.

Autoimmune hepatitis, SLE, vasculitides, myasthenia gravis, pemphigus.

Sources

ICD-10: M35.9 · ICD-11: 4A4Z

Generalized myasthenia gravis

Second line

In generalized myasthenia gravis, azathioprine is used as a steroid-sparing immunosuppressant alongside glucocorticoids. In a randomized trial (Palace, 1998), adding azathioprine to prednisolone reduced steroid requirements and relapse frequency. The European guideline (EFNS/EAN, 2010) and the international consensus for myasthenia management (2020) name azathioprine as the immunosuppressant of first choice among non-steroidal agents. The effect develops slowly, over months, so the drug is not suitable for rapid control of an exacerbation. Myasthenia is not among the indications in the AEMPS ficha, so this is off-label use. TPMT activity (and where possible NUDT15) must be tested before start, with blood-count monitoring for myelosuppression.

Sources

ICD-10: G70.0 · ICD-11: 8C60

Inflammatory bowel disease (IBD)

Second line

Per 2021, for moderate-to-severe Crohn disease and ulcerative colitis, biologics and small molecules are now preferred first-line; azathioprine has moved to second-line, used as a combination partner with an anti-TNF agent (to reduce immunogenicity, SONIC trial) or as maintenance in milder or step-up settings. Dose 2–2.5 mg/kg/day, effect over 8–16 weeks. Reduces flare frequency, corticosteroid requirements, and hospitalizations. Azathioprine monotherapy is not first-line for active moderate-to-severe disease. TPMT activity (and where possible NUDT15) must be tested before start, with blood-count monitoring for myelosuppression. The thiopurine plus anti-TNF combination carries the highest risk of hepatosplenic T-cell lymphoma, mainly in young men, and raises the risk of lymphoma and non-melanoma skin cancer.

Sources

ICD-10: K50/K51 · ICD-11: DD7Z

Transplant rejection prophylaxis

Second line

Azathioprine is a thiopurine antimetabolite that was part of maintenance immunosuppression after kidney transplantation for decades (indication no. 1 in the AEMPS ficha). Mycophenolate has since displaced it: on Cochrane review, mycophenolate mofetil produces less acute rejection, so azathioprine moved to reserve, used when mycophenolate is not tolerated and as the preferred antimetabolite in pregnant recipients because mycophenolate is teratogenic (KDIGO). Its role is reserve, prescribed and monitored by a transplant specialist. TPMT activity (and where possible NUDT15) must be tested before start, with blood-count monitoring for myelosuppression; the increased risk of lymphoma and skin cancer persists.

Sources

ICD-10: Z94 · ICD-11: QB63

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Anti-aging and longevity

Not recommended

Azathioprine is an antimetabolite immunosuppressant, a purine analogue. It is prescribed to prevent organ transplant rejection and for severe autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease) when other drugs are ineffective. In anti-aging circles, azathioprine is occasionally promoted as a means of resetting or renewing the immune system in healthy adults. In healthy adults, no clinical studies of such use exist. The drug has serious risks: myelosuppression with risk of severe neutropenia, increased risk of lymphoma and other malignancies (especially non-Hodgkin lymphoma and skin cancer), severe hepatotoxicity, and requires thiopurine methyltransferase testing before start to prevent severe toxicity in carriers of the defective variant. If azathioprine was recommended to a healthy person for the immune system, seek a second opinion immediately.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Prodrug converted to 6-mercaptopurine and then to 6-thioguanine nucleotides — structural analogues of purine bases. They are incorporated into DNA in dividing cells, disrupting lymphocyte proliferation and suppressing cellular immunity. Metabolism via thiopurine S-methyltransferase (TPMT) — 1 in 300 patients are TPMT-homozygous deficient and 10 % heterozygous. In these patients, severe myelosuppression risk is tens of times higher — TPMT and/or NUDT15 genotyping before initiation is mandatory.

Safety

Boxed warning

FDA boxed warning: increased risk of malignancy (lymphoma, skin cancers, hepatosplenic T-cell lymphoma in young IBD patients on long-term combination therapy with anti-TNF agents).

Contraindications

Hypersensitivity
Severe myelosuppression
Severe hepatic impairment
Active severe infections
Pregnancy (except SLE and transplant indications)
Concomitant allopurinol without dose adjustment (severe myelosuppression risk)

Serious adverse effects

Severe myelosuppression (especially in TPMT/NUDT15 deficiency)
Severe infections (including opportunistic — hepatitis B reactivation, CMV, EBV)
Lymphoproliferative disorders (2–4× risk)
Non-melanoma skin cancer (2–4× risk)
Hepatotoxicity
Acute pancreatitis (3–5 % of patients)

Common adverse effects

Nausea, vomiting (especially in the first weeks)
Leukopenia, thrombocytopenia
Transaminase elevation
Fatigue
Alopecia (mild)

Uncommon adverse effects

Myelosuppression (especially in TPMT-deficient patients)
Hepatotoxicity with veno-occlusive disease
Acute pancreatitis
Lymphomas with long-term therapy
Hypersensitivity syndrome

Pregnancy: can you take Azathioprine?

AEMPS summary of product characteristics (section 4.6): azathioprine caused malformations and teratogenic or embryolethal effects in animals, and human data on its teratogenic potential are conflicting, so it should not be used in pregnancy without a careful assessment of risks and benefits. Azathioprine and its metabolites cross the placenta and amniotic membranes to a considerable extent; leucopenia or thrombocytopenia has been reported in a number of newborns, so maternal blood counts are monitored closely and the dose is reduced if leucopenia develops. Intrauterine growth restriction, preterm birth and low birth weight have been reported with azathioprine plus corticosteroids, a temporary reduction in immune function after in utero exposure with prednisone, and miscarriages after maternal or paternal exposure. Cholestasis of pregnancy has occasionally been reported; early diagnosis and stopping azathioprine may limit the impact on the fetus. Men and women of childbearing potential should use contraception during treatment and for at least 6 months afterwards, and azathioprine may reduce the effectiveness of intrauterine devices.

Breastfeeding: can you take Azathioprine?

Transfers into milk in very small amounts. Per LactMed, use is acceptable with infant monitoring.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Once daily with food — reduces nausea. Mandatory TPMT and NUDT15 testing before initiation — in deficiency, starting dose is sharply reduced or the drug replaced. Start 50 mg daily for 1–2 weeks, then titrate to target 2–2.5 mg/kg/day.

Monitoring

CBC, ALT, AST at 1, 2, and 4 weeks after initiation and each dose change. Then every 3 months. With leukocyte count below 3.0 × 10⁹/L or ANC below 1.5 — temporary discontinuation. Lifetime risk of lymphoma and non-melanoma skin cancer is 2–4 fold higher in long-term users — special surveillance and UV protection.

Drug–drug interactions

2 pairs found. Sorted from critical to minor.

CriticalFebuxostatSelective xanthine oxidase inhibitor

Mechanism

Febuxostat inhibits xanthine oxidase, the enzyme that converts 6-mercaptopurine, the active metabolite of azathioprine, into an inactive form. In an interaction study febuxostat reduced 6-mercaptopurine clearance by about 83% after a single dose of azathioprine. The lists the combination as a contraindication in section 4 of the febuxostat label. The EU SmPC does not recommend it and, if it cannot be avoided, requires cutting the azathioprine dose to 20% or less of the previous dose.

Symptoms

Same as with allopurinol: pancytopenia with fever, infections and bleeding within the first weeks of therapy.

Management

Combination contraindicated. To treat hyperuricaemia in patients on azathioprine, use other classes: probenecid if renal function is preserved or pegloticase for severe gout.

Sources

Pair details →Febuxostat →

MajorAllopurinolXanthine oxidase inhibitors

Mechanism

Azathioprine is converted to 6-mercaptopurine, and xanthine oxidase turns its active metabolites into inactive 6-thiouric acid. Allopurinol blocks xanthine oxidase, so azathioprine and 6-mercaptopurine accumulate. Levels can reach the toxic range with pancytopenia and bone marrow suppression; the Spanish allopurinol SmPC mentions fatal cases. No official label lists the pair as a contraindication: the allopurinol SmPC and the label require a steep cut in the azathioprine dose.

Symptoms

Bone marrow suppression: falling white cells, platelets and haemoglobin, up to pancytopenia. The patient notices sore throat, fever, unexplained bruising or bleeding – the signs the allopurinol SmPC asks patients to report at once.

Management

Avoid the combination where possible, as the allopurinol SmPC requires. If it is clinically necessary, cut the azathioprine dose to a quarter of the usual dose (allopurinol and azathioprine SmPCs; label: 1/3 to 1/4) and check full blood counts often. The azathioprine SmPC already asks for weekly or more frequent counts with platelets during the first 8 weeks of therapy. Febuxostat is not a substitute: it blocks the same enzyme, the FDA contraindicates it with azathioprine and the EU SmPC does not recommend it.

Sources

Pair details →Allopurinol →

Label mentions33 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorAllopurinol
«El alopurinol, el oxipurinol el tiopurinol y otros inhibidores de la xantina oxidasa tienen un efecto inhibidor sobre el metabolismo de azatioprina mediante el bloqueo de la enzima xantinoxidasa. que…»
AEMPS, section 4.5 · Open on CIMA
MajorAllopurinol
«DRUG INTERACTIONS: Use with xanthine oxidase (XO) inhibitors: One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving…»
FDA, section 7 · Open on DailyMed
Majorantineoplásicosclass named in the label
«Siempre que sea posible, se debe evitar la administración concomitante de agentes citostáticos o medicamentos que puedan tener un efecto mielosupresor, como la penicilamina. Existen informes clínicos…»
AEMPS, section 4.5 · Open on CIMA
MajorCo-trimoxazole
«Siempre que sea posible, se debe evitar la administración concomitante de agentes citostáticos o medicamentos que puedan tener un efecto mielosupresor, como la penicilamina. Existen informes clínicos…»
AEMPS, section 4.5 · Open on CIMA
MajorFebuxostat
«Según los datos preclínicos, otros inhibidores de la xantina oxidasa (p. ej., febuxostat) pueden prolongar la actividad de la azatioprina, lo que podría derivar en una mayor supresión de la médula…»
AEMPS, section 4.5 · Open on CIMA
MajorFebuxostat
«DRUG INTERACTIONS: Use with xanthine oxidase (XO) inhibitors: One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving…»
FDA, section 7 · Open on DailyMed
MajorMethotrexate
«Metotrexato: El metotrexato en dosis de 20 mg/m 2 por vía oral aumentó el AUC de la 6 ‑ mercaptopurina en aproximadamente el 31 %, mientras que en dosis de 2 o 5 g/m 2 por vía intravenosa aumentó el…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantesclass named in the label
«Se ha notificado la inhibición del efecto anticoagulante de la warfarina y del acenocumarol al administrarse conjuntamente con azatioprina; por consiguiente, pueden ser necesarias dosis más altas del…»
AEMPS, section 4.5 · Open on CIMA
ModerateCiclosporin
«Si la azatioprina se combina con otros inmunosupresores, tales como ciclosporina o tacrolimus, debe considerarse que existe un mayor riesgo de inmunosupresión excesiva.»
AEMPS, section 4.5 · Open on CIMA
ModerateMesalazine
«Existe evidencia in vitro e in vivo de que los derivados de aminosalicilatos (por ejemplo, olsalazina, mesalazina o sulfasalazina) inhiben la enzima TPMT. Por consiguiente, puede ser necesario…»
AEMPS, section 4.5 · Open on CIMA
ModerateMesalazine
«DRUG INTERACTIONS: Use with Aminosalicylates: There is in vitro evidence that aminosalicylate derivatives (e.g., sulphasalazine, mesalazine, or olsalazine) inhibit the TPMT enzyme. Concomitant use of…»
FDA, section 7 · Open on DailyMed
ModerateSulfasalazine
«Existe evidencia in vitro e in vivo de que los derivados de aminosalicilatos (por ejemplo, olsalazina, mesalazina o sulfasalazina) inhiben la enzima TPMT. Por consiguiente, puede ser necesario…»
AEMPS, section 4.5 · Open on CIMA
ModerateTacrolimus
«Si la azatioprina se combina con otros inmunosupresores, tales como ciclosporina o tacrolimus, debe considerarse que existe un mayor riesgo de inmunosupresión excesiva.»
AEMPS, section 4.5 · Open on CIMA
ModerateWarfarin
«Se ha notificado la inhibición del efecto anticoagulante de la warfarina y del acenocumarol al administrarse conjuntamente con azatioprina; por consiguiente, pueden ser necesarias dosis más altas del…»
AEMPS, section 4.5 · Open on CIMA
ACE inhibitorsclass named in the label
«DRUG INTERACTIONS: Use with Angiotensin-Converting Enzyme Inhibitors: The use of angiotensin-converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to…»
FDA, section 7 · Open on DailyMed
anticoagulantsclass named in the label
«DRUG INTERACTIONS: Use with Warfarin: Azathioprine may inhibit the anticoagulant effect of warfarin.»
FDA, section 7 · Open on DailyMed
Co-trimoxazole
«DRUG INTERACTIONS: Use with Other Agents Affecting Myelopoesis: Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal…»
FDA, section 7 · Open on DailyMed
corticosteroidesclass named in the label
«Es probable una menor respuesta a vacunas inactivadas y tal respuesta se ha observado a la vacuna de la hepatitis B entre los pacientes que estaban siendo tratados con una combinación de azatioprina…»
AEMPS, section 4.5 · Open on CIMA
Furosemide
«Se ha observado que furosemida reduce el metabolismo de azatioprina por el tejido hepático humano in vitro . Se desconoce la relevancia clínica de este hallazgo.»
AEMPS, section 4.5 · Open on CIMA
inhibidores de la ECAclass named in the label
«Ha habido informes de casos que sugieren que se pueden desarrollar anomalías hematológicas debido a la administración concomitante de azatioprina e inhibidores de la ECA. Se ha sugerido que la…»
AEMPS, section 4.5 · Open on CIMA
relajantes muscularesclass named in the label
«Existe evidencia clínica de que la azatioprina antagoniza el efecto de los relajantes musculares no despolarizantes como el curare, la d ‑ tubocurarina y el pancuronio. Los datos experimentales…»
AEMPS, section 4.5 · Open on CIMA
Warfarin
«DRUG INTERACTIONS: Use with Warfarin: Azathioprine may inhibit the anticoagulant effect of warfarin.»
FDA, section 7 · Open on DailyMed

From other drugs’ labels

CriticalFebuxostat
«CONTRAINDICATIONS: Febuxostat tablets are contraindicated in patients being treated with azathioprine or mercaptopurine [see Drug Interactions (7) ] .»
FDA, section 4 · Open on DailyMed
MajorAllopurinol
«6-Mercaptopurina y azatioprina: La azatioprina se metaboliza a 6-mercaptopurina, que se inactiva por acción de la xantina oxidasa. Cuando 6-mercaptopurina o azatioprina se administra por vía oral…»
AEMPS, section 4.5 · Open on CIMA
MajorAllopurinol
«DRUG INTERACTIONS: • The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) • Capecitabine: Avoid concomitant use…»
FDA, section 7 · Open on DailyMed
MajorFebuxostat
«Mercaptopurina/azatioprina: Dado el mecanismo de acción de febuxostat sobre la inhibición de la XO, no se recomienda su uso concomitante. La inhibición de la XO por febuxostat puede ocasionar un…»
AEMPS, section 4.5 · Open on CIMA
MajorLeflunomide
«Combinaciones con otros tratamientos: Hasta el momento no se ha estudiado suficientemente en ensayos aleatorizados (a excepción del metotrexato, ver sección 4.5) el empleo de la leflunomida con los…»
AEMPS, section 4.4 · Open on CIMA
MajorMycophenolate mofetil
«Interacciones: No se recomienda administrar micofenolato de mofetilo al mismo tiempo que azatioprina, ya que no se ha estudiado su administración concomitante.»
AEMPS, section 4.4 · Open on CIMA
ModerateMesalazine
«Insuficiencia renal: No se recomienda el uso del fármaco en pacientes con la función renal deteriorada, y en pacientes con diátesis hemorrágica. Se debe monitorizar la función renal a intervalos…»
AEMPS, section 4.4 · Open on CIMA
Eltrombopag
«Medicamentos para el tratamiento de PTI: Los medicamentos utilizados en los ensayos clínicos en el tratamiento de PTI en combinación con eltrombopag incluyeron corticosteroides , danazol y/o…»
AEMPS, section 4.5 · Open on CIMA
Methotrexate
«Alcohol, medicamentos hepatotóxicos y medicamentos hematotóxicos: La probabilidad de que el metotrexato produzca un efecto hepatotóxico aumenta con el consumo regular de alcohol y con la…»
AEMPS, section 4.5 · Open on CIMA
Sulfasalazine
«Tiopurinas: 6-mercaptopurina/azatioprina: Debido a que la sulfasalazina inhibe la tiopurina metiltransferasa, se han notificado casos de supresión de médula ósea y leucopenia cuando se administraron…»
AEMPS, section 4.5 · Open on CIMA
Ustekinumab
«No se han realizado estudios de interacciones en humanos. En el análisis de farmacocinética poblacional de los ensayos en fase 3 se investigó el efecto de los medicamentos concomitantes más…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Azathioprine used for?

Azathioprine is evaluated for the following indications with varying evidence strength: Autoimmune hepatitis (evidence tier A), Transplant rejection prophylaxis (evidence tier B), Generalized myasthenia gravis (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Azathioprine?

Common side effects of Azathioprine (≥ 1 in 100): Nausea, vomiting (especially in the first weeks), Leukopenia, thrombocytopenia, Transaminase elevation, Fatigue, Alopecia (mild). See the Safety section for uncommon and serious reactions.

Is Azathioprine safe during pregnancy?

Is Azathioprine compatible with breastfeeding?

Transfers into milk in very small amounts. Per LactMed, use is acceptable with infant monitoring.

Who should not take Azathioprine?

Azathioprine is contraindicated in: Hypersensitivity; Severe myelosuppression; Severe hepatic impairment; Active severe infections; Pregnancy (except SLE and transplant indications). Full list in the Safety section.

Does Azathioprine carry an FDA boxed warning?

FDA boxed warning: increased risk of malignancy (lymphoma, skin cancers, hepatosplenic T-cell lymphoma in young IBD patients on long-term combination therapy with anti-TNF agents).

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 01/03/2026
EMALabel dated 06/21/2021
FDA / DailyMedLabel dated 05/05/2026
GRLSLabel dated 06/16/2025

Other drugs in this group

Ciclosporin, Dimethyl Fumarate, Leflunomide, Lenalidomide, Pomalidomide, Tacrolimus, Mycophenolate mofetil, Pirfenidone