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Azathioprine: Drug information

Azathioprine: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Azathioprine: Patient drug information" and "Azathioprine: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Special Alerts
Thiopurines Safety Alert May 2024

The FDA is alerting health care providers of the rare risk of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines (azathioprine, mercaptopurine, and thioguanine). Thiopurines have a known risk of hepatotoxicity and are currently labeled for risk of fetal harm with use during pregnancy. Pregnant patients should stop using thiopurines if they develop ICP. Reported cases of ICP occurred among pregnant patients using azathioprine or mercaptopurine for inflammatory bowel disease (eg, Crohn disease, ulcerative colitis) or systemic lupus erythematosus.

The FDA is requiring updates to the prescribing information to include the following: postmarketing cases of ICP have been reported in women treated with thiopurines during pregnancy; ICP symptoms and elevated bile acid levels improved following azathioprine discontinuation; and pregnant individuals should discontinue use of thiopurines if they develop ICP.

Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-pregnancy-problems-associated-thiopurines

ALERT: US Boxed Warning
Malignancy:

Chronic immunosuppression with azathioprine, a purine antimetabolite, increases risk of malignancy in humans. Reports of malignancy include post-transplant lymphoma and hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease. Health care providers using this drug should be very familiar with this risk, as well as with the mutagenic potential to both men and women, and with possible hematologic toxicities. Inform patients of the risk of malignancy with azathioprine.

Brand Names: US
  • Azasan;
  • Imuran
Brand Names: Canada
  • APO-AzaTHIOprine;
  • AzaTHIOprine-50 [DSC];
  • Imuran;
  • TEVA-AzaTHIOprine
Pharmacologic Category
  • Immunosuppressant Agent
Dosing: Adult

Dosage guidance:

Safety: Severe hematologic toxicity may occur, particularly in patients with thiopurine S-methyltransferase (TPMT) and/or nudix hydrolase 15 (nucleotide diphosphatase; NUDT15) deficiency. Testing for TPMT and/or NUDT15 deficiency may be considered; however, expert opinion differs on the role and timing of such testing (Ref). Initial dosage adjustments or alternative therapy may be recommended depending on TPMT and/or NUDT15 deficiency status; refer to "Dosage Adjustment for TPMT and/or NUDT15 Deficiency" below (Ref).

Behçet syndrome

Behçet syndrome (off-label use): Oral: Initial: 50 mg once daily; increase by 50 mg every 4 weeks as tolerated, to goal maintenance dose of 2.5 mg/kg once daily (maximum dose not established); may be given in combination with a glucocorticoid (Ref).

Bullous pemphigoid

Bullous pemphigoid (adjunctive agent) (off-label use): Oral: Initial: 0.5 mg/kg once daily; titrate as tolerated to goal maintenance dose of 1 to 3 mg/kg once daily (maximum dose not established); often given in combination with a glucocorticoid (Ref).

Crohn disease

Crohn disease (off-label use):

Induction of remission (adjunctive agent) or maintenance of remission: Oral: Initial: 50 mg once daily; titrate up to 2.5 mg/kg once daily over ≥12 weeks as indicated and tolerated (Ref). Despite lack of pharmacokinetic data to suggest optimal dosing weight, some experts favor using lean body weight given the toxicities of azathioprine (Ref). For induction, give in combination with a tumor necrosis factor-alpha inhibitor. Duration is generally ≥1 to 2 years (Ref).

Management after surgical resection:

Note: Reserve for patients at high risk of recurrence (eg, <30 years of age, tobacco use, ≥2 surgeries for Crohn disease) (Ref).

Oral: Initial: 50 mg once daily; titrate up to 2 to 2.5 mg/kg once daily over ≥12 weeks as indicated and tolerated (Ref). Despite lack of pharmacokinetic data to suggest optimal dosing weight, some experts favor using lean body weight given the toxicities of azathioprine (Ref). Initiate within 2 to 8 weeks of surgery; may give as part of an appropriate combination regimen (eg, with metronidazole for 3 months) (Ref).

Dermatomyositis/polymyositis

Dermatomyositis/polymyositis (adjunctive agent) (off-label use):

Note: Onset of clinical response to azathioprine may take 4 to 6 months or longer (Ref).

Oral: Initial: 50 mg once daily in combination with a glucocorticoid; increase daily dose by 50 mg/week to 1.5 mg/kg/day; if inadequate response at 3 months, may increase up to 2.5 mg/kg/day (Ref). Maximum dose has not been established; some experts do not exceed 250 mg/day (Ref). Once remission is achieved and glucocorticoids have been tapered, may consider slow taper at monthly intervals with planned cessation of therapy over ~6 months (Ref).

Eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (off-label use):

Note: May be used as alternative induction therapy (in combination with glucocorticoids) in patients with mild disease. May also be used as maintenance therapy in patients with severe disease or as glucocorticoid-sparing therapy for patients with glucocorticoid-dependent disease (Ref).

Oral: Initial: 25 to 50 mg once daily; increase by 0.5 mg/kg/day every 4 to 6 weeks as tolerated up to 2 mg/kg once daily (maximum dose: 200 mg/day) (Ref); usual duration: 12 to 18 months; however, longer maintenance therapy may be needed in patients with multiple relapses (Ref).

Granulomatosis with polyangiitis and microscopic polyangiitis

Granulomatosis with polyangiitis and microscopic polyangiitis (off-label use):

Note: For use as maintenance therapy (regardless of initial disease severity) to extend remission and prevent relapse; may also be used as alternative induction therapy (in combination with glucocorticoids) only for patients with non–organ- and non–life-threatening disease (Ref).

Oral: Initial: 50 mg once daily titrated over several weeks to 2 mg/kg once daily as tolerated (maximum dose: 200 mg/day); usual duration: 12 to 24 months after stable remission is induced (Ref).

Hepatitis, autoimmune

Hepatitis, autoimmune (adjunctive agent) (off-label use):

Note: Not recommended for patients with decompensated cirrhosis, acute severe hepatitis, or acute liver failure (Ref).

Oral: Initial: 50 mg once daily in combination with a glucocorticoid; may increase dose up to 2 mg/kg once daily based on response and toxicity (Ref). Maximum dose has not been established; some experts do not exceed 200 mg/day (Ref). Once remission has been established and maintained for 18 to 24 months, consider treatment withdrawal (eg, reduce azathioprine dose by 50 mg/day every 3 months as tolerated) (Ref).

Immune checkpo int inhibitor-induced autoimmune hepatitis , grade 3 or 4, steroid-refractory: Oral: 50 mg once daily, with subsequent incremental increases of 25 to 50 mg every 1 to 2 weeks up to a maximum of 2 mg/kg/day (Ref).

Immune thrombocytopenia, chronic, refractory or relapsed

Immune thrombocytopenia, chronic, refractory or relapsed (off-label use): Oral: 1 to 2 mg/kg/day; maximum dose: 150 mg/day (Ref). Initial response is observed at 30 to 90 days; may take up to 6 months for peak response (Ref).

Interstitial pneumonia/interstitial lung disease

Interstitial pneumonia/interstitial lung disease (adjunctive agent) (off-label use): Oral: Initial: 25 to 50 mg once daily; increase daily dose in 50 mg increments every 1 to 4 weeks as tolerated to typical goal maintenance dose of 1.5 to 2 mg/kg once daily (Ref); up to 3 mg/kg once daily has been described (Ref). Maximum dose has not been established; some experts do not exceed 200 mg/day (Ref). Generally given in combination with a glucocorticoid (Ref).

Lupus nephritis

Lupus nephritis (alternative agent) (off-label use):

Note: Use for subsequent therapy after initial therapy with another agent (eg, cyclophosphamide or mycophenolate) (Ref).

Oral: Initial: 50 mg once daily; increase daily dose in 50 mg increments (or by 0.5 mg/kg/day) every 4 weeks as tolerated to goal maintenance dose of 2 mg/kg once daily (Ref); maximum dose has not been established; some experts do not exceed 200 mg/day (Ref). Generally given in combination with a glucocorticoid. Duration is typically ≥2 years (Ref).

Myasthenia gravis, chronic immunosuppressive therapy

Myasthenia gravis, chronic immunosuppressive therapy (off-label use):

Note: For use as monotherapy or in combination with glucocorticoids in patients with glucocorticoid-resistant or glucocorticoid-dependent disease (Ref). Due to delayed onset of clinical response, most often given initially in combination with a glucocorticoid (Ref).

Oral: Initial: 50 mg once daily; increase daily dose by 50 mg every 1 to 4 weeks as tolerated to a target dose of 2 to 3 mg/kg once daily; maximum dose has not been established; some experts do not exceed 200 mg/day (Ref); more rapid titration has also been described (Ref). Onset of clinical response to azathioprine may take up to 1 year; maximum efficacy may not be apparent until 1 to 2 years (Ref).

Pemphigus vulgaris and pemphigus foliaceus

Pemphigus vulgaris and pemphigus foliaceus (alternative agent) (adjunctive agent) (off-label use): Oral: Initial: 1 mg/kg once daily (patients with normal TPMT activity); increase daily dose in 0.5 mg/kg increments over 2 to 3 weeks as tolerated to goal maintenance dose of 2.5 mg/kg once daily (Ref). Despite lack of pharmacokinetic data to suggest optimal dosing weight, some experts favor using ideal body weight given the toxicities of azathioprine (Ref). Administer in combination with a glucocorticoid (Ref).

Polyarteritis nodosa

Polyarteritis nodosa (off-label use):

Note: In patients with mild disease, may be used adjunctively as glucocorticoid-sparing therapy or for glucocorticoid-resistant disease; for patients with moderate to severe disease, may be used for remission-maintenance immunosuppression (Ref).

Oral: Initial: 50 mg once daily; if tolerated after 2 weeks, may increase daily dose by 50 mg (~0.5 mg/kg) at 4-week intervals to goal maintenance dose of 2 mg/kg once daily (maximum dose: 200 mg/day) (Ref).

Rheumatoid arthritis

Rheumatoid arthritis (alternative agent):

Note: Not commonly used; reserve for use in patients unable to tolerate methotrexate and other preferred agents (Ref). IV dosing regimens are in the prescribing information, but the IV route is not commonly employed.

Oral: Initial: 25 to 50 mg once daily; if tolerated after 2 weeks, may increase daily dose by 50 mg (~0.5 mg/kg) at 4-week intervals to goal maintenance dose of 1.5 mg/kg once daily; if inadequate response after 3 months, may increase up to 3 mg/kg once daily (Ref); maximum dose has not been established; some experts do not exceed 200 mg/day (Ref).

Sarcoidosis, pulmonary, steroid-refractory disease

Sarcoidosis, pulmonary, steroid-refractory disease (alternative agent) (off-label use): Oral: Initial: 25 to 50 mg once daily; increase daily dose by 50 mg every 2 to 4 weeks as tolerated to goal maintenance dose of ~2 mg/kg once daily (Ref); maximum dose has not been established; some experts do not exceed 200 mg/day (Ref). Generally given in combination with a glucocorticoid (Ref).

Solid organ transplantation

Solid organ transplantation (alternative agent):

Note: Alternative for patients who cannot tolerate or are not candidates for mycophenolate (Ref).

Heart transplantation (off-label use): Oral, IV: 1 to 3 mg/kg once daily as part of an appropriate combination regimen (Ref). Maximum dose has not been established; some experts do not exceed 200 mg/day (Ref).

Kidney transplantation: Oral, IV: 1 to 2 mg/kg once daily as part of an appropriate combination regimen (Ref); manufacturer’s labeling recommends up to 3 mg/kg once daily. Maximum dose has not been established; some experts do not exceed 150 mg/day (Ref).

Liver transplantation (off-label use): Oral, IV: 1 to 2 mg/kg once daily as part of an appropriate combination regimen (Ref). Maximum dose has not been established; some experts do not exceed 200 mg/day (Ref).

Lung transplantation (off-label use): Oral, IV: 1 to 2 mg/kg once daily as part of an appropriate combination regimen (Ref). Maximum dose has not been established; some experts do not exceed 200 mg/day (Ref).

Takayasu arteritis

Takayasu arteritis (adjunctive agent) (off-label use): Oral: Initial: 50 mg once daily for 1 week, then titrate over several weeks to goal maintenance dose of 1.5 to 2 mg/kg once daily (Ref); maximum dose has not been established; some experts do not exceed 200 mg/day (Ref). Give in combination with a glucocorticoid (Ref).

Ulcerative colitis

Ulcerative colitis (adjunctive agent) (alternative agent) (off-label use):

Note: The response to azathioprine may take as long as 3 to 6 months (Ref).

Oral: Initial: 50 mg once daily; titrate up to 2.5 mg/kg once daily over ≥12 weeks as indicated and tolerated (Ref). Despite lack of pharmacokinetic data to suggest optimal dosing weight, some experts favor using lean body weight given the toxicities of azathioprine (Ref). Give as part of an appropriate combination regimen (Ref).

Uveitis, noninfectious

Uveitis, noninfectious (alternative agent) (off-label use):

Note: Some experts reserve for use in patients with severe or bilateral disease, active inflammation, or glucocorticoid-resistant or glucocorticoid-dependent disease (Ref).

Oral: 2 to 3 mg/kg once daily (Ref); some experts may use up to 4 mg/kg once daily, however, they do not exceed 250 mg/day (maximum dose has not been established) (Ref).

Dosage adjustment for TPMT and/or NUDT15 deficiency:

Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary (may initiate with target dose rather than an upward titration); adjust dose based on markers of disease progression and/or myelosuppression. Allow 2 weeks between each dosage increase to reach steady state (Ref).

TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer: Initiate azathioprine with the dose reduced to 30% to 80% of the usual dose and adjust based on markers of disease progression and/or myelosuppression. Allow 2 to 4 weeks between each dosage increase to reach steady state (Ref).

TPMT poor metabolizer: When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy. For malignancy, initiate azathioprine at a drastically reduced dose (10% of the recommended daily dose and reduce the frequency from once daily to 3 times a week). Adjust dose based on markers of disease progression and/or myelosuppression. Allow 4 to 6 weeks between each dosage increase to reach steady state (Ref).

NUDT15 poor metabolizer: When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy. For malignancy, initiate azathioprine at a drastically reduced dose (10% of the recommended daily dose). Adjust dose based on the markers of disease progression and/or myelosuppression. Allow 4 to 6 weeks between each dosage increase to reach steady state (Ref).

Indeterminant TPMT and NUDT15 activity: If activities of both enzymes are indeterminant (ie, results of genetic testing include a combination of uncertain and/or unknown function alleles), monitor closely for toxicity; may consider evaluating TPMT erythrocyte activity to assess TPMT phenotype. If activity of either enzyme is known, follow recommendations above (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Azathioprine, 6-mercaptopurine (metabolic intermediate), and 6-thioguanine nucleotide (active metabolite) are not significantly renally eliminated (Ref). 6-thiouric acid (inactive metabolite) is renally eliminated and may contribute to accumulation of 6-thioguanine nucleotide and toxicity potential (Ref). Clearance (azathioprine and metabolites) may be delayed in oliguric patients, particularly in those with tubular necrosis in the immediate posttransplant phase (deceased donor transplant). Dose recommendations in patients with known or suspected thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase; NUDT15) deficiency and kidney impairment have not been established; also see dosage adjustment for TPMT and/or NUDT15 deficiency information in the adult dosing section.

Oral, IV:

Altered kidney function:

CrCl ≥30 mL/minute: Initial: No dosage adjustment necessary (Ref).

CrCl 10 to <30 mL/minute: Initial: Administer 75% to 100% of the usual indication-specific dose. If the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 75% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref).

CrCl <10 mL/minute: Initial: Administer 50% to 100% of the usual indication-specific dose. If the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 50% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref).

Hemodialysis, intermittent (thrice weekly): Dialyzable (45% removed during 8 hours of hemodialysis) (Ref): Initial: Administer 50% to 100% of the indication-specific dose; if the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 50% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref). When scheduled dose falls on a dialysis day, administer after hemodialysis. If not administered after hemodialysis, provide a 50% supplemental dose (Ref).

Peritoneal dialysis: Initial: Administer 50% to 100% of the indication-specific dose. If the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 50% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, hematologic toxicity) due to drug accumulation is important.

Initial: Administer 75% to 100% of the indication-specific dose. If the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 75% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, hematologic toxicity) due to drug accumulation is important.

Initial: Administer 75% to 100% of the indication-specific dose. Administer the dose after PIRRT therapy ends on PIRRT days (Ref). If the initial dose is a dose range then it is recommended to begin with the lowest end of the dose range (eg, if the usual dose is 2 to 3 mg/kg once daily then administering 75% to 100% of 2 mg/kg once daily as an initial dose is recommended) (Ref).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Adjustment for Toxicity: Adult

Rapid WBC count decrease, persistently low WBC count, or serious infection: Reduce dose or temporarily withhold treatment.

Severe toxicity (hematologic or other) in kidney transplantation: May require discontinuation.

Hepatic sinusoidal obstruction syndrome (SOS; veno-occlusive disease): Permanently discontinue.

Rheumatoid arthritis: Leukopenia and thrombocytopenia: Consider a 50% dose reduction or discontinuation; permanently discontinue for persistent cytopenias (Ref).

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Azathioprine: Pediatric drug information")

Dosage guidance:

Safety: Consider testing for thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (nucleotide diphosphatase; NUDT15) deficiency in patients who develop severe bone marrow toxicities (may require dose reduction or discontinuation). Dosage reduction or alternative therapy is recommended in patients with TPMT and/or NUDT15 deficiency.

Dosage form information: IV dose is equivalent to oral dose (dosing should be transitioned from IV to oral as soon as tolerated).

Hepatitis, autoimmune

Hepatitis, autoimmune: Limited data available: Children and Adolescents: Oral: Initial: 1 to 2 mg/kg/dose once daily typically in combination with corticosteroids; usual reported range: 0.5 to 2.5 mg/kg/dose; an open-label outcomes trial that followed 66 children and adolescents reported a final mean dose of 1.67 ± 0.55 mg/kg/day; for maintenance therapy, a lower-dose of 1 to 1.5 mg/kg/day may be effective in some patients (Ref).

Inflammatory bowel disease

Inflammatory bowel disease: Limited data available: Infants, Children, and Adolescents: Oral: 2 to 2.5 mg/kg/dose once daily; may titrate to effect; usual reported range: 1 to 3 mg/kg/dose once daily; reported maximum daily dose: 4 mg/kg/day or 200 mg/day; may take several weeks of therapy to be fully effective (Ref). Some data suggest that pediatric patients with early-onset disease (≤6 years) may require higher doses to achieve remission (Ref). In one trial, a median dose of 3.51 mg/kg/day (maximum daily dose: 5 mg/kg/day) was reported to induce remission in 62% of patients ≤6 years of age vs 17% of those receiving lower doses (ie, <2 to 3 mg/kg/day study group; median dose: 2.46 mg/kg/day) (Ref).

Immune thrombocytopenia, chronic refractory

Immune thrombocytopenia (ITP), chronic refractory: Limited data available: Children ≥2 years and Adolescents: Oral: Maintenance: 2 to 2.5 mg/kg/day, rounded to the nearest 50 mg (Ref).

Lupus nephritis

Lupus nephritis: Limited data available: Children and Adolescents: Oral: 2 to 2.5 mg/kg/dose once daily (Ref); Note: Some data suggest less effective in non-Caucasian pediatric patients; some centers recommend use for primary induction in Caucasian patients with less severe disease (Ref).

Myasthenia gravis, juvenile

Myasthenia gravis, juvenile: Limited data available: Children and Adolescents: Oral: 1 to 3 mg/kg/dose once daily (Ref); most experience in pediatric patients extrapolated from adult trials; most commonly used in combination with corticosteroids as a steroid-sparing agent; however, azathioprine may be a first choice in patients where corticosteroids are contraindicated (Ref).

Solid organ transplantation

Solid organ transplantation: Limited data available: Infants, Children, and Adolescents: IV, Oral: Initial: 3 to 5 mg/kg/dose once daily, beginning at the time of transplant; maintenance: 1 to 3 mg/kg/dose once daily (Ref).

Uveitis, juvenile idiopathic arthritis-associated; acute

Uveitis, juvenile idiopathic arthritis-associated; acute: Limited data available: Children and Adolescents: Oral: Initial mean dose: 2.4 mg/kg/dose once daily; reported range: 1.4 to 3.2 mg/kg/dose once daily; in a retrospective review of patients with acute uveitis (n=41, ages 1 to 15 years), a mean maintenance 2.1 mg/kg/dose (range: 1 to 2.8 mg/kg/dose) once daily was reported as monotherapy and/or in combination with other immunosuppressive agents; infectious etiology was excluded; the authors recommend doses of <3 mg/kg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for TPMT and/or NUDT15 deficiency: Infants, Children, and Adolescents:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines (Ref):

Normal TPMT or NUDT15 activity (wild type): No initial dosage adjustment necessary; adjust dose based on condition being treated. Allow 2 weeks after each dosage adjustment to reach steady state.

TPMT intermediate or possible intermediate metabolizer or NUDT15 intermediate or possible intermediate metabolizer: Initiate azathioprine with the dose reduced to 30% to 80% of the usual dose and adjust based on the degree of myelosuppression and condition being treated. Allow 2 to 4 weeks after each dosage adjustment to reach steady state. If the starting dose is already below the normal recommended dose, dose reduction may not be recommended.

TPMT poor metabolizer: When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy. For malignancy, initiate azathioprine at a drastically reduced dose (reduce the daily dose by 10-fold and reduce the frequency from once daily to 3 times a week). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state.

NUDT15 poor metabolizer: When used for nonmalignant conditions, consider alternative (non-thiopurine) immunosuppressant therapy. For malignancy, initiate azathioprine at a drastically reduced dose (reduce the daily dose by 10-fold). Adjust dose based on the degree of myelosuppression and condition being treated. Allow 4 to 6 weeks after each dosage adjustment to reach steady state.

Dosage adjustment for toxicity: Limited data is available; based on experience in adult patients the following has been suggested:

Rapid WBC count decrease, persistently low WBC count, or serious infection: Reduce dose or temporarily withhold treatment.

Severe toxicity in renal transplantation: May require discontinuation.

Hepatic sinusoidal obstruction syndrome (SOS; veno-occlusive disease): Permanently discontinue.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents (Ref):

GFR >50 mL/minute/1.73 m2: No adjustment required.

GFR 10 to 50 mL/minute/1.73 m2: Administer 75% of dose once daily.

GFR <10 mL/minute/1.73 m2: Administer 50% of dose once daily.

Hemodialysis (dialyzable; ~45% removed in 8 hours): Administer 50% of normal dose once daily.

CAPD: Administer 50% of normal dose once daily.

CRRT: Administer 75% of normal dose once daily.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions (Significant): Considerations
GI effects

Use of azathioprine may result in dose-related GI intolerance including nausea, vomiting, and diarrhea. Symptoms are generally reversible upon discontinuation or with dosage reduction (Ref). GI adverse effects may result in treatment discontinuation (Ref).

An immune-mediated GI reaction characterized by severe nausea and vomiting has been rarely reported (Ref); additional symptoms may include diarrhea, skin rash, fever, malaise, myalgia, hypotension, and liver enzyme abnormalities. Reaction may recur upon rechallenge (Ref).

Mechanism:

GI intolerance: Dose-related; related to the pharmacologic action (Ref). Azathioprine is metabolized to 6-mercaptopurine (6-MP) which can then be converted into the active 6-thioguanine nucleotide (6-TGN) and thioguanine triphosphate (TGTP) metabolites. The cytotoxic actions of 6-MP are at least partly due to the incorporation of 6-TGN into DNA during therapy (Ref). Because thiopurine methyltransferase (TPMT) catalyzes the inactivation of 6-MP, decreased activity of TPMT may result in a higher risk of azathioprine-induced GI effects (Ref).

GI hypersensitivity: Immune-mediated; may be IgE-mediated (type 1) (Ref).

Onset: Varied; symptoms typically develop within the first several weeks of treatment. However, late onset (≥5 months of therapy) has also been described (Labidi 2020; Qiu 2015). Although there is limited evidence that the immune-mediated reaction is a type 1 reaction, onset is not immediate and the reaction may take months to develop (Riedel 1990).

Risk factors:

• Higher doses; Note: Risk may be reduced with divided doses or administration after meals.

• TPMT homozygous or compound heterozygous deficient allele carriers (Ref).

• Females (Ref)

• Crohn disease (Ref)

Hematologic toxicity

Use of azathioprine may result in reversible, dose-related hematologic toxicities (eg, leukopenia, thrombocytopenia, and anemias, including macrocytic anemia and/or pancytopenia); death associated with pancytopenia has been reported in patients with absent thiopurine methyltransferase (TPMT) activity. Clinicians should note that severe and life-threatening myelotoxicity may occur even at conventional doses in patients with TPMT or nudix hydrolase 15 (nucleotide diphosphate [NUDT15]) deficiency. Hematologic toxicity may require treatment interruption, dose reduction, or selection of alternate therapy.

Mechanism: Dose-related; related to the pharmacologic action. Azathioprine is metabolized to 6-mercaptopurine (6-MP) which can then be converted into the active 6-thioguanine nucleotide (6-TGN) and thioguanine triphosphate (TGTP) metabolites. The cytotoxic actions of 6-MP are at least partly due to the incorporation of 6-TGN and TGTP into DNA during therapy (Ref). Because TPMT and NUDT15 catalyzes the inactivation of 6-MP and TGTP, respectively, decreased activity of TPMT and/or NUDT15 results in a higher risk of azathioprine-induced myelotoxicity (Ref).

Onset: Delayed; most often occurs early (eg, within 3 to 6 months of treatment initiation) but may also occur months or years later (Ref). Timing of onset may differ depending on genotype (Ref).

Risk factors:

• Reduced TPMT and/or NUDT15 activity (Ref); TPMT and/or NUDT15 poor metabolizers (homozygous or compound heterozygous deficiency) are at very high risk for severe myelosuppression (Ref)

- Genetic TPMT deficiency is the primary cause of thiopurine intolerance in patients from Europe and Africa (Ref)

- NUDT15 risk alleles are associated with a majority of thiopurine intolerance in patients from East Asia and are also common in Hispanic patients (Ref)

• Concomitant use of other myelosuppressive agents (such as those used to treat rejection)

• Concomitant use of agents that may increase the concentration of cytotoxic metabolites including xanthine oxidase inhibitors (eg, allopurinol, febuxostat) and ribavirin

• Concomitant use of angiotensin-converting enzyme inhibitors (eg, lisinopril) and loop diuretics

Infections

Azathioprine is an immunosuppressant; therefore, use may result in bacterial infections, viral infections, fungal infections, protozoal infections, and opportunistic infections, including reactivation of latent infections. Infections may be severe and potentially fatal. As the degree of immunosuppression increases (due to use of additional immunosuppressant agents, preexisting immunosuppression, etc), the risk of infectious complications will increase. The risk of infection with azathioprine as compared to other immunosuppressants also differs based on multiple factors including concomitant immunosuppressant regimen and disease state (Ref).

Viral infections reported with the use of azathioprine include JC virus infection resulting in progressive multifocal leukoencephalopathy, cytomegalovirus (CMV) disease, herpes simplex virus infection, human papillomavirus infection, and reactivation of hepatitis B and tuberculosis (Ref).

Mechanism: Exact mechanism unknown; related to pharmacologic action. Azathioprine metabolites are incorporated into replicating DNA and halt replication; also blocks the pathway for purine synthesis (Ref). Azathioprine and its metabolites may also be a direct inhibitor of cytotoxic T cell and natural killer cell function (Ref).

Onset: Varied; in general, the onset of infections following solid organ transplant varies greatly; the majority of clinically important infections occur within the first 180 days (Ref).

Risk factors:

• Concomitant use of other immunosuppressive agents or preexisting immune function impairment

CMV infection: Transplant recipients that are CMV seronegative at the time of transplant who receive a graft from a CMV seropositive donor (Ref)

Liver dysfunction

Cholestatic, hepatocellular, or mixed type hepatotoxicity may occur (Ref). Hepatic effects most often occur in transplant patients and symptoms are normally reversible with discontinuation (Ref). Patients may experience transient transaminase elevations without associated symptoms or clinically significant hepatotoxicity (Ref). In patients who develop cholestatic hepatitis, serum alkaline phosphatase concentrations may be low or even normal at the onset of jaundice (Ref). Rarely, hepatic sinusoidal obstruction syndrome (SOS; formerly called veno-occlusive disease [VOD]) has been reported (Ref). Patients who develop hepatoxicity may require treatment interruption, dose reduction, or selection of alternate therapy.

An immune-mediated reaction resulting in moderate-to-severe liver enzyme abnormalities as well as fever, rash, chills, nausea, and diarrhea suggestive of cholestasis has been rarely reported (Ref). Reaction may recur upon rechallenge (Ref).

Mechanism: Multiple mechanisms exist; hepatotoxicity may be characterized as cholestatic, hepatocellular, or mixed type and/or a result of an immune-mediated reaction (Ref). Azathioprine is metabolized to 6-mercaptopurine (6-MP) which can then be converted into the active 6-thioguanine nucleotide (6-TGN) and methylated metabolites (MeMP), including 6-methylmercaptopurine ribonucleotides (6-MMPR). Both 6-TGN and MeMP may cause hepatic damage due to inhibition of purine de novo synthesis (Ref).

Onset: Varied; hepatotoxicity usually occurs within 6 months of treatment initiation or dose escalation (Ref). Early onset (within days of treatment initiation) as well as late onset (years after treatment initiation) have also been reported (Ref). Immune-mediated hepatotoxicity has occurred within 2 weeks of treatment initiation (Ref).

Risk factors:

• Transplant recipients

• Elevated 6-MMPR concentration (>5,700 pmol/8 x 108 erythrocytes) (Ref)

• May be more common in males (Ref); however, some studies have shown females to have a higher incidence (Ref)

• Age >50 years (Ref)

• BMI >25 kg/m2 (Ref)

Malignancy

In general, the chronic use of immunosuppression agents (including azathioprine) increases the risk of lymphoproliferative disorders and/or neoplasms (including skin carcinoma) in adult and pediatric patients. Malignancies reported have included malignant lymphoma, hepatosplenic T-cell lymphoma (HSTCL), hemophagocytic lymphohistiocytosis (HLH), acute myelocytic leukemia, myelodysplastic syndrome, and malignant neoplasm of skin, among others (Ref). HSTCL and HLH are especially of concern in patients with inflammatory bowel disease (IBD) and the risk is further increased with use of thiopurines (Ref); HSTCL has also been reported in solid organ transplant recipients receiving azathioprine (Ref).

The risk of skin cancer in comparison to other immunosuppressants is unclear (Ref). There is some evidence that risk of developing nonmelanoma skin cancers returns to baseline in patients with IBD who discontinue use of azathioprine; however, further study is required (Ref).

Mechanism: Dose- and time-related; related to the pharmacologic action. Azathioprine metabolites are incorporated into replicating DNA and halt replication, including in lymphocytes; azathioprine also blocks the pathway for purine synthesis (Ref). A decrease in the ability to repair UV-induced DNA lesions may contribute to risk of skin cancer (Ref). Azathioprine and its metabolites may also be direct inhibitors of cytotoxic T cell and natural killer cell function (Ref).

Onset: Delayed. Post-transplant lymphoproliferative disorders (PTLD) and non-skin-non-lymphoma malignancies generally occur during the first year after transplant when immunosuppressive therapy is most aggressive; however, the incidence of skin malignancies increase more linearly with time (Ref).

Risk factors:

• Intensity and duration of immunosuppression (Ref)

• Concomitant use of other immunosuppressive agents or preexisting immune function impairment

• Epstein-Barr virus (EBV) seronegative transplant recipients (Ref)

- Note: In general, pediatric transplant recipients are at a higher risk of PTLD as these patients are more likely to be EBV seronegative at transplantation (Ref)

- Note: Clinicians may also consider the role that EBV acute infection and/or reactivation may play in the risk of EBV-associated lymphoma in patients receiving immunosuppressive therapies for any indication; risk not well defined (Ref)

• Pretransplant malignancy (Ref)

• Fewer HLA matches (Ref)

• History of at least 1 prior rejection episode (Ref)

• Age <25 years or >50 years (Ref)

HSTCL:

- Young age (between 10 and 35 years) (Ref)

- Males (Ref)

- History of inflammatory bowel disease (Ref)

- Concomitant use of tumor necrosis factor-α (TNF-α) inhibitors (Ref)

HLH:

- History of inflammatory bowel disease (Ref)

- Viral infection, primarily EBV infection (Ref)

- Note: Several other bacterial, fungal, or parasitic coinfections (eg, Mycobacterium tuberculosis, histoplasmosis, HIV, cytomegalovirus) have been associated with secondary HLH (Ref)

Skin carcinoma: Exposure to sunlight/UV light

Pancreatitis

Acute pancreatitis may occur in adult and pediatric patients receiving azathioprine (Ref). Cases are generally mild and reversible upon discontinuation (Ref); however, severe disease may occur (Ref). Azathioprine-related pancreatitis associated with polyarthralgia and panniculitis (PPP syndrome) has also been reported (Ref).

Mechanism: Non–dose-related; idiosyncratic (Ref)

Onset: Varied; in one trial, patients were diagnosed with acute pancreatitis after a median of 21 days of azathioprine therapy (range: 7 to 63 days) (Ref). Most cases were identified within 90 days of treatment initiation in pediatric patients receiving azathioprine for inflammatory bowel disease (Ref).

Risk factors:

• Smoking (Ref)

• Concomitant use of oral budesonide (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency dependent upon dose, duration, indication, and concomitant therapy.

>10%:

Gastrointestinal: Nausea and vomiting (rheumatoid arthritis: 12%)

Hematologic & oncologic: Leukopenia (dose dependent; renal transplant: >50%; rheumatoid arthritis: 28%)

Infection: Infection (renal transplant: 20%; rheumatoid arthritis <1%; includes bacterial infection, fungal infection, protozoal infection, viral infection, opportunistic infection, and reactivation of latent infections)

1% to 10%: Hematologic & oncologic: Neoplasm (excluding lymphoma; renal transplant: 3%)

<1%: Hematologic & oncologic: Malignant lymphoma

Frequency not defined:

Dermatologic: Alopecia, skin rash, Sweet's syndrome (acute febrile neutrophilic dermatosis)

Endocrine & metabolic: Negative nitrogen balance

Gastrointestinal: Diarrhea, steatorrhea

Hematologic & oncologic: Bone marrow depression, malignant neoplasm of skin, thrombocytopenia (dose-dependent)

Neuromuscular & skeletal: Arthralgia

Respiratory: Interstitial pneumonitis (reversible)

Miscellaneous: Fever

Postmarketing:

Dermatologic: Erythema nodosum (González-Olivares 2017)

Gastrointestinal: Cholestasis (Gisi 2019), gastrointestinal hypersensitivity (Riedel 1990), pancreatitis (including pancreatitis polyarthritis panniculitis [PPP] syndrome) (Mishra 2020, Teich 2016)

Hematologic & oncologic: Acute myelocytic leukemia (Yenson 2008), anemia, aplastic anemia (Yeter 2013), hemophagocytic lymphohistiocytosis (Biank 2011), hemorrhage (Perri 2007), hepatosplenic T-cell lymphomas (Carvão 2019), macrocytic anemia (Zazgornik 1997), malignant solid tumor, NK cell deficiency (Orandi 2007), pancytopenia (Jensen 2018)

Hepatic: Hepatic sinusoidal obstruction syndrome (formerly known as hepatic veno-occlusive disease) (Lemley 1989) hepatotoxicity (idiosyncratic) (Chalasani 2021; Romagnuolo 1998)

Hypersensitivity: Drug-induced hypersensitivity reaction (McKenzie 2021)

Infection: JC virus infection (Pagnoux 2003)

Nervous system: Progressive multifocal leukoencephalopathy (Pagnoux 2003)

Respiratory: Hypersensitivity pneumonitis (Lee 2016)

Contraindications

Hypersensitivity to azathioprine or any component of the formulation; pregnancy (in patients with rheumatoid arthritis [see Pregnancy Considerations]); patients with rheumatoid arthritis and a history of treatment with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan) may have a prohibitive risk of malignancy with azathioprine treatment

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues:

• Mercaptopurine: Azathioprine is metabolized to mercaptopurine; concomitant use may result in profound myelosuppression and should be avoided.

• Vaccines: Immune response to vaccines may be diminished. Toxicity or adverse reactions to live vaccines may be enhanced (depending on the azathioprine dose).

Special populations:

• Patients with systemic lupus erythematosus (SLE) undergoing hip or knee replacement surgery: Patients with severe SLE (referring to patients with severe organ manifestations such as nephritis) should not interrupt therapy when undergoing hip or knee replacement surgery. For patients with SLE without severe disease, hold azathioprine for at least 1 week prior to surgery to reduce infection risk; therapy can be restarted once surgical wound shows evidence of healing (eg, no swelling, erythema, or drainage), sutures/staples are removed, and no ongoing nonsurgical site infections (typically ~14 days to reduce infection risk) (ACR/AAHKS [Goodman 2022]).

Other warnings/precautions:

• Discontinuation of therapy: Myasthenia gravis: Abrupt cessation of this or any immunosuppressant, especially in clinically unstable individuals, may result in rapid deterioration of myasthenic symptoms and possibly myasthenic crisis (Melzer 2016).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection [preservative free]:

Generic: 100 mg (1 ea)

Tablet, Oral:

Azasan: 75 mg, 100 mg [scored]

Imuran: 50 mg [scored]

Generic: 50 mg, 75 mg, 100 mg

Generic Equivalent Available: US

Yes

Pricing: US

Solution (reconstituted) (azaTHIOprine Sodium Injection)

100 mg (per each): $300.00

Tablets (Azasan Oral)

75 mg (per each): $24.83

100 mg (per each): $11.07

Tablets (azaTHIOprine Oral)

50 mg (per each): $2.10 - $6.81

75 mg (per each): $20.71

100 mg (per each): $9.23

Tablets (Imuran Oral)

50 mg (per each): $10.58

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection:

Imuran: 50 mg (5 mL)

Tablet, Oral:

Imuran: 50 mg

Generic: 50 mg

Administration: Adult

Oral: Most commonly administered once daily. Administering tablets after meals or in divided doses may decrease adverse GI events.

IV: Infusion is usually administered over 30 to 60 minutes. Infusion time is dependent upon the final volume after dilution. While normally given over 30 to 60 minutes, it may be infused over 5 minutes or over up to 8 hours.

Administration: Pediatric

Oral: Administer with food or may administer in divided doses to decrease GI upset.

Parenteral: IV: May administer over 5 minutes at a concentration not to exceed 10 mg/mL; or may infuse as diluted solution (<10 mg/mL) over 30 to 60 minutes or longer (eg, 8 hours) dependent upon final volume and specific protocols.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Use: Labeled Indications

Kidney transplantation, prevention of rejection:

Guideline recommendations: While azathioprine is FDA approved for adjunctive therapy in prevention of rejection after kidney transplantation, it is no longer recommended as a first-line agent. The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines for care of kidney transplant recipients recommend a combination of maintenance immunosuppressive medications as maintenance therapy, including a calcineurin inhibitor and an antiproliferative agent (mycophenolate preferred) with or without corticosteroids. Azathioprine is recommended as a second-line antiproliferative agent for prevention of acute rejection (KDIGO 2009).

Rheumatoid arthritis: Treatment of active rheumatoid arthritis, to reduce signs and symptoms.

Appropriate use: While azathioprine is FDA approved for the treatment of active arthritis, the 2012 and 2015 guideline updates from the American College of Rheumatology for the treatment of rheumatoid arthritis do not include azathioprine due to infrequent use in rheumatoid arthritis and a lack of new data (ACR [Singh 2012]; ACR [Singh 2016a]). However, azathioprine may be acceptable in certain situations where methotrexate is contraindicated and other alternatives are unable to be used (Cohen 2021).

Use: Off-Label: Adult

Behçet syndrome; Bullous pemphigoid; Crohn disease; Dermatomyositis/Polymyositis; Eosinophilic granulomatosis with polyangiitis (Churg-Strauss); Granulomatosis with polyangiitis and microscopic polyangiitis; Heart transplantation, prevention of rejection; Hepatitis, autoimmune; Immune thrombocytopenia, refractory; Interstitial pneumonia/interstitial lung disease; Liver transplantation, prevention of rejection; Lung transplantation, prevention of rejection; Lupus nephritis; Myasthenia gravis, chronic immunosuppressive therapy; Pemphigus vulgaris and pemphigus foliaceus; Polyarteritis nodosa; Sarcoidosis, pulmonary, steroid-refractory disease; Takayasu arteritis; Ulcerative colitis; Uveitis, noninfectious

Medication Safety Issues
Sound-alike/look-alike issues:

AzaTHIOprine may be confused with azaCITIDine, azidothymidine, azithromycin, Azulfidine.

Imuran may be confused with Elmiron, Enduron, Imdur, Inderal, Tenormin.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (immunosuppressant agent, parenteral and oral; contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care and Long-Term Care Settings).

Other safety concerns:

Azathioprine is metabolized to mercaptopurine; concurrent use of these commercially-available products has resulted in profound myelosuppression.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase serum concentrations of the active metabolite(s) of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Allopurinol: May increase serum concentrations of the active metabolite(s) of AzaTHIOprine. More specifically, allopurinol may increase mercaptopurine serum concentrations and promote formation of active thioguanine nucleotides. Management: Reduce azathioprine dose to one third to one quarter of the usual dose if used with allopurinol, and monitor closely for systemic toxicity. Further dose reduction or alternative therapies should be considered for patients with low or absent TPMT activity. Risk D: Consider therapy modification

Angiotensin-Converting Enzyme Inhibitors: May enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Antithyroid Agents: Myelosuppressive Agents may enhance the neutropenic effect of Antithyroid Agents. Risk C: Monitor therapy

Anti-TNF Agents: May enhance the adverse/toxic effect of Thiopurine Analogs. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccines: AzaTHIOprine may diminish the therapeutic effect of COVID-19 Vaccines. Management: Rheumatology guidelines recommend holding azathioprine for 1 to 2 weeks after each vaccine dose as permitted by the underlying disease. This recommendation is specific to patients using azathioprine for rheumatic and musculoskeletal disease. Risk D: Consider therapy modification

CycloPHOSphamide: AzaTHIOprine may enhance the hepatotoxic effect of CycloPHOSphamide. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Febuxostat: May increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Febuxostat may increase the serum concentration of AzaTHIOprine. Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

InFLIXimab: May enhance the adverse/toxic effect of AzaTHIOprine. Specifically, the risk for T-cell non-Hodgkin's lymphoma (including hepatosplenic T-cell lymphoma) may be increased. InFLIXimab may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Linezolid: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Mercaptopurine: AzaTHIOprine may enhance the myelosuppressive effect of Mercaptopurine. Risk X: Avoid combination

Methotrexate: AzaTHIOprine may enhance the hepatotoxic effect of Methotrexate. Risk C: Monitor therapy

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ribavirin (Oral Inhalation): May increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Specifically, concentrations of potentially myelotoxic methylated metabolites may be increased, while concentrations of active 6-thioguanine nucleotides may be decreased. Management: Consider using alternative agent(s) when possible. When these drugs are used in combination, monitor patients extra closely for signs/symptoms of myelosuppression. Risk D: Consider therapy modification

Ribavirin (Systemic): May increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Specifically, concentrations of potentially myelotoxic methylated metabolites may be increased, while concentrations of active 6-thioguanine nucleotides may be decreased. Management: Consider using alternative agent(s) when possible. When these drugs are used in combination, monitor patients closely for signs/symptoms of myelosuppression. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Sulfamethoxazole: May enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination

Trimethoprim: May enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): AzaTHIOprine may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

The manufacturer recommends that patients avoid becoming pregnant during treatment. However, additional recommendations are available for use in females and males on azathioprine who are planning a pregnancy.

Azathioprine is an acceptable immunosuppressant for use in kidney transplant recipients planning a pregnancy (EBPG 2002; KDIGO 2009; López 2014). Azathioprine should be substituted for mycophenolate 6 weeks prior to conception. Conception may be considered for females on a stable/low maintenance dose for ≥1 year following transplant (EBPG 2002; López 2014).

Azathioprine may also be acceptable for use in patients with rheumatic and musculoskeletal diseases who are planning to become pregnant. Conception should be planned during a period of quiescent/low disease activity (ACR [Sammaritano 2020]).

Patients with autoimmune hepatitis who are planning to become pregnant should continue use of azathioprine prior to conception to decrease the risk of flare and hepatic decompensation; biological remission is recommended for 1 year prior to conception (AASLD [Mack 2020]).

Data related to paternal use of azathioprine are limited. However, available data have not shown azathioprine adversely impacting male fertility or increasing the risk of adverse pregnancy outcomes when used within 3 months prior to conception (Bermas 2019; Mouyis 2019). Azathioprine is acceptable for use in patients with rheumatic and musculoskeletal diseases who are planning to father a child (ACR [Sammaritano 2020]).

Pregnancy Considerations

Azathioprine crosses the placenta; the 6-methylmercaptopurine (6-MMP) and 6-thioguanine (6-TGN) metabolites can be detected in cord blood. Infant serum concentrations were undetectable by 6 weeks of age in one study (Flanagan 2021).

An increased risk of stillbirth, preterm birth, and infants large for gestational age may be observed with maternal use of thiopurines (Meyer 2021).

Adverse events, including congenital anomalies, immunosuppression, hematologic toxicities (lymphopenia, pancytopenia), and intrauterine growth retardation have been observed in case reports following maternal use in kidney allograft recipients. Some of these adverse outcomes may be dose-related or a result of maternal disease (ACR [Sammaritano 2020]; EBPG 2002). Adverse pregnancy outcomes may also be associated with a kidney transplant, including preterm delivery and low birth weight in the infant and hypertension and preeclampsia in the mother. Appropriate maternal use of lower risk immunosuppressants may help decrease these risks (KDIGO 2009).

Intrahepatic cholestasis of pregnancy (ICP) has been associated with thiopurine use. In one study, patients with a metabolite ratio of 6-MMP to 6-TGN >11 (referred to as thiopurine shunting) was associated with the risk of ICP (Prentice 2024). The pharmacokinetic properties of thiopurines may be altered by pregnancy. A decrease in 6-TGN and an increase in 6-MMP was observed in the second trimester (Flanagan 2021). Closely monitor liver transaminases and thiopurine metabolites during pregnancy. Split dosing (taking half the total daily dose every 12 hours) may also prevent shunting (Prentice 2024). Patients with symptoms of ICP and elevated bile acid levels should discontinue treatment. Symptoms improve after thiopurine is discontinued (FDA 2024).

Azathioprine can be continued and should be substituted for mycophenolate in patients who become pregnant following a kidney transplant (EBPG 2002; KDIGO 2009; López 2014). Azathioprine may also be used in some pregnant patients who have had a liver (AASLD [Lucey 2013]), heart (ISHLT [Costanzo 2010]) or uterine (Jones 2019 [limited data]) transplant.

Although use for rheumatoid arthritis in pregnant patients is contraindicated by the manufacturer, available guidelines suggest that use of azathioprine may be acceptable for the management of rheumatic and musculoskeletal diseases during pregnancy (ACR [Sammaritano 2020]).

Patients with inflammatory bowel disease who are on maintenance therapy with azathioprine monotherapy may continue treatment during pregnancy; initiating treatment during pregnancy is not recommended. Combination therapy with azathioprine should be avoided due to increased risk of newborn infection (AGA [Mahadevan 2019]).

Treatment with azathioprine for autoimmune hepatitis should be continued during pregnancy. Because pregnancy may increase the risk of a flare, monitor closely for 6 months' postpartum (AASLD [Mack 2020]). Azathioprine may also be useful for the treatment of immune thrombocytopenia in a pregnant patient refractory to preferred agents (Provan 2019). Azathioprine is considered acceptable for the treatment of myasthenia gravis in pregnant patients who are not controlled with or unable to tolerate corticosteroids (Sanders 2016).

The Transplant Pregnancy Registry International (TPR) is a registry that follows pregnancies that occur in maternal transplant recipients or those fathered by male transplant recipients. The TPR encourages reporting of pregnancies following solid organ transplant by contacting them at 1-877-955-6877 or https://www.transplantpregnancyregistry.org.

Breastfeeding Considerations

The azathioprine metabolite 6-mercaptopurine (6-MP) is present in breast milk.

Azathioprine is a prodrug which is rapidly metabolized to 6-MP. 6-MP is present in breast milk; however, it is inactive until further metabolized to 6-TGN metabolites which are present only within red blood cells (Christensen 2008; Mottet 2016).

Peak breast milk concentrations of 6-MP occurred within 4 hours in a study of eight lactating women (Christensen 2008). Another study measured the active metabolite concentrations in RBCs of four breastfeeding women ≥3 months' postpartum on chronic azathioprine therapy; sampling was conducted at variable times after the dose. Women in the study had normal thiopurine methyltransferase (TPMT) activity. All women had therapeutic concentrations of 6-TGN; however, none of the infants had detectable concentrations (Gardiner 2006). Newborn serum concentrations of 6-MP and 6-TGN were also undetectable in a study which evaluated seven breastfed infants between 1 and 28 days' postpartum. Mothers in this study were taking azathioprine 100 mg/day (Sau 2007).

Information is available from a report of 29 women taking azathioprine 50 to 175 mg/day throughout pregnancy and postpartum and their 30 breastfed newborns. Among 20 infants with blood cell counts evaluated after delivery, one infant was diagnosed with asymptomatic neutropenia on day 15 of life. Neutropenia fluctuated over 1.5 months of breastfeeding, continued for 15 days after breastfeeding was discontinued, and resolved 3.5 months later. No adverse outcomes were observed in the remaining infants who were followed for 1 to 17 months (Bernard 2013). A second study of 11 women taking azathioprine maintenance doses for inflammatory bowel disease (median: 150 mg/day) did not find an increased risk of infection in their 15 breastfed infants. The infants were followed for 6 months to 6 years (Angelberger 2011).

Recommendations for breastfeeding during azathioprine therapy vary. Due to the potential for serious adverse reactions in the infant, breastfeeding is not recommended by the manufacturer. The World Health Organization also recommends breastfeeding be avoided during maternal treatment (WHO 2002).

Recommendations for breastfeeding following a kidney transplant differ; generally breastfeeding may be considered with maternal use of maintenance doses (Constantinescu 2014; EBPG 2002; KDIGO 2009; López 2014). Azathioprine is considered compatible for use in patients with inflammatory bowel disease who wish to breastfeed (AGA [Mahadevan 2019]). Azathioprine may be continued or initiated in patients with rheumatic and musculoskeletal diseases who are breastfeeding (ACR [Sammaritano 2020]).

Patients who are concerned with the theoretical risks of immunosuppression may consider pumping and discarding breast milk for the first 4 hours after an azathioprine dose to decrease potential exposure to the breastfed infant (ACR [Sammaritano 2020; Christensen 2008). Monitoring infant blood cell count 10 to 15 days after breastfeeding is initiated or in infants with frequent infections may also be considered (ACR [Sammaritano 2020]; Bernard 2013).

Monitoring Parameters

CBC with differential and platelets (weekly during first month, twice monthly for months 2 and 3, then monthly thereafter; monitor more frequently with dosage modifications or as clinically indicated), total bilirubin, LFTs (every 3 months), CrCl, monitor for signs/symptoms of infection and malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss). Azathioprine has been associated with skin cancer with long-term use after kidney transplantation. Patients taking azathioprine for a prolonged time period should avoid sun exposure and be monitored for skin cancer regularly.

Rheumatoid arthritis: CBC with differential at baseline and every 1 to 2 weeks with dose changes, the every 1 to 3 months thereafter, serum creatinine at baseline, and liver function tests at baseline (American College of Rheumatology [ACR 2002]). After a stable dose is achieved, consider monitoring CBC every 4 to 6 weeks and liver function tests every 6 to 8 weeks during azathioprine treatment (Belmont 2022).

Thiopurine S-methyltransferase (TPMT) genotyping or phenotyping: Consider testing for TPMT deficiency, particularly in patients with abnormally low CBC unresponsive to dose reduction. TPMT genotyping or phenotyping may assist in identifying patients at risk for developing toxicity (CPIC [Relling 2019]).

Nudix hydrolase 15 (NUDT15) genotyping: Consider genotyping for NUDT15 deficiency in patients who experience severe bone marrow toxicities or repeated myelosuppressive episodes. NUDT15 genotyping may assist in identifying patients at risk for developing toxicity (CPIC [Relling 2019]).

TPMT and NUDT15 testing cannot substitute for monitoring CBC in patients receiving azathioprine.

The American Gastroenterological Association suggests routine TPMT testing (enzymatic or genotype) to guide thiopurine dosing in adult patients initiated on thiopurines. The AGA further suggests reactive thiopurine metabolite monitoring to guide therapy changes in adult patients treated with active inflammatory bowel disease or patients experiencing adverse effects potentially due to thiopurine toxicity (targeted 6-thioguanine level between 230 to 450 pmol/8 x 108 RBCs) (Feuerstein 2017).

Mechanism of Action

Azathioprine is an imidazolyl derivative of mercaptopurine; metabolites are incorporated into replicating DNA and halt replication; also block the pathway for purine synthesis (Taylor 2005). The 6-thioguanine nucleotide metabolites appear to mediate the majority of azathioprine's immunosuppressive and toxic effects.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Immune thrombocytopenia (oral): Initial response: 30 to 90 days; Peak response: 30 to 120 days (ASH [Neunert 2011]).

Absorption: Oral: Well absorbed.

Protein binding: ~30%.

Metabolism: Hepatic; metabolized to 6-mercaptopurine via glutathione S-transferase (GST) reduction. Further metabolized (in the liver and GI tract) via major pathways: Hypoxanthine guanine phosphoribosyltransferase (to active metabolites: 6-thioguanine-nucleotides, or 6-TGNs), nucleotide diphosphate (NUDT15; converts 6-TGN to inactive 6-TG monophosphates), xanthine oxidase (to inactive metabolite: 6-thiouric acid), and thiopurine methyltransferase (TPMT) (to inactive metabolite: 6-methylmercaptopurine).

Half-life elimination: Azathioprine and mercaptopurine: Variable: ~2 hours (Taylor 2005).

Time to peak: Oral: 1 to 2 hours (including metabolites).

Excretion: Urine (primarily as metabolites).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance (azathioprine and metabolites) may be delayed in oliguric patients, particularly in those with tubular necrosis in the immediate post-transplant phase (deceased donor transplant).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Azaprin | Imuran;
  • (AR) Argentina: Azatioprina | Azatioprina asofarma | Azatioprina filaxis | Azatioprina rontag | Imuran;
  • (AT) Austria: Azafalk | Azathioprin hexal pharma | Imurek;
  • (AU) Australia: Apo-azathioprine | Azahexal | Azamun | Azapin | Azathioprine | Azathioprine an | Azathioprine gh | Azathioprine pfizer | Azran | Imazan | Imuran | Noumed azathioprine | Thioprine;
  • (BD) Bangladesh: Imuran;
  • (BE) Belgium: Azathioprine bexal | Azathioprine merck-generics | Azathioprine Sandoz | Imuran;
  • (BG) Bulgaria: Azathioprine teva | Imuran;
  • (BR) Brazil: Aseroprin | Furp azatioprina | Imunem | Imuran;
  • (CH) Switzerland: Azafalk | Azarek | Imurek;
  • (CL) Chile: Azafalk | Azatioprina | Imuran;
  • (CN) China: Imuran;
  • (CO) Colombia: Azakem | Azatioprina | Imuran;
  • (CZ) Czech Republic: Azamun | Azathioprin medac | Imasup | Imuran;
  • (DE) Germany: Aza effect pharma | Aza-Q | Azafalk | Azamedac | Azaqvida | Azarek | Azathiodura | Azathioprin | Azathioprin Dura N | Azathioprin Heumann | Azathioprin neuraxpharm | Azathioprin Stada | Colinsan | Imurek | Imurel | Zytrim;
  • (DK) Denmark: Azathioprin ratiopharm | Imurel;
  • (DO) Dominican Republic: Imuran;
  • (EC) Ecuador: Azatioprina | Imuran;
  • (EE) Estonia: Atsimutin | Azarekhexal | Imuran;
  • (EG) Egypt: Azathioprine evapharma | Imuran;
  • (ES) Spain: Immufalk | Imurel;
  • (ET) Ethiopia: Azoran;
  • (FI) Finland: Azamun | Azathioprin medac | Azathioprin Stada | Imuprin | Imuran | Imurel;
  • (FR) France: Azathioprine eg | Azathioprine Merck | Imurel;
  • (GB) United Kingdom: Azapress | Azathioprine Almus | Azathioprine aps | Azathioprine berk | Azathioprine cox | Azathioprine dc | Azathioprine kent | Berkaprine | Immunoprin | Imuran | Oprisine;
  • (GR) Greece: Azathioprine/farmasyn | Imuran;
  • (HK) Hong Kong: Imuprin | Imuran;
  • (HR) Croatia: Atsimutin | Imuran;
  • (HU) Hungary: Atioprin | Azathioprin Ebewe | Azathioprine Ebewe | Imuran;
  • (ID) Indonesia: Imuran;
  • (IE) Ireland: Azopine | Imuger | Imuran;
  • (IL) Israel: Azopi | Imuran;
  • (IN) India: Aretha | Atz | Azaprin | Azapure | Azarid | Azimune | Azoalfa | Azofit | Azoran | Azotas | Azr | Azutrans | Imoprine | Imuran | Innomune | Thiopress | Transimune | Vaprin | Zesoris az | Zimine | Zymurine;
  • (IT) Italy: Azafor | Azatioprina;
  • (JO) Jordan: Imuprin | Imuran;
  • (JP) Japan: Azanin | Imuran;
  • (KE) Kenya: Azathioprine mylan | Azioprin | Azoran | Imuran;
  • (KR) Korea, Republic of: Azabio | Azafrine | Azaprine | Azathioprin | Immuthera | Imuran | Teva azathioprine;
  • (KW) Kuwait: Imuran;
  • (LB) Lebanon: Azion | Imupirin | Imuran;
  • (LT) Lithuania: Atsimutin | Azafalk | Azamun | Azarek-hexal | Azathioprin | Imuran;
  • (LU) Luxembourg: Azathioprin Sandoz | Imuran;
  • (LV) Latvia: Atsimutin | Azamun | Azarek-hexal | Azathioprin | Azathioprin hexal | Imuran;
  • (MA) Morocco: Imurel;
  • (MX) Mexico: Azatioprina | Azatrilem | Dexmitron | Imuran | Kaplin | Muparel | Murprima;
  • (MY) Malaysia: Apo-azathioprine | Azamun | Azoran | Imuran;
  • (NL) Netherlands: Azafalk | Imuran | Imurel;
  • (NO) Norway: Imurel;
  • (NZ) New Zealand: Azamun | Imuprine | Imuran | Thioprine;
  • (PE) Peru: Azatioprina | Azatioprina tecnofarma | Imuran;
  • (PH) Philippines: Azathioprine pharmachemie | Imuran | Renzat;
  • (PK) Pakistan: Amorin | Azap | Azaprine | Azoprine | Dysmorin | Imulite | Imuran | Pharmazorine;
  • (PL) Poland: Azamun | Azathioprin | Azathioprine vis | Immunoprin | Imuran;
  • (PR) Puerto Rico: Azasan | Azathioprine | Imuran;
  • (PT) Portugal: Azafalk | Azatioprina medac | Imuran;
  • (PY) Paraguay: Azatioprina fapasa | Azatioprina libra | Imuran;
  • (QA) Qatar: Imuran | Imurel;
  • (RO) Romania: Immunoprin | Imuprin | Imuran;
  • (RU) Russian Federation: Azathioprin | Imuran;
  • (SA) Saudi Arabia: Apo-azathioprine | Azaprin | Imuran;
  • (SE) Sweden: Azathioprin Actavis | Azathioprin Orifarm | Azathioprine medac | Azatioprin Merck NM | Azatioprin Mylan | Azatioprin nm pharma | Immunoprin | Imurel;
  • (SG) Singapore: Imuran;
  • (SI) Slovenia: Azafalk | Imuran;
  • (SK) Slovakia: Azathioprin medac | Imasup | Imuran;
  • (TH) Thailand: Azadus | Imuran | Zinothin;
  • (TN) Tunisia: Azathioprine Aqvida | Azathioprine mylan | Imuran | Imurek | Imurel;
  • (TR) Turkey: Imuran;
  • (TW) Taiwan: Asazipam | Azamun | Azapress | Azaprine | Imuprin | Imuran;
  • (UA) Ukraine: Azathioprin | Imuran;
  • (UY) Uruguay: Azatioprina | Azuprina | Imuran;
  • (VE) Venezuela, Bolivarian Republic of: Azaprin;
  • (ZA) South Africa: Azamun | Azapress | Azathioprine 50pch | Imuran | Zaprine;
  • (ZW) Zimbabwe: Azapress
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. A-Rahim YI, Farrell RJ. Overview of azathioprine and mercaptopurine use in inflammatory bowel disease. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2021.
  3. Adams A, MacDermott EJ, Lehman TJ. Pharmacotherapy of Lupus Nephritis in Children: A Recommended Treatment Approach. Drugs. 2006;66(9):1191-1207. [PubMed 16827597]
  4. Al Hashash J, Regueiro M. Medical management of moderate to severe Crohn disease in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 2, 2021.
  5. Al Rifai A, Prasad N, Shuttleworth E, et al. Natural history of azathioprine-associated lymphopenia in inflammatory bowel disease patients: a prospective observational study. Eur J Gastroenterol Hepatol. 2011;23(2):153-158. doi:10.1097/MEG.0b013e32834233a2 [PubMed 21164349]
  6. Amato AA, Griggs RC. Treatment of idiopathic inflammatory myopathies. Curr Opin Neurol. 2003;16(5):569-575. doi:10.1097/01.wco.0000093099.34793.40 [PubMed 14501840]
  7. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002;46(2):328-346. doi:10.1002/art.10148 [PubMed 11840435]
  8. Angelberger S, Reinisch W, Messerschmidt A, et al. Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. J Crohns Colitis. 2011;5(2):95-100. doi:10.1016/j.crohns.2010.10.005 [PubMed 21453877]
  9. Ansari A, Arenas M, Greenfield SM, et al. Prospective evaluation of the pharmacogenetics of azathioprine in the treatment of inflammatory bowel disease. Aliment Pharmacol Ther. 2008;28(8):973-983. doi:10.1111/j.1365-2036.2008.03788.x [PubMed 18616518]
  10. Armuzzi A, Felice C, Papa A, et al. Prevention of postoperative recurrence with azathioprine or infliximab in patients with Crohn's disease: an open-label pilot study. J Crohns Colitis. 2013;7(12):e623-9. doi:10.1016/j.crohns.2013.04.020 [PubMed 23810678]
  11. Arnold DM, Nazi I, Santos A, et al. Combination immunosuppressant therapy for patients with chronic refractory immune thrombocytopenic purpura. Blood. 2010;115(1):29-31. doi:10.1182/blood-2009-06-222448 [PubMed 19897578]
  12. Aronoff GR, Bennett WM, Berns JS, et al, Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. American College of Physicians; 2007, p 97, 177.
  13. Asada A, Nishida A, Shioya M, et al. NUDT15 R139C-related thiopurine leukocytopenia is mediated by 6-thioguanine nucleotide-independent mechanism in Japanese patients with inflammatory bowel disease. J Gastroenterol. 2016;51(1):22-29. doi:10.1007/s00535-015-1142-4 [PubMed 26590936]
  14. Ashraf VV, Taly AB, Veerendrakumar M, et al. Myasthenia Gravis in Children: A Longitudinal Study. Acta Neurol Scand. 2006;114(2):119-123. [PubMed 16867035]
  15. Assini JF, Hamilton R, Strosberg JM. Adverse reactions to azathioprine mimicking gastroenteritis. J Rheumatol. 1986;13(6):1117-1118. [PubMed 3560101]
  16. Attard NR, Karran P. UVA photosensitization of thiopurines and skin cancer in organ transplant recipients. Photochem Photobiol Sci. 2012;11(1):62-68. doi:10.1039/c1pp05194f [PubMed 21860872]
  17. Azasan (azathioprine) [prescribing information]. Wilmington, NC: Alcami Corporation; December 2021.
  18. Azathioprine injection [prescribing information]. Eatontown, NJ: West-Ward Pharmaceuticals; January 2019.
  19. Bach JF, Dardenne M. The metabolism of azathioprine in renal failure. Transplantation. 1971;12(4):253-259. doi:10.1097/00007890-197110000-00003 [PubMed 4939818]
  20. Bagg A, Dunphy CH. Immunosuppressive and immunomodulatory therapy-associated lymphoproliferative disorders. Semin Diagn Pathol. 2013;30(2):102-112. doi:10.1053/j.semdp.2012.08.005 [PubMed 23541274]
  21. Baughman RP, Valeyre D, Korsten P, et al. ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J. 2021;58(6):2004079. doi:10.1183/13993003.04079-2020 [PubMed 34140301]
  22. Beissert S, Werfel T, Frieling U, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of bullous pemphigoid. Arch Dermatol. 2007;143(12):1536-1542. doi:10.1001/archderm.143.12.1536 [PubMed 18087004]
  23. Beissert S, Werfel T, Frieling U, et al. A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus. Arch Dermatol. 2006;142(11):1447-1454. [PubMed 17116835]
  24. Belmont HM. Pharmacology and side effects of azathioprine when used in rheumatic diseases. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 4, 2022.
  25. Belmont HM. Pharmacology and side effects of azathioprine when used in rheumatic diseases. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 6, 2023.
  26. Bermas BL. Paternal safety of anti-rheumatic medications. Best Pract Res Clin Obstet Gynaecol. 2019;S1521-6934(19)30135-X. doi:10.1016/j.bpobgyn.2019.09.004 [PubMed 31727565]
  27. Bernabeu-Wittel M, Naranjo M, Cisneros JM, et al. Infections in renal transplant recipients receiving mycophenolate versus azathioprine-based immunosuppression. Eur J Clin Microbiol Infect Dis. 2002;21(3):173-180. doi:10.1007/s10096-001-0684-y [PubMed 11957018]
  28. Bernard N, Gouraud A, Paret N et al. Azathioprine and breastfeeding: long-term follow-up. Abstract 05-03. Abstracts of the 17th Annual Meeting of French Society of Pharmacology and Therapeutics, the 80th Annual Meeting of Society of Physiology, the 34th Pharmacovigilance Meeting, the 14th APNET Seminar, and the 11th CHU CIC Meeting. April 22-24, 2013. Angers, France. Fundam Clin Pharmacol. 2013;279(suppl 1):1-140. [PubMed 23614855]
  29. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771-1782. [PubMed 22851469]
  30. Bewtra M, Lewis JD. Safety profile of IBD: lymphoma risks. Med Clin North Am. 2010;94(1):93-113. doi:10.1016/j.mcna.2009.08.015 [PubMed 19944800]
  31. Biank VF, Sheth MK, Talano J, et al. Association of Crohn's disease, thiopurines, and primary epstein-barr virus infection with hemophagocytic lymphohistiocytosis. J Pediatr. 2011;159(5):808-812. doi:10.1016/j.jpeds.2011.04.045 [PubMed 21722918]
  32. Bird SJ. Chronic immunotherapy for myasthenia gravis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 28, 2022.
  33. Björnsson ES, Gu J, Kleiner DE, et al. Azathioprine and 6-mercaptopurine-induced liver injury: clinical features and outcomes. J Clin Gastroenterol. 2017;51(1):63-69. doi:10.1097/MCG.0000000000000568 [PubMed 27648552]
  34. Booth RA, Ansari MT, Loit E, et al. Assessment of thiopurine S-methyltransferase activity in patients prescribed thiopurines: a systematic review. Ann Intern Med. 2011;154(12):814-298. doi:10.7326/0003-4819-154-12-201106210-00009 [PubMed 21690596]
  35. Borradori L, Van Beek N, Feliciani C, et al. Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2022;36(10):1689-1704. doi:10.1111/jdv.18220 [PubMed 35766904]
  36. Boruchov DM, Gururangan S, Driscoll MC, et al. Multiagent Induction and Maintenance Therapy for Patients With Refractory Immune Thrombocytopenic Purpura (ITP). Blood. 2007;110(10):3526-3531. [PubMed 17698634]
  37. Brambilla B, Barbosa AM, Scholze CDS, et al. Hemophagocytic lymphohistiocytosis and inflammatory bowel disease: case report and systematic review. Inflamm Intest Dis. 2020;5(2):49-58. doi:10.1159/000506514 [PubMed 32596254]
  38. Briemberg HR, Amato AA. Dermatomyositis and polymyositis. Curr Treat Options Neurol. 2003;5(5):349-356. [PubMed 12895397]
  39. Bunch TW. Prednisone and azathioprine for polymyositis: long-term followup. Arthritis Rheum. 1981;24(1):45-48. doi:10.1002/art.1780240107 [PubMed 7008799]
  40. Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 2005;80(9):1233-1243. doi:10.1097/01.tp.0000179639.98338.39 [PubMed 16314791]
  41. Caillard S, Lelong C, Pessione F, Moulin B; French PTLD Working Group. Post-transplant lymphoproliferative disorders occurring after renal transplantation in adults: report of 230 cases from the French Registry. Am J Transplant. 2006;6(11):2735-2742. doi:10.1111/j.1600-6143.2006.01540.x [PubMed 17049061]
  42. Calmus Y, Scheele JR, Gonzalez-Pinto I, et al. Immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients. Liver Transpl. 2002;8(2):123-131. doi:10.1053/jlts.2002.30882 [PubMed 11862588]
  43. Carvão J, Magno Pereira V, Jacinto F, Sousa Andrade C, Jasmins L. Hepatosplenic T-cell lymphoma: a rare complication of monotherapy with thiopurines in Crohn's disease. GE Port J Gastroenterol. 2019;26(4):279-284. doi:10.1159/000493350 [PubMed 31328143]
  44. Chalasani NP, Hayashi PH, Bonkovsky HL, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. Am J Gastroenterol. 2014;109(7):950-967. doi:10.1038/ajg.2014.131 [PubMed 24935270]
  45. Chams-Davatchi C, Esmaili N, Daneshpazhooh M, et al. Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris. J Am Acad Dermatol. 2007;57(4):622-628. doi:10.1016/j.jaad.2007.05.024 [PubMed 17583373]
  46. Chams-Davatchi C, Mortazavizadeh A, Daneshpazhooh M, et al. Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris. J Eur Acad Dermatol Venereol. 2013;27(10):1285-1292. doi:10.1111/j.1468-3083.2012.04717.x [PubMed 23062214]
  47. Chan GL, Erdmann GR, Gruber SA, et al. Pharmacokinetics of 6-thiouric acid and 6-mercaptopurine in renal allograft recipients after oral administration of azathioprine. Eur J Clin Pharmacol. 1989;36(3):265-271. doi:10.1007/BF00558158 [PubMed 2526020]
  48. Chan GL, Erdmann GR, Gruber SA, Matas AJ, Canafax DM. Azathioprine metabolism: pharmacokinetics of 6-mercaptopurine, 6-thiouric acid and 6-thioguanine nucleotides in renal transplant patients. J Clin Pharmacol. 1990;30(4):358-363. doi:10.1002/j.1552-4604.1990.tb03606.x [PubMed 2341582]
  49. Chao K, Wang X, Cao Q, et al. Combined detection of NUDT15 variants could highly predict thiopurine-induced leukopenia in Chinese patients with inflammatory bowel disease: a multicenter analysis. Inflamm Bowel Dis. 2017;23(9):1592-1599. doi:10.1097/MIB.0000000000001148 [PubMed 28570428]
  50. Chaparro M, Ordás I, Cabré E, et al. Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients. Inflamm Bowel Dis. 2013;19(7):1404-1410. doi:10.1097/MIB.0b013e318281f28f [PubMed 23665964]
  51. Christensen LA, Dahlerup JF, Nielsen MJ, Fallingborg JF, Schmiegelow K. Azathioprine treatment during lactation. Aliment Pharmacol Ther. 2008;28(10):1209-1213. [PubMed 18761704]
  52. Chung SA, Gorelik M, Langford CA, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa. Arthritis Care Res (Hoboken). 2021b;73(8):1061-1070. doi:10.1002/acr.24633 [PubMed 34235889]
  53. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2021a;73(8):1366-1383. doi:10.1002/art.41773 [PubMed 34235894]
  54. Ciafaloni E. Myasthenia gravis and congenital myasthenic syndromes. Continuum (Minneap Minn). 2019;25(6):1767-1784. [PubMed 31794470]
  55. Cohen S, Mikuls TR. Alternatives to methotrexate for the initial treatment of rheumatoid arthritis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 5, 2022.
  56. Colombel JF, Sandborn WJ, Reinisch W, et al; SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383-1395. doi:10.1056/NEJMoa0904492 [PubMed 20393175]
  57. Connell WR, Kamm MA, Ritchie JK, Lennard-Jones JE. Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut. 1993;34(8):1081-1085. doi:10.1136/gut.34.8.1081 [PubMed 8174958]
  58. Constantinescu S, Pai A, Coscia LA, Davison JM, Moritz MJ, Armenti VT. Breast-feeding after transplantation. Best Pract Res Clin Obstet Gynaecol. 2014;28(8):1163-1173. doi:10.1016/j.bpobgyn.2014.09.001 [PubMed 25271063]
  59. Contreras G, Pardo V, Leclercq B, et al. Sequential therapies for proliferative lupus nephritis. N Engl J Med. 2004;350(10):971-980. doi:10.1056/NEJMoa031855 [PubMed 14999109]
  60. Corominas H, Domènech M, Laíz A, et al. Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?. Rheumatology (Oxford). 2003;42(1):40-45. doi:10.1093/rheumatology/keg028 [PubMed 12509611]
  61. Costanzo MR, Dipchand A, Starling R, et al; International Society of Heart and Lung Transplantation. The International Society of Heart and Lung Transplantation guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010;29(8):914-956. doi:10.1016/j.healun.2010.05.034 [PubMed 20643330]
  62. Cottone M, Renna S. IBD: incidence of HSV and HPV with azathioprine. Nat Rev Gastroenterol Hepatol. 2009;6(8):444-445. doi:10.1038/nrgastro.2009.110 [PubMed 19654597]
  63. Cowlrick I, Delventhal H, Kaipainen K, Krcmar C, Petan J, Schleibner S. Three-year follow-up of malignancies in tacrolimus-treated renal recipients--an analysis of European multicentre studies. Clin Transplant. 2008;22(3):372-377. doi:10.1111/j.1399-0012.2008.00796.x [PubMed 18279418]
  64. Cristelli MP, Tedesco-Silva H, Medina-Pestana JO, Franco MF. Safety profile comparing azathioprine and mycophenolate in kidney transplant recipients receiving tacrolimus and corticosteroids. Transpl Infect Dis. 2013;15(4):369-378. doi:10.1111/tid.12095 [PubMed 23701592]
  65. D'Haens GR, Vermeire S, Van Assche G, et al. Therapy of metronidazole with azathioprine to prevent postoperative recurrence of Crohn's disease: a controlled randomized trial. Gastroenterology. 2008;135(4):1123-1129. doi:10.1053/j.gastro.2008.07.010 [PubMed 18727929]
  66. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362(9388):971-982. doi:10.1016/S0140-6736(03)14368-1 [PubMed 14511932]
  67. Danese S, Fiocchi C. Ulcerative colitis. N Engl J Med. 2011;365(18):1713-1725. doi:10.1056/NEJMra1102942. [PubMed 2204756]
  68. Daniel LL, Dickson AL, Chung CP. Precision medicine for rheumatologists: lessons from the pharmacogenomics of azathioprine. Clin Rheumatol. 2021;40(1):65-73. doi:10.1007/s10067-020-05258-2 [PubMed 32617765]
  69. De Cruz P, Kamm MA, Hamilton AL, et al. Crohn's disease management after intestinal resection: a randomised trial. Lancet. 2015;385(9976):1406-1417. doi:10.1016/S0140-6736(14)61908-5 [PubMed 25542620]
  70. De Silva M, Hazleman BL. Long-term azathioprine in rheumatoid arthritis: a double-blind study. Ann Rheum Dis. 1981;40(6):560-563. doi:10.1136/ard.40.6.560 [PubMed 7036921]
  71. Della Corte C, Sartorelli MR, Sindoni CD, et al. Autoimmune Hepatitis in Children: An Overview of the Disease Focusing on Current Therapies. Eur J Gastroenterol Hepatol. 2012;24(7):739-746. [PubMed 22495399]
  72. Denfield SW. Strategies to Prevent Cellular Rejection in Pediatric Heart Transplant Recipients. Paediatr Drugs. 2010;12(6):391-403. [PubMed 21028918]
  73. Diamond JM, Kotloff RM. Maintenance immunosuppression following lung transplantation. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022.
  74. Díaz-Llopis M, Gallego-Pinazo R, García-Delpech S, Salom-Alonso D. General principles for the treatment of non-infectious uveitis. Inflamm Allergy Drug Targets. 2009;8(4):260-265. [PubMed 19754409]
  75. Dooley MA, Jayne D, Ginzler EM, et al; ALMS Group. Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011;365(20):1886-1895. doi:10.1056/NEJMoa1014460 [PubMed 22087680]
  76. Doubelt I, Pulenzas N, Carette S, Pagnoux C; Canadian Vasculitis Network (CanVasc). Efficacy of conventional immunosuppressants in relapsing or refractory eosinophilic granulomatosis with polyangiitis: evidence from a Canadian single-centre cohort. Clin Exp Rheumatol. 2020;38(suppl 124)(2):171-175. [PubMed 32167871]
  77. Dutch Pharmacogenetics Working Group (DPWG). TPMT PM: azathioprine/mercaptopurine. TPMT IM: azathioprine/mercaptopurine. https://www.knmp.nl/downloads/pharmacogenetic-recommendations-februari-2021.pdf. Updated September 17, 2019. Accessed May 12, 2021.
  78. EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant. 2002;(17)(suppl 4):50-55. [PubMed 12091650]
  79. Eisen HJ, Tuzcu EM, Dorent R, et al; RAD B253 Study Group. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847-858. doi:10.1056/NEJMoa022171 [PubMed 12944570]
  80. Ertz-Archambault N, Kosiorek H, Taylor GE, et al. Association of therapy for autoimmune disease with myelodysplastic syndromes and acute myeloid leukemia. JAMA Oncol. 2017;3(7):936-943. doi:10.1001/jamaoncol.2016.6435 [PubMed 28152123]
  81. European Association for the Study of the Liver. EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol. 2015;63(4):971-1004. doi:10.1016/j.jhep.2015.06.030 [PubMed 26341719]
  82. Expert opinion. Senior Renal Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  83. Falk RJ, Dall’Era M, Appel GB. Lupus nephritis: initial and subsequent therapy for focal or diffuse lupus nephritis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 27, 2022.
  84. Fan X, Yin D, Men R, Xu H, Yang L. NUDT15 polymorphism confer increased susceptibility to thiopurine-induced leukopenia in patients with autoimmune hepatitis and related cirrhosis. Front Pharmacol. 2019;10:346. doi:10.3389/fphar.2019.00346 [PubMed 31024313]
  85. Fanouriakis A, Kostopoulou M, Cheema K, et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723. doi:10.1136/annrheumdis-2020-216924 [PubMed 32220834]
  86. Farrugia ME, Goodfellow JA. A practical approach to managing patients with myasthenia gravis-opinions and a review of the literature. Front Neurol. 2020;11:604. doi:10.3389/fneur.2020.00604 [PubMed 32733360]
  87. Farthing PM, Maragou P, Coates M, et al. Characteristics of the oral lesions in patients with cutaneous recurrent erythema multiforme. J Oral Pathol Med. 1995;24(1):9-13. doi:10.1111/j.1600-0714.1995.tb01122.x [PubMed 7722922]
  88. Fei X, Shu Q, Zhu H, et al. NUDT15 R139C Variants increase the risk of azathioprine-induced leukopenia in Chinese autoimmune patients. Front Pharmacol. 2018;9:460. doi:10.3389/fphar.2018.00460 [PubMed 29867468]
  89. Feuerstein JD, Ho EY, Shmidt E, et al; American Gastroenterological Association Institute Clinical Guidelines Committee. AGA clinical practice guidelines on the medical management of moderate to severe luminal and perianal fistulizing Crohn's disease. Gastroenterology. 2021;160(7):2496-2508. doi:10.1053/j.gastro.2021.04.022 [PubMed 34051983]
  90. Feuerstein JD, Isaacs KL, Schneider Y, Siddique SM, Falck-Ytter Y, Singh S; AGA Institute Clinical Guidelines Committee. AGA clinical practice guidelines on the management of moderate to severe ulcerative colitis. Gastroenterology. 2020;158(5):1450-1461. doi:10.1053/j.gastro.2020.01 [PubMed 31945371]
  91. Feuerstein JD, Moss AC, Farraye FA. Ulcerative colitis. Mayo Clin Proc. 2019;94(7):1357-1373. doi:10.1016/j.mayocp.2019.01.018 [PubMed 31272578]
  92. Feuerstein JD, Nguyen GC, Kupfer SS, Falck-Ytter Y, Singh S; American Gastroenterological Association Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology. 2017;153(3):827-834. doi:10.1053/j.gastro.2017.07.032 [PubMed 28780013]
  93. Finnis MF, Jayawant S. Juvenile myasthenia gravis: a paediatric perspective. Autoimmune Dis. 2011;2011:404101. [PubMed 22110902]
  94. Flaherty KR. Treatment and prognosis of nonspecific interstitial pneumonia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 6, 2023.
  95. Flanagan E, Wright EK, Hardikar W, et al; PICCOLO Study Group. Maternal thiopurine metabolism during pregnancy in inflammatory bowel disease and clearance of thiopurine metabolites and outcomes in exposed neonates. Aliment Pharmacol Ther. 2021;53(7):810-820. doi:10.1111/apt.16294 [PubMed 33608894]
  96. Ford KA. Paediatric Immunosuppression Following Solid Organ Transplantation. Arch Dis Child Educ Pract. 2006;91:ep87-ep91.
  97. Formea CM, Myers-Huentelman H, Wu R, et al. Thiopurine S-methyltransferase genotype predicts azathioprine-induced myelotoxicity in kidney transplant recipients. Am J Transplant. 2004;4(11):1810-1817. doi:10.1111/j.1600-6143.2004.00575.x [PubMed 15476481]
  98. Fuentes D, Torrente F, Keady S, et al. High-Dose Azathioprine in Children With Inflammatory Bowel Disease. Aliment Pharmacol Ther. 2003;17(7):913-921. [PubMed 12656694]
  99. Funch DP, Ko HH, Travasso J, et al. Posttransplant lymphoproliferative disorder among renal transplant patients in relation to the use of mycophenolate mofetil. Transplantation. 2005;80(9):1174-1180. doi:10.1097/01.tp.0000169035.10572.c6 [PubMed 16314782]
  100. Galor A, Jabs DA, Leder HA, et al. Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmology. 2008;115(10):1826-1832. [PubMed 18579209]
  101. Gardiner SJ, Gearry RB, Roberts RL, Zhang M, Barclay ML, Begg EJ. Exposure to thiopurine drugs through breast milk is low based on metabolite concentrations in mother-infant pairs. Br J Clin Pharmacol. 2006;62(4):453-456. [PubMed 16995866]
  102. Germani G, Pleguezuelo M, Villamil F, et al. Azathioprine in liver transplantation: a reevaluation of its use and a comparison with mycophenolate mofetil. Am J Transplant. 2009;9(8):1725-1731. doi:10.1111/j.1600-6143.2009.02705.x [PubMed 19538488]
  103. Girgin S, Yurumez S, Omma A, et al. Comparison of relapse rates in Behçet's disease with venous involvement on different doses of azathioprine therapy, a retrospective observational study. Int J Rheum Dis. 2021;24(4):562-566. doi:10.1111/1756-185X.14075 [PubMed 33638242]
  104. Gisbert JP, Linares PM, McNicholl AG, Maté J, Gomollón F. Meta-analysis: the efficacy of azathioprine and mercaptopurine in ulcerative colitis. Aliment Pharmacol Ther. 2009;30(2):126-137. doi:10.1111/j.1365-2036.2009.04023.x. [PubMed 19392869]
  105. Gisi K, Ispiroglu M, Kantarceken B, Sayar H. Severe cholestasis due to azathioprine in Behcet's disease. BMJ Case Rep. 2019;12(3):e226340. doi:10.1136/bcr-2018-226340 [PubMed 30936327]
  106. Gjuladin-Hellon T, Iheozor-Ejiofor Z, Gordon M, Akobeng AK. Azathioprine and 6-mercaptopurine for maintenance of surgically-induced remission in Crohn's disease. Cochrane Database Syst Rev. 2019;8(8):CD010233. doi:10.1002/14651858.CD010233.pub3 [PubMed 31425621]
  107. Goebel JC, Roesel M, Heinz C, Michels H, Ganser G, Heiligenhaus A. Azathioprine as a treatment option for uveitis in patients with juvenile idiopathic arthritis. Br J Ophthalmol. 2011;95(2):209-213.
  108. Goel R, Danda D, Joseph G, et al. Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: single centre experience from a large tertiary care teaching hospital in Southern India. Semin Arthritis Rheum. 2018;47(5):718-726. doi:10.1016/j.semarthrit.2017.09.014 [PubMed 29096935]
  109. Golightly LK, Teitelbaum I, Kiser TH, et al, eds. Renal Pharmacotherapy: Dosage Adjustment of Medications Eliminated by the Kidneys. Springer Science; 2013.
  110. González-Olivares M, Khedaoui R, Martínez-Morán C, Borbujo J. Azathioprine-induced hypersensitivity reaction presenting as erythema nodosum. Eritema nudoso como reacción de hipersensibilidad a la azatioprina. Actas Dermosifiliogr. 2017;108(6):591-593. doi:10.1016/j.ad.2016.12.006 [PubMed 28262113]
  111. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons guideline for the perioperative management of antirheumatic medication in patients with rheumatic diseases undergoing elective total hip or total knee arthroplasty. Arthritis Care Res (Hoboken). 2022;74(9):1399-1408. doi:10.1002/acr.24893 [PubMed 35718887]
  112. Green M. Introduction: Infections in solid organ transplantation. Am J Transplant. 2013b;13(suppl 4):3-8. doi:10.1111/ajt.12093 [PubMed 23464993]
  113. Green M, Michaels MG. Epstein-Barr virus infection and posttransplant lymphoproliferative disorder. Am J Transplant. 2013a;13(suppl 3):41-54. doi:10.1111/ajt.12004 [PubMed 23347213]
  114. Griger Z, Nagy-Vincze M, Dankó K. Pharmacological management of dermatomyositis. Expert Rev Clin Pharmacol. 2017;10(10):1109-1118. doi:10.1080/17512433.2017.1353910 [PubMed 28691537]
  115. Grossman AB, Noble AJ, Mamula P, et al. Increased Dosing Requirements for 6-Mercaptopurine and Azathioprine in Inflammatory Bowel Disease Patients Six Years and Younger. Inflamm Bowel Dis. 2008;14(6):750-755. [PubMed 18266236]
  116. Guirao-Arrabal E, Santos F, Redel-Montero J, et al. Risk of tuberculosis after lung transplantation: the value of pretransplant chest computed tomography and the impact of mTOR inhibitors and azathioprine use. Transpl Infect Dis. 2016;18(4):512-519. doi:10.1111/tid.12555 [PubMed 27224905]
  117. Hagen JW, Pugliano-Mauro MA. Nonmelanoma skin cancer risk in patients with inflammatory bowel disease undergoing thiopurine therapy: a systematic review of the literature. Dermatol Surg. 2018;44(4):469-480. doi:10.1097/DSS.0000000000001455 [PubMed 29315147]
  118. Hahn BH, McMahon MA, Wilkinson A, et al; American College of Rheumatology. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012;64(6):797-808. [PubMed 22556106]
  119. Hatemi I, Esatoglu SN, Hatemi G, Erzin Y, Yazici H, Celik AF. Characteristics, treatment, and long-term outcome of gastrointestinal involvement in Behcet's syndrome: a strobe-compliant observational study from a dedicated multidisciplinary center. Medicine (Baltimore). 2016;95(16):e3348. doi:10.1097/MD.0000000000003348 [PubMed 27100417]
  120. Heckmann JM, Rawoot A, Bateman K, Renison R, Badri M. A single-blinded trial of methotrexate versus azathioprine as steroid-sparing agents in generalized myasthenia gravis. BMC Neurol. 2011;11:97. doi:10.1186/1471-2377-11-97 [PubMed 21819556]
  121. Hellmich B, Agueda A, Monti S, et al. 2018 update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79(1):19-30. doi:10.1136/annrheumdis-2019-215672 [PubMed 31270110]
  122. Hellmich B, Sanchez-Alamo B, Schirmer JH, et al. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024;83(1):30-47. doi:10.1136/ard-2022-223764 [PubMed 36927642]
  123. Heneghan MA. Management of autoimmune hepatitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 4, 2022.
  124. Hertl M, Geller S. Initial management of pemphigus vulgaris and pemphigus foliaceus. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 28, 2022.
  125. Hiemstra TF, Walsh M, Mahr A, ET AL; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil vs azathioprine for remission maintenance in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized controlled trial. JAMA. 2010;304(21):2381-2388. doi:10.1001/jama.2010.1658 [PubMed 21060104]
  126. Hörl MP, Schmitz M, Ivens K, Grabensee B. Opportunistic infections after renal transplantation. Curr Opin Urol. 2002;12(2):115-123. doi:10.1097/00042307-200203000-00006 [PubMed 11859257]
  127. Houssiau FA, D'Cruz D, Sangle S, et al; MAINTAIN Nephritis Trial Group. Azathioprine versus mycophenolate mofetil for long-term immunosuppression in lupus nephritis: results from the MAINTAIN nephritis trial. Ann Rheum Dis. 2010;69(12):2083-2089. doi:10.1136/ard.2010.131995 [PubMed 20833738]
  128. Huapaya JA, Silhan L, Pinal-Fernandez I, ET AL. Long-term treatment with azathioprine and mycophenolate mofetil for myositis-related interstitial lung disease. Chest. 2019;156(5):896-906. doi:10.1016/j.chest.2019.05.023 [PubMed 31238042]
  129. Imperatore N, Foggia M, Patturelli M, et al. Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting. J Gastroenterol Hepatol. 2021;36(7):1859-1868. doi:10.1111/jgh.15367 [PubMed 33283312]
  130. Imuran (azathioprine) [prescribing information]. Roswell, GA: Sebela Pharmaceuticals Inc; December 2018.
  131. Imuran (azathioprine) [product monograph]. Oakville, Ontario, Canada: Aspen Pharmacare Canada Inc; April 2022.
  132. Jack KL, Koopman WJ, Hulley D, Nicolle MW. A review of azathioprine-associated hepatotoxicity and myelosuppression in myasthenia gravis. J Clin Neuromuscul Dis. 2016;18(1):12-20. doi:10.1097/CND.0000000000000133 [PubMed 27552384]
  133. Jayne D, Rasmussen N, Andrassy K, ET AL; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003;349(1):36-44. doi:10.1056/NEJMoa020286 [PubMed 12840090]
  134. Jensen CH, Tiu J, Catalanotti JS. Azathioprine-induced pancytopenia with normal TPMT activity presenting with HSV oral ulcers. BMJ Case Rep. 2018;2018:bcr2018225209. doi:10.1136/bcr-2018-225209 [PubMed 30002211]
  135. Jeurissen ME, Boerbooms AM, van de Putte LB, Kruijsen MW. Azathioprine induced fever, chills, rash, and hepatotoxicity in rheumatoid arthritis. Ann Rheum Dis. 1990;49(1):25-27. doi:10.1136/ard.49.1.25 [PubMed 2138007]
  136. Jiyad Z, Olsen CM, Burke MT, Isbel NM, Green AC. Azathioprine and risk of skin cancer in organ transplant recipients: systematic review and meta-analysis. Am J Transplant. 2016;16(12):3490-3503. doi:10.1111/ajt.13863 [PubMed 27163483]
  137. Johnson PJ, McFarlane IG, Williams R. Azathioprine for long-term maintenance of remission in autoimmune hepatitis. N Engl J Med. 1995;333(15):958-963. doi:10.1056/NEJM199510123331502 [PubMed 7666914]
  138. Jones BP, Saso S, Bracewell-Milnes T, et al. Human uterine transplantation: a review of outcomes from the first 45 cases. BJOG. 2019;126(11):1310-1319. doi:10.1111/1471-0528.15863 [PubMed 31410987]
  139. Jones RR. Azathioprine Therapy in the Management of Persistent Erythema Multiforme. Br J Dermatol. 1981;105(4):465-467. [PubMed 7295560]
  140. Kakuta Y, Kawai Y, Okamoto D, et al. NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study. J Gastroenterol. 2018;53(9):1065-1078. doi:10.1007/s00535-018-1486-7 [PubMed 29923122]
  141. Kakuta Y, Naito T, Onodera M, et al. NUDT15 R139C causes thiopurine-induced early severe hair loss and leukopenia in Japanese patients with IBD. Pharmacogenomics J. 2016;16(3):280-285. doi:10.1038/tpj.2015.43 [PubMed 26076924]
  142. Kasiske BL, Zeier MG, Chapman JR, et al; Kidney Disease: Improving Global Outcomes. KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary. Kidney Int. 2010;77(4):299-311. doi:10.1038/ki.2009.377 [PubMed 19847156]
  143. Keogh A, Richardson M, Ruygrok P, et al. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation. 2004;110(17):2694-2700. doi:10.1161/01.CIR.0000136812.90177.94 [PubMed 15262845]
  144. Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant. 2009;9(suppl 3):S1-S155. [PubMed 19845597]
  145. Kim JH, Cheon JH, Hong SS, et al. Influences of thiopurine methyltransferase genotype and activity on thiopurine-induced leukopenia in Korean patients with inflammatory bowel disease: a retrospective cohort study. J Clin Gastroenterol. 2010;44(10):e242-e248. doi:10.1097/MCG.0b013e3181d6baf5 [PubMed 20308917]
  146. Kim SY, Shin JH, Park JS, et al. NUDT15 p.R139C variant is common and strongly associated with azathioprine-induced early leukopenia and severe alopecia in Korean patients with various neurological diseases. J Neurol Sci. 2017;378:64-68. doi:10.1016/j.jns.2017.04.041 [PubMed 28566182]
  147. King TE Jr. Cryptogenic organizing pneumonia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 2, 2023.
  148. King TE Jr. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed April 11, 2022.
  149. King TE Jr. Treatment of pulmonary sarcoidosis refractory to initial therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed November 1, 2021.
  150. Kobashigawa J, Miller L, Renlund D, et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients. Mycophenolate Mofetil Investigators. Transplantation. 1998;66(4):507-515. doi:10.1097/00007890-199808270-00016 [PubMed 9734496]
  151. Kotlyar DS, Lewis JD, Beaugerie L, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol. 2015;13(5):847-e50. doi:10.1016/j.cgh.2014.05.015 [PubMed 24879926]
  152. Kuschal C, Thoms KM, Schubert S, et al. Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair. Exp Dermatol. 2012;21(1):2-6. doi:10.1111/j.1600-0625.2011.01413.x [PubMed 22151386]
  153. Kvien TK, Hoyeraal HM, and Sandstad B, "Azathioprine Versus Placebo in Patients With Juvenile Rheumatoid Arthritis: A Single Center Double Blind Comparative Study," J Rheumatol, 1986, 13(1):118-23. [PubMed 3517321]
  154. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood. 2019;133(23):2465-2477. doi:10.1182/blood.2018894618 [PubMed 30992265]
  155. Labidi A, Hafi M, Ben Mustapha N, Serghini M, Fekih M, Boubaker J. Toxicity profile of thiopurines in inflammatory bowel disease: a retrospective cohort analysis. Tunis Med. 2020;98(5):404-412. [PubMed 32548844]
  156. Lamers MM, van Oijen MG, Pronk M, Drenth JP. Treatment options for autoimmune hepatitis: a systematic review of randomized controlled trials. J Hepatol. 2010;53(1):191-198. doi:10.1016/j.jhep.2010.01.037 [PubMed 20400196]
  157. Lee A, Bridges LR, Lloyd M, Barker R, Wren DR, Galtrey CM. Epstein-Barr virus associated CNS lymphoproliferative disorder after long-term immunosuppression. Pract Neurol. 2020;20(1):83-86. doi:10.1136/practneurol-2019-002356 [PubMed 31467148]
  158. Lee IH, Kang GW, Kim KC. Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis. Rheumatol Int. 2016;36(7):1027-1032. doi:10.1007/s00296-016-3489-0 [PubMed 27155976]
  159. Lee RA, Gabardi S. Current trends in immunosuppressive therapies for renal transplant recipients. Am J Health Syst Pharm. 2012;69(22):1961-1975. doi:10.2146/ajhp110624 [PubMed 23135563]
  160. Lémann M, Mary JY, Duclos B, et al; Groupe d'Etude Therapeutique des Affections Inflammatoires du Tube Digestif (GETAID). Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a randomized placebo-controlled trial. Gastroenterology. 2006;130(4):1054-1061. doi:10.1053/j.gastro.2006.02.014 [PubMed 16618399]
  161. Lemley DE, DeLacy LM, Seeff LB, Ishak KG, Nashel DJ. Azathioprine induced hepatic veno-occlusive disease in rheumatoid arthritis. Ann Rheum Dis. 1989;48(4):342-346. doi:10.1136/ard.48.4.342 [PubMed 2712618]
  162. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn's disease in adults. Am J Gastroenterol. 2018;113(4):481-517. doi:10.1038/ajg.2018.27 [PubMed 29610508]
  163. Lightner AL, Vogel JD, Carmichael JC, et al. The American Society of Colon and Rectal Surgeons clinical practice guidelines for the surgical management of Crohn's disease. Dis Colon Rectum. 2020;63(8):1028-1052. doi:10.1097/DCR.0000000000001716 [PubMed 32692069]
  164. Lindner A, Schalke B, Toyka KV. Outcome in juvenile-onset myasthenia gravis: a retrospective study with long-term follow-up of 79 patients. J Neurol. 1997;244(8):515-520. doi: 10.1007/s004150050135 [PubMed 9309559]
  165. Liu YP, Xu HQ, Li M, et al. Association between thiopurine S-methyltransferase polymorphisms and azathioprine-induced adverse drug reactions in patients with autoimmune diseases: a meta-analysis. PLoS One. 2015;10(12):e0144234. doi:10.1371/journal.pone.0144234 [PubMed 26633017]
  166. López LF, Martínez CJ, Castañeda DA, Hernández AC, Pérez HC, Lozano E. Pregnancy and kidney transplantation, triple hazard? Current concepts and algorithm for approach of preconception and perinatal care of the patient with kidney transplantation. Transplant Proc. 2014;46(9):3027-3031. doi:10.1016/j.transproceed.2014.07.013 [PubMed 25420815]
  167. López-Sanromán A, Vera-Mendoza I, Domènech E, et al; Spanish GETECCU group [APPRECIA study]. Adalimumab vs azathioprine in the prevention of postoperative Crohn's disease recurrence. A GETECCU randomised trial. J Crohns Colitis. 2017;11(11):1293-1301. doi:10.1093/ecco-jcc/jjx051 [PubMed 28402454]
  168. Lucey MR, Terrault N, Ojo L, et al. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013;19(1):3-26. doi:10.1002/lt.23566 [PubMed 23281277]
  169. Mack CL, Adams D, Assis DN, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases (AASLD). Hepatology. 2020;72(2):671-722. doi:10.1002/hep.31065 [PubMed 31863477]
  170. Mahadevan U, Robinson C, Bernasko N, et al. Inflammatory bowel disease in pregnancy clinical care pathway: a report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology. 2019;156(5):1508-1524. doi:10.1053/j.gastro.2018.12.022 [PubMed 30658060]
  171. Manns MP, Czaja AJ, Gorham JD, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193-2213. [PubMed 20513004]
  172. Manzano-Alonso ML, Castellano-Tortajada G. Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy. World J Gastroenterol. 2011;17(12):1531-1537. doi:10.3748/wjg.v17.i12.1531 [PubMed 21472116]
  173. Marbet U, Schmid I. Severe life-threatening diarrhea caused by azathioprine but not by 6-mercaptopurine. Digestion. 2001;63(2):139-142. doi:10.1159/000051882 [PubMed 11244253]
  174. Marinaki AM, Arenas-Hernandez M. Reducing risk in thiopurine therapy. Xenobiotica. 2020;50(1):101-109. doi:10.1080/00498254.2019.1688424 [PubMed 31682552]
  175. Marks SD, Tullus K. Modern Therapeutic Strategies for Paediatric Systemic Lupus Erythematosus and Lupus Nephritis. Acta Paediatr. 2010; 99(7):967-974. [PubMed 20222881]
  176. Matsuoka K. NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease. Intest Res. 2020;18(3):275-281. doi:10.5217/ir.2020.00002 [PubMed 32482022]
  177. McNeil K, Glanville AR, Wahlers T, et al. Comparison of mycophenolate mofetil and azathioprine for prevention of bronchiolitis obliterans syndrome in de novo lung transplant recipients. Transplantation. 2006;81(7):998-1003. doi:10.1097/01.tp.0000202755.33883.61 [PubMed 16612275]
  178. Melzer N, Ruck T, Fuhr P, Gold R, et al. Clinical features, pathogenesis, and treatment of myasthenia gravis: a supplement to the Guidelines of the German Neurological Society. J Neurol. 2016;263(8):1473-1494. doi:10.1007/s00415-016-8045-z [PubMed 26886206]
  179. Merkel PA. Treatment and prognosis of polyarteritis nodosa. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022a.
  180. Merkel PA. Treatment of Takayasu arteritis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022b.
  181. Merkel PA, Kaplan AA, Falk RJ. Granulomatosis with polyangiitis and microscopic polyangiitis: induction and maintenance therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed July 27, 2022c.
  182. Meyer A, Drouin J, Weill A, Carbonnel F, Dray-Spira R. Comparative study of pregnancy outcomes in women with inflammatory bowel disease treated with thiopurines and/or anti-TNF: a French nationwide study 2010-2018. Aliment Pharmacol Ther. 2021;54(3):302-311. doi:10.1111/apt.16448 [PubMed 34162011]
  183. Mishra S, Garg S, Mahajan R, Patil A, Bhatia P, Sharma V. Azathioprine induced pancreatitis, polyarthritis and panniculitis (PPP) syndrome in a patient with Crohn's disease. Acta Gastroenterol Belg. 2020;83(1):87-89. [PubMed 32233278]
  184. Mottet C, Schoepfer AM, Juillerat P, et al. Experts opinion on the practical use of azathioprine and 6-mercaptopurine in inflammatory bowel disease. Inflamm Bowel Dis. 2016;22(11):2733-2747. [PubMed 27760078]
  185. Mouyis M, Flint JD, Giles IP. Safety of anti-rheumatic drugs in men trying to conceive: a systematic review and analysis of published evidence. Semin Arthritis Rheum. 2019;48(5):911-920. doi:10.1016/j.semarthrit.2018.07.011 [PubMed 30220537]
  186. Müller-Quernheim J, Kienast K, Held M, Pfeifer S, Costabel U. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J. 1999;14(5):1117-1122. doi:10.1183/09031936.99.14511179 [PubMed 10596700]
  187. Murrell DF, Ramirez-Quizon M. Management and prognosis of bullous pemphigoid. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 24, 2023.
  188. Myasthenia Gravis Clinical Study Group. A randomised clinical trial comparing prednisone and azathioprine in myasthenia gravis. Results of the second interim analysis. J Neurol Neurosurg Psychiatry. 1993;56(11):1157-1163. [PubMed 8229026]
  189. Nemecek BD, Hammond DA, eds. Demystifying Drug Dosing in Renal Dysfunction. American Society of Health-System Pharmacists; 2019.
  190. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA; American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207. doi:10.1182/blood-2010-08-302984 [PubMed 21325604]
  191. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966 [PubMed 31794604]
  192. Nguyen GC, Loftus EV Jr, Hirano I, Falck-Ytter Y, Singh S, Sultan S; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute guideline on the management of Crohn's disease after surgical resection. Gastroenterology. 2017;152(1):271-275. doi:10.1053/j.gastro.2016.10.038 [PubMed 27840074]
  193. Nicolle MW. Myasthenia gravis and Lambert-Eaton myasthenic syndrome. Continuum (Minneap Minn). 2016;22(6, Muscle and Neuromuscular Junction Disorders):1978-2005. [PubMed 27922503]
  194. Nitsche CJ, Jamieson N, Lerch MM, Mayerle JV. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol. 2010;24(2):143-155. doi:10.1016/j.bpg.2010.02.002 [PubMed 20227028]
  195. Nygaard U, Toft N, Schmiegelow K. Methylated metabolites of 6-mercaptopurine are associated with hepatotoxicity. Clin Pharmacol Ther. 2004;75(4):274-281. doi:10.1016/j.clpt.2003.12.001 [PubMed 15060506]
  196. Odlind B, Hartvig P, Lindström B, Lönnerholm G, Tufveson G, Grefberg N. Serum azathioprine and 6-mercaptopurine levels and immunosuppressive activity after azathioprine in uremic patients. Int J Immunopharmacol. 1986;8(1):1-11. doi:10.1016/0192-0561(86)90067-6 [PubMed 3957504]
  197. Oldham JM, Lee C, Valenzi E, et al. Azathioprine response in patients with fibrotic connective tissue disease-associated interstitial lung disease. Respir Med. 2016;121:117-122. doi:10.1016/j.rmed.2016.11.007 [PubMed 27888985]
  198. Oldroyd AGS, Lilleker JB, Amin T, et al; British Society for Rheumatology Standards, Audit and Guidelines Working Group. British Society for Rheumatology guideline on management of paediatric, adolescent and adult patients with idiopathic inflammatory myopathy. Rheumatology (Oxford). 2022;61(5):1760-1768. doi:10.1093/rheumatology/keac115 [PubMed 35355064]
  199. Orandi AB, Vogel TP, Keppel MP, Utterson EC, Cooper MA. Azathioprine-associated complete NK cell deficiency. J Clin Immunol. 2017;37(6):514-516. doi:10.1007/s10875-017-0414-6 [PubMed 28639167]
  200. Pacheco PA, Taylor SR, Cuchacovich MT, Diaz GV. Azathioprine in the management of autoimmune uveitis. Ocul Immunol Inflamm. 2008;16(4):161-165. [PubMed 18716951]
  201. Pagnoux C, Hayem G, Roux F, et al. JC virus leukoencephalopathy complicating Wegener's granulomatosis. Joint Bone Spine. 2003;70(5):376-379. doi:10.1016/s1297-319x(03)00062-9 [PubMed 14563468]
  202. Pagnoux C, Mahr A, Hamidou MA, et al; French Vasculitis Study Group. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359(26):2790-803. doi:10.1056/NEJMoa0802311 [PubMed 19109574]
  203. Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Myasthenia Gravis Study Group. Neurology. 1998;50(6):1778-1783. [PubMed 9633727]
  204. Palmer SM, Baz MA, Sanders L, et al. Results of a randomized, prospective, multicenter trial of mycophenolate mofetil versus azathioprine in the prevention of acute lung allograft rejection. Transplantation. 2001;71(12):1772-1776. doi:10.1097/00007890-200106270-00012 [PubMed 11455257]
  205. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146(2):392-400.e3. doi:10.1053/j.gastro.2013.10.052 [PubMed 24512909]
  206. Papaliodis GN. Uveitis: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022.
  207. Pasadhika S, Kempen JH, Newcomb CW, et al. Azathioprine for ocular inflammatory diseases. Am J Ophthalmol. 2009;148(4):500-509.e2. [PubMed 19570522]
  208. Penner RM. Management of Crohn disease after surgical resection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 24, 2021.
  209. Perri D, Cole DE, Friedman O, Piliotis E, Mintz S, Adhikari NK. Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase. Eur Respir J. 2007;30(5):1014-1017. doi:10.1183/09031936.00026107 [PubMed 17978158]
  210. Peyrin-Biroulet L, Deltenre P, Ardizzone S, et al. Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis. Am J Gastroenterol. 2009;104(8):2089-2096. doi:10.1038/ajg.2009.301 [PubMed 19568226]
  211. Pham MX. Heart transplantation in adults: induction and maintenance of immunosuppressive therapy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022.
  212. Plasmeijer EI, Sachse MM, Gebhardt C, Geusau A, Bouwes Bavinck JN. Cutaneous squamous cell carcinoma (cSCC) and immunosurveillance - the impact of immunosuppression on frequency of cSCC. J Eur Acad Dermatol Venereol. 2019;33 Suppl 8:33-37. doi:10.1111/jdv.16025 [PubMed 31833604]
  213. Prentice R, Flanagan E, Wright E, et al. Thiopurine metabolite shunting in late pregnancy increases the risk of intrahepatic cholestasis of pregnancy in women with inflammatory bowel disease, and can be managed with split-dosing. J Crohns Colitis. Published online February 15, 2024. doi:10.1093/ecco-jcc/jjae023 [PubMed 38366352]
  214. Provan D, Arnold DM, Bussel JB, et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv. 2019;3(22):3780-3817. doi:10.1182/bloodadvances.2019000812 [PubMed 31770441]
  215. Provan D, Stasi R, Newland AC, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115(2):168-186. doi:10.1182/blood-2009-06-225565 [PubMed 19846889]
  216. Puéchal X, Pagnoux C, Baron G, et al; French Vasculitis Study Group. Adding azathioprine to remission-induction glucocorticoids for eosinophilic granulomatosis with polyangiitis (Churg-Strauss), microscopic polyangiitis, or polyarteritis nodosa without poor prognosis factors: a randomized, controlled trial. Arthritis Rheumatol. 2017;69(11):2175-2186. doi:10.1002/art.40205 [PubMed 28678392]
  217. Punati J, Markowitz J, Lerer T, et al. Effect of Early Immunomodulator Use in Moderate to Severe Pediatric Crohn Disease. Inflamm Bowel Dis. 2008;14(7):949-954. [PubMed 18306311]
  218. Qiu Y, Mao R, Zhang SH, et al. Safety profile of thiopurines in Crohn disease: analysis of 893 patient-years follow-up in a southern China cohort. Medicine (Baltimore). 2015;94(41):e1513. doi:10.1097/MD.0000000000001513 [PubMed 26469893]
  219. Quiquandon I, Fenaux P, Caulier MT, Pagniez D, Huart JJ, Bauters F. Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases. Br J Haematol. 1990;74(2):223-228. doi:10.1111/j.1365-2141.1990.tb02569.x [PubMed 2317458]
  220. Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2014;73(3):529-535. doi:10.1136/annrheumdis-2013-204575 [PubMed 24401994]
  221. Refer to manufacturer's labeling.
  222. Relling MV, Gardner EE, Sandborn WJ, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther. 2011;89(3):387-391. doi:10.1038/clpt.2010.320 [PubMed 21270794]
  223. Relling MV, Gardner EE, Sandborn WJ, et al; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther. 2013;93(4):324-325. doi:10.1038/clpt.2013.4 [PubMed 23422873]
  224. Relling MV, Schwab M, Whirl-Carrillo M, et al. Clinical Pharmacogenetics Implementation Consortium guideline for thiopurine dosing based on TPMT and NUDT15 genotypes: 2018 update. Clin Pharmacol Ther. 2019;105(5):1095-1105. doi:10.1002/cpt.1304 [PubMed 30447069]
  225. Remuzzi G, Cravedi P, Costantini M, et al. Mycophenolate mofetil versus azathioprine for prevention of chronic allograft dysfunction in renal transplantation: the MYSS follow-up randomized, controlled clinical trial. J Am Soc Nephrol. 2007;18(6):1973-1985. doi:0.1681/ASN.2006101153 [PubMed 17460145]
  226. Ribi C, Cohen P, Pagnoux C, et al. Treatment of Churg-Strauss syndrome without poor-prognosis factors: a multicenter, prospective, randomized, open-label study of seventy-two patients. Arthritis Rheum. 2008;58(2):586-594. doi:10.1002/art.23198 [PubMed 18240234]
  227. Ribi C, Cohen P, Pagnoux C, et al; French Vasculitis Study Group. Treatment of polyarteritis nodosa and microscopic polyangiitis without poor-prognosis factors: a prospective randomized study of one hundred twenty-four patients. Arthritis Rheum. 2010;62(4):1186-1197. doi:10.1002/art.27340 [PubMed 20131268]
  228. Riedel RR, Schmitt A, de Jonge JP, Hartmann A. Gastrointestinal type 1 hypersensitivity to azathioprine. Klin Wochenschr. 1990;68(1):50-52. doi:10.1007/BF01648893 [PubMed 2308269]
  229. Riello L, Talbotec C, Garnier-Lengliné H, et al. Tolerance and Efficacy of Azathioprine in Pediatric Crohn's Disease. Inflamm Bowel Dis. 2011;17(10):2138-2143. [PubMed 21910176]
  230. Romagnuolo J, Sadowski DC, Lalor E, Jewell L, Thomson AB. Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity. Can J Gastroenterol. 1998;12(7):479-483. doi:10.1155/1998/294752 [PubMed 9812167]
  231. Ross DJ, Waters PF, Levine M, Kramer M, Ruzevich S, Kass RM. Mycophenolate mofetil versus azathioprine immunosuppressive regimens after lung transplantation: preliminary experience. J Heart Lung Transplant. 1998;17(8):768-774. [PubMed 9730425]
  232. Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384-413. doi:10.14309/ajg.0000000000000152. [PubMed 30840605]
  233. Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease. J Crohns Colitis. 2014;8(10):1179-1207. [PubMed 24909831]
  234. Saadoun D, Wechsler B, Terrada C, et al. Azathioprine in severe uveitis of Behçet's disease. Arthritis Care Res (Hoboken). 2010;62(12):1733-1738. [PubMed 20665749]
  235. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol. 2020;72(4):529-556. doi:10.1002/art.41191 [PubMed 32090480]
  236. Sandborn WJ. A Review of Immune Modifier Therapy for Inflammatory Bowel Disease: Azathioprine, 6-mercaptopurine, Cyclosporine, and Methotrexate. Am J Gastroenterol. 1996;91(3):423-433. [PubMed 8633486]
  237. Sanders DB, Wolfe GI, Benatar M, et al. International consensus guidance for management of myasthenia gravis: executive summary. Neurology. 2016;87(4):419-425. doi:10.1212/WNL.0000000000002790 [PubMed 27358333]
  238. Sandhu BK, Fell JME, Beattie RM, et al. Guidelines for the Management of Inflammatory Bowel Disease in Children in the United Kingdom. JPGN. 2010;50:S1-S13.
  239. Saperstein DS, Barohn RJ. Management of myasthenia gravis. Semin Neurol. 2004;24(1):41-48. doi:10.1055/s-2004-829586 [PubMed 15229791]
  240. Sato T, Takagawa T, Kakuta Y, et al. NUDT15, FTO, and RUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases. Intest Res. 2017;15(3):328-337. doi:10.5217/ir.2017.15.3.328 [PubMed 28670229]
  241. Sau A, Clarke S, Bass J, Kaiser A, Marinaki A, Nelson-Piercy C. Azathioprine and breastfeeding: is it safe?. BJOG. 2007;114(4):498-501. doi:10.1111/j.1471-0528.2006.01232.x [PubMed 17261122]
  242. Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update. J Clin Oncol. 2021;39(36):4073-4126. doi:10.1200/JCO.21.01440 [PubMed 34724392]
  243. Schofield JK, Tatnall FM, Leigh IM. Recurrent erythema multiforme: clinical features and treatment in a large series of patients.Br J Dermatol. 1993;128(5):542-545. doi:10.1111/j.1365-2133.1993.tb00232.x [PubMed 8504046]
  244. Schram ME, Borgonjen RJ, Bik CM, et al; Off-Label Working and Project Group of Dutch Society of Dermatology and Venereology. Off-label use of azathioprine in dermatology: a systematic review. Arch Dermatol. 2011;147(4):474-488. doi:10.1001/archdermatol.2011.79 [PubMed 21482898]
  245. Schusziarra V, Ziekursch V, Schlamp R, Siemensen HC. Pharmacokinetics of azathioprine under haemodialysis. Int J Clin Pharmacol Biopharm. 1976;14(4):298-302. [PubMed 1002367]
  246. Sebbag L, Boucher P, Davelu P, et al. Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients. Transplantation. 2000;69(7):1524-1527. doi:10.1097/00007890-200004150-00057 [PubMed 10798786]
  247. Shaffer D, Hammer SM, Monaco AP. Infectious complications with the use of cyclosporine versus azathioprine after cadaveric kidney transplantation. Am J Surg. 1987;153(4):381-386. doi:10.1016/0002-9610(87)90582-4 [PubMed 3105340]
  248. Shah ED, Coburn ES, Nayyar A, Lee KJ, Koliani-Pace JL, Siegel CA. Systematic review: hepatosplenic T-cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System. Aliment Pharmacol Ther. 2020;51(5):527-533. doi:10.1111/apt.15637 [PubMed 31990422]
  249. Sharshar T, Porcher R, Demeret S, et al; MYACOR Study Group. Comparison of corticosteroid tapering regimens in myasthenia gravis: a randomized clinical trial. JAMA Neurol. 2021;78(4):426-433. doi:10.1001/jamaneurol.2020.5407 [PubMed 33555314]
  250. Sheiko MA, Sundaram SS, Capocelli KE, Pan Z, McCoy AM, Mack CL. Outcomes in pediatric autoimmune hepatitis and significance of azathioprine metabolites. J Pediatr Gastroenterol Nutr. 2017;65(1):80-85. [PubMed 28272159]
  251. Simon L, Lipman AG, Jacox A, et al. Guideline for the Management of Osteoarthritis, Rheumatoid Arthritis and Juvenile Chronic Arthritis Pain. 2nd ed. American Pain Society; 2002.
  252. Simons-Linares CR, Elkhouly MA, Salazar MJ. Drug-induced acute pancreatitis in adults: an update. Pancreas. 2019;48(10):1263-1273. doi:10.1097/MPA.0000000000001428 [PubMed 31688589]
  253. Singh A, Mahajan R, Kedia S, et al. Use of thiopurines in inflammatory bowel disease: an update [published online ahead of print, 2021 Apr 15]. Intest Res. 2021;10.5217/ir.2020.00155. doi:10.5217/ir.2020.00155 [PubMed 33845546]
  254. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639. doi:10.1002/acr.21641 [PubMed 22473917]
  255. Singh JA, Hossain A, Kotb A, Wells G. Risk of serious infections with immunosuppressive drugs and glucocorticoids for lupus nephritis: a systematic review and network meta-analysis. BMC Med. 2016b;14(1):137. doi:10.1186/s12916-016-0673-8 [PubMed 27623861]
  256. Singh JA, Saag KG, Bridges SL Jr, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol. 2016a;68(1):1-26. doi:10.1002/art.39480 [PubMed 26545940]
  257. Smith EL, Yazici Y. Treatment of Behçet syndrome. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed June 22, 2022.
  258. Smith JM, Rudser K, Gillen D, et al. Risk of lymphoma after renal transplantation varies with time: an analysis of the United States Renal Data System. Transplantation. 2006;81(2):175-180. doi:10.1097/01.tp.0000188687.18972.a8 [PubMed 16436959]
  259. Soman S, Ashok D, Connolly SA, Cordell SJ, Taylor CJ, Campbell DI. Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprine. Drugs R D. 2010;10(4):213-217. doi:10.2165/11539930-000000000-00000 [PubMed 21171667]
  260. Stellon AJ, Keating JJ, Johnson PJ, McFarlane IG, Williams R. Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal. Hepatology. 1988;8(4):781-784. doi:10.1002/hep.1840080414 [PubMed 3292363]
  261. Stocco G, Martelossi S, Arrigo S, et al. Multicentric case-control study on azathioprine dose and pharmacokinetics in early-onset pediatric inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(4):628-634. [PubMed 28296824]
  262. Subramaniam K, D'Rozario J, Pavli P. Lymphoma and other lymphoproliferative disorders in inflammatory bowel disease: a review. J Gastroenterol Hepatol. 2013;28(1):24-30. doi:10.1111/jgh.12015 [PubMed 23094824]
  263. Tantisira K, Weiss ST. Overview of pharmacogenomics. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 24, 2021.
  264. Targoff IN. Initial treatment of dermatomyositis and polymyositis in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 25, 2022.
  265. Taylor AL, Watson CJ, Bradley JA. Immunosuppressive agents in solid organ transplantation: Mechanisms of action and therapeutic efficacy. Crit Rev Oncol Hematol. 2005;56(1):23-46. [PubMed 16039869]
  266. Teich N, Mohl W, Bokemeyer B, et al. Azathioprine-induced acute pancreatitis in patients with inflammatory bowel diseases--a prospective study on incidence and severity. J Crohns Colitis. 2016;10(1):61-68. doi:10.1093/ecco-jcc/jjv188 [PubMed 26468141]
  267. Thorne JE. Uveitis: treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 24, 2021.
  268. Torrisi SE, Kahn N, Wälscher J, et al. Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases. BMC Pulm Med. 2019;19(1):213. doi:10.1186/s12890-019-0937-0 [PubMed 31718637]
  269. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 12, 2016.
  270. US Food and Drug Administration (FDA). FDA alerts health care professionals of pregnancy problems associated with thiopurines. https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerts-health-care-professionals-pregnancy-problems-associated-thiopurines. Published April 29, 2024. Accessed May 1, 2024.
  271. Valsakumar AK, Valappil UC, Jorapur V, Garg N, Nityanand S, Sinha N. Role of immunosuppressive therapy on clinical, immunological, and angiographic outcome in active Takayasu's arteritis. J Rheumatol. 2003;30(8):1793-1798. [PubMed 12913937]
  272. van Gennep S, Konté K, Meijer B, et al. Systematic review with meta-analysis: risk factors for thiopurine-induced leukopenia in IBD. Aliment Pharmacol Ther. 2019;50(5):484-506. doi:10.1111/apt.15403 [PubMed 31342537]
  273. Velvet AJ, Bhutani S, Papachristos S, et al. A single-center experience of post-transplant lymphomas involving the central nervous system with a review of current literature. Oncotarget. 2019;10(4):437-448. doi:10.18632/oncotarget.26522 [PubMed 30728897]
  274. Venkatesh PG, Navaneethan U. Azathioprine induced pancreatitis in a patient with co-existing autoimmune pancreatitis and hepatitis. JOP. 2011;12(3):250-254. [PubMed 21546702]
  275. Vierling JM. Liver transplantation in adults: Overview of immunosuppression. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 28, 2022.
  276. Vitfell-Pedersen J, Jorgensen MH, Müller K, et al. Autoimmune Hepatitis in Children in Eastern Denmark. J Pediatr Gastroenterol Nutr. 2012;55(4):376-379. [PubMed 22644464]
  277. Vorselaars ADM, Wuyts WA, Vorselaars VMM, et al. Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest. 2013;144(3):805-812. doi:10.1378/chest.12-1728 [PubMed 23538719]
  278. Wiesner R, Rabkin J, Klintmalm G, et al. A randomized double-blind comparative study of mycophenolate mofetil and azathioprine in combination with cyclosporine and corticosteroids in primary liver transplant recipients. Liver Transpl. 2001;7(5):442-450. doi:10.1053/jlts.2001.23356 [PubMed 11349266]
  279. Wintzell V, Svanström H, Olén O, Melbye M, Ludvigsson JF, Pasternak B. Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease: a Swedish-Danish nationwide cohort study. Lancet Child Adolesc Health. 2019;3(3):158-165. doi:10.1016/S2352-4642(18)30401-2 [PubMed 30685366]
  280. Wong DR, Coenen MJ, Derijks LJ, et al. Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease. Aliment Pharmacol Ther. 2017;45(3):391-402. doi:10.1111/apt.13879 [PubMed 27943397]
  281. Woodland J, Chaput de Saintonge DM, Evans SJ, Sharman VL, Currey HL. Azathioprine in rheumatoid arthritis: double-blind study of full versus half doses versus placebo. Ann Rheum Dis. 1981;40(4):355-359. doi:10.1136/ard.40.4.355 [PubMed 7020612]
  282. World Health Organization (WHO). Breastfeeding and maternal medication, recommendations for drugs in the eleventh WHO model list of essential drugs. https://apps.who.int/iris/handle/10665/62435. Published 2002.
  283. Wüthrich RP, Cicvara S, Ambühl PM, Binswanger U. Randomized trial of conversion from mycophenolate mofetil to azathioprine 6 months after renal allograft transplantation. Nephrol Dial Transplant. 2000;15(8):1228-1231. doi:10.1093/ndt/15.8.1228 [PubMed 10910450]
  284. Yang J, Wang P, Qin Z, et al. NUDT15 and TPMT genetic polymorphisms are related to azathioprine intolerance in Chinese patients with rheumatic diseases. Genet Test Mol Biomarkers. 2019;23(10):751-757. doi:10.1089/gtmb.2018.0313 [PubMed 31556692]
  285. Yang SK, Hong M, Baek J, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46(9):1017-1020. doi:10.1038/ng.3060 [PubMed 25108385]
  286. Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behçet's syndrome. N Engl J Med. 1990;322(5):281-285. doi:10.1056/NEJM199002013220501 [PubMed 2404204]
  287. Yenson PR, Forrest D, Schmiegelow K, Dalal BI. Azathioprine-associated acute myeloid leukemia in a patient with Crohn's disease and thiopurine S-methyltransferase deficiency. Am J Hematol. 2008;83(1):80-83. doi:10.1002/ajh.21014 [PubMed 17696202]
  288. Yeter KC, Afkhami M, Brynes RK, Quismorio FP Jr. Aplastic anemia secondary to azathioprine in systemic lupus erythematosus: report of a case with normal thiopurine S-methyltransferase enzyme activity and review of the literature. Lupus. 2013;22(14):1526-1528. doi:10.1177/0961203313504636 [PubMed 24029750]
  289. Zazgornik J. Azathioprine induced macrocytosis and red cell aplasia in renal transplant patients. Nephrol Dial Transplant. 1997;12(3):628. doi:10.1093/ndt/12.3.628a [PubMed 9075169]
  290. Zhu X, Wang XD, Chao K, et al. NUDT15 polymorphisms are better than thiopurine S-methyltransferase as predictor of risk for thiopurine-induced leukopenia in Chinese patients with Crohn's disease. Aliment Pharmacol Ther. 2016;44(9):967-975. doi:10.1111/apt.13796 [PubMed 27604507]
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