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Details

Stereochemistry ACHIRAL
Molecular Formula C9H6N7O2S.Na
Molecular Weight 299.2459
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AZATHIOPRINE SODIUM

SMILES

Cn1cnc(c1Sc2c3c([n-]cn3)ncn2)N(=O)=O.[Na+]

InChI

InChIKey=WISNYKIQFMKSDQ-UHFFFAOYSA-N
InChI=1S/C9H6N7O2S.Na/c1-15-4-14-7(16(17)18)9(15)19-8-5-6(11-2-10-5)12-3-13-8;/h2-4H,1H3;/q-1;+1

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C9H7N7O2S
Molecular Weight 277.264
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18020555

Azathioprine remains one of the most important and widely prescribed drugs for immunosuppression/immunomodulation in autoimmune disease over 30 years after its introduction. Azathioprine is licensed for the treatment of only a limited range of autoimmune disorders, which is probably a reflection on the age of the drug. Widening the license for a drug is both costly and time consuming, and it would make no commercial sense for manufacturers to do so, at this late stage of life, for azathioprine. However, azathioprine is now so well established as an immunomodulating drug in autoimmune disorders that it represents the gold standard by which other drugs are compared. Azathioprine is indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of azathioprine tablets with these agents cannot be recommended. Azathioprine is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Azathioprine acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication. Azathioprine is metabolized to 6-mercaptopurine (6-MP). Both compounds are rapidly eliminated from blood and are oxidized or methylated in erythrocytes and liver; no azathioprine or mercaptopurine is detectable in urine after 8 hours. Activation of 6-mercaptopurine occurs via hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and a series of multi-enzymatic processes involving kinases to form 6-thioguanine nucleotides (6-TGNs) as major metabolites.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
IMURAN

Approved Use

Azathioprine tablets are indicated as an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of active rheumatoid arthritis to reduce signs and symptoms. Renal Homotransplantation Azathioprine tablets are indicated as an adjunct for the prevention of rejection in renal homotransplantation. Experience with over 16,000 transplants shows a 5-year patient survival of 35% to 55%, but this is dependent on donor, match for HLA antigens, anti-donor or anti-B-cell alloantigen antibody, and other variables. The effect of azathioprine tablets on these variables has not been tested in controlled trials. Rheumatoid Arthritis Azathioprine tablets are indicated for the treatment of active rheumatoid arthritis (RA) to reduce signs and symptoms. Aspirin, non-steroidal anti-inflammatory drugs and/or low dose glucocorticoids may be continued during treatment with azathioprine tablets. The combined use of azathioprine tablets with disease modifying anti-rheumatic drugs (DMARDs) has not been studied for either added benefit or unexpected adverse effects. The use of azathioprine tablets with these agents cannot be recommended.

Launch Date

-5.63328E10
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
69.5 ng/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MERCAPTOPURINE ANHYDROUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
135.8 ng × h/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MERCAPTOPURINE ANHYDROUS plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Disc. AE: Discomfort epigastric, Serum transaminase increased...
AEs leading to
discontinuation/dose reduction:
Discomfort epigastric (severe, 1.4%)
Serum transaminase increased (5.6%)
Leukopenia (9.9%)
Pancreatitis (acute, 4.2%)
Thrombocytopenia (1.4%)
Sources: Page: p.735
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.2797
unhealthy, 25.2–78.6
n = 63
Health Status: unhealthy
Condition: Wegener's granulomatosis |microscopic polyangiitis
Age Group: 25.2–78.6
Sex: M+F
Population Size: 63
Sources: Page: p.2797
Disc. AE: Hepatotoxicity, Digestion impaired...
AEs leading to
discontinuation/dose reduction:
Hepatotoxicity (6.3%)
Digestion impaired (4.8%)
Sources: Page: p.2797
7500 mg single, oral
Overdose
Dose: 7500 mg
Route: oral
Route: single
Dose: 7500 mg
Co-administed with::
prednisone, p.o(1 g)
Sources: Page: p.134
unhealthy, 44
n = 1
Health Status: unhealthy
Condition: Renal Homotransplantation
Age Group: 44
Sex: M
Population Size: 1
Sources: Page: p.134
Disc. AE: Vomiting, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Vomiting (mild)
Diarrhea (mild)
Sources: Page: p.134
5 mg/kg 1 times / day multiple, oral
Recommended
Dose: 5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Renal Homotransplantation
Sources: Page: p.1
Disc. AE: Malignant neoplasm NOS, Lymphoma...
AEs leading to
discontinuation/dose reduction:
Malignant neoplasm NOS
Lymphoma
Hepatosplenic T-cell lymphoma
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Thrombocytopenia 1.4%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Serum transaminase increased 5.6%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Leukopenia 9.9%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Pancreatitis acute, 4.2%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Discomfort epigastric severe, 1.4%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.735
unhealthy, 18–70
n = 71
Health Status: unhealthy
Condition: Crohn's disease
Age Group: 18–70
Sex: M+F
Population Size: 71
Sources: Page: p.735
Digestion impaired 4.8%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.2797
unhealthy, 25.2–78.6
n = 63
Health Status: unhealthy
Condition: Wegener's granulomatosis |microscopic polyangiitis
Age Group: 25.2–78.6
Sex: M+F
Population Size: 63
Sources: Page: p.2797
Hepatotoxicity 6.3%
Disc. AE
2 mg/kg 1 times / day multiple, oral
Recommended
Dose: 2 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources: Page: p.2797
unhealthy, 25.2–78.6
n = 63
Health Status: unhealthy
Condition: Wegener's granulomatosis |microscopic polyangiitis
Age Group: 25.2–78.6
Sex: M+F
Population Size: 63
Sources: Page: p.2797
Diarrhea mild
Disc. AE
7500 mg single, oral
Overdose
Dose: 7500 mg
Route: oral
Route: single
Dose: 7500 mg
Co-administed with::
prednisone, p.o(1 g)
Sources: Page: p.134
unhealthy, 44
n = 1
Health Status: unhealthy
Condition: Renal Homotransplantation
Age Group: 44
Sex: M
Population Size: 1
Sources: Page: p.134
Vomiting mild
Disc. AE
7500 mg single, oral
Overdose
Dose: 7500 mg
Route: oral
Route: single
Dose: 7500 mg
Co-administed with::
prednisone, p.o(1 g)
Sources: Page: p.134
unhealthy, 44
n = 1
Health Status: unhealthy
Condition: Renal Homotransplantation
Age Group: 44
Sex: M
Population Size: 1
Sources: Page: p.134
Hepatosplenic T-cell lymphoma Disc. AE
5 mg/kg 1 times / day multiple, oral
Recommended
Dose: 5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Renal Homotransplantation
Sources: Page: p.1
Lymphoma Disc. AE
5 mg/kg 1 times / day multiple, oral
Recommended
Dose: 5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Renal Homotransplantation
Sources: Page: p.1
Malignant neoplasm NOS Disc. AE
5 mg/kg 1 times / day multiple, oral
Recommended
Dose: 5 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 5 mg/kg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Renal Homotransplantation
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
[IgA nephropathy (Berger's disease) in children].
1992 Dec
[Hepatic hemangiomas and rheumatoid arthritis in patients treated with azathioprine].
1992 Oct
Crohn's disease presenting as a breast abscess: a case report.
2001 Jul
[Pulmonary changes in rheumatoid arthritis].
2001 Jul
[Influence of cyclosporin on steroid-induced cataract].
2001 Jul
[Nephrogenic diabetes insipidus secondary to chronic interstitial nephritis associated with mesalazine therapy].
2002 Apr
Azathioprine inhibits vaccinia virus replication in both BSC-40 and RAG cell lines acting on different stages of virus cycle.
2002 Aug 15
[Autoimmune hepatitis and overlap syndrome: therapy].
2002 Aug 21
[Therapy of Crohn disease according to the guidelines of the German Society for the treatment of digestive and metabolic diseases].
2002 May
[Thalidomide therapy of cutaneous lupus erythematosus].
2002 Nov
Azathioprine in refractory sprue: results from a prospective, open-label study.
2002 Oct
Azathioprine-induced fatal macrocytic anemia in rabbits.
2002 Sep-Oct
[Treatment of rheumatoid arthritis].
2003
Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.
2003
[Incidence and characteristics of tuberculosis in patients with autoimmune rheumatic diseases].
2003 Apr
Veno-occlusive disease (VOD) in Crohn's disease (CD) treated with azathioprine.
2003 Aug
[Immunomodulation in penetrating keratoplasty. Current status and perspectives].
2003 Dec
Colchicine-induced myopathy in a teenager with familial Mediterranean fever.
2003 Dec
Potential involvement of the immune system in the development of endometriosis.
2003 Dec 2
Is thiopurine methyltransferase genetic polymorphism a major factor for withdrawal of azathioprine in rheumatoid arthritis patients?
2003 Jan
Systemic lupus erythematosus with presentation as vertigo and vertical nystagmus: report of one case.
2003 May-Jun
Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study.
2003 May-Jun
Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.
2003 Nov
Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses.
2003 Sep-Oct
Fibrosing cholestatic hepatitis in renal transplant recipient with CMV infection: a case report.
2004
A case of refractory anemia with 17p- syndrome following azathioprine treatment for heart transplantation.
2004 Apr
Sinusoidal dilatation: a rare side effect of azathioprine.
2004 Dec
Effect of antimetabolite immunosuppressants on Flaviviridae, including hepatitis C virus.
2004 Feb 27
New approaches to the treatment of pemphigus.
2004 Jan
Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase).
2004 Mar
[Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations].
2004 May 28
Immunomodulatory therapy for Crohn's disease resulting in acute liver failure.
2004 Nov
Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine.
2004 Nov
[Disseminated intravascular coagulation, perimyocarditis and bilateral pleural empyema in adult Still's disease].
2004 Nov 19
[New horizons in heart transplantation].
2004 Oct
Colitic cancer developed after introduction of azathioprine.
2004 Oct
Genetic determinants of the pre- and post-azathioprine therapy thiopurine methyltransferase activity phenotype.
2004 Oct
Mutation in the ITPA gene predicts intolerance to azathioprine.
2004 Oct
[Panzytopenia from combination therapy with azathioprin and allopurinol].
2004 Oct
The impact of thiopurine S-methyltransferase polymorphisms on azathioprine dose 1 year after renal transplantation.
2004 Oct
Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases.
2004 Oct 15
[Life-threatening adverse effects of pharmacologic antihyperuricemic therapy].
2004 Sep
Hypersensitivity reaction to azathioprine in a patient with ulcerative colitis. Infrequent manifestations.
2004 Sep
Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease.
2004 Sep 15
Severe cholestatic hepatitis caused by azathioprine.
2005
Monozygotic twins concordant for intestinal Behçet's disease.
2005 Apr
[Adamantiades-Behcet's disease].
2005 Apr
Development of multiple malignancies after immunosuppression in a patient with Wegener's granulomatosis.
2005 Apr
Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events.
2005 Apr 15
Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase.
2005 Feb 12
Patents

Sample Use Guides

Rheumatoid Arthritis: is given on a daily basis. The initial dose should be approximately 1.0 mg/kg (50 to 100 mg) given as a single dose or on a twice-daily schedule. The dose may be increased, beginning at 6 to 8 weeks and thereafter by steps at 4-week intervals, if there are no serious toxicities and if initial response is unsatisfactory. Dose increments should be 0.5 mg/kg daily, up to a maximum dose of 2.5 mg/kg per day. Therapeutic response occurs after several weeks of treatment, usually 6 to 8 an adequate trial should be a minimum of 12 weeks.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Cell cycle progression was evaluated by PI staining and flow cytometry. Epithelial restitution was not significantly affected by any of the substances tested. However, proliferation of intestinal epithelial cells was inhibited in a dose-dependent manner (maximal effect 92%) by azathioprine (AZA). In HT-29 cells, purine antagonist-effected inhibition of cell proliferation was explained by a cell cycle arrest in the G2 phase. In contrast, AZA induced no cell cycle arrest in Caco-2, T-84 and IEC-6 cells. AZA induced apoptosis in the non-transformed IEC-6 cell line but not in human Caco-2, T-84 and HT-29 cells
Unknown
Substance Class Chemical
Created
by admin
on Sat Jun 26 00:52:55 UTC 2021
Edited
by admin
on Sat Jun 26 00:52:55 UTC 2021
Record UNII
AM94R510MS
Record Status Validated (UNII)
Record Version
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Name Type Language
AZATHIOPRINE SODIUM
ORANGE BOOK   USP   WHO-DD  
Common Name English
AZATHIOPRINE SODIUM SALT [MI]
Common Name English
AZATHIOPRINE SODIUM [ORANGE BOOK]
Common Name English
AZATHIOPRINE SODIUM [USP]
Common Name English
AZATHIOPRINE SODIUM SALT
MI  
Common Name English
6-((1-METHYL-4-NITROIMIDAZOL-5-YL)THIO)PURINE SODIUM SALT
Common Name English
1H-PURINE, 6-((1-METHYL-4-NITRO-1H-IMIDAZOL-5-YL)THIO)-, SODIUM SALT
Common Name English
AZATHIOPRINE SODIUM [WHO-DD]
Common Name English
IMURAN INJECTION
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C1556
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
NCI_THESAURUS C574
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
Code System Code Type Description
CAS
55774-33-9
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
ChEMBL
CHEMBL1542
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
RXCUI
267476
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY RxNorm
PUBCHEM
11529527
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PRIMARY
EVMPD
SUB00641MIG
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
MERCK INDEX
M2165
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PRIMARY Merck Index
FDA UNII
AM94R510MS
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
DRUG BANK
DBSALT000012
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
NCI_THESAURUS
C47961
Created by admin on Sat Jun 26 00:52:55 UTC 2021 , Edited by admin on Sat Jun 26 00:52:55 UTC 2021
PRIMARY
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