pharmacopeia
GET
/api/v1/drug/azathioprine

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 (HSTCL) in patients with inflammatory bowel disease. Physicians 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. Physicians should inform patients of the risk of malignancy with azathioprine. See WARNINGS .

2D structure
6-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-7H-purine
SMILES CN1C=NC(=C1SC2=NC=NC3=C2NC=N3)[N+](=O)[O-]
InChIKey LMEKQMALGUDUQG-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

Mechanism-of-action classes: Alkylating Activity; Nucleic Acid Synthesis Inhibitors.

Nucleic Acid Synthesis

Indications

Sourced from openFDA
  • Azathioprine tablets, USP 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.ICD-10: M06.9

Contraindications

Sourced from openFDA
  • Azathioprine tablets should not be given to patients who have shown hypersensitivity to the drug. Azathioprine tablets should not be used for treating rheumatoid arthritis in pregnant women.contraindicated

Dosage & administration

Sourced from openFDA

Renal Homotransplantation The dose of azathioprine tablets required to prevent rejection and minimize toxicity will vary with individual patients; this necessitates careful management. The initial dose is usually 3 to 5 mg/kg daily, beginning at the time of transplant. Azathioprine tablets are usually given as a single daily dose on the day of, and in a minority of cases 1 to 3 days before, transplantation. Dose reduction to maintenance levels of 1 to 3 mg/kg daily is usually possible. The dose of azathioprine tablets should not be increased to toxic levels because of threatened rejection. Discontinuation may be necessary for severe hematologic or other toxicity, even if rejection of the homograft may be a consequence of drug withdrawal. Rheumatoid Arthritis Azathioprine tablets are usually 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. Patients not improved after 12 weeks can be considered refractory.

Warnings & precautions

Sourced from openFDA

Malignancy Patients receiving immunosuppressants, including azathioprine, are at increased risk of developing lymphoma and other malignancies, particularly of the skin. Physicians should inform patients of the risk of malignancy with azathioprine. As usual for patients with increased risk for skin cancer, exposure to sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with a high protection factor. Post-transplant Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. The risk of post-transplant lymphomas may be increased in patients who receive aggressive treatment with immunosuppressive drugs, including azathioprine. Therefore, immunosuppressive drug therapy should be maintained at the lowest effective levels. Rheumatoid Arthritis Information is available on the risk of malignancy with the use of azathioprine in rheumatoid arthritis (see ADVERSE REACTIONS ). It has not been possible to define the precise risk of malignancy due to azathioprine. The data suggest the risk may be elevated in patients with rheumatoid arthritis, though lower than for renal transplant patients. However, acute myelogenous leukemia as well as solid tumors have been reported in patients with rheumatoid arthritis who have received azathioprine. Inflammatory Bowel Disease Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with azathioprine.

Adverse reactions

Sourced from openFDA

The principal and potentially serious toxic effects of azathioprine tablets are hematologic and gastrointestinal. The risks of secondary infection and malignancy are also significant (see WARNINGS ). The frequency and severity of adverse reactions depend on the dose and duration of azathioprine tablets as well as on the patient’s underlying disease or concomitant therapies. The incidence of hematologic toxicities and neoplasia encountered in groups of renal homograft recipients is significantly higher than that in studies employing azathioprine tablets for rheumatoid arthritis. The relative incidences in clinical studies are summarized below: Toxicity Renal Homograft Rheumatoid Arthritis * Data on the rate and risk of neoplasia among persons with rheumatoid arthritis treated with azathioprine are limited. The incidence of lymphoproliferative disease in patients with RA appears to be significantly higher than that in the general population. In one completed study, the rate of lymphoproliferative disease in RA patients receiving higher than recommended doses of azathioprine (5 mg/kg per day) was 1.8 cases per 1000 patient-years of follow-up, compared with 0.8 cases per 1000 patient-years of follow-up in those not receiving azathioprine. However, the proportion of the increased risk attributable to the azathioprine dosage or to other therapies (i.e., alkylating agents) received by patients treated with azathioprine cannot be determined.

Use in specific populations

Sourced from openFDA

Pregnancy Azathioprine tablets can cause fetal harm when administered to a pregnant woman. Azathioprine tablets should not be given during pregnancy without careful weighing of risk versus benefit. Whenever possible, use of azathioprine tablets in pregnant patients should be avoided. This drug should not be used for treating rheumatoid arthritis in pregnant women. 3 Azathioprine tablets are teratogenic in rabbits and mice when given in doses equivalent to the human dose (5 mg/kg daily). Abnormalities included skeletal malformations and visceral anomalies. 2 Postmarketing cases of intrahepatic cholestasis of pregnancy (ICP) have been reported in women treated with azathioprine during pregnancy. ICP symptoms and evaluated bile acid levels improved following azathioprine discontinuation. Discontinue azathioprine tablets if ICP develops in a pregnant woman. Limited immunologic and other abnormalities have occurred in a few infants born of renal allograft recipients on azathioprine tablets. In a detailed case report, 4 documented lymphopenia, diminished IgG and IgM levels, CMV infection, and a decreased thymic shadow were noted in an infant born to a mother receiving 150 mg azathioprine and 30 mg prednisone daily throughout pregnancy. At 10 weeks most features were normalized.

Overdosage

Sourced from openFDA

The oral LD 50 s for single doses of azathioprine tablets in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death. About 30% of azathioprine is bound to serum proteins, but approximately 45% is removed during an 8-hour hemodialysis. 14 A single case has been reported of a renal transplant patient who ingested a single dose of 7500 mg azathioprine. The immediate toxic reactions were nausea, vomiting, and diarrhea, followed by mild leukopenia and mild abnormalities in liver function. The white blood cell count, SGOT, and bilirubin returned to normal 6 days after the overdose.

Approval history

Sourced from openFDA
  • Mar 20, 1968NDANDA016324Legacy Pharma
  • Mar 31, 1995ANDAANDA074419Hikma
  • Feb 16, 1996ANDAANDA074069Amneal
  • Jun 7, 1999ANDAANDA075252Aaipharma Llc
  • Dec 13, 1999ANDAANDA075568Rising
  • Mar 15, 2007ANDAANDA077621Zydus Pharms Usa
  • Mar 27, 2020ANDAANDA208687Alkem Labs Ltd

FAERS reports

View JSON
Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
88,113 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Off Label Use13,83316%
  2. 2Drug Ineffective13,34115%
  3. 3Condition Aggravated6,9707.9%
  4. 4Arthralgia6,1797.0%
  5. 5Diarrhoea5,5846.3%
  6. 6Fatigue5,4576.2%
  7. 7Nausea5,4326.2%
  8. 8Headache4,6835.3%
  9. 9Pain4,4485.0%
  10. 10Crohn^s Disease4,3604.9%
  11. 11Pyrexia4,1224.7%
  12. 12Pneumonia4,0554.6%
  13. 13Drug Intolerance3,9554.5%
  14. 14Malaise3,9554.5%
  15. 15Dyspnoea3,8814.4%

Literature

View JSON

Recent PubMed references pinned to Azathioprine as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 313 ClinicalTrials.gov registrations naming Azathioprine as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Azathioprine. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

Frequently asked questions

How does Azathioprine work?
Mechanism-of-action classes: Alkylating Activity; Nucleic Acid Synthesis Inhibitors.
What is Azathioprine used for?
According to FDA labeling, Azathioprine carries indications including: Azathioprine tablets, USP 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Azathioprine?
Azathioprine is classified as Other immunosuppressants, Purine Antimetabolite, Alkylating Activity, Nucleic Acid Synthesis Inhibitors, Cellular Growth Phase Reduction, Decreased DNA Replication, Decreased Mitosis, Immunologic Activity Alteration.
What are the brand names for Azathioprine?
Azathioprine is marketed under brand names including Azasan, Imuran.
What are the contraindications for Azathioprine?
Azathioprine labeling lists contraindications including: Azathioprine tablets should not be given to patients who have shown hypersensitivity to the drug. Azathioprine tablets should not be used for treating rheumatoid arthritis in pregnant women.. Always consult the full prescribing information and a clinician.
Note. Data for azathioprine is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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