Trade name sold Imuran among others.
An immunosuppressive medication.
Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins.
A purine analogue and antimetabolite family of medication.
Works via 6-thioguanine to disrupt the making of RNA and DNA by cells.
It may decrease proliferation of immune cells, which results in lower autoimmune activity.
Not effective treatment for acute rejection episodes but remains a choice for long-term immunosuppression.
Prescribed in rheumatoid arthritis, granulomatosis with polyangiitis, Crohn’s disease, ulcerative colitis, and in kidney transplants to prevent rejection.
Taken orally or intravenously.
Pregnancy category US: D (Evidence of risk)u
Mainly administered by mouth.
Bioavailability 60±31%.
Protein binding 20–30%.
Activated non-enzymatically, deactivated mainly by xanthine oxidase.
Elimination half-life is 26–80 minutes and 3–5 hours plus metabolites.
Excretion is renal, 98% as metabolites
Side effects include: bone marrow suppression and vomiting.
Bone marrow suppression is common in patients with a genetic deficiency of the enzyme thiopurine S-methyltransferase.
Use associated. with an increased risk of lymphoma.
Use during pregnancy may result in harm the fetus.
Used alone or in combination with other immunosuppressive therapy to prevent rejection following organ transplantation.
Actively replicating cells, such as cancer cells and the T cells and B cells of the immune system, are most active in synthesizing purine making new DNA, these cells are most strongly affected.
It is used alone or in combination to treat autoimmune diseases, including: rheumatoid arthritis, pemphigus, systemic lupus erythematosus, Behçet’s disease, other forms of vasculitis, autoimmune hepatitis, atopic dermatitis, myasthenia gravis, neuromyelitis optic disease and restrictive lung disease, inflammatory bowel disease and for multiple sclerosis.
Used in the management of active Crohn’s disease.
Associated with an increased risk of lymphoma.
Used to prevent flares in those with ulcerative colitis.
Sometimes used in systemic lupus erythematosus patients who require a maintenance dose of 15 mg or higher of prednisone.
Used as a steroid sparing agent in a number of diseases.
Effective in eczema and atopic dermatitis.
Azathioprine oral tablets are 50 mg.
Side effects include: dizziness, diarrhea, fatigue, and skin rashes.
Hair loss is often seen in transplant patients.
Patients can develop anemia, and are more susceptible to infection.
Regular monitoring of the blood count is recommended.
Acute pancreatitis can occur.
A group 1 carcinogen.
Thiopurine S-methyltransferase (TPMT) is responsible for various activation and deactivation steps in azathioprine’s mechanism of action.
Azathioprine undergoes conversion to 6-mercaptopurine.
6-mercaptopurine is also an immunosuppressant prodrug, and Thiopurine S-methyltransferase is responsible, in part, for its methylation into the inactive metabolite 6-methylmercaptopurine.
Genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity.
Patients who are homozygous or heterozygous for these types of genetic variations may have increased levels of metabolites and an increased risk of severe bone marrow suppression when receiving azathioprine.
TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of patients are homozygous for these variants.
An assay of TPMT activity in red blood cells or a TPMT genetic test can identify patients with reduced TPMT activity, allowing for the adjustment of azathioprine dose or avoidance of the drug entirely.
It is recommended to test for TPMT activity to identify patients at risk for myelotoxicity.
Known to be a human carcinogen.
Cases of hepatosplenic T-cell lymphoma, a rare type of lymphoma have been reported.
The use in organ transplantation has been linked to increased rates of developing skin cancer.
Use causes the accumulation of 6-thioguanine (6-TG) in patient’s DNA.
Other purine analogues such as allopurinol inhibit xanthine oxidase, the enzyme that breaks down azathioprine, thus increasing the toxicity of azathioprine.
Low doses of allopurinol have been shown to safely enhance the efficacy of azathioprine, especially in inflammatory bowel disease non-responders.
It decreases the effects of the warfarin and of non-depolarizing muscle relaxants, but increases the effect of depolarizing muscle relaxants.
Has also been reported to cause vitamin B12 deficiency.
Can cause birth defects.
It is absorbed from the gut to about 88%.
Bioavailability varies greatly between individual patients, between 30 and 90%.
The drug is partly inactivated in the liver.
Highest blood plasma concentrations, are reached after one to two hours.
The average plasma half-life is 26 to 80 minutes for azathioprine and three to five hours for drug plus metabolites.