Azathioprine 50 mg Tablet, 100-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Purine Antimetabolite class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Azathioprine is used with other medications to prevent transplant rejection (attack of the transplanted organ by the immune system) in people who received kidney transplants. It is also used to treat severe rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function) when other medications and treatments have not helped. Azathioprine is in a class of medications called immunosuppressants. It works by decreasing the activity of the body's immune system so it will not attack the transplanted organ or the joints.
Read the full MedlinePlus article ↗- You're right that it treats two quite different conditions, but the common thread is the immune system. After a kidney transplant, your immune system sees the new kidney as foreign...
- What exactly is azathioprine being used for — it seems like a drug used for very different things?
- Azathioprine is not a quick fix — it typically takes 6 to 8 weeks before you start feeling any improvement, and your doctor will usually give it a full 12 weeks before deciding if...
- How long will it take before I notice it working for my rheumatoid arthritis?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Azathioprine — tap one for details:
Azathioprine may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII M28OL1HH48
Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII FZ989GH94E
Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.125 | $12.49 / 100 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.2827 | $28.27 / 100 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.3186 | $31.86 / 100 tablets |
| Medicare Part B allowsASP · J7500 | $0.136 / J7500 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Azathioprine 50 mg 16571-0835-01 | Rising | 100 tablets | $0.125 | AB | Availability likely | — |
| Azathioprine 50 mg 60219-1076-01 | Amneal | 100 tablets | $0.125 | AB | Availability likely | — |
| Azathioprine 50 mg 67877-0493-01 | Ascend | 100 tablets | $0.125 | AB | Availability likely | — |
| Azathioprine 50 mg 68084-0229-01 | American | 100 tablets | $0.125 | AB | Availability likely | — |
| Azathioprine 50 mgthis 68382-0003-01 | Zydus | 100 tablets | $0.125 | AB | Availability likely | — |
| Azathioprine 50 mg 68462-0502-01 | Glenmark | 100 tablets | $0.125 | AB | Availability likely | — |
| Imuran 50 mg 54766-0590-10 | Sebela | 100 tablets | $8.891 | AB | Availability likely | +7021% |
| Azathioprine 50 mg 42291-0071-01 | AvKARE | 100 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 51407-0182-01 | Golden | 100 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 65841-0602-01 | Zydus | 100 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 68071-3772-06 | NuCare | 60 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 68071-3997-06 | NuCare | 60 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 69238-1076-01 | Amneal | 100 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 70518-3544-00 | REMEDYREPACK | 100 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 71610-0124-09 | Aphena | 9000 tablets | — | AB | FDA listed | — |
| Azathioprine 50 mg 72789-0129-30 | PD-Rx | 30 tablets | — | AB | FDA listed | — |
| Imuran 50 mg 83107-0025-10 | Legacy | 100 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 68382-0003-01 You're viewing this | 100 TABLET in 1 BOTTLE (68382-003-01) | $0.1249 / ea | $12.49 | 2007-07-11 | Active |
| 68382-0003-05 | 500 TABLET in 1 BOTTLE (68382-003-05) | $0.1249 / ea | $62.43 | 2007-07-11 | Active |
You're viewing the smallest of 2 pack sizes for this product.
This pack has the lowest per-ea cost of the 2 priced pack sizes ($0.1249 NADAC).
In Medicaid, this is the most-dispensed pack of this product — about 83% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 68382-0003-01?
What is the difference between NDC 68382-0003-01 and NDC 68382-0003-05?
What NDC number is used to bill for this package of Azathioprine 50 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
BOXED WARNING 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 .
🎯 Indications and Usage ▾
INDICATIONS AND USAGE 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. Renal Homotransplantation Azathioprine tablets, USP 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, USP 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.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION 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.
Azathioprine tablets may be continued long-term in patients with clinical response, but patients should be monitored carefully, and gradual dosage reduction should be attempted to reduce risk of toxicities. Maintenance therapy should be at the lowest effective dose, and the dose given can be lowered decrementally with changes of 0.5 mg/kg or approximately 25 mg daily every 4 weeks while other therapy is kept constant. The optimum duration of maintenance azathioprine tablets has not been determined.
Azathioprine tablets can be discontinued abruptly, but delayed effects are possible. Patients with TPMT and/or NUDT15 Deficiency Consider testing for TPMT and NUDT15 deficiency in patients who experience severe bone marrow toxicities. Early drug discontinuation may be considered in patients with abnormal CBC results that do not respond to dose reduction (see CLINICAL PHARMACOLOGY , WARNINGS: Cytopenias , and PRECAUTIONS: Laboratory Tests ).
Homozygous deficiency in either TPMT or NUDT15 Because of the risk of increased toxicity, consider alternative therapies for patients who are known to have TPMT or NUDT15 deficiency (see CLINICAL PHARMACOLOGY , WARNINGS: Cytopenias , and PRECAUTIONS: Laboratory Tests ). Heterozygous deficiency in TPMT and/or NUDT15 Because of the risk of increased toxicity, dosage reduction is recommended in patients known to have heterozygous deficiency of TPMT or NUDT15. Patients who are heterozygous for both TPMT and NUDT15 deficiency may require more substantial dosage reductions (see CLINICAL PHARMACOLOGY , WARNINGS: Cytopenias , and PRECAUTIONS: Laboratory Tests ).
Use in Renal Dysfunction Relatively oliguric patients, especially those with tubular necrosis in the immediate postcadaveric transplant period, may have delayed clearance of azathioprine tablets or its metabolites, may be particularly sensitive to this drug, and are usually given lower doses. Procedures for proper handling and disposal of this immunosuppressive antimetabolite drug should be considered. Several guidelines on this subject have been published.
15-21 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
⛔ Contraindications ▾
CONTRAINDICATIONS 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. Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others) may have a prohibitive risk of malignancy if treated with azathioprine tablets.
⚠️ Warnings ▾
WARNINGS 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. These cases have had a very aggressive disease course and have been fatal.
The majority of reported cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Some of the patients were treated with azathioprine as monotherapy and some had received concomitant treatment with a TNFα blocker at or prior to diagnosis. The safety and efficacy of azathioprine for the treatment of Crohn's disease and ulcerative colitis have not been established.
Cytopenias Severe leukopenia, thrombocytopenia, anemias including macrocytic anemia, and/or pancytopenia may occur in patients being treated with azathioprine. Severe bone marrow suppression may also occur. Hematologic toxicities are dose-related and may be more severe in renal transplant patients whose homograft is undergoing rejection.
It is suggested that patients on azathioprine have complete blood counts, including platelet counts, weekly during the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary. Delayed hematologic suppression may occur. Prompt reduction in dosage or temporary withdrawal of the drug may be necessary if there is a rapid fall in or persistently low leukocyte count, or other evidence of bone marrow depression.
Leukopenia does not correlate with therapeutic effect; therefore the dose should not be increased intentionally to lower the white blood cell count. TPMT or NUDT15 Deficiency Patients with thiopurine S-methyl transferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency may be at an increased risk of severe and life-threatening myelotoxicity if receiving conventional doses of azathioprine (see CLINCIAL PHARMACOLOGY ). Death associated with pancytopenia has been reported in patients with absent TPMT activity receiving azathioprine.
In patients with severe myelosuppression, consider evaluation for TPMT and NUDT15 deficiency (see PRECAUTIONS: Laboratory Tests ). Consider alternative therapy in patients with homozygous TPMT or NUDT15 deficiency and reduced dosages in patients with heterozygous deficiency (see DOSAGE AND ADMINISTRATION ). Serious infections Patients receiving immunosuppressants, including azathioprine, are at increased risk for bacterial, viral, fungal,protozoal, and opportunistic infections, including reactivation of late…
🤒 Adverse Reactions ▾
ADVERSE REACTIONS 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. Leukopenia (any degree) >50% 28% <2,500 cells/mm 3 16% 5.3% Infections 20% <1% Neoplasia * Lymphoma 0.5% Others 2.8% Hematologic Leukopenia and/or thrombocytopenia are dose-dependent and may occur late in the course of therapy with azathioprine tablets.
Dose reduction or temporary withdrawal may result in reversal of these toxicities. Infection may occur as a secondary manifestation of bone marrow suppression or leukopenia, but the incidence of infection in renal homotransplantation is 30 to 60 times that in rheumatoid arthritis. Anemias, including macrocytic anemia and/or bleeding have been reported.
Patients with low or absent TPMT or NUDT15 activity are at increased risk for severe, life-threatening myelosuppression from azathioprine (see CLINICAL PHARMACOLOGY , WARNINGS: Cytopenias and PRECAUTIONS: Laboratory Tests , DOSAGE AND ADMINISTRATION ). Gastrointestinal Nausea and vomiting may occur within the first few months of therapy with azathioprine tablets, and occurred in approximately 12% of 676 rheumatoid arthritis patients. The frequency of gastric disturbance often can be reduced by administration of the drug in divided doses and/or after meals.
However, in some patients, nausea and vomiting may be severe and may be accompanied by symptoms such as diarrhea, fever, malaise, and myalgias (see PRECAUTIONS ). Vomiting with abdominal pain may occur rarely with a hypersensitivity pancreatitis. Hepatotoxicity manifest by elevation of serum alkaline phosphatase, bilirubin, and/or serum transaminases is known to occur following azathioprine use, primarily in allograft recipients.
Hepatotoxicity has been uncommon (less than 1%) in rheumatoid arthritis patients. Hepatotoxicity following transplantation most often occurs within 6 months of transplantation and is generally reversible after interruption of azathioprine tablets. A rare, but life-threatening hepatic veno-occlusive disease associated with chronic administration of azathioprine has been described in transplant patients and in one patient receiving azathioprine tablets for panuveitis.
11, 12, 13 Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity. If hepatic veno-occlusive disease is clinically suspected, azathioprine tablets should be permanently withdrawn. Others Additional side effects of low frequency have been reported.
These include skin rashes, alopecia, fever, arthralgias, diarrhea, steatorrhea, negative nitrogen balance, reversible inte…
🔄 Drug Interactions ▾
Drug Interactions Use with xanthine oxidase (XO) inhibitors : One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of azathioprine, to approximately 1/ 3 to 1/ 4 the usual dose. Concomitant use of azathioprine with febuxostat is not recommended.
Inhibition of XO may cause increased plasma concentrations of azathioprine or its metabolite, 6-MP, leading to toxicity. It is recommended that a further dose reduction or alternative therapies be considered for patients with low or absent TPMT activity receiving azathioprine and xanthine oxidase inhibitors because both TPMT and XO inactivation pathways are affected (see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS: Laboratory Tests and ADVERSE REACTIONS sections). Use with Aminosalicylates There is in vitro evidence that aminosalicylate derivatives (e.g., sulphasalazine, mesalazine, or olsalazine) inhibit the TPMT enzyme.
Concomitant use of these agents with azathioprine tablets should be done with caution. Use with Other Agents Affecting Myelopoesis Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients. Use with Angiotensin-Converting Enzyme Inhibitors The use of angiotensin-converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce anemia and severe leukopenia.
Use with Warfarin Azathioprine tablets may inhibit the anticoagulant effect of warfarin. Use with ribavirin The use of ribavirin for hepatitis C in patients receiving azathioprine has been reported to induce severe pancytopenia and may increase the risk of azathioprine-related myelotoxicity. Inosine monophosphate dehydrogenase (IMDH) is required for one of the metabolic pathways of azathioprine.
Ribavirin is known to inhibit IMDH, thereby leading to accumulation of an azathioprine metabolite, 6-methylthioionosine monophosphate (6MTITP), which is associated with myelotoxicity (neutropenia, thrombocytopenia, and anemia). Patients receiving azathioprine with ribavirin should have complete blood counts, including platelet counts, monitored weekly for the first month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage or other therapy changes are necessary. Carcinogenesis, Mutagenesis, Impairment of Fertility See WARNINGS section .
🤰 Pregnancy ▾
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.
DeWitte et al reported pancytopenia and severe immune deficiency in a preterm infant whose mother received 125 mg azathioprine and 12.5 mg prednisone daily. 5 There have been two published reports of abnormal physical findings. Williamson and Karp described an infant born with preaxial polydactyly whose mother received azathioprine 200 mg daily and prednisone 20 mg every other day during pregnancy.
6 Tallent et al described an infant with a large myelomeningocele in the upper lumbar region, bilateral dislocated hips, and bilateral talipes equinovarus. The father was on long-term azathioprine therapy. 7 Benefit versus risk must be weighed carefully before use of azathioprine tablets in patients of reproductive potential.
There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing age should be advised to avoid becoming pregnant.
🧒 Pediatric Use ▾
Pediatric Use Safety and efficacy of azathioprine in pediatric patients have not been established.
🆘 Overdosage ▾
OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Azathioprine is well absorbed following oral administration. Maximum serum radioactivity occurs at 1 to 2 hours after oral 35 S-azathioprine and decays with a half-life of 5 hours. This is not an estimate of the half-life of azathioprine itself, but is the decay rate for all 35 S-containing metabolites of the drug.
Because of extensive metabolism, only a fraction of the radioactivity is present as azathioprine. Usual doses produce blood levels of azathioprine, and of mercaptopurine derived from it, which are low (<1 mcg/mL). Blood levels are of little predictive value for therapy since the magnitude and duration of clinical effects correlate with thiopurine nucleotide levels in tissues rather than with plasma drug levels.
Azathioprine and mercaptopurine are moderately bound to serum proteins (30%) and are partially dialyzable see OVERDOSAGE . 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. The cytotoxicity of azathioprine is due, in part, to the incorporation of 6-TGN into DNA. 6-MP undergoes two major inactivation routes.
One is thiol methylation, which is catalyzed by the enzyme thiopurine S-methyltransferase (TPMT), to form the inactive metabolite methyl-6-MP (6-MeMP). Another inactivation pathway is oxidation, which is catalyzed by xanthine oxidase (XO) to form 6-thiouric acid. The nucleotide diphosphatase (NUDT15) enzyme is involved in conversion of the 6-TGNs to inactive 6-TG monophosphates.
TPMT activity correlates inversely with 6-TGN levels in erythrocytes and presumably other hematopoietic tissues, since these cells have negligible xanthine oxidase (involved in the other inactivation pathway) activities. Genetic polymorphisms influence TPMT and NUDT15 activity. Several published studies indicate that patients with reduced TPMT or NUDT15 activity receiving usual doses of 6-MP or azathioprine, accumulate excessive cellular concentrations of active 6-TGNs, and are at higher risk for severe myelosuppression.
Because of the risk of toxicity, patients with TPMT or NUDT15 deficiency require alternative therapy or dose modification (see DOSAGE and ADMINISTRATION ). Approximately 0.3% (1:300) of patients of European or African ancestry have two loss-of-function alleles of the TPMT gene and have little or no TPMT activity (homozygous deficient or poor metabolizers), and approximately 10% of patients have one loss-of-function TPMT allele leading to intermediate TPMT activity (heterozygous deficient or intermediate metabolizers).
The TPMT*2, TPMT*3A, and TPMT*3C alleles account for about 95% of individuals with reduced levels of TPMT activity. NUDT15 deficiency is detected in <1% of patients of European or African ancestry. Among patients of East Asian ancestry (i.e., Chinese, Japanese, Vietnamese), 2% have two loss-of-function alleles of the NUDT15 gene, and approximately 21% have one loss-of-function allele.
The p.R139C variant of NUDT15 (present on the *2 and *3 alleles) is the most commonly observed, but other less common loss-of-function NUDT15 alleles have been observed. Inhibition of xanthine oxidase (XO) may cause increased plasma concentrations of azathioprine or its metabolites leading to toxicity (see PRECAUTIONS: Drug Interactions ). Proportions of metabolites are different in individual patients, and this presumably accounts for variable magnitude and duration of drug effects.
Renal clearance is probably not important in predicting biological effectiveness or toxicities, although dose reduction is practiced in patients with poor renal function. Homograft Survival The use of azathioprine for in…
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Azathioprine Tablets USP, 25 mg are yellow, round, flat, radial edge tablets with bisect on one side and other side is plain; one side of the bisect is debossed with logo of "ZD" and other side is debossed with "11" and are supplied as follows: NDC 68382-118-01 in bottles of 100 tablets NDC 68382-118-05 in bottles of 500 tablets Azathioprine Tablets USP, 50 mg are yellow, round, flat, beveled edge tablets with bisect on one side; one side of the bisect is debossed with logo of "ZC" and other side is debossed with "59" and other side is plain and are supplied as follows: NDC 68382-003-01 in bottles of 100 tablets NDC 68382-003-05 in bottles of 500 tablets Azathioprine Tablets USP, 75 mg are yellow, round, flat, radial-edged tablets with bisect on one side and other side of tablet is plain; one side of the bisect is debossed with "ZD" and other side is debossed with "10" and are supplied as follows: NDC 68382-119-01 in bottles of 100 tablets NDC 68382-119-05 in bottles of 500 tablets Azathioprine Tablets USP, 100 mg are yellow, round, flat, radial-edged tablets with bisect on one side and other side of tablet is plain; one side of the bisect is debossed with "ZD" and other side is debossed with "09" and are supplied as follows: NDC 68382-120-01 in bottles of 100 tablets NDC 68382-120-05 in bottles of 500 tablets STORAGE Store at 20°C to 25° C (68°F to 77° F) [See USP Controlled Room Temperature] in a dry place and protect from light.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
📋 Description ▾
DESCRIPTION Azathioprine is an immunosuppressive antimetabolite. Each uncoated azathioprine tablet intended for oral administration contains 25 mg or 50 mg or 75 mg or 100 mg of azathioprine. In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, povidone and starch.
Azathioprine is chemically 6-[(1-methyl-4-nitro-1 H -imidazol-5-yl)thio]-1 H -purine. The structural formula of azathioprine is: It is an imidazolyl derivative of 6-mercaptopurine and many of its biological effects are similar to those of the parent compound. Azathioprine, USP is a pale yellow, odorless powder.
It is insoluble in water, soluble in dilute solutions of alkali hydroxides, sparingly soluble in dilute mineral acids, very slightly soluble in alcohol and in chloroform. The sodium salt of azathioprine is sufficiently soluble to make a 10 mg/mL water solution which is stable for 24 hours at 59° to 77°F (15° to 25°C). Azathioprine is stable in solution at neutral or acid pH but hydrolysis to mercaptopurine occurs in excess sodium hydroxide (0.1N), especially on warming.
Conversion to mercaptopurine also occurs in the presence of sulfhydryl compounds such as cysteine, glutathione, and hydrogen sulfide. structure formula for Azathioprine
💬 Information for Patients ▾
Information for Patients Patients being started on azathioprine tablets should be informed of the necessity of periodic blood counts while they are receiving the drug and should be encouraged to report any unusual bleeding or bruising to their physician. They should be informed of the danger of infection while receiving azathioprine tablets and asked to report signs and symptoms of infection to their physician. Careful dosage instructions should be given to the patient, especially when azathioprine tablets are being administered in the presence of impaired renal function or concomitantly with allopurinol (see Drug Interactions subsection and DOSAGE AND ADMINISTRATION ).
Patients should be advised of the potential risks of the use of azathioprine tablets during pregnancy and during the nursing period. The increased risk of malignancy following therapy with azathioprine tablets should be explained to the patient.