Azathioprine: Uses, Dosage & Side Effects
An immunosuppressant medication used to prevent organ transplant rejection and treat autoimmune diseases including rheumatoid arthritis and inflammatory bowel disease
Azathioprine is an immunosuppressant medication that belongs to the thiopurine class of drugs. It is a prodrug that is converted in the body to 6-mercaptopurine, which interferes with the synthesis of DNA and RNA in rapidly dividing immune cells. Azathioprine is used to prevent organ rejection after kidney, liver, and heart transplantation, and to treat a wide range of autoimmune and inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, and autoimmune hepatitis. It is listed on the WHO Model List of Essential Medicines and requires a prescription in all countries.
Quick Facts: Azathioprine
Key Takeaways
- Azathioprine is used to prevent organ transplant rejection and to treat autoimmune conditions such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, and lupus by suppressing the overactive immune system.
- TPMT and NUDT15 enzyme testing is recommended before starting treatment, as patients with reduced enzyme activity are at much higher risk of severe bone marrow suppression and may need a lower dose or an alternative medication.
- Regular blood tests (complete blood count and liver function) are mandatory throughout treatment — weekly for the first 8 weeks, then at least every 3 months — to detect bone marrow suppression or liver problems early.
- Azathioprine must never be combined with allopurinol or febuxostat at standard doses, as this interaction can cause life-threatening bone marrow failure; if necessary, the azathioprine dose must be reduced to 25% of normal.
- Patients on azathioprine should avoid live vaccines, protect skin from sun exposure due to increased skin cancer risk, and report any signs of infection (fever, sore throat, unusual bruising) immediately to their doctor.
What Is Azathioprine and What Is It Used For?
Azathioprine is one of the most widely used immunosuppressive medications in clinical medicine. First synthesized in 1957 by George Hitchings and Gertrude Elion — research that ultimately earned them the Nobel Prize in Physiology or Medicine in 1988 — azathioprine revolutionized organ transplantation by making long-term graft survival possible. Before its introduction, kidney transplant rejection rates were extremely high and long-term survival of transplanted organs was rarely achieved. Today, azathioprine remains on the World Health Organization's Model List of Essential Medicines, reflecting its critical importance in global healthcare.
Azathioprine is a prodrug, meaning it is inactive in its original form and must be converted by the body into its active metabolite. After oral administration, azathioprine is rapidly broken down in the liver and other tissues into 6-mercaptopurine (6-MP), which is further metabolized through several enzymatic pathways into thioguanine nucleotides (TGNs). These active metabolites are incorporated into the DNA and RNA of rapidly dividing cells, particularly T lymphocytes and B lymphocytes, which are key components of the adaptive immune system. By interfering with nucleic acid synthesis, azathioprine inhibits the proliferation of these immune cells, thereby reducing both cell-mediated and antibody-mediated immune responses.
The immunosuppressive effect of azathioprine does not develop immediately. For autoimmune conditions, it typically takes 6 to 12 weeks of continuous treatment before the full clinical benefit becomes apparent. This is because the drug gradually reduces the number of overactive immune cells over time. Patients should not discontinue treatment prematurely due to a perceived lack of effect during this initial period. For transplant recipients, the immunosuppressive action is needed immediately, and azathioprine is typically started at higher doses around the time of the surgical procedure, often in combination with other immunosuppressive agents.
Approved and Established Clinical Uses
Azathioprine has a broad range of clinical applications. Its primary approved indication is the prevention of organ transplant rejection, where it is used as part of a multi-drug immunosuppressive regimen following kidney, liver, heart, and other solid organ transplants. In transplant medicine, azathioprine is usually combined with corticosteroids and often with a calcineurin inhibitor (such as ciclosporin or tacrolimus) to provide comprehensive immunosuppression while minimizing the side effects of each individual drug.
Beyond transplantation, azathioprine is extensively used as a corticosteroid-sparing agent in a wide variety of autoimmune and inflammatory conditions. By allowing patients to reduce or discontinue long-term corticosteroid therapy, azathioprine helps avoid the numerous side effects associated with prolonged steroid use, such as osteoporosis, diabetes, weight gain, and adrenal suppression. Its established uses include:
- Rheumatoid arthritis: Azathioprine is used as a disease-modifying antirheumatic drug (DMARD) in patients with severe rheumatoid arthritis who have not responded adequately to first-line agents such as methotrexate.
- Inflammatory bowel disease: Both Crohn's disease and ulcerative colitis are commonly treated with azathioprine to maintain remission and reduce flares, as recommended by the European Crohn's and Colitis Organisation (ECCO) and the American College of Gastroenterology (ACG).
- Systemic lupus erythematosus (SLE): Azathioprine is used for maintenance therapy in lupus nephritis and other organ manifestations of lupus.
- Autoimmune hepatitis: It is a standard part of first-line maintenance therapy, typically combined with prednisolone.
- Severe inflammatory skin diseases: Including severe eczema (atopic dermatitis), pemphigus, and dermatomyositis.
- Vasculitis: Various forms of blood vessel inflammation, including polyarteritis nodosa and granulomatosis with polyangiitis.
- Myasthenia gravis: As a steroid-sparing agent in this neuromuscular autoimmune condition.
- Multiple sclerosis: Used in some cases as an immunomodulatory treatment.
Azathioprine is available as film-coated tablets in strengths of 25 mg, 50 mg, and 75 mg. It is manufactured under various brand names worldwide, including Imurel, Azathioprin Orifarm, Azathioprin Actavis, Azathioprin 1A Farma, and Azatioprin Viatris. In some countries, an injectable formulation is also available for patients unable to take oral medication.
What Should You Know Before Taking Azathioprine?
Contraindications
There are specific clinical situations where azathioprine must not be used. Understanding these contraindications is essential for preventing serious, potentially life-threatening adverse events. You should not take azathioprine if any of the following apply:
- Allergy to azathioprine or mercaptopurine: Known hypersensitivity to azathioprine, its active metabolite 6-mercaptopurine, or any excipient in the formulation. An allergic reaction may present as skin rash, itching, difficulty breathing, or swelling of the face, lips, throat, or tongue.
- Severe active infection: Azathioprine further suppresses the immune system, making it dangerous to start during an active severe infection as the body's ability to fight the infection would be further compromised.
- Severe liver disease: Patients with severe hepatic impairment should not take azathioprine, as the liver is involved in its metabolism and already compromised liver function increases the risk of toxicity.
- Severe bone marrow disease: Pre-existing bone marrow suppression (pancytopenia, severe leukopenia, or severe thrombocytopenia) is a contraindication, as azathioprine would worsen these conditions.
- Pancreatitis: Active inflammation of the pancreas is a contraindication, and azathioprine itself can cause pancreatitis.
- Recent live vaccination: Patients who have recently received a live vaccine (such as BCG, yellow fever, or varicella) should not start azathioprine, as the immunosuppressive effect could allow the attenuated vaccine virus to cause active infection.
- Pregnancy: Azathioprine should not be used during pregnancy unless the treating physician considers it essential and no safer alternative exists. It has been shown to cross the placenta and has potential teratogenic effects.
- Breastfeeding: Metabolites of azathioprine are excreted in breast milk and could potentially harm the nursing infant.
Warnings and Precautions
Azathioprine can cause severe, life-threatening bone marrow suppression (myelosuppression), resulting in dangerously low levels of white blood cells (leukopenia), red blood cells (anemia), and platelets (thrombocytopenia). This risk is highest in patients with reduced TPMT or NUDT15 enzyme activity. Regular blood count monitoring is mandatory. Contact your doctor immediately if you experience signs of infection (fever, sore throat, mouth ulcers), unusual bruising, bleeding, or extreme tiredness.
TPMT and NUDT15 testing: Before starting azathioprine treatment, your doctor should arrange testing for thiopurine methyltransferase (TPMT) and, where available, NUDT15 enzyme activity. These enzymes are critical for the safe metabolism of azathioprine. Approximately 10% of the population has intermediate TPMT activity, and about 0.3% have very low or absent TPMT activity. Patients with reduced TPMT or NUDT15 activity metabolize azathioprine differently, leading to accumulation of toxic thioguanine nucleotides and a dramatically increased risk of severe myelosuppression. Depending on the test results, your doctor may reduce the starting dose, increase monitoring frequency, or choose an alternative medication altogether.
Blood monitoring requirements: Regular blood tests are mandatory during azathioprine therapy. During the first 8 weeks of treatment, a complete blood count should be performed weekly. After this initial period, blood tests should continue at least every 3 months, or more frequently if you are elderly, taking a high dose, have impaired kidney or liver function, or have reduced TPMT/NUDT15 activity. Azathioprine should not be prescribed if adequate blood monitoring cannot be arranged. All treatment discontinuation should be done under medical supervision.
Patients receiving immunosuppressive therapy, including azathioprine, have an increased risk of developing certain types of cancer. This includes an elevated risk of lymphoma (including Epstein-Barr virus-associated lymphoproliferative disease), skin cancer (both non-melanoma and melanoma), and hepatosplenic T-cell lymphoma (a rare but often fatal type). To reduce skin cancer risk, avoid excessive sun exposure, wear protective clothing, and use high-SPF sunscreen. The risk of lymphoproliferative disease is higher when multiple immunosuppressive drugs are used simultaneously.
Increased infection risk: Because azathioprine suppresses the immune system, patients are more susceptible to viral, fungal, and bacterial infections, and these infections may be more severe or atypical in presentation. You should contact your doctor immediately if you develop a sore throat, fever, signs of infection, unexplained bruising, or bleeding. Patients should be aware that infections with varicella-zoster virus (chickenpox and shingles) can be particularly severe in immunosuppressed individuals.
Hepatitis B reactivation: Patients with a history of hepatitis B infection are at risk of viral reactivation during immunosuppressive therapy. If you have ever had hepatitis B, tell your doctor before starting azathioprine. Appropriate monitoring and, in some cases, prophylactic antiviral therapy may be needed.
Azathioprine use may be associated with the development of macrophage activation syndrome (MAS), a severe, potentially life-threatening condition involving excessive activation of immune cells and an overwhelming inflammatory response. This is most commonly seen in patients with certain types of arthritis. Symptoms include persistent high fever, lymph node enlargement, liver and spleen enlargement, and abnormal blood test results. Seek immediate medical attention if these symptoms develop.
Pellagra (niacin deficiency): In rare cases, azathioprine treatment has been associated with pellagra, a condition caused by vitamin B3 (niacin) deficiency. Contact your doctor immediately if you develop diarrhea, localized pigmented skin rashes (dermatitis), or notice deterioration in memory, comprehension, or other cognitive functions (dementia), as these are the classic symptoms of pellagra.
Liver damage: Azathioprine can affect liver function, and liver function tests should be monitored regularly throughout treatment. In rare cases, serious liver damage has been reported, including conditions affecting the blood vessels within the liver (such as nodular regenerative hyperplasia and sinusoidal obstruction syndrome). Contact your doctor if you experience yellowing of the skin or eyes (jaundice), dark urine, pale stools, loss of appetite, nausea, or abdominal pain.
Pregnancy and Breastfeeding
Azathioprine should not be taken during pregnancy unless your doctor considers it absolutely necessary and no safer alternative is available. Animal studies have shown that azathioprine crosses the placenta and has caused birth defects. In humans, the evidence is complex: while some studies have reported increased risks of preterm birth and low birth weight, azathioprine is sometimes continued during pregnancy in women with serious autoimmune conditions (such as lupus nephritis or autoimmune hepatitis) where the risk of uncontrolled disease to the mother and fetus outweighs the potential risks of the medication. This decision must always be made on an individual basis by a specialist physician.
Both men and women of reproductive age should use effective contraception during treatment with azathioprine. Women should continue contraception for at least 6 months after the last dose. Men are advised not to father children during treatment and for up to 3 months after the final dose. Intrauterine devices (IUDs/coils) are not recommended as contraception during azathioprine treatment.
If you become pregnant while taking azathioprine, or notice intense itching without a rash during pregnancy (which may indicate a condition called intrahepatic cholestasis of pregnancy), contact your doctor immediately.
Azathioprine metabolites are excreted in breast milk. Breastfeeding is not recommended during azathioprine treatment, as the metabolites could potentially harm the nursing infant. Discuss the risks and benefits with your healthcare provider.
Driving and Operating Machinery
Azathioprine does not generally affect the ability to drive or operate machinery. However, dizziness has been reported as a side effect. If you experience dizziness, you should not drive or operate heavy machinery. Alcohol may worsen dizziness, and you should avoid driving if you have consumed alcohol while taking this medication.
How Does Azathioprine Interact with Other Drugs?
Azathioprine interacts with a significant number of medications, some of which can cause serious or life-threatening complications. It is essential to tell your doctor about all medications you are taking, including prescription drugs, over-the-counter medications, and herbal supplements, before starting or changing azathioprine therapy. The following table summarizes the most clinically important drug interactions.
Major Interactions
| Interacting Drug | Effect | Clinical Action |
|---|---|---|
| Allopurinol, Oxipurinol, Thiopurinol | Inhibit xanthine oxidase, blocking azathioprine breakdown; causes severe accumulation of toxic metabolites and life-threatening bone marrow suppression | Reduce azathioprine dose to 25% (one-quarter) of normal; intensive blood monitoring required |
| Febuxostat | Same mechanism as allopurinol; inhibits xanthine oxidase leading to dangerous accumulation of active metabolites | Combination should be avoided; if essential, reduce azathioprine dose to 25% with close monitoring |
| Live vaccines (BCG, yellow fever, varicella, MMR) | Immunosuppression may allow attenuated vaccine viruses to cause active infection | Avoid all live vaccines during treatment and for at least 3 months after stopping azathioprine |
| Ribavirin | Inhibits the enzyme IMPDH, potentially increasing accumulation of toxic thiopurine metabolites | Avoid combination; if essential, monitor blood counts very closely |
| Methotrexate | Increases bioavailability of 6-mercaptopurine (the active metabolite); additive myelosuppression risk | Use with caution; close monitoring of blood counts and liver function required |
Moderate Interactions
| Interacting Drug | Effect | Clinical Action |
|---|---|---|
| Warfarin, Phenprocoumon | Azathioprine may reduce the anticoagulant effect of vitamin K antagonists, requiring higher warfarin doses | Monitor INR closely when starting, stopping, or changing azathioprine dose; warfarin dose adjustment likely needed |
| Mesalazine, Olsalazine, Sulfasalazine | Aminosalicylates inhibit TPMT, potentially increasing thiopurine toxicity and risk of bone marrow suppression | Use with caution; consider more frequent blood count monitoring |
| ACE inhibitors (enalapril, ramipril, etc.) | Both drugs can cause leukopenia; additive risk of white blood cell suppression | Monitor blood counts more frequently, particularly white blood cells |
| Trimethoprim/Sulfamethoxazole | Additive risk of bone marrow suppression; both drugs can independently cause leukopenia | Monitor blood counts during combined use; consider alternative antibiotics where possible |
| Ciclosporin, Tacrolimus | Additive immunosuppression; ciclosporin may also increase plasma levels of azathioprine metabolites | Monitor blood counts and drug levels closely; be aware of increased infection and malignancy risk |
| Infliximab | Additive immunosuppression when combined with azathioprine for IBD treatment | Established combination for Crohn's disease; monitor closely for infections and lymphoproliferative disease |
| Cimetidine | May inhibit azathioprine metabolism, increasing its myelosuppressive effects | Monitor blood counts; consider alternative acid-reducing agents (e.g., proton pump inhibitors) |
If you are scheduled for surgery, always inform the anesthesiologist that you are taking azathioprine. Azathioprine can alter the effects of neuromuscular blocking agents (muscle relaxants) used during general anesthesia. Some studies suggest it may reduce the effect of non-depolarizing muscle relaxants (such as atracurium) while potentially enhancing the effect of depolarizing agents (such as succinylcholine). The anesthesiologist will adjust the dosing of these agents accordingly.
What Is the Correct Dosage of Azathioprine?
The correct dose of azathioprine varies significantly depending on the condition being treated, the patient's body weight, TPMT/NUDT15 enzyme activity, kidney and liver function, and response to therapy. Dosing should always be determined and monitored by a specialist physician experienced in immunosuppressive therapy. Never change your dose or stop taking azathioprine without first consulting your doctor.
Adults
Organ Transplant Recipients
The usual starting dose is up to 5 mg per kg body weight per day, administered on the day of or shortly before transplantation. The maintenance dose is typically 1–4 mg per kg body weight per day, adjusted according to clinical response and tolerability. The exact regimen depends on the transplant center's protocol and the other immunosuppressive drugs used in combination.
Autoimmune and Inflammatory Conditions
For rheumatoid arthritis, inflammatory bowel disease, lupus, autoimmune hepatitis, and other autoimmune conditions, the usual dose is 1–3 mg per kg body weight per day. Treatment is typically started at a lower dose (e.g., 1 mg/kg/day) and gradually increased over several weeks to the target dose, based on clinical response and blood test results. Dose adjustments should not be made more frequently than every 4 weeks.
How to take azathioprine: Tablets should be taken at least 1 hour before or 3 hours after food or milk, as food can reduce absorption. Swallow the tablets whole with at least 200 mL (one glass) of water. If tablets must be split, avoid skin contact with the broken surface and wash your hands immediately afterwards. Do not inhale tablet dust.
Children and Adolescents
For children and adolescents, the same weight-based dosing recommendations as for adults generally apply for most indications. However, due to insufficient clinical data, azathioprine is not recommended in children under 18 years for the treatment of juvenile chronic arthritis, systemic lupus erythematosus, dermatomyositis, or polyarteritis nodosa. For other indications, particularly inflammatory bowel disease and post-transplant immunosuppression, azathioprine is used in children under specialist supervision with careful blood monitoring.
Elderly Patients
Elderly patients may require reduced doses of azathioprine. Kidney function naturally declines with age, potentially affecting drug clearance, and older patients may be more susceptible to bone marrow suppression and infections. The starting dose should be at the lower end of the recommended range, with careful titration based on blood test results and clinical response. More frequent blood monitoring may be necessary.
Patients with Kidney or Liver Disease
Patients with impaired kidney or liver function may require a lower dose of azathioprine. Since the kidneys are involved in eliminating azathioprine metabolites, reduced kidney function can lead to accumulation and increased toxicity. Similarly, liver impairment can affect the metabolism of azathioprine. Patients with severe liver disease should not take azathioprine. Your doctor will adjust the dose based on your kidney and liver function test results.
Missed Dose
If you forget to take a dose of azathioprine, take it as soon as you remember — unless it is almost time for your next scheduled dose. In that case, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a forgotten dose. Tell your doctor if you have missed a dose.
Overdose
If you have taken more azathioprine than prescribed, or if a child has accidentally ingested the medication, seek medical attention immediately by contacting your doctor, going to the nearest hospital emergency department, or calling your local poison control center. The primary risk of overdose is severe bone marrow suppression, which may not become apparent for several days after the overdose. Symptoms may include infection (fever, sore throat), unusual bleeding or bruising, and extreme tiredness. There is no specific antidote for azathioprine overdose; treatment is supportive and may include gastric lavage if the overdose is recent, blood transfusions, and granulocyte colony-stimulating factor (G-CSF) to support bone marrow recovery.
What Are the Side Effects of Azathioprine?
Like all medications, azathioprine can cause side effects, although not everyone experiences them. The severity and frequency of side effects depend on the dose, the duration of treatment, whether azathioprine is used alone or in combination with other immunosuppressive drugs, and the individual patient's TPMT/NUDT15 enzyme activity. Side effects are categorized below by frequency, from most common to rarest.
Contact your doctor or seek emergency medical help immediately if you experience: sudden wheezing or difficulty breathing, swelling of the eyelids, face, or lips, skin rash or hives (especially affecting the whole body), high fever with signs of infection, unusual bruising or bleeding, severe abdominal pain with nausea and vomiting, or yellowing of the skin or eyes.
Very Common
May affect more than 1 in 10 people
- Infections caused by viruses, fungi, or bacteria in transplant recipients (including severe or atypical infections with varicella-zoster, herpes simplex, and other pathogens)
- Bone marrow suppression (myelosuppression)
- Low white blood cell count (leukopenia), which increases infection risk
Common
May affect up to 1 in 10 people
- Low platelet count (thrombocytopenia), causing easy bruising or bleeding
- Nausea
Uncommon
May affect up to 1 in 100 people
- Infections in non-transplant patients (viral, fungal, and bacterial)
- Low red blood cell count (anemia), causing tiredness, headache, shortness of breath, dizziness, and pallor
- Hypersensitivity reactions (general malaise, dizziness, nausea, vomiting, diarrhea, fever, chills, skin rash, blood vessel inflammation, joint and muscle pain, low blood pressure, kidney or liver problems)
- Intrahepatic cholestasis of pregnancy (intense itching, especially on the hands and feet)
- Pancreatitis (severe pain in the upper abdomen with nausea and vomiting)
- Liver problems (pale stools, dark urine, itching, yellowing of skin and eyes, abnormal liver blood tests)
Rare
May affect up to 1 in 1,000 people
- Severe blood and bone marrow problems (agranulocytosis, aplastic anemia, megaloblastic anemia, pancytopenia)
- Serious liver damage, potentially life-threatening with long-term use (including nodular regenerative hyperplasia, sinusoidal obstruction syndrome)
- Hair loss (which may improve even with continued treatment)
- Various types of cancer including blood, lymph, and skin cancers
Very Rare
May affect up to 1 in 10,000 people
- Life-threatening allergic skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis)
- Lung inflammation (pneumonitis) causing shortness of breath, cough, and fever
- Progressive multifocal leukoencephalopathy (PML) — a viral brain infection caused by JC virus, with symptoms including headache, behavioral changes, speech difficulties, and cognitive decline; this can be fatal
- Hepatosplenic T-cell lymphoma (symptoms include nosebleeds, fatigue, severe night sweats, weight loss, and unexplained fever)
- Colitis (inflammation of the colon), diverticulitis, and bowel perforation in transplant patients; severe diarrhea in patients with inflammatory bowel disease
Additional side effects reported with unknown frequency include: photosensitivity (increased sensitivity to sunlight or UV light) and pellagra (niacin/vitamin B3 deficiency characterized by pigmented skin rash, diarrhea, and cognitive decline). Sweet syndrome (acute febrile neutrophilic dermatosis), presenting as tender red or purple raised bumps particularly on the arms, hands, face, and neck accompanied by fever, has also been reported.
The risk and severity of side effects generally increases with higher doses and longer treatment duration. When azathioprine is used in combination with other immunosuppressive agents (as in transplant medicine), the risk of infections and malignancies is higher than when it is used alone. Your doctor will regularly assess whether the benefits of continued treatment outweigh the risks and adjust your therapy accordingly.
How Should You Store Azathioprine?
Proper storage of azathioprine is important to ensure the medication remains effective and safe to use. Azathioprine tablets are light-sensitive and should always be stored in their original packaging to protect them from light exposure. Store the tablets at room temperature, below 25°C (77°F), in a dry place. Avoid storing the medication in bathrooms or near sinks where humidity levels are high, as moisture can affect the stability of the film-coated tablets.
Keep azathioprine out of sight and reach of children at all times. Accidental ingestion by a child can have serious consequences due to the medication's potent immunosuppressive properties. Do not use the tablets after the expiry date (marked “EXP”) printed on the container and outer packaging. The expiry date refers to the last day of the stated month.
Because azathioprine is a cytotoxic (cell-killing) medication, unused or expired tablets should not be disposed of via household waste or flushed down the toilet. Return any unused medication to your pharmacy, where it will be disposed of safely according to local regulations for cytotoxic waste. This protects the environment and prevents accidental exposure to others.
What Does Azathioprine Contain?
Azathioprine tablets contain the active pharmaceutical ingredient azathioprine at a strength of 25 mg, 50 mg, or 75 mg per film-coated tablet. In addition to the active ingredient, each tablet contains various inactive ingredients (excipients) that serve manufacturing and stability purposes.
Inactive Ingredients (Excipients)
The typical formulation includes the following excipients, although the exact composition may vary slightly between manufacturers:
- Tablet core: Microcrystalline cellulose (E 460), lactose monohydrate, maize starch, povidone K25 (E 1201), croscarmellose sodium (disintegrant), magnesium stearate (E 572), colloidal anhydrous silica
- Film coating: Polyvinyl alcohol, talc (E 553b), macrogol 3350, polysorbate 80 (E 433)
Azathioprine tablets contain lactose monohydrate as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should consult their doctor before taking this medication. The tablets contain less than 1 mmol sodium (23 mg) per film-coated tablet and are therefore considered essentially sodium-free.
Azathioprine film-coated tablets are typically round or oblong, biconvex (curved on both sides), and yellow in color, with a score line (breakline) on one side to facilitate dose splitting when necessary. They are packaged in polyethylene containers with polypropylene screw caps, available in quantities of 50 or 100 tablets. Not all pack sizes may be marketed in all countries.
Azathioprine is classified as a cytotoxic substance. While no special handling precautions are needed when the tablet's film coating is intact, if tablets must be split, avoid direct skin contact with the broken surface and avoid inhaling tablet dust. Wash hands immediately after handling split tablets. Healthcare professionals should follow their institution's guidelines for handling cytotoxic drugs when breaking or crushing tablets.
Frequently Asked Questions About Azathioprine
Azathioprine is an immunosuppressant medication used primarily to prevent organ rejection after kidney, liver, and heart transplantation, and to treat a wide range of autoimmune and inflammatory conditions. These include rheumatoid arthritis, systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, autoimmune hepatitis, severe inflammatory skin diseases, vasculitis, and myasthenia gravis. It works by suppressing the activity of the immune system, reducing the body's tendency to attack its own tissues (in autoimmune diseases) or a transplanted organ.
TPMT (thiopurine methyltransferase) is an enzyme involved in the metabolism of azathioprine. Genetic variation means that about 10% of the population has intermediate TPMT activity and approximately 0.3% have very low or absent activity. Patients with reduced TPMT activity cannot safely metabolize standard doses of azathioprine, leading to accumulation of toxic metabolites and a significantly increased risk of severe, potentially life-threatening bone marrow suppression. TPMT genotyping or phenotyping before treatment allows doctors to tailor the dose to each patient's metabolic capacity, dramatically improving the safety of therapy.
Combining azathioprine with allopurinol is one of the most dangerous drug interactions in clinical medicine. Allopurinol inhibits the enzyme xanthine oxidase, which is one of the major pathways for metabolizing azathioprine. When this pathway is blocked, toxic metabolites of azathioprine accumulate to dangerous levels, causing severe and potentially fatal bone marrow suppression. If the combination is absolutely necessary (for example, in a patient with gout who also needs immunosuppression), the azathioprine dose must be reduced to 25% (one-quarter) of the normal dose, with intensive and frequent blood count monitoring. The same caution applies to other xanthine oxidase inhibitors such as febuxostat.
Azathioprine is a slow-acting medication. For autoimmune and inflammatory conditions, it typically takes 6 to 12 weeks of continuous treatment before the full clinical benefit becomes apparent, and in some cases it may take up to 3 to 4 months. This delayed onset of action is because the drug gradually reduces the population of overactive immune cells over time. It is important not to discontinue treatment prematurely because of a perceived lack of effect during this initial period. For organ transplant recipients, the immunosuppressive effect is needed more immediately, and the drug is started at higher doses at the time of transplantation.
While there is no absolute prohibition on alcohol consumption during azathioprine therapy, caution is strongly advised. Both azathioprine and alcohol are metabolized by the liver, and combining them may increase the risk of liver damage. Alcohol can also worsen dizziness, a known side effect of azathioprine, and may impair your ability to drive safely. If you have an underlying liver condition or if your liver function tests are elevated, you should avoid alcohol entirely. It is best to discuss alcohol consumption with your doctor, who can advise you based on your individual health situation and liver function test results.
While taking azathioprine, you must avoid all live vaccines, as the suppressed immune system may allow the weakened vaccine virus to cause an active infection. Live vaccines include BCG (tuberculosis), yellow fever, varicella (chickenpox), MMR (measles, mumps, rubella), oral polio, and live influenza nasal spray. You should also avoid contact with people who have recently received live vaccines. However, inactivated (killed) vaccines are generally safe to receive, although the immune response may be reduced, meaning the vaccine may be less effective. Examples of inactivated vaccines include the annual flu injection, pneumococcal vaccine, hepatitis B vaccine, and COVID-19 mRNA vaccines. Discuss your vaccination schedule with your doctor.
References
This article is based on the following peer-reviewed sources and international guidelines:
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Editorial Team
This article has been written and reviewed by our medical editorial team, which includes licensed specialist physicians in immunology, clinical pharmacology, rheumatology, and gastroenterology. All content follows the GRADE evidence framework and adheres to international medical guidelines from the EMA, FDA, WHO, BSR, ACR, ECCO, and NICE.
iMedic Medical Editorial Team — specialists in immunology, clinical pharmacology, and rheumatology with extensive experience in immunosuppressive therapy, autoimmune diseases, and transplant medicine.
iMedic Medical Review Board — independent panel of physicians who review all content according to international guidelines (EMA SmPC, FDA prescribing information, BNF, BSR/ACR/ECCO guidelines).
Evidence standard: All medical claims in this article are based on Evidence Level 1A — the highest level of evidence, derived from systematic reviews and meta-analyses of randomized controlled trials, international guidelines from recognized medical organizations, and approved drug labeling from regulatory agencies. This article has no commercial funding and is free from pharmaceutical company sponsorship or advertising.