What to Know About Azathioprine

Azathioprine is a prescription immunosuppressant medication used to treat rheumatoid arthritis (RA) and to prevent organ rejection after a kidney transplant. This medication is taken by mouth, and it is available in an injectable form as well. Azathioprine is a generic formulation, with the brand names Imuran and Azasan available.

This medication is commonly used off-label to treat some inflammatory conditions, including ulcerative colitis and systemic lupus erythematosus. It is often well tolerated, but it can cause serious side effects, such as different types of anemia and certain types of cancer.

Uses 

Azathioprine prevents the inflammatory process that leads to immune diseases and immune system rejection of a kidney transplant. It works by inhibiting immune cell proliferation as it stops cell division by interfering with DNA replication.

Renal (kidney) transplant: After a kidney transplant, the body’s immune system can reject the donor organ. Organ rejection after a kidney transplant can lead to fever, hypertension (high blood pressure), heart failure, and loss of consciousness, and will eventually be fatal.

Azathioprine suppresses immune activity to prevent rejection of the transplanted kidney. It has been shown to improve survival after renal transplant.

Rheumatoid arthritis (RA): RA is a chronic inflammatory autoimmune condition that affects the joints and other tissues of the body, causing pain, swelling, and other systemic effects. Azathioprine may be used to reduce the signs and symptoms of RA.

Azathioprine should not be used with other disease-modifying anti-rheumatic drugs (DMARDs) that are used to treat RA, but it can be used with aspirin, nonsteroidal anti-inflammatory drugs, and steroids.

Off-Label Uses

Azathioprine is used off-label for the treatment of several conditions.

Common off-label uses:

• Systemic lupus erythematosus (SLE)
• Ulcerative colitis
• Skin conditions, including intractable pruritus, atopic dermatitis, and psoriasis

Azathioprine can be used for short-term or long-term management of these conditions. The same treatment contraindications and recommendations for blood test monitoring apply when used off-label as when used for its approved indications.

Before Taking 

You should not take azathioprine if you have had an adverse reaction to this drug in the past. It is not recommended during pregnancy or for women who are breastfeeding.

Azathioprine has a "black box" warning—the strongest warning on a drug label—saying that the drug may increase the risk of certain types of cancer, including skin cancer and T cell lymphoma in people who have Crohn's disease or ulcerative colitis.

For skin cancer, your healthcare provider may recommend that you avoid exposure to ultraviolet light and use sun protection (such as covering your skin with clothing and applying sunscreen) to prevent excessive exposure. Your practitioner may also suggest annual skin checks with your dermatologist.

Additionally, if you have previously taken alkylating agents, including cyclophosphamide, chlorambucil, or melphalan for treatment of your RA, the manufacturer warns of an increased risk of cancer with the use of azathioprine.

Precautions and Contraindications

You will need blood tests to monitor for adverse effects before starting azathioprine and during use.

These include:

• Thiopurine S-methyltransferase (TPMT) testing is suggested before starting the medication. A deficiency of this enzyme would impair the metabolism of azathioprine and increase the risk of toxicity.
• A pregnancy test may be done before starting treatment.
• Testing for hepatitis B and C is often done before beginning the medication.
• Tuberculosis testing with a PPD skin test may be necessary before starting.
• Complete blood count (CBC) and liver function tests (LFTs) are monitored weekly or every other week for the first few months of treatment, then every month or as recommended by your healthcare provider.

Other Immunosuppressants

Some immunosuppressants, including methotrexate, cyclosporine, and mercaptopurine, are used for similar indications and off-label uses as azathioprine. These medications can interact with each other and exacerbate the potential for adverse effects.

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Dosage

Imuran is available in 50 milligram (mg) scored tablets. The manufacturer provides general guidelines for the dose of azathioprine. Your dose may vary based on your healthcare provider's assessment of your needs, and you will require careful monitoring while you are taking this medication.

• Renal transplant: The initial dose is usually 3 to 5 mg/kilogram (kg) of body weight per day on the day of your transplant procedure or up to three days before the surgery. A maintenance dose may be reduced to 1 to 3 mg/kg per day. This medication may need to be discontinued, even at the risk of organ rejection, if toxicity is detected by blood tests.
• RA: The recommended dose is 1.0 mg/kg per day, which can be taken at once or divided into two doses per day. The dose may be increased according to your healthcare provider's instructions up to 2.5 mg/kg per day. If you have not had improvement after 12 weeks, this medication is considered to be ineffective for treating your RA.

For intravenous use (IV, in a vein), this medication is administered over five minutes, at a maximum concentration of 5 mg/milliliter (ml).

Modifications

For people who have kidney disease, the dose may need to be reduced to avoid toxicity.

How to Take and Store 

Azathioprine should be taken after meals to prevent gastrointestinal symptoms. If you miss your dose, you should take it as soon as you are able. However, do not take extra doses if it is almost time for your next dose.

Imuran should be stored at 68 to 77 degrees Fahrenheit (20 to 25 degrees Celsius) and kept dry and away from sunlight.

Side Effects 

You might not have any adverse effects from taking azathioprine, but it can cause several side effects. Many of the common side effects are not dangerous, and sometimes they can cause varying degrees of discomfort.

This medication can also cause severe side effects that may have a serious impact on your health and may even be life-threatening. The severe side effects might not cause noticeable symptoms initially and may be detected with surveillance testing, such as a complete blood count (CBC).

Common

The common side effects of azathioprine might be tolerable for you, or they can cause substantial discomfort. Be sure to let your healthcare provider know about any side effects you are experiencing. These symptoms could be a result of taking azathioprine, or they could be caused by something else.

Common side effects include:

• Nausea
• Fever
• Fatigue
• Muscle aches
• Rash
• Diarrhea

Your symptoms might resolve with time. And your healthcare provider might consider reducing your dose of azathioprine to a level that is therapeutic without causing side effects.

Severe

The serious side effects can cause long-term health issues and may necessitate stopping your medication.

Severe side effects include:

• Liver damage
• Infections
• Pancreatitis
• Anemia (low red blood cell function)
• Macrocytic anemia (enlarged red blood cells)
• Leukopenia (low white blood cells)
• JC virus, which can cause progressive multifocal leukoencephalopathy (PML), a severe brain condition

Warnings and Interactions

Azathioprine can interact with several other medications, resulting in adverse effects.

Medication interactions include:

• Allopurinol
• Cyclophosphamide
• Aminosalicylate derivatives (sulphasalazine, mesalazine, or olsalazine): Should be used with caution
• Coumadin (warfarin): May have reduced action when taken with azathioprine
• Angiotensin-converting enzyme inhibitors: Can cause anemia and leukopenia when used with azathioprine