11 Off-Label Uses for Azathioprine

Azathioprine is an immunosuppressant medication that is available in generic form. It is also sold under the brand names Imuran and Azasan. Azathioprine is prescribed to prevent transplant rejection in renal transplant patients. It is used to treat rheumatoid arthritis (RA). Besides oral tablets, azathioprine is also available as an injectable medication. In addition to its role in the prevention of kidney transplant rejection and treatment of active RA, azathioprine is used off-label to treat several other medical conditions. Please continue reading to learn more about off-label azathioprine use.

How does azathioprine prevent transplant rejection?

People with kidney disease (renal insufficiency or renal failure) may need a kidney transplant when their kidneys are not able to remove waste and fluid from the body. Azathioprine is an FDA-approved medication to prevent rejection in organ transplant patients after receiving a transplanted kidney from a live or deceased donor. After an organ transplant, the immune system recognizes the “new” transplanted kidney as a foreign object and mounts an attack against this transplanted organ. Azathioprine works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

Is azathioprine used for rheumatoid arthritis?

Yes, oral azathioprine is used to treat severe rheumatoid arthritis (RA) that has not responded to other treatments. RA is an autoimmune disease in which the immune system mistakenly attacks the body’s own joints, causing pain, swelling, and loss of mobility. Azathioprine works by decreasing the activity of the immune system so that it does not attack the joints.

What is azathioprine indicated for?

The dose of azathioprine to prevent rejection in organ transplant patients depends on the individual patient. The initial dose is usually 3 to 5 mg/kilogram (kg) per day starting at the time of the transplant or up to three days prior to the surgery. A maintenance dose is usually 1 to 3 mg/kg per day.

For active rheumatoid arthritis, azathioprine is given daily at an initial dose of approximately 1 mg/kg per day, taken as a single dose or in two divided doses. The dose can be increased by 0.5 mg/kg after 6-8 weeks and then at 4-week intervals later, if needed, up to a maximum dose of 2.5 mg/kg per day. If the treatment with azathioprine does not show any improvement after 12 weeks, azathioprine is deemed to be ineffective.

What are other uses of azathioprine?

The U.S. Food and Drug Administration (FDA) approves medications to treat specific conditions, including the prevention of kidney transplant rejection and the treatment of active rheumatoid arthritis (RA). However, several medications that are FDA-approved for specific diagnoses are sometimes prescribed by doctors to treat different diagnoses — this is called “off-label” use. Off-label use of azathioprine means prescribing azathioprine for conditions other than rheumatoid arthritis or organ rejection. The use of azathioprine in dermatology to treat psoriasis and severe atopic dermatitis are a few examples. Historically, the traditional systemic agents used to treat psoriasis include methotrexate, cyclosporine, and oral retinoids such as acitretin. However, azathioprine has been used off-label in combination therapy in patients who have not responded well to the traditional systemic agents.

Some of the conditions in which a healthcare provider might use off-label azathioprine include:

Multiple sclerosis
Inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis
Systemic lupus erythematosus (SLe)
Myasthenia gravis
Autoimmune hepatitis
Neuromyelitis optica spectrum disorder
Chronic actinic dermatitis
Psoriatic arthritis
Skin disorders such as atopic dermatitis, erythema multiforme, and lichen planus
Prevention of lung transplant rejection
Prevention of liver transplant rejection

What are the adverse effects of azathioprine?

Possible side effects of azathioprine include gastrointestinal symptoms such as abdominal pain, nausea, vomiting, and diarrhea. More serious side effects can occur in a small number of people. You should seek immediate medical attention if you develop a skin rash, fever, muscle pain, or weakness. Call your doctor without delay in case of any unusual adverse events.

Is there an increased risk of skin cancer with azathioprine?

Azathioprine therapy can increase the risk of developing certain types of cancer, including skin cancer and lymphoma. Kidney transplant patients are at an increased risk of developing cancer even if they are not on azathioprine.

Give your doctor a complete list of all the medicines you take. Tell your doctor if you have a history of cancer or if you have ever taken cancer medications such as cyclophosphamide (Cytoxan), chlorambucil (Leukeran), or melphalan (Alkeran).

To lower your risk of skin cancer, take precautions such as avoiding prolonged or unnecessary sun exposure. Wear protective clothing, sunglasses, and sunscreen.

Tell your doctor immediately if you notice any lumps or masses in your body or any skin changes.

What are the other risks of taking azathioprine?

Azathioprine can be harmful to an unborn baby. If you are a woman of childbearing age, your doctor will ask you to take a pregnancy test before starting this medicine. They will also ask you and your partner to use a reliable birth control method to prevent pregnancy while on azathioprine.

There are reports of teenagers and young adult males who developed hepatosplenic T-cell lymphoma (HSTCL) after taking azathioprine alone or in combination with a TNF blocker (tumor necrosis factor blocker) to treat Crohn's disease or ulcerative colitis. This serious cancer is fatal if left undetected, and azathioprine carries a “black box” warning for this risk. Tell your doctor immediately if you develop fever, stomach pain, night sweats, easy bruising or bleeding, or unexplained weight loss while on this medication.

Azathioprine can lead to a decrease in the number of blood cells in the bone marrow, which can lead to serious and potentially life-threatening infections. The risk of this happening is highest in people with an inherited risk factor. Your healthcare provider may order a test to check if you have this risk factor. Certain medications can also increase the risk of a fall in blood cells. Give your doctor a complete list of all your medications before starting treatment with azathioprine. Your doctor will order blood tests before, during, and after azathioprine treatment to keep an eye on your blood counts.

Whether azathioprine is used to prevent kidney transplant rejection or to treat active rheumatoid arthritis, your healthcare provider still discontinues this medication if lab tests reveal toxicity.

References: