Azathioprine

Azathioprine

Azathioprine (brand names Azasan™, Imuran™) is an immunosuppressant medication used to treat various autoimmune diseases. It works by suppressing the immune system, which helps to slow down the body's attack on its own tissues and organs and reduce inflammation [1][2]. Azathioprine is a prodrug that converts to 6-mercaptopurine (6-MP), which then interferes with nucleotide synthesis, thereby inhibiting the proliferation of lymphocytes and decreasing cellular proliferation [3][4].

Conditions Treated 

Azathioprine is used for a range of autoimmune conditions, including:

• Autoimmune hepatitis

• Polymyositis (inflammatory muscle disease)

• Connective tissue diseases, lupus nephritis, inflammatory muscle disease, inflammatory eye disease (e.g., Behçet’s disease), psoriatic arthritis, reactive arthritis, and various forms of vasculitis.

• Refractory cases of skin (cutaneous) lupus like discoid and subacute cutaneous lupus

• Systemic sclerosis (Scleroderma) and overlap syndromes, particularly with interstitial lung disease or joint involvement.

• Crohn's disease (inflammatory bowel disease)

Dosage and Administration 

Azathioprine is available as a prescription pill. Your healthcare provider will determine your specific dosage based on your medical condition and history, and it may be adjusted over time. It can take about 8 to 12 weeks to see the benefits, and sometimes longer. For adults, the dose is typically started with 50 to 100 mg orally once daily, which may increase up to 150 mg/day, with the lowest effective dose used for maintenance.

Important Considerations Before Starting 

• Before beginning azathioprine, inform your healthcare provider if you:

• Take other medications, including prescription, over-the-counter drugs, dietary or herbal supplements, and vitamins. Specifically mention if you are taking allopurinol (Zyloprim™) or anticoagulant/antiplatelet medications like warfarin (Coumadin™, Jantoven™) or Plavix™.  Concomitant use of allopurinol (often used for gout) can significantly increase azathioprine toxicity, requiring a dose reduction of azathioprine to approximately 1/3 to 1/4 of the usual dose.

• Have allergies to any medicines.

• Have medical problems such as kidney, liver, or lung disease.

• You may undergo a blood test called TPMT (thiopurine methyltransferase) before starting azathioprine to assess how your body metabolizes the drug and identify potential risks of severe toxicity, such as bone marrow suppression (low blood counts). Patients with low or absent TPMT activity are at risk for severe drug-induced myelotoxicity (severe low blood counts).

Potential Side Effects 

Azathioprine can cause various side effects, some common and some serious:

Common side effects include:

Fever (when first starting), nausea, upset stomach, vomiting, decreased appetite, diarrhea, rash, headaches, fatigue, and mild hair loss [1][19][20]. Oral ulcers can occur, which may be prevented by daily folic acid and taking the medication with food [20].

Serious side effects include:

• Low blood counts (leukopenia, anemia, thrombocytopenia), making it harder to fight infection.

• Pancreatitis (inflammation of the pancreas).

• Liver toxicity (elevated liver enzymes, unusual bleeding, bruising, weakness, yellowing of skin or eyes, dark urine).

• Increased risk of infection.

• Increased risk of certain cancers, particularly skin cancer and lymphoma. Patients should limit sun exposure and use sunscreen.

• Sensitiviey to sunlight.

• Hypersensitivity reactions [20].

• Monitoring Regular follow-up appointments and blood tests are crucial while taking azathioprine to monitor for side effects and assess its effectiveness.

• Blood tests will check complete blood counts (including platelet counts), liver function (AST, ALT, bilirubin), and kidney function .

• Initially, blood counts should be monitored every 2 weeks for the first 2 months and then every 4-8 weeks thereafter, or more frequently if dosage changes occur.

• Once on a stable dose, blood counts and liver function tests are typically monitored every 2-3 months [15].

Precautions and Warnings

Alcohol

Stop or limit alcohol use while taking azathioprine, as drinking alcohol increases the risk of liver damage.

Other Medications

Be cautious with other medications, including over-the-counter drugs, vitamins, supplements, probiotics, and herbal products, as some can change how immunosuppressants work.

Vaccinations

Stay up-to-date with vaccinations. Get a flu shot every year. Discuss live virus vaccinations (e.g., shingles vaccine) with your healthcare provider before getting them, as they may be contraindicated.

Malignancy Risk

There is an increased risk of developing certain cancers, particularly skin cancer and lymphoma, with azathioprine use. Patients should be informed of this risk and take precautions like limiting sun exposure and using sunscreen.

Bone Marrow Suppression

This is a common, dose-related side effect that can lead to leukopenia, anemia, and thrombocytopenia.

Follow-up Care 

It is essential to attend all your follow-up appointments and testing. These appointments allow your care team to monitor your progress, check for side effects, and adjust your treatment as needed. If you have questions about any medications, talk with your healthcare provider.

This information is not a substitute for professional medical advice. Always discuss your specific situation with your healthcare provider.