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Azathioprine

Comprehensive Guide to Azathioprine: Uses, Dosage, Side Effects, and More

What is Azathioprine?

Azathioprine is an immunosuppressive medication used to prevent organ rejection in transplant patients and to manage autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, and ulcerative colitis. As a prodrug, this drug is metabolized into 6-mercaptopurine (6-MP), which inhibits DNA synthesis and suppresses immune responses. Marketed under the brand name Imuran and as generics, the medication is available as tablets or an intravenous formulation. Azathioprine’s benefits include its role in long-term disease control, but it requires careful monitoring for side effects like leukopenia or hepatotoxicity.

Overview

Generic Name: Azathioprine

Brand Name: Imuran, generics

Drug Group: Immunosuppressant

Commonly Used For

  • Prevent rejection in renal, hepatic, and cardiac transplant recipients.
  • Treat rheumatoid arthritis in patients unresponsive to conventional therapies.
  • Manage inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis).
  • Off-label uses include systemic lupus erythematosus (SLE), myasthenia gravis, or autoimmune hepatitis under specialist guidance.

Key Characteristics

Form: Tablets (25 mg, 50 mg, 100 mg) and intravenous powder for injection (100 mg/vial).

A box of Imuran (Azathioprine) 50 mg tablets by Aspen, showing both English and Arabic text, indicating a quantity of 100 tablets, used as an immunosuppressant medication.
Imuran (Azathioprine) 50 mg tablets are an immunosuppressant medication, commonly prescribed to prevent organ rejection after transplant and to treat various autoimmune conditions.

Mechanism: Metabolized to 6-MP, inhibiting purine synthesis and T-cell proliferation.

Approval: FDA-approved (1968 for Imuran) and EMA-approved for transplantation and autoimmune conditions.

Indications and Uses of Azathioprine

Azathioprine is indicated for:

Transplant Rejection Prevention: Reduces immune response in kidney, liver, and heart transplant patients, often with corticosteroids.

Rheumatoid Arthritis: Manages severe cases unresponsive to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).

Inflammatory Bowel Disease (IBD): Controls Crohn’s disease and ulcerative colitis flares.

Off-Label Uses: Treats SLE, autoimmune hepatitis, pemphigus vulgaris, or dermatomyositis under specialist oversight.

Note: This drug requires combination therapy and regular monitoring due to its immunosuppressive effects.

Dosage of Azathioprine

Important Note: The dosage of this immunosuppressant must be prescribed by a healthcare provider. Dosing is individualized based on condition, weight, and thiopurine methyltransferase (TPMT) enzyme activity.

Dosage for Adults

Transplant Rejection Prevention:

  • Initial: 3–5 mg/kg once daily, starting within 24 hours post-transplant.
  • Maintenance: 1–3 mg/kg once daily, adjusted with corticosteroids.

Rheumatoid Arthritis:

  • Initial: 1 mg/kg once daily for 6–8 weeks.
  • Maintenance: 2–3 mg/kg once daily, maximum 2.5 mg/kg/day.

Inflammatory Bowel Disease:

  • Initial: 1–2 mg/kg once daily.
  • Maintenance: 1.5–2.5 mg/kg once daily, titrated based on response.

Dosage for Children

Transplant Rejection Prevention:

  • Initial: 3–5 mg/kg once daily.
  • Maintenance: 1–3 mg/kg once daily, adjusted for weight and tolerance.

IBD or Autoimmune Conditions: 1–2 mg/kg once daily, with a maximum of 2.5 mg/kg/day.

Dosage for Pregnant Women

Pregnancy Category D: Potential fetal risk; use only if benefits outweigh risks. Consult a specialist or obstetrician, and monitor fetal development.

Dosage Adjustments

Renal Impairment:

  • CrCl 10–50 mL/min: Reduce by 50%.
  • CrCl <10 mL/min: Avoid or use with extreme caution.

Hepatic Impairment: Reduce dose by 50% in moderate to severe cases; monitor liver function.

TPMT Deficiency: Reduce dose significantly (e.g., 10–20% of standard) or avoid use due to increased toxicity risk.

Elderly: Start with lower doses (e.g., 1 mg/kg/day); adjust cautiously.

Additional Considerations

  • Take this active ingredient with or without food at the same time daily.
  • Monitor complete blood counts (CBC) and liver function tests weekly during initial therapy, then monthly.

How to Use Azathioprine

Administration: Swallow tablets whole with water, with or without food; reconstitute IV form with sterile water as directed.

Timing: Take once daily, preferably at the same time, or as split doses if prescribed.

Monitoring: Watch for signs of infection, bruising, or jaundice.

Additional Tips:

  • Avoid crushing tablets; use liquid formulations if swallowing is difficult.
  • Report fever, sore throat, or unusual fatigue immediately.

Contraindications for Azathioprine

  • Patients with hypersensitivity to Azathioprine or 6-mercaptopurine.
  • Patients with severe bone marrow suppression or pancytopenia.
  • Pregnant women unless benefits outweigh risks, due to teratogenic potential.

Warnings & Precautions for Azathioprine

General Warnings

Bone Marrow Suppression: Risk of leukopenia, thrombocytopenia, or anemia; monitor CBC regularly.

Hepatotoxicity: Elevated liver enzymes or jaundice; perform liver function tests.

Infections: Increased susceptibility to bacterial, viral, or fungal infections; screen for active infections.

Malignancy Risk: Long-term use linked to lymphoma or skin cancer; assess risk-benefit ratio.

Allopurinol Interaction: Enhances toxicity; reduce Azathioprine dose to 25–33% if co-administered.

Use in Specific Populations

Pregnancy: Category D; fetal harm reported; use only if essential with monitoring.

Breastfeeding: Excreted in breast milk; avoid during treatment.

Elderly: Higher risk of myelosuppression; monitor closely.

Children: Approved for specific indications; monitor growth and development.

Renal/Hepatic Impairment: Adjust dose in severe cases; avoid if critical.

Additional Precautions

  • Inform your doctor about liver disease, prior cancers, or infection history before starting this medication.
  • Avoid live vaccines during treatment due to immunosuppression.

Overdose and Management of Azathioprine

Overdose Symptoms

  • Severe nausea, vomiting, or diarrhea.
  • Bone marrow suppression (e.g., leukopenia, thrombocytopenia).
  • Hepatic dysfunction or jaundice.

Immediate Actions

Contact Emergency Services: Call 911 or seek immediate medical help.

Supportive Care: Administer antiemetics, monitor CBC, and provide supportive therapy.

Monitor: Check liver function, blood counts, and renal parameters for 1–2 weeks.

Additional Notes

  • Overdose risk increases with TPMT deficiency; store securely.
  • Report persistent symptoms promptly.

Side Effects of Azathioprine

Common Side Effects

  • Nausea (15–20%)
  • Fatigue (10–15%)
  • Loss of appetite (8–12%)
  • Mild rash (5–10%)

These effects may decrease with dose adjustment.

Serious Side Effects

Hematologic: Unusual bruising, bleeding, or persistent fever (infection risk).

Hepatic: Yellowing of skin/eyes or severe abdominal pain.

Infections: Fever, chills, or signs of sepsis.

Neoplastic: New lumps or skin changes (potential malignancy).

Additional Notes

  • Regular monitoring of CBC, liver function, and infection signs is critical.
  • Report any unusual symptoms immediately.

Drug Interactions with Azathioprine

This active ingredient may interact with:

Allopurinol: Increases 6-MP levels; reduce Azathioprine dose to 25–33%.

Warfarin: Reduces anticoagulant effect; monitor INR.

ACE Inhibitors: Enhanced myelosuppression; use cautiously.

Sulfasalazine: Additive bone marrow suppression; avoid combination.

Action: Provide your healthcare provider with a complete list of medications and supplements.

Patient Education or Lifestyle

Medication Adherence: Take this immunosuppressant daily as prescribed to manage autoimmune or transplant conditions.

Monitoring: Report infections, bruising, or liver changes immediately.

Lifestyle: Avoid sun exposure and use sunscreen to reduce skin cancer risk.

Diet: No specific restrictions; take with food if nausea occurs.

Emergency Awareness: Know signs of severe infection or liver failure; seek care if present.

Follow-Up: Schedule regular blood tests (CBC, liver function) and specialist visits every 1–3 months.

Pharmacokinetics

Absorption: Well-absorbed orally; peak plasma concentration at 1–2 hours.

Distribution: Volume of distribution ~0.6–0.8 L/kg; 30% protein-bound.

Metabolism: Hepatic conversion to 6-MP via glutathione-S-transferase, further metabolized by TPMT and xanthine oxidase.

Excretion: Primarily urinary (as metabolites, <1% unchanged); fecal excretion minimal.

Half-Life: 3–5 hours (Azathioprine); 0.5–1 hour (6-MP), with active metabolites persisting longer.

Pharmacodynamics

This drug exerts its effects by:

  • Converting to 6-MP, which inhibits purine synthesis via IMPDH and HGPRT enzymes.
  • Suppressing T-cell and B-cell proliferation, reducing immune-mediated damage.
  • Offering efficacy in autoimmune diseases and transplant rejection prevention.
  • Requiring TPMT genotyping for personalized dosing to avoid toxicity.

Storage of Azathioprine

Temperature: Store at 15–25°C (59–77°F); protect from moisture.

Protection: Keep in original container, away from light and humidity.

Safety: Store out of reach of children.

Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.

Frequently Asked Questions (FAQs)

Q: What does Azathioprine treat?
A: This medication treats transplant rejection, rheumatoid arthritis, and IBD.

Q: Can this active ingredient cause infections?
A: Yes, increased infection risk is a concern; report fever immediately.

Q: Is Azathioprine safe for children?
A: Approved for specific uses; consult a pediatric specialist.

Q: How is this drug taken?
A: Once daily as a tablet or IV, with or without food.

Q: How long is Azathioprine treatment?
A: Long-term for chronic conditions, with periodic reassessment.

Regulatory Information

This medication is approved by:

U.S. Food and Drug Administration (FDA): Approved in 1968 (Imuran) for transplant and autoimmune diseases.

European Medicines Agency (EMA): Approved for similar indications.

Other Agencies: Approved globally for equivalent uses; consult local guidelines.

References

  1. U.S. Food and Drug Administration (FDA). (2023). Imuran (Azathioprine) Prescribing Information.
    • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
  2. European Medicines Agency (EMA). (2023). Azathioprine Summary of Product Characteristics.
    • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
  3. National Institutes of Health (NIH). (2023). Azathioprine: MedlinePlus Drug Information.
    • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
  4. World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Azathioprine.
    • WHO’s inclusion of Azathioprine for immunosuppression.
  5. Annals of the Rheumatic Diseases. (2020). Azathioprine in Rheumatoid Arthritis and IBD.
    • Peer-reviewed article on Azathioprine efficacy (note: access may require a subscription).
Disclaimer: This article provides general information about Azathioprine for educational purposes only and is not a substitute for professional medical advice. Always consult a qualified healthcare provider, such as a rheumatologist, gastroenterologist, or primary care physician, before using this drug or making any medical decisions. Improper use of this active ingredient can lead to serious health risks, including bone marrow suppression or increased infection susceptibility.

Dr. Andrew Parker is a board-certified internal medicine physician with over 10 years of clinical experience. He earned his medical degree from the University of California, San Francisco (UCSF), and has worked at leading hospitals including St. Mary’s Medical Center. Dr. Parker specializes in patient education and digital health communication. He now focuses on creating clear, accessible, and evidence-based medical content for the public.

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