What lab workup is recommended for patients starting and continuing Imuran (azathioprine)?

Laboratory Workup for Starting and Continuing Azathioprine (Imuran)

For patients starting azathioprine therapy, obtaining CBC counts and renal/hepatic profiles every 1 to 3 months is recommended, with more frequent monitoring initially. 1

Pre-Treatment Laboratory Testing

Essential Pre-Treatment Tests

• TPMT testing (genotype or enzyme activity): Recommended before starting azathioprine to guide dosing 1, 2

  • Patients with normal TPMT: standard dosing
  • Patients with intermediate TPMT activity: 50% dose reduction
  • Patients with low/absent TPMT activity: azathioprine is contraindicated 1

• Complete Blood Count (CBC) with differential 1, 2

• Liver Function Tests (LFTs) 1, 2

• Renal Function Tests 1, 2

Additional Pre-Treatment Screening

• Hepatitis B and C screening: All candidates for immunosuppressive treatment should be screened for HBsAg and anti-HBc antibodies prior to treatment 1
• HIV screening: Consider in patients with risk factors 1
• Varicella zoster virus (VZV) serology: For patients with uncertain history of chickenpox 1
• Pregnancy test: For women of childbearing potential 2

Monitoring Schedule During Treatment

Initial Monitoring (First Month)

• Weekly CBC and LFTs for the first 4 weeks or until maintenance dose is achieved 1, 2

Continued Monitoring

• CBC and LFTs every 1-3 months for the duration of therapy 1
• More frequent monitoring (weekly) following any dose increase 1
• More frequent monitoring in patients with:
  • Hepatic or renal impairment
  • Elderly patients
  • Patients on high doses of azathioprine 1

Special Monitoring Considerations

Drug Interactions Requiring Dose Adjustment

• Allopurinol: Reduce azathioprine dose to approximately 1/3 to 1/4 the usual dose 1, 2
• Aminosalicylates (e.g., sulfasalazine): Use with caution as they may inhibit TPMT enzyme 2
• ACE inhibitors: Monitor closely as they may induce anemia and severe leukopenia 2
• Ribavirin: Increases risk of myelotoxicity; requires more frequent monitoring 2

Monitoring for Toxicity

• Bone marrow suppression: Most common serious adverse effect

  • Leucopenia (WBC < 3.0 × 10^9/L) occurs in approximately 3.8% of patients 3
  • Can develop at any time during treatment (range: 2 weeks to 11 years) 3
  • Consider dose reduction if lymphocyte count falls below 0.5 × 10^9/L 1

• Hepatotoxicity: Monitor LFTs regularly

  • Reduce dose if hepatic toxicity occurs 1

When to Discontinue or Adjust Therapy

• Severe neutropenia: WBC < 2.0 × 10^9/L 3
• Thrombocytopenia: Platelet count < 100,000 × 10^6/L 3
• Persistent elevation of liver enzymes above baseline 1
• Pancreatitis: Consider in patients with acute abdominal pain/vomiting 1

Important Caveats

• Despite TPMT testing, regular blood monitoring remains essential for all patients on azathioprine, as toxicity can occur regardless of TPMT status 1, 2
• Myelosuppression can occur suddenly or develop gradually over several months 3
• Instruct patients to report immediately any signs of infection, unexpected bruising/bleeding, or jaundice 1, 2
• If no therapeutic response is observed within 3 months, consider withdrawing treatment 1

By following this structured monitoring protocol, clinicians can maximize the safety and efficacy of azathioprine therapy while minimizing the risk of serious adverse events.