What tests should be ordered prior to initiating azathioprine therapy in a patient with Crohn’s disease?

Pre-Azathioprine Testing Requirements for Crohn's Disease Patients

Prior to initiating azathioprine therapy in a patient with Crohn's disease, TPMT activity testing, complete blood count, liver function tests, and renal function tests must be performed. 1

Essential Baseline Tests

TPMT Testing

• TPMT (thiopurine methyltransferase) activity should be checked in all patients prior to receiving azathioprine (Strength of recommendation A; level of evidence 1+) 1
• TPMT genotyping is only required for patients with indeterminate phenotype (borderline values) or those who have had a recent blood transfusion 1
• Accurate phenotyping (red blood cell TPMT activity) results are not possible in patients who have received blood transfusions within the previous 3 months 2

Complete Blood Count

• Full blood count (FBC) with differential white cell count should be obtained as baseline 1
• This is critical as myelosuppression is a potentially serious complication of azathioprine therapy 3
• Patients with pre-existing cytopenias may require dose adjustments or consideration of alternative therapy 1

Liver Function Tests

• Liver blood tests including transaminases (alanine aminotransferase or aspartate aminotransferase) must be performed 1
• Azathioprine can cause hepatotoxicity, and pre-existing liver disease may require dose adjustments 1
• Severe hepatic impairment is a contraindication to azathioprine use 1

Renal Function Tests

• Baseline renal function should be assessed 1
• Patients with renal impairment may require dose reduction, with doses at the lower end of the normal range recommended 1

Additional Considerations

Screening for Infections

• Consider screening for severe infections, as these are contraindications to azathioprine therapy 1
• Viral hepatitis screening may be prudent as immunosuppression can lead to reactivation of hepatitis B virus 1

Pregnancy Testing

• Pregnancy testing should be considered in women of childbearing age, as pregnancy is a relative contraindication 1
• Women should be advised to avoid pregnancy during treatment with azathioprine 1

Drug Interaction Assessment

• Review current medications for potential interactions 2
• Special attention to:
  • Allopurinol (requires azathioprine dose reduction to 1/3-1/4 of usual dose) 2
  • Aminosalicylates (may inhibit TPMT enzyme) 2
  • ACE inhibitors (may induce anemia and severe leukopenia) 2
  • Warfarin (azathioprine may inhibit anticoagulant effect) 2

Monitoring Protocol After Initiation

Once azathioprine therapy is initiated, regular monitoring is essential:

• Complete blood counts should be performed weekly during the first month, twice monthly for the second and third months, then monthly thereafter 2
• Liver function tests should be monitored regularly, with similar frequency to blood counts 1
• Dose adjustments may be needed based on monitoring results and development of side effects 1

Common Pitfalls to Avoid

1. Failure to check TPMT activity: This can lead to severe myelosuppression in patients with TPMT deficiency 1
2. Inadequate monitoring: Myelotoxicity can develop at any time during treatment (from 2 weeks to 11 years) 3
3. Missing drug interactions: Particularly with allopurinol, which requires significant dose reduction 2
4. Overlooking hepatotoxicity risk: Regular liver function monitoring is essential as hepatotoxicity can develop without symptoms 1
5. Ignoring renal function: Doses should be adjusted in patients with renal impairment 1

By following this comprehensive pre-treatment testing protocol, clinicians can minimize the risk of serious adverse events and optimize the therapeutic benefit of azathioprine in patients with Crohn's disease.