What blood work is required before starting allopurinol (xanthine oxidase inhibitor) therapy?

Blood Work Required Before Starting Allopurinol

Before initiating allopurinol therapy, baseline renal function tests including serum creatinine and estimated glomerular filtration rate (eGFR) are essential, along with serum uric acid levels and liver function tests. 1

Essential Laboratory Tests

• Renal Function Tests:

  • Serum creatinine
  • Estimated glomerular filtration rate (eGFR)
  • Creatinine clearance

• Uric Acid Levels:

  • Baseline serum uric acid level

• Liver Function Tests:

  • ALT/AST
  • Bilirubin
  • Alkaline phosphatase

Rationale for Testing

Renal Function Assessment

Renal function testing is critical before starting allopurinol for several reasons:

1. Dose Adjustment: Allopurinol and its active metabolite oxipurinol are primarily excreted by the kidneys. The American College of Rheumatology recommends a starting dose of ≤100 mg/day in patients with renal impairment, with gradual titration until target uric acid level is reached 2, 1.

2. Risk Management: Patients with renal impairment have increased risk of allopurinol hypersensitivity syndrome (AHS), a potentially fatal adverse reaction. Starting at a dose of 1.5 mg per unit of estimated GFR may be associated with reduced risk of AHS 3.

3. Monitoring Requirements: Patients with renal insufficiency require more careful monitoring during allopurinol therapy, as oxipurinol accumulation can occur 4.

Uric Acid Levels

Baseline uric acid levels are necessary to:

1. Establish Treatment Goals: The European League Against Rheumatism recommends targeting serum uric acid levels <6 mg/dL 1.

2. Assess Severity: Hyperuricemia severity (particularly levels >9 mg/dL) may influence treatment approach 1.

3. Monitor Efficacy: Baseline values are needed to evaluate treatment response.

Liver Function Tests

Liver function tests are important because:

1. Safety Monitoring: Allopurinol can cause hepatotoxicity as part of AHS 2.

2. Risk Assessment: Abnormal liver function may increase risk of adverse reactions.

Special Considerations

Genetic Testing

• HLA-B*5801 Testing: Consider HLA-B*5801 testing in selected high-risk populations before initiating allopurinol 2:
  • Korean patients with stage 3 or worse CKD (allele frequency ~12%)
  • Han Chinese or Thai patients regardless of renal function (allele frequency ~6-8%)

Additional Testing Based on Clinical Context

• G6PD Deficiency Screening: In patients of African American, Mediterranean, or Southeast Asian descent, especially if allopurinol is being used for tumor lysis syndrome management 2.

• Complete Blood Count: To establish baseline values before treatment.

Monitoring After Initiation

• Monitor serum uric acid levels every 2-4 weeks during dose titration 1.
• Regularly check renal function, particularly in patients with pre-existing renal impairment.
• Monitor for signs of hypersensitivity reactions, including rash, pruritis, and eosinophilia 2.

Common Pitfalls to Avoid

1. Starting with too high a dose: Beginning with doses >100 mg daily increases risk of AHS, particularly in patients with renal impairment 3.

2. Ignoring renal function: Failing to adjust allopurinol dose based on renal function can lead to toxicity 4.

3. Inadequate monitoring: Not following up with appropriate laboratory testing after initiation.

4. Overlooking drug interactions: Allopurinol can interact with medications such as azathioprine, 6-mercaptopurine, thiazide diuretics, and warfarin 2.

By ensuring appropriate laboratory testing before initiating allopurinol, clinicians can optimize dosing, minimize adverse effects, and improve treatment outcomes for patients requiring urate-lowering therapy.