What test should be done before initiating allopurinol (xanthine oxidase inhibitor) therapy?

Testing Before Allopurinol Initiation

HLA-B*5801 genetic testing should be performed before starting allopurinol in patients of Southeast Asian descent (Han Chinese, Korean, Thai) and African American patients, while baseline renal function assessment is essential for all patients to guide appropriate dosing. 1

HLA-B*5801 Genetic Testing

High-Risk Populations Requiring Testing

• Southeast Asian patients (Han Chinese, Korean, Thai) should undergo HLA-B*5801 testing before allopurinol initiation, as these populations have HLA-B*5801 allele frequencies of 6-8% and hazard ratios in the hundreds for allopurinol hypersensitivity syndrome (AHS). 1

• African American patients should also be tested for HLA-B*5801, with an allele prevalence of 3.8% and a 3-fold increased risk of AHS compared to white patients. 1

• Korean patients with stage 3 or worse chronic kidney disease (CKD) warrant testing, as this subgroup has an HLA-B*5801 allele frequency of approximately 12%. 1

Populations Where Testing Is NOT Recommended

• Universal HLA-B*5801 screening is conditionally recommended against in Caucasians, Hispanics, and other ethnic groups not specified above, as these populations have substantially lower HLA-B*5801 prevalence (~0.7-2%) with lower hazard ratios and negative predictive values. 1

Clinical Significance of HLA-B*5801

• The mortality rate of allopurinol hypersensitivity syndrome is 20-25%, making this a critical safety consideration. 1

• HLA-B*5801 testing is cost-effective in Asian and African American populations, with incremental cost-effectiveness ratios <$109,000 per quality-adjusted life year. 1

• The test should be performed using rapid PCR-based methods, which are widely available and require follow-up sequencing in only ~10% of cases with inconclusive results. 1

• If HLA-B*5801 is positive in high-risk individuals, prescribe an alternative urate-lowering therapy such as febuxostat rather than allopurinol. 1

Renal Function Assessment

Essential Baseline Testing

• Measure serum creatinine and calculate creatinine clearance or estimated glomerular filtration rate (eGFR) before starting allopurinol, as renal function profoundly affects dosing and elimination of both allopurinol and its active metabolite oxipurinol. 2

• Blood urea nitrogen (BUN) should also be assessed at baseline in patients with pre-existing renal disease or concurrent conditions affecting renal function such as hypertension and diabetes. 2

Dosing Implications Based on Renal Function

• Start with 50 mg daily in patients with stage 4 or worse CKD (eGFR <30 mL/min/1.73m²), as the half-life of oxipurinol is greatly prolonged in severe renal impairment. 1

• Start with no more than 100 mg daily in patients with normal or mildly impaired renal function, as higher starting doses increase the risk of hypersensitivity reactions in the first few months of therapy. 1

• In severely impaired renal function, doses as low as 100 mg per day or 300 mg twice weekly may be sufficient to maintain adequate xanthine oxidase inhibition. 2

Baseline Serum Uric Acid

• Measure baseline serum uric acid before initiating allopurinol to establish a starting point for the treat-to-target strategy, with a goal of <6 mg/dL. 3, 2

• Serial serum uric acid measurements every 2-4 weeks should guide dose titration in increments of 100 mg until the target is reached. 3

Liver Function Testing

• In patients with pre-existing liver disease, obtain baseline liver function tests (transaminases) before starting allopurinol, as monitoring for elevated hepatic transaminases is recommended during early therapy. 1, 2

Common Pitfalls to Avoid

• Do not rely on fixed-dose allopurinol (e.g., 300 mg daily) without checking baseline renal function, as this non-evidence-based approach fails to achieve target serum uric acid in more than half of patients and increases hypersensitivity risk in those with renal impairment. 1

• Do not skip HLA-B*5801 testing in high-risk populations based on cost concerns, as the test prevents life-threatening reactions with 20-25% mortality and is cost-effective. 1, 4

• Renal function cannot be assumed normal based on age or appearance alone—concurrent thiazide use and renal impairment are established risk factors for AHS. 1