From the Guidelines
Allopurinol is recommended as the first-line urate-lowering therapy (ULT) for patients with gout, starting at a low dose of 100 mg daily and increasing by 100 mg increments every 2-4 weeks if required, to reach the target serum uric acid (SUA) level of <6 mg/dL. This recommendation is based on the most recent and highest quality study, which is the 2020 American College of Rheumatology guideline for the management of gout 1.
Key Considerations
- The dose of allopurinol should be adjusted in patients with renal impairment, with a lower starting dose and slower titration 1.
- When initiating allopurinol, patients should be aware that it may temporarily increase gout flares, so colchicine or an anti-inflammatory medication is often prescribed concurrently for the first few months 2.
- Common side effects of allopurinol include rash, gastrointestinal upset, and headache, and rarely, a severe hypersensitivity reaction called DRESS syndrome can occur, particularly in patients with HLA-B*5801 genetic variant 3.
- Allopurinol should be taken with food to minimize stomach upset, and patients should maintain adequate hydration, with regular monitoring of uric acid levels and liver and kidney function recommended during treatment 2.
Management Strategy
- A treat-to-target management strategy with ULT dose titration guided by serial serum urate measurements is recommended, with an SU target of <6 mg/dL 1.
- Concomitant anti-inflammatory prophylaxis therapy for a duration of at least 3-6 months is strongly recommended when initiating ULT 1.
- For management of gout flares, colchicine, nonsteroidal anti-inflammatory drugs, or glucocorticoids (oral, intraarticular, or intramuscular) are strongly recommended 1.
Patient Education
- Patients should receive full information and be fully involved in decision-making concerning the use of ULT, including the potential benefits and risks of allopurinol therapy 2.
- Patients should be educated on lifestyle modifications, including weight loss, avoidance of alcohol and sugar-sweetened drinks, and regular exercise, to help manage their gout and reduce the risk of flares 2.
From the FDA Drug Label
THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol tablets reduce serum and urinary uric acid concentrations. Allopurinol tablets are indicated in:
- the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy).
- the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels
- the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients Asymptomatic hyperuricemia is not an indication for treatment with allopurinol tablets
The primary use of allopurinol is for the management of patients with:
- Gout (primary or secondary)
- Leukemia, lymphoma, and malignancies with elevated uric acid levels
- Recurrent calcium oxalate calculi with high uric acid excretion It is not recommended for the treatment of asymptomatic hyperuricemia [4] [5]
From the Research
Allopurinol Overview
- Allopurinol is a commonly used urate-lowering therapy in gout treatment 6
- It works by reducing uric acid production in the body
Allopurinol Dosage and Hypersensitivity Syndrome
- The starting dose of allopurinol is a risk factor for allopurinol hypersensitivity syndrome (AHS) 6
- A proposed safe starting dose of allopurinol is 1.5 mg per unit of estimated glomerular filtration rate (eGFR) to reduce the risk of AHS 6
- Dosing guidelines based on creatinine clearance have been proposed to minimize the risk of AHS, particularly in patients with renal impairment 6
Comparative Effectiveness of Allopurinol and Febuxostat
- Allopurinol and febuxostat are both effective in reducing uric acid levels and achieving serum urate targets in patients with gout 7, 8
- Allopurinol is noninferior to febuxostat in controlling flares in patients with gout 7
- Febuxostat may be more effective in reducing uric acid levels and improving renal outcomes in patients with chronic kidney disease (CKD) 8, 9
Renal Outcomes and Allopurinol
- Allopurinol and febuxostat have similar effects on renal function changes in patients with CKD 8
- Febuxostat may be more renoprotective than allopurinol in patients with both hyperuricemia and CKD, but more studies are needed to confirm this 9