From the Guidelines
Starting allopurinol at 200 mg daily instead of 100 mg for severe gout is generally not recommended, despite the severity of symptoms. The standard approach is to begin with a low dose of 100 mg daily and gradually increase by 100 mg every 2-4 weeks until reaching the target serum uric acid level, typically below 6 mg/dL, as recommended by the 2016 updated EULAR evidence-based recommendations for the management of gout 1. This gradual titration approach is important because starting at higher doses increases the risk of allopurinol hypersensitivity syndrome and gout flares.
Key Considerations
- The goal of allopurinol is long-term uric acid reduction, not acute symptom relief.
- For immediate relief of severe gout symptoms, use anti-inflammatory medications like colchicine, NSAIDs, or corticosteroids rather than starting with a higher allopurinol dose.
- During the initial weeks of allopurinol therapy, patients should also receive prophylactic medication such as colchicine (0.6 mg once or twice daily), a low-dose NSAID, or a low-dose corticosteroid for 3-6 months to prevent paradoxical gout flares that commonly occur when uric acid levels are changing.
Additional Recommendations
- Patient education on diet, lifestyle, treatment objectives, and management of comorbidities, are recommended core therapeutic measures in gout, as suggested by the 2012 American College of Rheumatology guidelines for management of gout 2.
- Serum urate should be lowered sufficiently to durably improve signs and symptoms of gout, with the target <6 mg/dL at a minimum, and often <5 mg/dL.
- Prior to initiation of allopurinol, rapid, PCR-based HLA-B5801 screening should be considered as a risk management component in sub-populations where both HLA-B5801 allele frequency is elevated and the HLA-B*5801 positive subjects have a very high hazard ratio for severe allopurinol hypersensitivity reaction.
From the FDA Drug Label
To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.
The recommended starting dose for allopurinol is 100 mg daily, and it should be increased at weekly intervals by 100 mg until the desired serum uric acid level is attained.
- The dosage may be increased to 200 mg daily after the first week if necessary and tolerated.
- However, the decision to start with 200 mg of allopurinol instead of 100 mg for severe gout should be made with caution, considering the risk of flare-up of acute gouty attacks.
- It is essential to monitor the patient's serum uric acid levels and adjust the dosage accordingly to minimize the risk of adverse effects 3.
From the Research
Gout Treatment Options
- The treatment of gout involves lowering serum uric acid (sUA) levels to prevent the formation of monosodium urate crystals, which cause the disease 4.
- Allopurinol is a commonly used urate-lowering medication, but the optimal starting dose is not clearly established, especially for patients with severe gout.
Starting Dose of Allopurinol
- There is no direct evidence to support starting a patient with severe gout on 200mg of allopurinol instead of 100mg 5, 4, 6, 7, 8.
- However, studies suggest that febuxostat may be more effective than allopurinol in achieving target sUA levels, especially in patients with severe gout or renal dysfunction 5, 7, 8.
Considerations for Treatment
- The goal of treatment is to lower sUA levels to less than 6mg/dL, and less than 5mg/dL for patients with severe gout 6.
- Prophylaxis with colchicine or NSAIDs may be necessary to prevent acute gout flares, especially when initiating urate-lowering therapy 4, 8.
- The choice of urate-lowering medication and starting dose should be individualized based on patient factors, such as renal function, comorbidities, and disease severity.