From the Guidelines
Allopurinol should be started 1-2 weeks after a gout attack has completely resolved, with a low dose of 100 mg daily, and gradually increased every 2-4 weeks until reaching the target serum uric acid level of less than 6 mg/dL, as recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. This approach is supported by the guideline's strong recommendation for a treat-to-target management strategy with ULT dose titration guided by serial serum urate measurements. When initiating ULT, concomitant anti-inflammatory prophylaxis therapy for a duration of at least 3–6 months is strongly recommended to prevent gout flares that commonly occur when uric acid levels are changing 1. Some key points to consider when starting allopurinol include:
- Starting with a low dose and gradually increasing it to minimize the risk of adverse effects
- Monitoring serum uric acid levels regularly to ensure the allopurinol dose is appropriate
- Providing anti-inflammatory prophylaxis during the first 3-6 months of allopurinol therapy to prevent gout flares
- Adjusting the allopurinol dose based on kidney function and individual response, with typical maintenance doses ranging from 100-800 mg daily. The 2017 updated EULAR evidence-based recommendations for the management of gout also support the use of allopurinol as a first-line ULT, starting at a low dose and increasing it until the SUA target is reached 1. However, the 2020 American College of Rheumatology guideline provides more recent and specific guidance on the management of gout, including the use of allopurinol and anti-inflammatory prophylaxis 1.
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 patient should start allopurinol at a low dose of 100 mg daily after a gout attack, and the dose should be increased at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained.
- The dose should not exceed the maximal recommended dosage of 800 mg daily.
- It is recommended to start allopurinol after the acute gout attack has resolved, but the exact timing is not specified in the label 2.
From the Research
Timing of Allopurinol Initiation Post Gout Attack
- The optimal time to start allopurinol after a gout attack is a topic of discussion, with some studies suggesting that it can be initiated during an acute attack without prolonging the painful arthritis 3.
- A randomized clinical trial found that initiating allopurinol at low doses during an acute gout attack did not prolong the acute, treated attack 3.
- However, another study suggested that the risk of gout flare is associated with flare in the month before starting allopurinol and allopurinol 100 mg starting dose 4.
- The "start-low go-slow" dose escalation strategy is recommended when commencing allopurinol, with anti-inflammatory prophylaxis targeted at those who have had a gout flare in the month before starting allopurinol and are commencing allopurinol 100 mg daily 4.
Considerations for Allopurinol Initiation
- Allopurinol is an agent of first choice for urate lowering therapy, but screening for HLA*B58:01 mutation is recommended in Southeast Asian and Black populations to decrease the occurrence of allopurinol hypersensitivity syndrome 5.
- Febuxostat is another efficacious urate lowering therapy, but has received a U.S. FDA black box warning for cardiovascular safety 5.
- The choice of urate-lowering therapy should be individualized, taking into account comorbidities, such as chronic kidney disease and ischemic heart disease, as well as patient preference 6.