When should allopurinol be started after a gout attack?

From the Guidelines

Allopurinol can be started during a gout flare, as conditionally recommended by the 2020 American College of Rheumatology guideline for the management of gout 1. When starting allopurinol, it is essential to begin with a low dose (typically ≤100 mg/day, and lower in patients with chronic kidney disease (CKD)) and gradually increase it every 2-4 weeks until reaching the target serum uric acid level of less than 6 mg/dL, as strongly recommended by the same guideline 1. Some key points to consider when initiating allopurinol include:

• Starting with a low dose and titrating upwards to minimize the risk of adverse effects and to ensure the patient can tolerate the medication
• Continuing prophylaxis for 3–6 months rather than <3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience flares, as strongly recommended by the 2020 American College of Rheumatology guideline for the management of gout 1
• Initiating concomitant anti-inflammatory prophylaxis therapy (e.g., colchicine, NSAIDs, prednisone/prednisolone) to prevent gout flares that commonly occur when uric acid levels are changing, as strongly recommended by the same guideline 1
• Patients should be advised to continue taking allopurinol even if they experience a gout attack during initial therapy, while treating the acute attack separately with appropriate anti-inflammatory medications. It is crucial to weigh the benefits and risks of starting allopurinol during a gout flare, considering factors such as the severity of the flare, the patient's medical history, and their ability to tolerate the medication. The 2020 American College of Rheumatology guideline for the management of gout provides the most recent and highest-quality evidence for the management of gout, including the initiation of allopurinol 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. An increase in acute attacks of gout has been reported during the early stages of administration of allopurinol tablets, even when normal or subnormal serum uric acid levels have been attained. Accordingly, maintenance doses of colchicine generally should be given prophylactically when allopurinol tablets are begun

The patient should start allopurinol after a gout attack, but it is recommended to start with a low dose (100 mg daily) and increase at weekly intervals. Colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases. It is also recommended to start allopurinol during the intercritical period, when the patient is not experiencing an acute gout attack, to minimize the risk of flare-up. 2 2

From the Research

Allopurinol Initiation After a Gout Attack

• The optimal timing for starting allopurinol after a gout attack is a topic of interest, with studies suggesting that it can be initiated during an acute attack without prolonging the painful arthritis 3, 4, 5.
• A randomized clinical trial found that initiating allopurinol at low doses during an acute gout attack did not prolong the acute, treated attack 3.
• Another study found that allopurinol initiation during an acute gout attack caused no significant difference in daily pain, recurrent flares, or inflammatory markers 4.
• A more recent randomized controlled trial compared early and late allopurinol initiation in acute gout flare and found that early initiation did not lead to significant changes in time to resolution, flare recurrence, and inflammatory markers 5.
• It is also important to note that colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares, and reduces the likelihood of recurrent flares 6.

Key Findings

• Allopurinol can be started during an acute gout attack without worsening the condition 3, 4, 5.
• Early initiation of allopurinol does not significantly affect the time to resolution of acute gout flare 5.
• Colchicine prophylaxis is effective in reducing the frequency and severity of acute flares during allopurinol initiation 6.

Considerations for Allopurinol Initiation

• Patients with crystal-proven gout and meeting criteria for urate-lowering therapy can be started on allopurinol during an acute attack 3.
• The dose of allopurinol can be initiated at 100 mg daily and increased to 200 mg daily after 14 days 3.
• Colchicine prophylaxis should be considered during allopurinol initiation to reduce the risk of acute flares 6.