Gout is a painful form of inflammatory arthritis caused by the long-term buildup of uric acid in the blood. When serum uric acid (sUA) levels become too high, the substance can crystallize into monosodium urate, which deposits in joints, tendons, and surrounding tissues, triggering acute inflammatory attacks. Allopurinol, a medication classified as a xanthine oxidase inhibitor, is the most frequently prescribed long-term treatment for this condition. It works by blocking the enzyme responsible for converting purines into uric acid, thereby reducing the overall production of this waste product in the body.
The Primary Goal of Allopurinol Treatment
Allopurinol is designed to manage the underlying cause of gout, not to provide immediate relief during an acute flare. Its function is to lower the concentration of uric acid in the bloodstream over time. By reducing the body’s uric acid production, the treatment aims to bring the sUA level below its saturation point, which is approximately 6.8 mg/dL.
The therapeutic objective is to achieve and maintain a specific sUA level for life. For most patients, this target is set at less than 6 mg/dL. Maintaining the sUA below this threshold ensures that new urate crystals cannot form and allows existing deposits to slowly dissolve.
Patients experiencing more severe manifestations of the disease, such as the presence of visible urate deposits called tophi or frequent, debilitating flares, require a more aggressive goal. In these cases, the recommended target is often less than 5 mg/dL to facilitate faster and more complete dissolution of the crystalline burden.
Clinical Thresholds for Starting Allopurinol
The decision to begin long-term urate-lowering therapy (ULT) with allopurinol is based on specific clinical signs that indicate the gout is chronic or severe, requiring intervention beyond just treating flares. This form of prevention is recommended for any patient who has accumulated significant evidence of disease activity. A key indicator is the frequency of acute attacks; patients who experience two or more gout flares annually should start ULT.
Another compelling reason to initiate allopurinol is the presence of tophi, which are characteristic lumps of urate crystals that can form under the skin or around joints. The existence of tophi indicates a substantial and chronic burden of crystals that requires active dissolution. Similarly, any evidence of joint damage on X-ray or other imaging directly attributable to gout warrants starting allopurinol therapy.
The presence of certain coexisting medical conditions can also lower the threshold for starting treatment, even after a single flare. Patients with chronic kidney disease (CKD), specifically those with moderate-to-severe impairment (stage 3 or higher), are recommended to begin ULT. Gout combined with a history of kidney stones, or urolithiasis, also makes allopurinol initiation necessary to prevent further stone formation.
In patients who do not meet these criteria, a conditional recommendation exists for starting allopurinol if they have a very high sUA level, defined as greater than 9 mg/dL, or if they have gout and concurrent CKD stage 2.
Timing the Initiation of Therapy
The timing of when to start allopurinol relative to an acute gout flare has evolved. Historically, it was standard practice to wait until the acute inflammatory attack had completely subsided, often weeks after the flare began. The concern was that rapidly changing uric acid levels might mobilize urate crystals, potentially worsening or prolonging the painful flare.
However, current guidelines now conditionally recommend that allopurinol can be started during an acute gout flare, rather than delaying treatment. Research has shown that initiating the medication early does not significantly prolong the attack, provided a low starting dose is used and appropriate anti-inflammatory medication is given simultaneously. Using concurrent prophylaxis, such as colchicine or a nonsteroidal anti-inflammatory drug (NSAID), is a necessary measure to suppress the inflammation triggered by the early mobilization of crystals.
For patients who are already taking allopurinol when a flare occurs, the medication should not be stopped. Discontinuing allopurinol during an attack causes a sudden rise in sUA levels, which can further destabilize the crystal deposits and potentially prolong the episode. Maintain the established dose while treating the acute pain and inflammation with separate medications.
Monitoring and Adjusting Treatment
Allopurinol therapy is managed using a “start-low, go-slow” approach to minimize the risk of adverse reactions and mobilization flares. For most patients, the starting dose is 100 mg per day, though a lower dose of 50 mg daily is recommended for those with severe chronic kidney disease. This low initial dose is gradually increased until the target sUA level is achieved.
Dose adjustments are made based on laboratory monitoring of sUA levels, which should be checked every two to five weeks during the titration phase. The dosage is increased in 100 mg increments until the target of less than 6 mg/dL or less than 5 mg/dL is consistently reached. Many patients will ultimately require doses higher than 300 mg daily to achieve control, with the maximum recommended dose being up to 800 mg daily.
Concomitant anti-inflammatory prophylaxis is recommended for the first three to six months after starting allopurinol. Medications such as low-dose colchicine or an NSAID are used during this period to prevent the initial surge in flares that can occur as crystals begin to dissolve. Once the sUA target is stable and the patient is free of flares for several months, the prophylaxis medication can be stopped. Long-term maintenance requires continued sUA monitoring, every six to twelve months, to ensure the target remains in range.