From the Guidelines
Allopurinol is a first-line treatment for gout, recommended to be started at a low dose of 100 mg/day and increased by 100 mg increments every 2–4 weeks if required, to reach the uricaemic target. This recommendation is based on the 2017 updated EULAR evidence-based recommendations for the management of gout 1. The goal of treatment is to maintain the serum uric acid (SUA) level <6 mg/dL, which is below the saturation point for monosodium urate (MSU) to dissolve all crystal deposits.
Key Points to Consider
- Allopurinol is recommended for first-line ULT, due to its efficacy, low cost, and safety 1.
- The dose can be raised above 300 mg daily, even with renal impairment, as long as this is accompanied by adequate patient education and monitoring for drug toxicity 1.
- Prior to initiation, consider HLA-B*5801 in selected patients, specifically in higher risk sub-populations for severe allopurinol hypersensitivity reaction 1.
- Common side effects include rash, stomach upset, and liver function abnormalities, and rarely, a severe hypersensitivity reaction called DRESS syndrome can occur.
Monitoring and Maintenance
- SUA level should be monitored and maintained to <6 mg/dL (360mmol/L) for most patients, and <5 mg/dL (300mmol/L) for patients with severe gout until total crystal dissolution and resolution of gout 1.
- All ULTs should be started at a low dose and then titrated upward until the SUA target is reached, and SUA <6 mg/dL (360mmol/L) should be maintained lifelong 1.
From the FDA Drug Label
Allopurinol acts on purine catabolism, without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analogue of the natural purine base, hypoxanthine It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid, the end product of purine metabolism in man.
Allopurinol is a xanthine oxidase inhibitor that acts on purine catabolism to reduce the production of uric acid. It is a structural analogue of the natural purine base hypoxanthine.
- Main use: to treat hyperuricemia
- Mechanism of action: inhibiting the biochemical reactions immediately preceding uric acid formation 2 2 2
From the Research
Definition and Use of Allopurinol
- Allopurinol is a medication used to reduce concentrations of uric acid in the body 3.
- It is an effective treatment for gout, a common inflammatory arthritis caused by the deposition of urate crystals 3, 4.
- Allopurinol works by inhibiting the enzyme xanthine oxidase, which is involved in the production of uric acid 5.
Indications and Administration
- Allopurinol is used to prevent flare-ups of gout, particularly in patients with chronic kidney disease, two or more flare-ups per year, urolithiasis, the presence of tophus, chronic gouty arthritis, and joint damage 4.
- The starting dose of allopurinol is guided by renal function, and the maintenance dose is guided by the baseline serum uric acid concentration 3.
- Allopurinol can be used in combination with other medications, such as colchicine or non-steroidal anti-inflammatory drugs (NSAIDs), to manage gout symptoms 6.
Safety and Efficacy
- Allopurinol has been shown to be safe and effective in reducing serum uric acid levels and preserving kidney function in patients with mild to moderate chronic kidney disease 5.
- However, allopurinol can cause adverse events, such as diarrhea, nausea, and myocardial infarction, particularly when used in combination with colchicine or NSAIDs 6.
- Febuxostat is another xanthine oxidase inhibitor that is clinically equivalent to allopurinol, but it is associated with an increase in all-cause and cardiovascular mortality and is not routinely recommended 4.