From the Guidelines
The starting dose of allopurinol should be no greater than 100 mg per day, and less than that in moderate to severe chronic kidney disease (CKD). This low initial dose is recommended to reduce the risk of hypersensitivity reactions and allopurinol-induced flares of gout, as suggested by the 2020 American College of Rheumatology guideline for the management of gout 1. For patients with normal kidney function, the dose can be gradually increased by 100 mg every 2-4 weeks until the target serum uric acid level is achieved (usually below 6 mg/dL) or until reaching the maximum dose of 800 mg daily. Some key points to consider when initiating allopurinol include:
- Using a lower starting dose mitigates safety issues specific to allopurinol hypersensitivity syndrome (AHS) 1
- The choice of allopurinol as the preferred first-line agent is strongly recommended for all patients, including those with moderate-to-severe CKD (stage ≥3) 1
- Concurrent prophylaxis with colchicine (0.6 mg once or twice daily) or a low-dose NSAID for 3-6 months is recommended to prevent gout flares that commonly occur during the early phase of urate-lowering therapy 1
- Regular monitoring of serum uric acid levels and kidney function is essential during dose titration 1.
From the FDA Drug Label
The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily 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 starting dose of allopurinol is 100 mg daily to reduce the possibility of flare-up of acute gouty attacks, as stated in the drug label 2.
From the Research
Starting Dose of Allopurinol
- The starting dose of allopurinol is a crucial factor in minimizing the risk of allopurinol hypersensitivity syndrome (AHS) 3.
- A study published in Arthritis and Rheumatism in 2012 proposed a safe starting dose of allopurinol as 1.5 mg per unit of estimated glomerular filtration rate (eGFR) to reduce the risk of AHS 3.
- Another study published in the British Journal of Clinical Pharmacology in 2013 found that the optimal dose of allopurinol is dependent on the pre-treatment plasma urate concentration and is not influenced by creatinine clearance 4.
- A daily dose of 100 mg of allopurinol was found to be associated with a higher risk of gout flares in the first six months of treatment 5.
- The "start-low go-slow" dose escalation strategy is recommended when commencing allopurinol to minimize the risk of gout flares 5.
Dose Escalation Strategy
- The dose of allopurinol can be gradually increased to achieve the target serum urate level in patients who tolerate the initial dose 3.
- A study published in the Annals of the Rheumatic Diseases in 1975 found that a single daily dose of allopurinol can provide sustained control of plasma levels 6.
- The optimal dose of allopurinol can be predicted using a non-linear equation that takes into account the daily dose of allopurinol and the plasma concentration of urate pre-treatment 4.
Comparison with Other Treatments
- Febuxostat was found to have better efficacy than allopurinol in the treatment of gout with hyperuricemia, with a lower adverse reaction rate 7.
- Colchicine prophylaxis may be beneficial in reducing the risk of gout flares when starting allopurinol using the "start-low go-slow" dose escalation strategy 5.