Allopurinol for first-line urate-lowering therapy

Becker, Schumacher, Wortmann, MacDonald, Eustace, 2005Graf, 2015Graham, 2013Hill, 2015Kydd, Seth, Buchbinder, Edwards, 2014Kydd, Seth, Buchbinder, Falzon, 2014Seth, 2014Sivera, Andres, Carmona, 2014Stocker, 2011Taylor, 2012

High-certainty evidence indicates that allopurinol, a xanthine oxidase inhibitor, is effective in lowering serum uric acid concentration by reducing uric acid production. There is strong consensus that allopurinol should be used as first-line urate-lowering therapy. For drug regimens, see Drug regimens for chronic gout.

Patients with a higher baseline serum uric acid concentration are likely to need a higher allopurinol dose to achieve the target serum uric acid concentration. Many patients require allopurinol doses above 300 mg daily; however, nonadherence should always be ruled out before increasing the allopurinol dose.

Kidney impairment is not a contraindication to the use of allopurinol. The same (or lower) starting dose of allopurinol and the same (or slower) rate of dose increase is recommended for patients with kidney impairment, with close monitoring of kidney function.

Allopurinol reduces the metabolism of azathioprine and mercaptopurine, increasing the risk of severe bone marrow toxicity. If possible, avoid the combination of allopurinol with either azathioprine or mercaptopurine. If these combinations cannot be avoided, reduce the dose of azathioprine or mercaptopurine to approximately one-quarter to one-third of the usual dose and monitor full blood count closely.

Adverse effects occur in less than 1% of patients treated with allopurinol. Skin rash is the most common adverse effect and may present as a maculopapular rash or allopurinol hypersensitivity syndrome. Allopurinol hypersensitivity syndrome is a rare, but potentially fatal, adverse effect comprising erythematous desquamating rash, fever, hepatitis, eosinophilia, and worsening kidney function. Most allopurinol hypersensitivity syndrome occurs in the first 3 months of treatment. Risk factors for allopurinol hypersensitivity syndrome include use of a high starting dose and rapid up-titration, kidney impairment, older age, and the presence of human leucocyte antigen (HLA)-B*5801 allele, which is more common in people of Southeast Asian ethnicity, especially the Han Chinese, Korean and Thai populations. Allopurinol hypersensitivity syndrome is a contraindication to further exposure to allopurinol. Advise patients to stop allopurinol immediately and seek medical advice if a skin rash develops. Patients who develop a maculopapular rash alone may be treated with an allopurinol desensitisation program; refer patients to a specialist for desensitisation.