The overall risk for hospitalization due to allopurinol-associated severe cutaneous adverse reactions is rare, although blacks, Asians, and Native Hawaiians/Pacific Islanders have a substantially higher risk compared with whites and Hispanics, particularly in older women, according to the results of a cohort study recently published in the Annals of the Rheumatic Diseases.1

The investigators used Medicaid data to identify incident allopurinol users between 1999 and 2012. They assessed the risk for hospitalized allopurinol-associated severe cutaneous adverse reactions based on race and ethnicity and purported key risk factors and calculated relative risks (RRs). The primary end point was the number of incident cases of patients hospitalized with allopurinol-associated adverse reactions with a principal hospital discharge diagnosis of a relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code that took place within the first 3 months after filling the first allopurinol prescription and for which the drug was discontinued after the event.

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The cohort included 400,401 individuals who initiated allopurinol treatment, 203 of whom experienced a hospitalized allopurinol-associated adverse reaction.  Of the 400,401 allopurinol initiators, 62% were white, 53% were men, and 52% were <60 years. The average duration of hospitalization for an adverse reaction was 9.6 days; 21% of the patients hospitalized with an adverse reaction died.

Multivariable-adjusted RRs for allopurinol-associated adverse reactions in blacks, Asians, and Native Hawaiians/ Pacific Islanders vs whites and Hispanics were 3.00 (95% CI, 2.18-4.14), 3.03 (95% CI, 1.72-5.34), and 6.68 (95% CI, 4.37-10.22), respectively. Female gender, chronic kidney disease, initial allopurinol dose >100 mg/day, and older age (≥60 years) were all independently associated with a 2.5-fold, 2.3-fold, 1.9-fold, and 1.7-fold increased risk for adverse reactions, respectively.

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According to a combined demographic analysis, older women (≥60 years) of high-risk race and ethnicity had a >12-fold increased risk for hospitalized allopurinol-associated adverse reactions compared with younger men of low-risk race and ethnicity (multivariable-adjusted RR, 12.25; 95% CI, 6.46-23.25).

The investigators concluded that heightened vigilance should be exercised when initiating allopurinol in blacks, Asians, and Native Hawaiians/ Pacific Islanders. In addition, female gender, chronic kidney disease, an initial allopurinol dose >100 mg/day, and older age are all independent risk factors for allopurinol-associated adverse reactions that need to be taken into account when initiating allopurinol therapy.

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Keller SF, Lu N, Blumenthal KG, et al. Racial/ethnic variation and risk factors for allopurinol-associated severe cutaneous adverse reactions: a cohort study [published online April 13, 2018].  Ann Rheum Dis. doi:10.1136/annrheumdis-2017-212905