August 07, 2015
JAMA internal medicine
TAKE-HOME MESSAGE
- The authors of this retrospective population study examined the incidence of allopurinol hypersensitivity and its risk factors. The annual incidence of allopurinol hypersensitivity among new users was 4.68 per 1000, the incidence of related hospitalization was 2.02 per 1000, and the incidence of mortality was 0.39 per 1000. Renal or cardiovascular comorbidities, female gender, initial allopurinol dosage >100 mg/day, use for treating asymptomatic hyperuricemia, and age ≥60 years were among the risk factors for hypersensitivity. For patients with both asymptomatic hyperuricemia and renal or cardiovascular disease, the risks for hypersensitivity and death were significantly increased.
- There is a significantly increased risk for hypersensitivity in patients with asymptomatic hyperuricemia combined with renal or cardiovascular disease who are given allopurinol.
Abstract
IMPORTANCE
Allopurinol, a first-line drug used for treating gout, is increasingly prescribed worldwide to patients with asymptomatic hyperuricemia and comorbid renal or cardiovascular diseases. Nevertheless, allopurinol use has been associated with fatal hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The overall risks of allopurinol use remain unclear.
OBJECTIVE
To investigate the incidence of, risk factors for, and mortality associated with allopurinol hypersensitivity in new users of allopurinol.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective nationwide population study was conducted using data from the Taiwan National Health Insurance Research Database, which includes detailed medical records of more than 23 million insured enrollees. Data were collected from January 1, 2005, through December 31, 2011, using the Anatomical Therapeutic Chemical classification system and International Classification of Diseases, Ninth Revision, Clinical Modification codes. Among 1 613 719 patients receiving allopurinol prescriptions, 495 863 were identified as new users.
MAIN OUTCOMES AND MEASURES
Allopurinol hypersensitivity was identified within 3 months since the first prescription. The period for measuring related hospitalizations was 1 month since the episode, and the period for measuring renal complications or mortality was 2 months since the episode. Poisson regression test and multivariable logistic regression analysis were performed, and P < .01 was considered statistically significant.
RESULTS
Among the more than 23 million insured enrollees, the annual incidence rates were 4.68 per 1000 new users for allopurinol hypersensitivity, 2.02 per 1000 new users for related hospitalization, and 0.39 per 1000 new users for related mortality. The annual incidence of allopurinol hypersensitivity rose statistically significantly during the study period (P < .001). Risk factors for allopurinol hypersensitivity included female sex, age 60 years or older, initial allopurinol dosage exceeding 100 mg/d, renal or cardiovascular comorbidities, and use for treating asymptomatic hyperuricemia. Patients with asymptomatic hyperuricemia and renal or cardiovascular diseases had statistically significantly increased risk of allopurinol hypersensitivity (odds ratio [OR], 1.61; 95% CI, 1.33-1.94; P < .001 for renal diseases and OR, 1.52; 95% CI, 1.19-1.93; P < .001 for cardiovascular diseases). They also had statistically significantly increased risk of mortality (OR, 5.59; 95% CI, 2.61-11.94; P < .001 for renal diseases and OR, 3.57; 95% CI, 2.31-5.51; P < .001 for cardiovascular diseases).
CONCLUSIONS AND RELEVANCE
The use of allopurinol in patients with asymptomatic hyperuricemia accompanied by renal or cardiovascular diseases statistically significantly increased the risk of hypersensitivity reactions. Physicians should be cautious when prescribing allopurinol to high-risk populations and should consider the potential risks of fatal adverse reactions.