From the Journals

Heart disease raises risk of severe cutaneous adverse reactions to allopurinol



Researchers have found that patients with heart disease have an increased risk of hospitalization for severe cutaneous adverse reactions to allopurinol, with factors like chronic kidney disease and high initial dosage adding to that risk.

“Physicians who prescribe allopurinol should look for these risk factors so that they may consider initiating lower-dosage allopurinol and other precautions, which may prevent this rare but serious adverse reaction,” Chio Yokose, MD, of Massachusetts General Hospital in Boston and coauthors wrote in the Canadian Medical Association Journal.

To further investigate known associations between heart disease and severe cutaneous adverse reactions to allopurinol – including Stevens-Johnson syndrome and toxic epidermal necrolysis – the researchers used an administrative database known as Population Data BC to conduct a cohort study of allopurinol initiators in British Columbia between 1997 and 2015. Individuals with a history of severe cutaneous adverse reactions before starting allopurinol were excluded.

Of the 130,325 allopurinol users identified, 109 were hospitalized for allopurinol-associated severe cutaneous adverse reactions within 3 months of starting the drug. One in 655 allopurinol users with heart disease were admitted to the hospital for allopurinol-associated severe cutaneous adverse reaction (risk ratio = 1.53 per 1,000; 95% confidence interval, 1.10-2.06), compared with 1 in 1,548 allopurinol users without heart disease (risk ratio = 0.65 per 1,000; 95% CI, 0.50-0.82).

After multivariable analysis, other significant associations with hospital admission included chronic kidney disease (relative risk, 1.88; 95% CI, 1.17-3.02) and an initial allopurinol dosage greater than 100 mg/day (RR, 2.78; 95% CI, 1.75-4.43). In addition, patients with heart disease, chronic kidney disease, and an initial dosage greater than 100 mg/day had an 11-fold higher risk of hospital admission (RR, 11.13; 95% CI, 4.66-26.58).

The authors acknowledged their study’s limitations, including potential misclassification of reactions and comorbidities that can stem from a reliance on ICD codes. However, they also noted that “any misclassification is expected to be nondifferential” and bias results toward the null accordingly.

The study was funded by the Canadian Institutes of Health Research. One author reported receiving a grant from the National Institutes of Health and research support from AstraZeneca, along with consulting fees from Takeda, Selecta Biosciences, and Horizon. No other conflicts of interest were reported.

SOURCE: Yokose C et al. CMAJ. 2019 Sep 30. doi: 10.1503/cmaj.190339.

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