Reaction to allopurinol are few, but severe

Severe cutaneous adverse actions requiring hospitalization occurred in 45 of 90,358 patients who began allopurinol treatment within a specified time period, for an incidence rate of 0.69 per 1,000 person years.

The standardized incidence rate of hospitalization for severe cutaneous adverse reactions was 0.03 per 1,000 person-years in nearly 9 million individuals who had never received a prescription for the drug, said at the meeting.

Allopurinol is primarily prescribed for patients who have gout, and most data on severe cutaneous reactions to the drug have been based on case series or chart reviews from a single academic center.

For their study, used Medicaid claims data for 1999-2005 from five states (California, Florida, New York, Ohio, and Pennsylvania), which accounts for a third of Medicare claims.

The researchers identified all adults aged 20 years and older who had one or more medical claims at least 180 days before the first prescription of allopurinol. Individuals were excluded from the study if they had solid tumors, hematologic malignancies; myelodysplastic syndrome, or chemotherapy. They were compared with patients who had never received a prescription for allopurinol.

The primary outcome was hospitalization for severe cutaneous reactions, identified by the principal discharge diagnosis code 695.1 for erythema multiforme and related conditions after initiation of allopurinol.

“We chose this method, not to make any conclusions about specific dermatopathology; just wanted to make sure how many people were being admitted with some kind of severe cutaneous adverse reaction,” said Brigham and Women’s Hospital in Boston. The secondary outcome was in-hospital death during that hospitalization for severe cutaneous adverse reaction.

“Allopurinol users were much older, a greater percentage were male, they used the health care system a lot more frequently, and had more comorbidities.”

The average age for allopurinol users was 66 years, compared with 37 years for nonusers. The findings were adjusted for age, high dose (at least 300 mg per day of allopurinol), comorbidities, and any diuretic use.

The hazard rate for severe cutaneous adverse reactions with allopurinol was 21.3 after adjusting for age. The hazard rate dropped to 11.8 after adjusting for age, sex, and comorbidities.

The bulk of the severe cutaneous adverse reactions, 20 of the 45 cases, occurred within the first 30 days of treatment (incidence rate, l.05), and 4 occurred after 180 days (incidence rate, 0.69).

In the crude analysis, age, comorbidity index score, and any use of diuretics were significantly associated with a severe cutaneous adverse reaction. In the multivariate analysis, only age and comorbidity index remained significant, according to the researchers.