The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with nonsteroidal antiinflammatory drugs: a multinational perspective.

OBJECTIVE: To quantify the risk of the severe cutaneous adverse reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) associated with use of nonsteroidal antiinflammatory drugs (NSAID).

METHODS: Three large data sources were analyzed: an international case-control study on severe cutaneous reactions (SCAR Study), a population based registry in Germany, and the US Food and Drug Administration (FDA) spontaneous reporting system.

RESULTS: In the international case-control study, the oxicams were associated with the greatest increase in risk of SJS and TEN (relative risk 34, 95% confidence interval 11-105). When the risk for only recently initiated use was compared to that for longterm use of these agents (> 8 weeks), the relative risk of SJS and TEN associated with oxicams was significantly increased (p < 0.05). German data registry confirm these findings. The incidence of spontaneous US reports of SJS and TEN (per 1,000,000 visits with a prescription) for diflusinal, sulindac, oxaprozin, and etodolac were not significantly lower than that of piroxicam (p > 0.05, all comparisons).

CONCLUSION: Although the absolute risks of SJS and TEN associated with NSAID use are low, these risks should be considered in monitoring patients who recently began therapy. In 3 independent databases, oxicams have higher risk of SJS and TEN than other NSAID widely used on the 2 continents. The FDA spontaneous reporting systems suggest some NSAID not widely used in Europe may have risks comparable to the oxicams.