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).


CONCLUSIONS
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.
Mockenhaupt
Maja
M
Dokumentationszentrum schwerer Hautreaktionen, Freiburg, Germany.
Kelly
Judith Parsells
JP
Kaufman
David
D
Stern
Robert S
RS
D016907:Adverse Drug Reaction Reporting Systems; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007391:International Cooperation; D008297:Male; D015999:Multivariate Analysis; D012307:Risk Factors; D013262:Stevens-Johnson Syndrome / Q000453:epidemiology / Q000209:etiology*; D014481:United States / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal