La Grenade Lois, Lee Lauren, Weaver Joyce, Bonnel Renan, Karwoski Claudia, Governale Laura, Brinker Allen
Food and Drug Administration, Rockville, Maryland 20857, USA.
Drug Saf. 2005;28(10):917-24. doi: 10.2165/00002018-200528100-00008.
Stevens-Johnson syndrome and toxic epidermal necrolysis are closely related severe acute life-threatening, drug-induced skin disorders. The US FDA Adverse Events Reporting System (AERS) has received reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of the recently introduced selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs, two of which are also sulfonamides.
The objective of this study is to review cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA associated with the use of the selective COX-2 inhibitor NSAIDs celecoxib, rofecoxib and valdecoxib, and to compare reporting rates of the two conditions associated with these drugs to each other, meloxicam (an oxicam NSAID that came on the US market at a similar time) and the background incidence rate.
We reviewed all US cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA AERS database associated with the use of celecoxib, rofecoxib, valdecoxib and meloxicam since these agents were first marketed. We utilised AERS and drug use data to calculate reporting rates for each drug after the first 2 years of marketing. We obtained the background rate from the medical literature.
Up to the end of March 2004, there were 63 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis reported with valdecoxib use, 43 with celecoxib, 17 with rofecoxib (the non-sulfonamide coxib) and none for meloxicam. In the first 2 years of marketing the reporting rate for Stevens-Johnson syndrome/toxic epidermal necrolysis with valdecoxib was 49 cases per million person-years of use, 6 cases per million person-years for celecoxib and 3 cases per million person-years for rofecoxib. The reporting rates for the sulfonamide coxibs were substantially higher than the background rate of 1.9 cases per million population per year, with the valdecoxib rate being 8-9 times that of celecoxib and approximately 25 times that of the background rate.
There is a strong association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of the sulfonamide COX-2 inhibitors, particularly valdecoxib. Physicians should be aware of the possibility of this serious life-threatening event when prescribing these drugs and advise patients to discontinue use at the earliest possible sign or symptom.
史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症是密切相关的、严重的、危及生命的药物性皮肤疾病。美国食品药品监督管理局不良事件报告系统（AERS）已收到与最近引入的选择性环氧化酶（COX）-2抑制剂非甾体抗炎药使用相关的史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症的报告，其中两种也是磺胺类药物。
本研究的目的是回顾向美国食品药品监督管理局报告的与使用选择性COX-2抑制剂非甾体抗炎药塞来昔布、罗非昔布和伐地昔布相关的史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症病例，并比较与这些药物相关的这两种病症的报告率，与美洛昔康（一种同时在美国上市的昔康类非甾体抗炎药）以及背景发病率进行比较。
我们回顾了自塞来昔布、罗非昔布、伐地昔布和美洛昔康首次上市以来向美国食品药品监督管理局AERS数据库报告的所有与使用这些药物相关的美国史蒂文斯-约翰逊综合征和中毒性表皮坏死松解症病例。我们利用AERS和药物使用数据计算每种药物上市后前两年的报告率。我们从医学文献中获取背景发病率。
截至2004年3月底，有63例使用伐地昔布后报告的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症病例，43例使用塞来昔布的病例，17例使用罗非昔布（非磺胺类COX-2抑制剂）的病例，美洛昔康无相关病例报告。在上市的前两年，伐地昔布的史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症报告率为每百万使用人年49例，塞来昔布为每百万使用人年6例，罗非昔布为每百万使用人年3例。磺胺类COX-2抑制剂的报告率显著高于每年每百万人口1.9例的背景发病率，伐地昔布的报告率是塞来昔布的8 - 9倍，约为背景发病率的25倍。
史蒂文斯-约翰逊综合征/中毒性表皮坏死松解症与磺胺类COX-2抑制剂的使用之间存在密切关联，尤其是伐地昔布。医生在开具这些药物处方时应意识到这种严重危及生命事件的可能性，并建议患者一旦出现最早的体征或症状就停止使用。
