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美国食品药物管理局（FDA）发表指出，有人类白血球抗原（HLA）对偶基因HLA-B*1502可能与phenytoin引起的史蒂文生症候群及毒性表皮溶解（SJS/TEN）有关。
Phenytoin是一个结构与Carbamazepine类似的抗癫痫药物，最近发现有这个对偶基因的病患发生SJS/TEN的风险较高。亚洲人种（汉人、菲律宾人、马来西亚人、南亚人与泰国人）普遍有该对偶基因。
当FDA致力于确认有关这项议题的相关资讯时，临床医师被建议考虑避免使用phenytoin与fosphenytoin作为有该对偶基因病患的carbamazepine替代疗法。
根据FDA安全资讯及不良反应通报系统MedWatch发表的警讯，然而，目前并没有足够的资讯可以建议对于打算使用phenytoin的亚洲人进行HLA-B*1502的基因检测。
于2008年5月发表于癫痫期刊的初期研究结果显示，有该对偶基因病患开始使用phenytoin发生SJS/TEN的风险是大约3%，相较于整体刚开始使用病患则是0.3%。在这项研究中，所有4位与phenytoin有关SJS的病患被发现其HLA-B*1502对偶基因呈阳性，对phenytoin具耐受性组则是18%。除此之外，2007年5月在同一个期刊发表的文献显示，一位发生SJS的中国病患被发现该对偶基因检测呈阳性。
Phenytoin与其原型药物Fosphenytoin被用于控制大发作与复杂性局部癫痫发作。Phenytoin以Dilantin（辉瑞药厂）与Phenytek（Mylan药厂）的商品名销售。Fosphenytoin以Cerebyx（辉瑞药厂）的商品名销售，这两个产品都有许多俗名药剂型。
与使用carbamazepine有关的不良反应事件应该通报到FDA的Medwatch通报系统，可以透过打电话到1-800-FDA-1088或传真到-800-FDA-0178，线上通报网址为http://www.fda.gov/medwatch或邮寄到5600 Fishers Lane, Rockville, Maryland 20852-9787。
FDA Investigates Genetic Link to Phenytoin Skin Reactions
By Yael Waknine
Medscape Medical News
Patients positive for the human leukocyte antigen (HLA) allele HLA-B*1502 may be at increased risk for phenytoin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), the US Food and Drug Administration announced today.
Phenytoin is an antiepileptic drug with some structural similarity to carbamazepine, which was recently linked to an increased risk for SJS/TEN in patients positive for the allele. The allele occurs almost exclusively in individuals of Asian ancestry (Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais).
While the FDA is working to identify additional information regarding this issue, clinicians are advised to consider avoiding phenytoin and fosphenytoin as alternatives to carbamazepine therapy in patients who test positive for the allele.
However, there is not yet enough information to recommend testing for HLA-B*1502 in Asian patients for whom phenytoin treatment is contemplated, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program.
Preliminary data published in the May 2008 issue of Epilepsia suggest that the preliminary estimate of SJS risk in allele-positive patients new to phenytoin therapy is about 3% vs 0.3% for new users overall. In the study, all 4 patients with phenytoin-associated SJS were found to be positive for the HLA-B*1502 allele compared with 18% of those in the phenytoin-tolerant group. In addition, a May 2007 article in the same journal identified a single case of SJS in a Chinese patient who tested positive for the allele.
Phenytoin and its prodrug, fosphenytoin, are used to control tonic-clonic (grand-mal) and complex-partial epileptic seizures. Phenytoin is marketed as Dilantin (Pfizer Pharmaceuticals, Inc) and Phenytek (Mylan Pharmaceuticals, Inc). Fosphenytoin is marketed as Cerebyx (Pfizer); both products are also available in generic formulations from several manufacturers.
Adverse events related to use of carbamazepine should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.