ST LOUIS (MD Consult) - On August 26, 2009, the US Food and Drug Administration announced that Tibotec Therapeutics has issued a letter to health care professionals to inform them of updated safety information for the drug Intelence (etravirine). Intelence is considered an antiretroviral non-nucleoside reverse transcriptase inhibitor and is used in the treatment of infection with human immunodeficiency virus (HIV).
The safety update can be found in the revised product label for Intelence. Tibotec has updated the Warnings and Precautions section of the label to reflect an increased level of concern regarding the risk of severe skin reactions. The new label mentions that postmarketing reports have been received about a fatality resulting from toxid epidermal necrolysis, as well as hypersensitivity reactions that have sometimes been accompanied by hepatic failure.
Prescribers of Intelence are now advised to have their patients discontinue use of the drug immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions occur (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, and eosinophilia). In addition, the clinical status of affected patients should be monitored, liver transaminase testing should be performed, and appropriate therapy should be initiated. Physicians are being warned that delays in stopping treatment with Intelence after the onset of severe rash may result in a life-threatening reaction.
Tibotec relates that in phase 3 studies of Intelence, the most frequently reported adverse drug reaction of at least grade 2 in severity was rash (9.0%). Stevens-Johnson syndrome, hypersensitivity reaction, and erythema multiforme were reported in <0.1% of patients during clinical development with Intelence. In clinical trials, rash was generally considered mild to moderate, occurred primarily in the second week of therapy, and was infrequent after 4 weeks of therapy. Rash generally resolved within 1 to 2 weeks on continued therapy. In phase 3 trials, a total of 2% of HIV-1–infected patients receiving Intelence discontinued participation as a result of rash.
圣路易斯(MD Consult)——美国食品药品管理局(FDA)在2009年8月26日宣布：Tibotec Therapeutics 公司发出信件，告知医务工作人员 Intelence(通用名：依曲韦林)的安全性信息已经更新。该药属于非核苷类逆转录酶抑制剂(NNRTI)，用于治疗人类免疫缺陷病毒(HIV)感染。
在Intelence修改后的药品标签中可找到该安全更新。Tibotec 公司更新了标签的“警告及注意事项”栏目，反映出对严重皮肤反应风险忧虑的不断加深。新标签提到，上市后已收到中毒性表皮坏死松解症引发死亡以及发生超敏性反应时伴有肝衰竭的报告。
若患者出现严重皮肤反应或过敏反应的症状或体征，则建议医生应立即停止使用Intelence。此类症状或体征包括但不限于严重皮疹或皮疹伴有发热、全身不适、乏力、肌肉或关节疼痛、水疱、口腔溃疡、结膜炎、面部水肿、肝炎、嗜酸细胞增多等。此外，对发生副作用的患者，应监测其临床状况并测定肝转氨酶水平，着手进行合理的治疗。新安全性信息警告称，倘若发生严重皮疹而未及时停药，则可能因过敏反应而危及生命。
Tibotec 陈述道：在Intelence的III期临床试验中，严重程度达2级以上最常见的药物不良反应为皮疹(9.0%)。据报告称，Stevens-Johnson综合征、过敏性反应、多形性红斑在试验患者中的发生率小于0.1%。试验中出现的皮疹通常呈轻至中度，主要发生于治疗第2周，第4周以后并不常见。如继续治疗，皮疹一般在1~2周内消失。在III期临床试验中，接受Intelence 治疗的HIV-1感染患者中有2% 的受试者因发生皮疹而退出试验。
