ST LOUIS (MD Consult) - On June 3, 2009, the US Food and Drug Administration (FDA) announced that it is notifying health care professionals of the risk of serious liver injury, including liver failure and death, with the use of propylthiouracil (PTU) in adult and pediatric patients. PTU is used for the treatment of hyperthyroidism that occurs as a result of Graves' disease.

Reports to the FDA's Adverse Event Reporting System (AERS) suggest that PTU treatment is associated with a higher risk of hepatotoxicity than treatment with methimazole (MMI), another drug indicated for hyperthyroidism in Graves' disease. The FDA has identified 32 cases (22 adult and 10 pediatric) of serious liver injury associated with PTU use. Of the adult cases, 12 deaths and 5 liver transplants occurred. Among the pediatric patients, 1 case resulted in death and 6 resulted in liver transplants. In contrast, only 5 AERS cases of serious liver injury were identified in patients who had received MMI. All 5 cases occurred in adults and 3 patients died.

In general, PTU is considered second-line drug therapy except in patients who are allergic to or intolerant of MMI. Rare cases of embryopathy, including aplasia cutis, have been reported with the use of MMI during pregnancy, whereas no such cases have been reported with PTU use. Thus, PTU may be more appropriate for patients with Graves' disease who are in their first trimester of pregnancy.

The FDA is urging health care professionals to carefully consider which of the two drugs to initiate in patients recently diagnosed with Graves' disease. Physicians should closely monitor patients on PTU therapy for manifestations of liver injury, especially during the first 6 months after treatment initiation. PTU should not be used in pediatric patients unless a patient is allergic to or intolerant of MMI, and only if no other treatment options are available.

On April 18, 2009, the FDA held a public workshop with the American Thyroid Association (ATA) to discuss PTU-related hepatotoxicity. The FDA is continuing to monitor these serious reported adverse events and is working to make changes to the PTU prescribing information, particularly in the area of pediatric use. In addition, the ATA plans to update its treatment guidelines for Graves' disease in the upcoming months.

圣路易斯(MD Consult)——2009年6月3日，美国食品药品管理局(FDA)通告卫生专业人员：对成人和儿童患者应用丙基硫氧嘧啶(PTU)有导致严重肝损伤(包括肝功能衰竭和死亡)的风险。PTU日前用于治疗由Graves病导致的甲状腺功能亢进。

FDA不良事件报告系统(AERS)收到的报告显示，与另一种适用于治疗Graves病所致的甲状腺功能亢进的药物甲巯咪唑(MMI)相比，PTU治疗会增加发生肝毒性的风险。FDA已确认32例发生严重肝损伤的患者与使用PTU有关(成人22例，儿童10例)。在成人患者中，有12例死亡，5例进行了肝移植。在儿童患者中，有1例死亡，6例进行了肝移植。相比之下，接受MMI治疗的患者中AERS确认仅有5例出现严重肝损伤。这5例均为成人，其中3例死亡。

除非对甲巯咪唑过敏或不耐受，在一般患者中PTU一般作为二线药使用。已有报道指出，妊娠期间使用MMI治疗可偶发生育缺陷等胚胎病，而PTU未见此类相关报道，故PTU可能更适用于治疗处于妊娠期前3个月的Graves病患者。

FDA敦促卫生专业人员，对新确诊的Graves病患者应慎重考虑从这两种药物中选择哪种开始治疗。选择PTU治疗后，医生应密切监测患者是否有肝损伤的征象，特别是在开始治疗后的前6个月。PTU不应当用于儿童患者，除非其对甲巯咪唑过敏或不耐受且无其他选择。

2009年4月18日，FDA与美国甲状腺协会(ATA)就PTU相关的肝毒性举行了公开讨论会。FDA会继续关注这些严重的不良事件报告，同时努力对PTU的处方资料进行更改，尤其是在儿科领域的应用。此外，ATA拟于下个月对Graves病的治疗指南进行更新。

爱思唯尔 版权所有