双氯芬酸产品标签更新，警示该品可导致肝脏酶升高
时间:2009-12-24 09:56:26
发布/来源：爱思维尔中国医学网站
2009年12月4日，美国食品药品管理局(FDA)宣布，Endo和诺华公司召告广大医务人员：对于所有含双氯芬酸钠的产品(包括Voltaren止痛凝胶)，现已修改了处方信息中“对肝脏的影响”部分的文字。更新后的产品标签增加了有关治疗期间肝功能检查结果可能出现酶升高的警示语及相关注意事项。
上市后报告显示，用药第1个月内有出现药物致肝脏毒性的病例报道，但只要是在双氯芬酸治疗期间，任何时候都可能出现肝脏毒性。上市后监测报告发现了重度肝脏不良反应病例，包括肝脏坏死、黄疸、暴发性肝炎伴或不伴黄疸、肝衰竭等。在部分病例中，该不良反应甚至导致患者死亡或肝移植。
FDA建议，对于长期接受双氯芬酸治疗的患者，医生应定期监测其转氨酶水平。目前尚不清楚初次及后续转氨酶检测的最佳时机。基于临床试验数据和上市后经验，FDA建议在患者开始双氯芬酸治疗后4~8周内对转氨酶水平进行监测。临床医生应该意识到，重度肝脏毒性可能在不出现任何明显前驱症状的情况下发生。如果肝功能检查结果持续异常或不断加重，临床体征或症状符合肝病表现，或出现了明显的全身性表现，如嗜酸性粒细胞增多、皮疹、腹痛、腹泻或深色尿，则应立即终止双氯芬酸治疗。
为了最大程度地避免在两次转氨酶检测之间的间隔期内患者发展成重度肝损害，建议医生告知正在服药的患者有关肝脏损害的警示症状和体征(如恶心、乏力、嗜睡、腹泻、瘙痒、黄疸、右上腹压痛以及流感样症状)。还应告知患者一旦出现了这类症状和体征应采取的恰当措施。
为了尽可能地降低接受双氯芬酸治疗的患者出现肝脏相关不良事件的潜在风险，应采用最小有效剂量，并尽量缩短用药时间。采用双氯芬酸钠治疗期间，还应谨慎考虑其他合并用药，避免使用已知具有潜在肝脏毒性的药物(如抗生素和抗癫痫药物)。
Updated labels for diclofenac products now contain warnings about elevated liver enzymes
2009-12-11 【发表评论】
中文 | ENGLISH | 打印
ST LOUIS (MD Consult) - On December 4, 2009, the US Food and Drug Administration (FDA) announced that Endo and Novartis issued a notification to health care professionals about revisions to the Hepatic Effects section of the prescribing information for all products containing diclofenac sodium (including Voltaren gel). The updated labels contain new warnings and precautions about the possibility of elevations in liver function test results during treatment.
In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month but can occur at any time during treatment with diclofenac. Postmarketing surveillance reports include cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these reported cases resulted in fatalities or liver transplantation.
The FDA is advising physicians to periodically measure transaminase levels in patients receiving long-term therapy with diclofenac. The optimum times for making the first and subsequent transaminase measurement are not known. On the basis of clinical trial data and postmarketing experiences, the FDA recommends that transaminase levels be monitored within 4 to 8 weeks after patients initiate treatment with diclofenac. Physicians should be aware that severe hepatotoxicity may occur without a prodrome of distinguishing symptoms. If abnormal liver function values persist or worsen, if clinical signs and/or symptoms consistent with liver disease emerge, or if systemic manifestations such as eosinophilia, rash, abdominal pain, diarrhea, or dark urine become evident, treatment with diclofenac should be discontinued immediately.
To minimize the possibility that hepatic injury will become severe between transaminase measurements, physicians are being advised to inform patients receiving the drug of the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and flu-like symptoms). Patients should also be instructed about the appropriate action to take if these signs and symptoms appear.
To minimize the potential risk for an adverse liver-related event in patients treated with diclofenac, the lowest effective dose should be used for the shortest duration possible. Caution should be exercised in prescribing diclofenac sodium with concomitant drugs that are known to be potentially hepatotoxic
