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July 30, 2008 — 食品药物管理局(FDA)发出一项警讯，通知健康照护专家们有关于多发性硬化症（MS）病患接受mitoxantrone（以Novaantrone名称贩售）需要额外接受心脏检查的建议 [1]。
在2005年，mitoxantrone的仿单变更建议，在开始使用该药物进行治疗前，以及MS病患每次接受mitoxantrone治疗前，都应该评估病患的左心室射出分率（LVEF）；这些变更是根据上市后医疗文献病例报告描述，MS病患接受累积剂量100 mg/m2以下，有LVEF下降与新心脏衰竭的问题。
从那时候开始，FDA接受到一个显示临床执业上对该建议接受不佳的上市后研究报告，这项研究使用保险数据与回顾病历的方式，来检验临床执业上对此类病患监测心脏功能的现况；这项研究发现，4位病患在完成mitoxantrone治疗后4至17个月之间发生心脏衰竭。
有鉴于心脏毒性的潜在严重度，以及证据显示对于监测心脏功能的接受度不高，FDA目前正与mitoxantrone厂商合作来提醒健康照护专家们，针对使用该药物MS病患进行监测心脏功能的重要性。
除此之外，FDA与该厂商目前建议所有完成mitoxantrone疗程的MS病患，每年应该接受一次定量式LVEF评估，来侦测晚发性心脏毒性。
FDA针对接受mitoxantrone的MS病患做出以下建议：
对所有病患而言：
* 在开始使用mitoxantrone之前，以病史、理学检查与ECG评估心脏疾病的病征与症状。
* 进行治疗前定量式LVEF评估
罹患MS的病患：
* 治疗前LVEF低于正常值下限时，不应接受mitoxantrone的治疗。
* 病患应该接受心脏疾病相关病征与症状的检查、病史询问、理学检查与ECG
* 病患每次在接受mitoxantrone治疗后，都应该接受定量LVEF评估，且在每次评估时都使用相同的方法；病患在接受mitoxantrone治疗前，LVEF降低到低于正常值下限或是临床上显著变化时，就不应该再进行额外的治疗。
* 病患接受mitoxantrone累积剂量不要超过140 mg/m2
* 病患在停药后，应该每年接受定量LVEF评估，以监测是否发生延迟性心脏毒性，且在治疗期间也使用同样的评估方式。
对罹患癌症病患：
* 过去已经接受daunorubicin或是doxorubicin的病患，因为可能的心脏毒性，应考量到使用mitoxantrone所能带来的好处与坏处。
* 有心脏疾病病史的病患、过去曾接受胸膈与心包膜部位放射线治疗、过去曾经接受其他anthracyclines类药物或是anthracenediones类药物，或是同时使用其他具心脏毒性药物都可能增加心脏毒性风险；具有这些危险因子的病患应该常规地接受LVEF监测。
[1]. 给健康照护专家的资讯：mitoxantrone hydrochloride（以Novantrone与学名药物于市面上贩卖）；FDA警讯发布于2008年7月29日，相关资讯可以前往www.fda.gov网站查询。
完整的Heartwire内容，可以于www.heart.org上找到，这是ＷebMD的一个专业新闻服务，该网站是为心脏血管健康照护专家设立。
Additional Cardiac Monitoring for Patients on Mitoxantrone
By Sue Hughes
Medscape Medical News
July 30, 2008 — The FDA has issued an alert informing healthcare professionals about additional recommendations for cardiac monitoring of patients with multiple sclerosis (MS) who are treated with mitoxantrone (marketed as Novantrone and as generics) [1].
In 2005, the labeling for mitoxantrone was changed to recommend that left ventricular ejection fraction (LVEF) be evaluated before initiating treatment and before administering each dose of mitoxantrone to patients with MS. These changes were established in response to postmarketing and case reports in the medical literature that described decreases in LVEF or frank congestive heart failure in patients with MS who had received cumulative doses of mitoxantrone that were lower than 100?mg/m2.
Since that time, the FDA has received information from a postmarketing safety study that demonstrated poor adherence to these recommendations in clinical practice. This study used insurance-claims data and medical-record reviews to examine cardiac monitoring patterns in clinical practice. In this study, it was noted that four patients developed congestive heart failure 4 to 17 months after completing therapy with mitoxantrone.
Given the potential severity of cardiotoxicity and evidence suggesting poor adherence to the recommendations for monitoring cardiac function, the FDA is currently working with the manufacturers of mitoxantrone to remind healthcare professionals of the importance of adhering to the recommendations for patients with MS who are treated with mitoxantrone.
In addition, the FDA and the manufacturers are now advising that all patients with MS who have finished treatment with mitoxantrone receive yearly quantitative LVEF evaluations to detect late-occurring cardiac toxicity.
The FDA has issued the following recommendations for patients treated with mitoxantrone.
For All Patients
Assess signs and symptoms of cardiac disease with a history, physical examination, and ECG before initiating therapy with mitoxantrone.
Perform a baseline quantitative evaluation of LVEF.
For Patients With MS
Patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone.
Patients should be assessed for cardiac signs and symptoms with a history, physical examination, and ECG before each dose.
Patients should undergo a quantitative reevaluation of LVEF before each dose, using the same methodology for each assessment. Additional doses of mitoxantrone should not be administered to patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF during mitoxantrone therapy.
Patients should not receive a cumulative mitoxantrone dose greater than 140?mg/m2.
Patients should undergo yearly quantitative LVEF evaluations after stopping mitoxantrone to monitor for late-occurring cardiotoxicity, using the same methodology that was used for assessments that were done during treatment.
For Patients With cancer
The possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin should be considered when weighing the benefits and risks of mitoxantrone.
The presence or history of cardiovascular disease, previous or concomitant radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or the concomitant use of other cardiotoxic drugs might increase the risk of cardiac toxicity. LVEF should be monitored regularly after the initiation of therapy in patients with these risk factors.
Information for healthcare professionals: mitoxantrone hydrochloride (marketed as Novantrone and generics). FDA Alert. July 29, 2008. Available at www.fda.gov.
The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.