作者：Laurie Barclay, MD
出處：WebMD醫學新聞
January 14, 2009 — 根據日前一篇由MedWatch發出的警訊，美國食品藥物管理局（FDA）繼續審查與使用Montelukast（Singulair，默克藥廠）有關的神經精神效應；MedWatch是FDA的安全資訊與不良事件通報系統。
這篇警訊代表FDA發表在2008年3月快訊的更新資訊。
FDA繼續審核對作用於白三烯素有關途徑的藥物，包括montelukast、Zafirlukast（Accolate，阿斯特捷利康藥廠）與Zileuton（Zyflo與Zyflo CR，Cornerstone Therapeutics藥廠），評估這些藥物造成神經精神藥物不良反應的臨床研究數據。FDA尚未對有關於montelukast、zafirlukast與zileuton的臨床研究數據對情緒與行為不良反應做出確定的結論。
FDA的不良反應通報系統已經取得上市後與montelukast、zafirlukast及zileuton有關神經精神事件報告。大部分神經精神事件報告都與montelukast有關，這是目前最常被處方，作用於白三烯素途徑的藥物。
有關於montelukast臨床研究的部分報告與藥物引起的事件有關。FDA指出，因為僅有少數報告是與zafirlukast與zileuton有關，評估這些藥物引起的事件是有限的。
FDA建議健康照護專業人員與照護者應該監測使用montelukast、zafirlukast與zileuton的病患可能有自殺、行為與情緒變化。有有關於這些可能效應問題的病患，在諮詢醫師之前不應該停止用藥。
在2008年3月27日，FDA通知健康照護專業人員與病患，該局對於使用montelukast與行為及情緒變化、自殺行為與執行自殺可能關聯的研究。
當時，FDA要求分析來自默克、阿斯特捷利康與Coenerstone Therapeutics藥廠的臨床研究數據，這些公司被指示使用哥倫比亞自殺評估分類流程來分類自殺事件。
在9,929位接受momtelukast治療的病患中，1位（0.01%）病患有自殺意圖，但沒有執行自殺的事件；接受zafirlukast或是zileuton的病患沒有自殺意圖或是執行自殺的事件。
根據FDA的新聞稿表示，這些研究數據並不代表montelukast、zafirlukast或是zileuton與自殺或是自殺行為有關，這些臨床研究並未被設計以檢驗神經精神事件，因此，某些事件可能並沒有被報導出來。
Montelukast是一種白三烯素受體拮抗劑，適用於治療氣喘或是過敏性鼻炎症狀（打噴嚏、鼻塞、流鼻水與鼻子癢），且用於預防運動引起的氣喘。
Zafirlukast也是一種用於治療氣喘的白三烯素受體拮抗劑；Zileuton是一種三烯素製造抑制劑，同樣用於治療氣喘。
與montelukast有關的不良反應事件都應該與FDA的MedWatch通報系統通報，可以透過電話1-800-FDA-1088或是傳真到1-800-FDA-0178，或是線上通報到http://www.fda.gov/medwatch或是以郵件寄到5600 Fishers Lane, Rockville, Maryland 20852-9787。
FDA Continues to Review Link Between Montelukast and Neuropsychiatric Effects
By Laurie Barclay, MD
Medscape Medical News
January 14, 2009 — The US Food and Drug Administration (FDA) is continuing to review clinical trial data regarding neuropsychiatric events associated with montelukast (Singulair, Merck), according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.
The alert represents updated information to the FDA's Early Communication issued in March 2008.
The FDA is continuing to review data from clinical trials to evaluate adverse neuropsychiatric events affecting mood and behavior associated with drugs acting through the leukotriene pathway, namely montelukast, zafirlukast (Accolate, AstraZeneca), and zileuton (Zyflo and Zyflo CR, Cornerstone Therapeutics). The FDA has not yet reached a definitive conclusion regarding these clinical trial data on mood and behavioral adverse events associated with montelukast, zafirlukast, and zileuton.
The FDA's Adverse Event Reporting System has received postmarketing reports of neuropsychiatric events associated with montelukast, zafirlukast, and zileuton. Although most of the neuropsychiatric event reports are associated with montelukast, it is currently the most commonly prescribed drug that acts through the leukotriene pathway.
"The clinical details of some reports involving montelukast are consistent with a drug-induced effect. Because of the paucity of reports involving zafirlukast and zileuton, assessment of a drug-induced effect with these is limited," the FDA points out.
The FDA advises healthcare professionals and caregivers to monitor patients taking montelukast, zafirlukast, and zileuton for suicidality and changes in behavior and mood. Patients with questions regarding these possible effects should not stop taking the drugs before consulting their physician.
On March 27, 2008, the FDA informed healthcare professionals and patients of the FDA's investigation of the possible link between use of montelukast and behavioral and mood changes, notably suicidal thinking, suicidal behavior, and completed suicide.
At that time, the FDA requested analyses of clinical trial data from Merck, AstraZeneca, and Cornerstone Therapeutics. The companies were instructed to use the Columbia Classification Algorithm of Suicide Assessment to classify suicidal events.
Of the 9929 patients treated with montelukast, 1 patient (0.01%) had suicidal ideation, and there were no completed suicides. None of the patients treated with zafirlukast or zileuton had suicidal ideation or completed suicide.
"Although these data do not suggest that montelukast, zafirlukast, or zileuton are associated with suicide or suicidal behavior, these clinical trials were not designed specifically to examine neuropsychiatric events. As a result, some events may not have been reported," according to an FDA news release.
Montelukast is a leukotriene receptor antagonist indicated for the treatment of asthma and symptoms of allergic rhinitis (sneezing and stuffy, runny, and itchy nose) and to prevent exercise-induced asthma.
Zafirlukast is also a leukotriene receptor antagonist used to treat asthma. Zileuton is a leukotriene synthesis inhibitor also used in the treatment of asthma.
Adverse events related to the use of montelukast 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. |
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