ST LOUIS (MD Consult) - On March 27, 2008, the US Food and Drug Administration (FDA) announced it was reviewing safety data that raised concerns about a possible association between the use of montelukast and behavior/mood changes, suicidality (suicidal thinking and behavior), and suicide.

The FDA requested manufacturers of products indicated for treating asthma and/or allergic rhinitis that act through the leukotriene pathway (montelukast, zafirlukast, zileuton) to submit adverse-event data for suicidality adverse events as well as mood and behavioral-related adverse events from all available placebo-controlled clinical trials. (Early Communication About an Ongoing Safety Review of Montelukast (Singulair), http://www.fda.gov/cder/drug/early_comm/montelukast.htm).

The FDA said at the time it expected its preliminary review to take about 9 months and that it would communicate conclusions and any resulting recommendations to the public at the completion of the review.

The FDA is continuing to review clinical trial data to assess other neuropsychiatric events (mood and behavioral adverse events) related to drugs that act through the leukotriene pathway. As a result, the FDA hasn't reached a conclusion regarding the clinical trial data on mood and behavioral adverse events associated with montelukast, zafirlukast, and zileuton. The FDA will communicate conclusions and any recommendations to the public at the conpletion of the review, which may take months.

Postmarketing reports of neuropsychiatric events associated with montelukast, zafirlukast, and zileuton have been reported to the FDA's Adverse Event Reporting System (AERS). Most of the reports of neuropsychiatric events are associated with montelukast, 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. Therefore, patients and prescribers should monitor for the possibility of neuropsychiatric events associated with these agents.

Singulair (montelukast) is a medicine in the drug class known as leukotriene receptor antagonists. Leukotriene receptor antagonists work by blocking substances in the body called leukotrienes. Leukotrienes are chemicals the body releases in response to an inflammatory stimulus, such as when a person breathes in an allergen. Singulair is used to treat asthma and the symptoms of allergic rhinitis (sneezing, stuffy nose, runny nose, itching of the nose) and to prevent exercise-induced asthma.

Accolate (zafirlukast) is also a medicine in the drug class known as leukotriene receptor antagonists. Accolate is used to treat asthma. Zyflo and Zyflo CR (zileuton) are medicines in the drug class known as leukotriene synthesis inhibitors. Leukotriene synthesis inhibitors work by stopping the formation of certain natural substances that cause swelling, tightening, and mucus production in the airways. Zyflo and Zyflo CR are used to treat asthma.

The FDA urges health care professionals and patients to report adverse effects from the use of Singulair, Accolate, Zyflo, and Zyflo CR to the FDA's MedWatch Adverse Event Reporting program:

• Report online at www.fda.gov/medwatch/report.htm.
  
   
• Return the postage-paid FDA form 3500 available in PDF format at www.fda.gov/medwatch/getforms.htm to 5600 Fishers Lane, Rockville, MD 20852-9787.
  
   
• Fax the form to 1-800-FDA-0178.
  
   
• Phone 1-800-332-1088. 

圣路易斯（MD Consult）——2008年3月27日，美国食品与药物管理局（FDA）宣布正在评估引起关注的应用孟鲁司特可能引起行为/情绪改变、自杀倾向（自杀意念和行为）和自杀的相关安全性数据。

FDA要求生产孟鲁司特、扎鲁司特和齐留通这类通过白三烯路径起作用的治疗哮喘和（或）过敏性鼻炎药品的厂家提供不良事件数据，包括来自所有已完成的安慰剂对照临床试验的自杀倾向及情绪和行为相关不良事件的数据。[此前FDA对孟鲁司特(顺尔宁)进行的安全性评估见：http://www.fda.gov/cder/drug/early_comm/montelukast.htm]

当时，FDA声称预期初步评估时间约需9个月，当评估完成后将向公众宣布结论及形成推荐意见。

目前，FDA仍在继续审查临床试验数据，以评估通过白三烯路径起作用药品的其它相关神经精神（情绪和行为）不良事件。目前，FDA仍未根据临床试验数据就孟鲁司特、扎鲁司特和齐留通是否与情绪和行为不良事件相关形成结论。评估仍将持续数月，FDA将在评估完成时向公众宣布结论和形成推荐意见。

产品上市后报告的孟鲁司特、扎鲁司特和齐留通相关神经精神不良事件已经上报至FDA不良事件报告系统（AERS）。大多数报告的神经精神不良事件与孟鲁司特（目前最常处方的通过白三烯路径起作用的药品）相关。某些涉及孟鲁司特的报告中描述的临床表现与药物性副作用表现相一致。

由于缺乏关于扎鲁司特和齐留通的报告，限制了对这两种药物相关副作用的评估。因此，患者和处方者应监测这两种药物相关神经精神不良事件出现的可能性。

顺尔宁（孟鲁司特）是一种白三烯受体拮抗剂。白三烯受体拮抗剂通过阻滞人体内白三烯而起效。白三烯是人体在发生炎症刺激（例如当人吸入过敏原）时释放的一种化学物质。顺尔宁用于治疗哮喘和过敏性鼻炎症状（喷嚏、鼻塞、流鼻涕、鼻痒）及预防运动性哮喘。

安可来（扎鲁司特）也是一种用于治疗哮喘的白三烯受体拮抗剂。Zyflo和Zyflo CR (齐留通)是一种白三烯合成抑制剂。白三烯合成抑制剂通过终止某些可引起气道内水肿、收缩和黏液产生的物质形成而起效。Zyflo和Zyflo CR也是用于治疗哮喘。

FDA要求医生和患者将与使用顺尔宁、安可来、Zyflo和Zyflo CR相关的不良反应上报至FDA MedWatch不良事件报告系统：
 

• 在线报告： www.fda.gov/medwatch/report.htm.
• 邮寄预付邮资的FDA 3500表格（可从www.fda.gov/medwatch/getforms.htm下载PDF格式）至：5600 Fishers Lane, Rockville, MD 20852-9787。
• 将上述表格传真至：1-800-FDA-0178
• 电话：1-800-332-1088

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