Marcum Zachary A, Vande Griend Joseph P, Linnebur Sunny A
Department of Medicine, Division of Geriatric Medicine, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, USA.
Am J Geriatr Pharmacother. 2012 Aug;10(4):264-71. doi: 10.1016/j.amjopharm.2012.05.002. Epub 2012 Jun 8.
The US Food and Drug Administration (FDA) has new regulatory authorities intended to enhance drug safety monitoring in the postmarketing period. This has resulted in an increase in communication from the FDA in recent years about the safety profile of certain drugs. It is important to stay abreast of the current literature on drug risks to effectively communicate these risks to patients, other health care providers, and the general public.
To summarize 4 new FDA drug safety communications by describing the evidence supporting the risks and the clinical implications for older adults.
The FDA Web site was reviewed for new drug safety communications from May 2011 to April 2012 that would be relevant to older adults. Approved labeling for each drug or class was obtained from the manufacturer, and PubMed was searched for primary literature that supported the drug safety concern.
FDA drug safety communications for 4 drugs were chosen because of the potential clinical importance in older adults. A warning for citalopram was made because of potential problems with QT prolongation in patients taking less than 40 mg per day. The evidence suggests minor changes in QT interval. Given the flat dose-response curve in treating depression with citalopram, the new 20-mg/d maximum dose in older adults is sensible. Another warning was made for proton pump inhibitors (PPIs) and an increased risk of Clostridium difficile infection. A dose-response relationship was found for this drug risk. With C. difficile infections on the rise in older adults, along with other safety risks of PPI therapy, PPIs should only be used in older adults indicated for therapy for the shortest duration possible. In addition, a warning about dabigatran was made. There is strong evidence from a large clinical trial, as well as case reports, of increased bleeding risk in older adults taking dabigatran, especially in older adults with decreased renal function. This medication should be used with caution in older adults. Finally, several warnings were made about statins. Routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury from statin use; thus, liver enzymes are no longer recommended to be routinely monitored. Statin-induced cognitive changes are rare, and insufficient evidence is currently available to establish causality. Statins appear to moderately increase the risk of developing diabetes (versus placebo), and regular screening for diabetes should be considered, especially for patients taking high-dose statins and patients with multiple risk factors for diabetes.
FDA drug safety communications incorporate complex methodologies that investigate the risks (and relative benefits) of medication therapy. Clinicians caring for older adults need to be aware of the most current evidence behind these drug risks to effectively communicate with and care for their patients.
美国食品药品监督管理局（FDA）拥有新的监管权力，旨在加强上市后药品安全性监测。这导致近年来FDA关于某些药物安全性概况的沟通有所增加。及时了解有关药物风险的最新文献对于有效地向患者、其他医疗保健提供者和公众传达这些风险非常重要。
通过描述支持风险的证据以及对老年人的临床意义，总结FDA的4项新的药品安全沟通。
审查FDA网站，查找2011年5月至2012年4月与老年人相关的新药品安全沟通。从制造商处获取每种药物或药物类别的批准标签，并在PubMed上搜索支持该药物安全问题的原始文献。
选择了4种药物的FDA药品安全沟通，因为它们对老年人具有潜在的临床重要性。对西酞普兰发出警告，因为每天服用剂量低于40毫克的患者存在QT间期延长的潜在问题。证据表明QT间期有轻微变化。鉴于西酞普兰治疗抑郁症时剂量反应曲线较为平缓，老年人新的每日最大剂量20毫克是合理的。对质子泵抑制剂（PPI）发出另一项警告，其艰难梭菌感染风险增加。发现了这种药物风险的剂量反应关系。随着老年人艰难梭菌感染率上升，以及PPI治疗的其他安全风险，PPI仅应用于有明确治疗指征的老年人，且使用时间应尽可能短。此外，对达比加群发出警告。一项大型临床试验以及病例报告提供了有力证据，表明服用达比加群的老年人出血风险增加，尤其是肾功能减退的老年人。这种药物在老年人中应谨慎使用。最后，对他汀类药物发出了几项警告。定期常规监测肝酶似乎无法有效检测或预防他汀类药物使用导致的严重肝损伤；因此，不再建议常规监测肝酶。他汀类药物引起的认知变化很少见，目前尚无足够证据确定因果关系。他汀类药物似乎会适度增加患糖尿病的风险（与安慰剂相比），应考虑定期筛查糖尿病，特别是对于服用高剂量他汀类药物的患者以及有多种糖尿病风险因素的患者。
FDA的药品安全沟通采用了复杂的方法来调查药物治疗的风险（和相对益处）。照顾老年人的临床医生需要了解这些药物风险背后的最新证据，以便有效地与患者沟通并提供护理。
