FDA要求降低某些安眠药的推荐剂量

美国食品药品管理局(FDA)于1月10日宣布降低某些含有唑吡坦(zolpidem)安眠药剂量的新要求，这些药物包括安必恩(Ambien)、安必恩缓释片、Edluar和ZolpiMist。安必恩和安必恩缓释片的仿制药也已上市。这项行动是模拟驾驶和实验室研究最新数据公布的结果，该研究数据显示，服用唑吡坦的部分患者次日早晨仍维持较高血药水平，足以影响包括驾车在内的需要警觉的活动。

“在分析最新数据之后，我们认为有必要在这些药品的标签中添加新的药物安全信息，包括降低推荐剂量。”FDA药物评价与研究中心药物评价办公室主任Ellis Unger在1月10日的电话会议期间说道。“我们希望通过服用较小剂量唑吡坦而降低次日早晨血药水平。我们强烈要求医疗专业人员提醒所有服用这些药物的患者有关药物影响次日早晨需要充分精神警觉活动的风险。”

对于女性，FDA目前推荐速释产品唑吡坦剂量由10 mg降至5 mg，缓释产品的剂量由12.5 mg 降至6.25 mg(安必恩和安必恩缓释片的仿制药也已上市。)“我们最近了解到，女性对次日早晨影响风险更为敏感，因为她们体内消除唑吡坦的速率小于男性。”Unger博士指出，这一关联的原因尚不清楚。“校正患者身材大小后，药物水平并不能解释男女(在药物消除方面)的差异。”对于男性，FDA建议医疗专业人员应考虑给予同样较低剂量的唑吡坦(速释产品5 mg，缓释产品6.25 mg)。

详细内容参见同时发布的《药物安全通讯》。尽管发布新建议，但Unger博士强调，目前正在服用较高剂量上述安眠药的患者“在与他们的医生讨论其情况并决定如何安全服药之前，应继续按照原来的处方服药。每位患者的情况不同，应与各自的医生讨论合适剂量。”

Unger博士还解释说，对次日早晨活动的影响不仅限于含有唑吡坦的安眠药物。“所有安眠药物均有可能产生这一影响。因此，对于所有的安眠药物，医疗专业人员均应开具能够预防失眠的最低剂量。较低剂量将会减少对次日早晨活动的潜在影响。患者若次日早晨必须驾车或完成其他需要充分警觉的活动，应与其医疗专业人员讨论他们是否适合服用安眠药物问题。”

他总结指出，FDA将继续评估其他安眠药物对精神警觉损害的风险，包括非处方药物。

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By: DOUG BRUNK, Internal Medicine News Digital Network

The U.S. Food and Drug Administration announced Jan. 10 new, lower dosing requirements for certain sleep drugs that contain zolpidem, including Ambien, Ambien CR, Edluar, and ZolpiMist. Ambien and Ambien CR are also available as generics. The move comes on the heels of new data from driving simulation and laboratory studies showing that zolpidem blood levels in some individuals may be high enough the morning after use to impair activities that require alertness, including driving.

"After analyzing these new data we felt it necessary to add new drug safety information to the labeling, including lowering of the recommended dose," Dr. Ellis Unger, director of the Office of Drug Evaluation in the FDA’s Center for Drug Evaluation and Research, said during a Jan. 10 teleconference. "We hope that use of lower doses of zolpidem will mean that less drug will be in the bloodstream in the morning hours. We urge health care professionals to caution all patients who use these products about the risks of next morning impairment for activities that require complete mental alertness."

For women, the FDA now recommends that the dose of zolpidem should be lowered from 10 mg to 5 mg for immediate-release products and from 12.5 mg to 6.25 mg for extended-release products. (Ambien and Ambien CR are also available as generics.) "We have learned rather recently that women appear to be more susceptible to the risk of next morning impairment, because they eliminate zolpidem more slowly from their bodies than men," Dr. Unger said, noting that reasons for this association remain unclear. The supposition that women are smaller in size, compared with men, "is the first thing that one would think of," he said. "But if you correct the drug level data for patient size, that doesn’t account for the difference between men and women [in how the drug is eliminated]." For men, the FDA advises health care professionals to consider these same lower doses (5 mg for immediate-release products and 6.25 mg for extended release products).

More details about the development can be found in a Drug SafetyCommunication that was issued concomitantly. Despite the new recommendations, Dr. Unger emphasized that patients who are currently taking the higher doses of these sleep drugs "should continue to take the drug as it’s been prescribed until they discuss their situation with their health care provider and figure out how to continue to take the medication safely. We know that each patient is unique. The appropriate dose should be discussed with their health care professional."

Dr. Unger also explained that next morning impairment is not limited to sleep drugs that contain zolpidem. "All sleep drugs have the potential to cause this," he said. "So for all sleep medications all health care professionals should prescribe the lowest dose that is capable of preventing insomnia. The lower doses will decrease the potential for next morning impairment. Patients who must drive the next morning or perform other activities requiring full alertness should talk to their health care professional about whether sleep medicine is appropriate for them."

He concluded his remarks by noting that the FDA is continuing to evaluate the risk of impaired mental alertness with other insomnia drugs, including those sold over the counter.