FDA要求加强对喹诺酮类外周神经病变风险的警告

美国食品药品管理局(FDA)要求对口服或注射剂型的氟喹诺酮类抗生素的潜在外周神经病变风险发出更强警告，必须更新相关药品的标签和患者用药指导。警告不适用于外用氟喹诺酮类制剂，因为这些制剂与神经病变无关。

FDA指出，神经病变可能性在2004年首次被加入所有喹诺酮类药物的标签，但当时的标签“未充分描述病变可能迅速发生和持续的风险”，因此有必要发出新的警告。

FDA对其不良事件报告系统（FAERS，也曾被称为AERS）数据库进行了回顾。FDA发现，2003年1月~2012年8月期间报告了若干与氟喹诺酮类药物相关、结局为“致残”的外周神经病变病例，但FDA未指明发现的病例数。这些报告提示，外周神经病变发病迅速，通常在开始喹诺酮类药物治疗后的数日内发生。一些报告称，即使已停药，神经病变仍可能持续长达1年之久。数据库中无法显示神经病变是否为永久性。

FDA称，尚无法确定任何外周神经病变发生的危险因素，但这种病变的发生似乎与患者年龄或使用抗生素治疗的时间无关。

更新的警告适用于所有经核准的氟喹诺酮类药物：左氧氟沙星(Levaquin)、环丙沙星(Cipro)、莫西沙星(Avelox)、诺氟沙星(Noroxin)、氧氟沙星(Floxin)和吉米沙星(Factive)。

根据FDA的数据，2011年有2300万例门诊患者按照处方接受了口服喹诺酮类药物治疗。其中，有70%接受环丙沙星处方治疗，28%接受左氧氟沙星处方治疗，9%接受莫西沙星处方治疗。2011年分别接受吉米沙星、氧氟沙星和诺氟沙星处方治疗的门诊患者均不足1%。

2011年有380万例住院患者接受注射用喹诺酮类药物治疗。最常见的处方药物为左氧氟沙星，占所有处方的63%，其次为环丙沙星(28%)和莫西沙星(13%)。

FDA建议，除非喹诺酮类药物治疗的效应超出风险，否则发生神经病变症状的患者应停用喹诺酮类药物，并改用另外一种抗生素治疗。患者在接受此类药物治疗期间如发生神经病变症状，应立即告知医生。

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By: ALICIA AULT, Clinical Neurology News Digital Network

The Food and Drug Administration is requiring a stronger warning about the potential for peripheral neuropathy with fluoroquinolone antibiotics that are taken orally or by injection.

The warning does not apply to topical formulations, which have not been associated with neuropathy. Drug labels and patient medication guides must be updated, said the agency.

The potential for neuropathy was first added to the labels of all drugs in the class in 2004. The new warning was necessary because "the potential rapid onset and risk of permanence were not adequately described" in the 2004 label iteration, the FDA noted.

Before requiring new warnings, the FDA reviewed its Adverse Event Reporting System (FAERS, formerly known as AERS) database. The agency found that cases of fluoroquinolone-associated peripheral neuropathy with an outcome of "disability" had been reported to the AERS database between January 2003 and August 2012, although the FDA did not say how many cases it found. The reports indicated a rapid onset of peripheral neuropathy, often within a few days of starting the quinolone. Some cases reported neuropathy that continued for a year, even though the medication had been stopped.

The database was not able to show whether neuropathy was permanent, however, because it is designed to collect spontaneous reports.

The FDA said it had not been able to identify any risk factors for the development of peripheral neuropathy. But the onset of the condition seemed to have no correlation with the patient’s age or how long they took the antibiotic.

The updated warnings apply to all approved fluoroquinolones: levofloxacin (Levaquin), ciprofloxacin (Cipro), moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), and gemifloxacin (Factive).

According to the FDA, 23 million outpatients were prescribed an oral quinolone in 2011. A total of 70% received ciprofloxacin; 28% were prescribed levofloxacin; and 9% were given moxifloxacin. Gemifloxacin, ofloxacin, and norfloxacin each accounted for less than 1% of those patients in 2011.

There were 3.8 million inpatients who received an injectable quinolone in 2011. The most-prescribed was levofloxacin, accounting for 63% of prescriptions, followed by ciprofloxacin (28%) and moxifloxacin (13%).

The agency recommended that patients who develop neuropathy symptoms stop taking the quinolone and be treated with a different antibiotic, unless the benefit outweighs the risk. Patients taking the medications who develop symptoms are urged to tell their physician immediately.