September 11, 2007 — 美國食品藥物管理局(FDA)對健康專業人員提出警告,臨時限定nelfinavir mesylate (Viracept,輝瑞藥廠製造)在孩子和孕婦的使用上應有所限制。
  這是依據生產過程不潔造成的高濃度乙基甲磺酸(ethyl methanesulfonate,EMS)所提出的警告,雖然沒有人類資料,但動物研究指出EMS是致畸胎、致突變、致癌物質。
  根據FDA安全資訊與不良事件通報系統MedWatch所發出的警訊,對於使用含nelfinavir處方而情形穩定的小兒病患,以及沒有其他治療選擇之懷孕婦女,利益風險比仍可接受,且可以繼續 nelfinavir治療。
  目前採取的行動是確認 EMS符合最終可接受限制,該公司和FDA同意的暫時說明書中,理論上每十萬件有不到17例會增加癌症風險;長期說明書則將風險限制到每十萬件有不到 1例;HIV族群的背景發生率,目前估計是每1000病患-年(patient-years)有20到30個案例。
  Nelfinavir是一種蛋白酶抑制劑,與其他抗反轉錄病毒藥物(antiretroviral agents)用於治療HIV感染。

Viracept Use Should Be Limited

By Yael Waknine
Medscape Medical News

September 11, 2007 — Interim specifications for use of nelfinavir mesylate (Viracept, Pfizer, Inc) preclude initiation of therapy in children and pregnant women, the US Food and Drug Administration warned healthcare professionals yesterday.

These measures are based on the risk for high levels of ethyl methanesulfonate (EMS), a process-related impurity. Although no human data exist, animal studies indicate that EMS is teratogenic, mutagenic, and carcinogenic.

For pediatric patients who are stable on nelfinavir-containing regimens and pregnant women with no other therapeutic options, the benefit-risk ratio remains favorable, and nelfinavir therapy may be continued, according to an alert sent from MedWatch, the FDA's safety information and adverse event reporting program.

Although other patients are not currently affected by these measures, a temporary interruption of drug supply in the future may require switching to alternative products.

Earlier this year, excess levels of EMS prompted a recall of nelfinavir in the European Union; subsequent testing revealed levels to be substantially lower in the US product and within final acceptable limits.

Toxicology experts generally agree that the lifetime risk associated with exposure to a carcinogen is about 3-fold greater among pediatric patients aged 2 to 16 years and is even higher for those aged younger than 2 years, the company said in a letter to doctors. These data were used to determine acceptable levels of EMS in pediatric formulations of nelfinavir.

Action is currently being taken to ensure that EMS levels meet final acceptable limits. Interim specifications agreed on by the company and the FDA limit the theoretical lifetime increased cancer risk in adults to fewer than 17 cases per 100,000 exposed; long-term specifications limit the risk to less than 1 case per 100,000 exposed. The background incidence in the HIV population is currently estimated to be 20 to 30 cases per 1000 patient-years.

Nelfinavir is a protease inhibitor indicated with other antiretroviral agents for the treatment of HIV infection.

2009/11/19 下午 03:17:00
2009/5/27 上午 11:40:00
2009/4/2 上午 10:57:00

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