FDA担心CF药物Kalydeco可致儿童白内障

圣路易斯(MD Consult)——2012年8月29日，美国食品药品管理局(FDA)发布一则通告，表达了对于服用Kalydeco(ivacaftor)的囊性纤维化(CF)患儿可能发生白内障的安全性顾虑。FDA是在审查了近期一项动物研究的结果后提出这一潜在安全性问题的，这项青春期大鼠实验原本被用来支持对年龄小于2岁的幼儿使用该药。

Kalydeco已获准用于治疗年龄≥6岁、CF跨膜调节蛋白(CFTR)基因存在G551D突变的CF患儿。该药有助于使CFTR基因表达的蛋白更好地发挥功能，从而改善肺功能和CF的其他方面，例如增加体重。

这项动物研究的信息已被添加到Kalydeco产品标签的非临床毒理学-动物毒理学和(或)药理学部分。在接受ivacaftor治疗(剂量≥10 mg/kg•d，约为人类最大推荐剂量的1/10)的青春期大鼠(产后7~35天)中，研究者发现了白内障的情况。由于人类和大鼠的眼部发育存在差异，因此这一风险是否也存在于人类儿童目前尚不清楚。

为了更好地评估接受Kalydeco治疗的患儿的潜在白内障风险，FDA已要求该药生产商Vertex制药公司开展一项针对正在使用Kalydeco的患儿(年龄最大者11岁)的临床研究。这些患儿将接受至少2年的随访，并将每6个月接受1次眼科检查以评估视敏度和白内障/眼球混浊。

在获得进一步发现之前，建议正在接受Kalydeco 治疗的CF患儿和存在G551D突变的CF患儿继续使用该药。但是，同时建议医务人员与患儿家长/看护者讨论Kalydeco治疗的收益与风险。FDA还鼓励正在使用Kalydeco的患儿加入囊性纤维化基金会的患者登记。

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ST LOUIS (MD Consult) - On August 29, 2012, the US Food and Drug Administration (FDA) issued a notice about a potential safety concern for cataract development in children with cystic fibrosis (CF) taking the medication Kalydeco (ivacaftor). This potential safety concern arose after a review of recent results from an animal study in juvenile rats that was conducted to support the treatment of young children younger than 2 years with ivacaftor.

Kalydeco is approved for the treatment of CF in patients aged 6 years and older with the specific G551D mutation in the CF transmembrane regulator (CFTR) gene. In patients with this mutation, Kalydeco helps the protein made by the CFTR gene to function better and, as a result, improve lung function and other aspects of CF such as increasing weight gain.

Information about the animal study has been added to the Nonclinical Toxicology-Animal Toxicology and/or Pharmacology section of the Kalydeco product label. Cataracts were seen in juvenile rats treated with ivacaftor from postnatal days 7 to 35 at dose levels of 10 mg/kg/d and higher (approximately 1/10th of the maximum recommended human dose). Uncertainty exists about the relevance of this risk to children, because of differences in eye development between humans and rats.

To better assess the potential risk of cataracts in children receiving Kalydeco, the FDA is requiring the manufacturer, Vertex Pharmaceuticals, to conduct a clinical study in pediatric patients up to the age of 11 years who are being treated with Kalydeco. Patients will be followed up for at least 2 years and will receive eye examinations from an ophthalmologist at 6-month intervals to assess for both visual acuity and cataracts/eye opacities.

Until further information about these findings is known, it is recommended that patients with CF who are receiving Kalydeco and who carry a G551D mutation in the CFTR continue treatment. However, parents/caregivers are is also being encouraged to discuss the benefits and risks of Kalydeco treatment with their child's health care professional. The FDA is also encouraging patients taking Kalydeco to become part of the Cystic Fibrosis Foundation's Patient Registry.

学科代码：呼吸病学 儿科学 眼科学　　　关键词：囊性纤维化药物Kalydeco 儿童白内障
来源： MDC