FDA警告：肺动脉高压治疗药物Revatio禁用于儿童

圣路易斯(MD Consult)——2012年8月30日，美国食品药品管理局(FDA)发布了一则关于使用Revatio (西地那非)治疗肺动脉高压(PAH)儿童患者的安全通告。经过对长期临床试验数据的回顾性分析， FDA建议临床医生不要将Revatio用于年龄介于1~17岁的PAH患者。Revatio从未获准用于PAH儿童患者的治疗，但FDA担心可能存在超适应证使用的问题。

在一项随机、双盲、多中心、安慰剂对照、平行组、剂量范围临床试验中，234例年龄介于1~17岁的PAH患者被随机分组，接受小剂量、中等剂量或大剂量的Revatio或者安慰剂，共治疗16周。该试验的主要目的是评估Revatio对患者运动能力的影响，平均随访3年。该试验的结果促使FDA得出结论：与服用小剂量Revatio的患儿相比，服用大剂量Revatio的患儿死亡风险更高，并且小剂量Revatio无法有效改善患者的运动能力。

Revatio获准用于改善PAH成年患者的运动能力并延缓疾病的临床进展。尚不清楚长期使用Revatio对成年患者死亡风险的影响。FDA现要求Revatio的生产商辉瑞公司开展研究以评估该药对PAH成年患者死亡风险的影响。

西地那非是一种磷酸二酯酶-5抑制剂。该药还有一种商品名是万艾可，获准用于治疗勃起功能障碍。鉴于这两种产品在目标患者人群以及推荐剂量方案上的差异，FDA目前并不认为万艾可的使用也存在这一安全性隐患。

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ST LOUIS (MD Consult) - On August 30, 2012, the US Food and Drug Administration (FDA) issued a safety notice about the use of Revatio (sildenafil) for the treatment of children with pulmonary arterial hypertension (PAH). A recent review of data from a long-term clinical trial has prompted the FDA to recommend that Revatio not be prescribed for patients aged 1 to 7 years with PAH. Revatio has never been approved for the treatment of PAH in children, but the FDA is concerned that the drug may be considered for use in an off-label manner.

In a randomized, double-blind, multicenter, placebo-controlled, parallel-group, dose-ranging clinical trial, 234 patients with PAH, aged 1 to 17 years, were randomly assigned to receive low-, medium-, or high-dose Revatio or placebo for 16 weeks of treatment. The primary objective of the trial was to assess the effect of Revatio on exercise capacity. Patients were followed for a mean of 3 years. Results from that trial led the FDA to conclude that children taking a high dose of Revatio had a higher risk of death than children taking a low dose, and that low doses of Revatio are not effective in improving exercise ability.

Revatio is approved to improve exercise ability and delay clinical worsening of PAH in adult patients. The effect of Revatio on the risk of death with long-term use in adults is unknown. The FDA is requiring the manufacturer of Revatio (Pfizer) to evaluate the drug's effect on the risk of death in adults with PAH.

Sildenafil ia a phosphodiesterase-5 inhibitor. The drug is also marketed as Viagra, and is approved for the treatment of erectile dysfunction. At this time, the FDA does not believe that this safety concern applies to the use of Viagra, given the differences in patient population and the different recommended dosing regimens.