抗丙肝药波西普韦处方标签添加药物相互作用

8月1日，美国食品药品管理局(FDA)在抗病毒药物波西普韦的处方信息部分增加了有关该药与其他多种药物间相互作用的新信息。

根据FDA的声明，波西普韦(Victrelis)是一种蛋白酶抑制剂，曾在2011年获准用于治疗丙型肝炎，可与环孢菌素、他克莫司(普乐可复)、艾司西酞普兰(来士普)、阿托伐他汀(立普妥)以及普伐他汀(普拉固)发生相互作用。

新标签注明，阿托伐他汀与波西普韦联用时暴露量会增加。FDA表示，这两种药物一起使用时，应采用阿托伐他汀的最低有效剂量，不得超过40 mg/d。

环孢菌素与波西普韦联用时，应谨记对环孢菌素进行剂量调整，“并应密切监测环孢菌素的血药浓度，经常对肾功能及环孢菌素相关的副作用进行评估”。

这份声明还指出，艾司西酞普兰与波西普韦联用时暴露量“轻微减少”。尽管艾司西酞普兰等选择性5-羟色胺再摄取抑制剂(SSRI)的治疗指数较大，但与波西普韦联用时可能也有必要进行剂量调整。

根据该声明，波西普韦与普伐他汀联用时，暴露量也增加，但两药联用时可以将普伐他汀的推荐剂量设为起始剂量，同时“应进行密切的临床监测”。

他克莫司与波西普韦联用“需要大幅减少他克莫司的剂量，并延长给药间隔时间，同时还要对他克莫司的血药浓度进行密切监测，对肾功能和他克莫司相关的副作用经常进行评估”。

波西普韦是默沙东公司(默克公司的子公司)生产的一种胶囊制剂，为口服用药，3次/d。

以上药物间相互作用的数据来自体内药物相互作用试验，该试验是默沙东公司履行的上市后承诺的一部分。

在2011年4月的一次会议上，由于波西普韦的抗病毒疗效很好，FDA顾问委员会大力支持批准波西普韦用于治疗丙型肝炎感染，但强调需要进行与其他药物(包括抗抑郁药)间相互作用的上市后研究。

By: ELIZABETH MECHCATIE, Cardiology News Digital Network

New information about interactions between boceprevir and several other drugs has been added to the prescribing information for the antiviral drug, the Food and Drug Administration announced Aug. 1.

Boceprevir (Victrelis), a protease inhibitor approved for treating hepatitis C in 2011, interacts with cyclosporine, tacrolimus (Prograf), escitalopram (Lexapro), atorvastatin (Lipitor), and pravastatin (Pravachol), according to the FDA statement.

The new information states that, when administered with boceprevir, exposure to atorvastatin increases. When the two drugs are used together, the lowest effective dose of atorvastatin should be used, not to exceed a daily dose of 40 mg, according to the FDA.

Dose adjustments of cyclosporine should be anticipated when it is given with boceprevir, and "should be guided by close monitoring of cyclosporine blood concentrations, and frequent assessments of renal function and cyclosporine-related side effects."

When administered with boceprevir, exposure of escitalopram "was slightly decreased," the statement said. Although selective serotonin reuptake inhibitors (SSRIs) such as escitalopram have a wide therapeutic index, it may be necessary to adjust the dosage when it is administered with boceprevir.

Coadministration of boceprevir with pravastatin increases exposure to pravastatin, but pravastatin can be started at the recommended dosage when coadministered with boceprevir. "Close clinical monitoring is warranted," the statement said.

Giving tacrolimus and boceprevir together "requires significant dose reduction and prolongation of the dosing interval for tacrolimus, with close monitoring of tacrolimus blood concentrations and frequent assessments of renal function and tacrolimus-related side effects," the statement said.

Boceprevir is manufactured in a capsule formulation by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., and is taken by mouth three times a day.

The drug-drug interaction data are from in vivo drug interaction trials, which the company conducted as part of its postmarketing commitments.

At a meeting in April 2011, an FDA advisory panel enthusiastically supported the approval of boceprevir for treating hepatitis C infection because of the antiviral’s efficacy but emphasized that postmarketing studies on interactions with other drugs, including antidepressants, were needed.