当前我国已完成了多项应用直接抗病毒药物（DAA）治疗丙型肝炎的Ⅲ期临床试验，我国丙型肝炎患者将逐渐步入规范化应用DAA治疗的新时代，临床医生应做好准备，对DAA治疗慢性丙型肝炎方方面面的知识都有所掌握。其中，DAA与其他同时服用药物的相互作用（DDI）具有重要的临床意义。如何做好DDI的管理呢？请听上海交通大学医学院附属瑞金医院谢青教授和德国歌德大学医院Stefan Zeuzem教授的建议。

 

从三个方面做好DAAs药物的相互作用管理

 

谢青教授表示，今年一定会有DAAs药物在中国内地上市，我国临床医生需要对此做好准备。DAA与其他药物之间的相互作用可能影响药物在血液中的浓度，可能导致疗效下降或是增加毒性反应，因此是每个临床医生都要关注的问题。对我国医生未来如何做好DDI的管理，谢青教授提出了三个方面的建议。

 

第一，在使用DAAs之前详细询问患者的病史和用药情况。“中国医生可能会碰到很多年纪大、合并肝硬化、高血压、糖尿病等基础疾病的患者，他们常常正在服用治疗这些并发症或者基础疾病的药物，比如心血管药、代谢紊乱药物，甚至还可能有抗结核药等。开具DAAs处方前，应对患者原来的用药情况有全面的了解。”

 

第二，注意不同DAA治疗方案的DDI特点。“这需要我们关注给患者选择的DAAs方案是否会与患者目前应用的治疗基础疾病或者合并疾病的药物产生相互作用。因此我们要仔细阅读药物说明书、关注相关研究、学习指南和利用现有数据库等，对已经发现的DDI有所认识。”

 

第三，对给药方案进行调整。“如果发现有可能存在的DDI，我们要在不影响基础治疗的同时，尽可能选择相互作用风险小的药物或减少相关药物的剂量，以避免或者尽量消除DAAs与治疗这些基础疾病所用的药物间的DDI不良反应。需要补充的一点是，可能还有一些中草药与DAAs间存在相互作用，也应引起重视。”

 

“所以我们的原则就是可用可不用的药物原则上不用。如果一定要用，就要注意防范和监测可能存在的DDI及其可能导致的严重后果，并在需要时进行用药方案的调整”，谢青教授最后强调到。

 

当前DDI的管理并不困难

 

Zeuzem教授则针对三类主要DAA的DDI管理进行了概述。他表示，“核苷类NS5B抑制剂的药物相互作用很少。可能需要牢记的最重要的相互作用药物是胺碘酮，可能导致严重的心动过缓，甚至心源性死亡。NS5A抑制剂通常也比较容易管理，需要考虑的药物相互作用很少，也是很安全的药物。蛋白酶抑制剂的（DDI）问题当前也有了很大改善。这类药物有多种重要的药物相互作用，随着新药的出现，这些问题变得相对不那么明显和严重。不过在联合蛋白酶抑制剂进行三联治疗时，医生必须要记住它们与一些他汀类药物有相互作用，如阿托伐他汀。另外，它们还与一些抗逆转录酶药物，特别是依法韦仑有相互作用”。他强调，医生需要到利物浦大学的药物相互作用数据库中进行检索，确定可能存在哪些相互作用。

 

以上文章由Gilead Sciences赞助以支持科学及医学教育，且无推广意图。

 

The above posting is sponsored by Gilead Sciences to support scientific and medical education, and with non-promotional intent. 

 

等线 [Peak Dialogue]Drug-drug interactions of DAA: A very important topic in DAA era

 

As several phase III studies on treatingchronic hepatitis C with direct-acting antiviral agents have been completed in China, the new era of hepatitis C patients having access to standardized DAA therapies in China is approaching. Meanwhile, Chinese physicians should be well prepared and have a comprehensive understanding of all the related knowledge when using DAAs. Among all these knowledge, drug-drug interactions(DDIs) between DAAs and other concomitant drugs are of great clinical significance. In the following, we will share some suggestions given by Professor Qing Xie from Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Professor Stefan Zeuzem from J. W. Goethe University Hospital. 

 

Three aspects of managing DDIs of DAAs

 

Professor Xie told that there will be the launch of DAAs in China this year and Chinese physicians should be prepared. DDIs between DAAs and other concomitant drugs might influence the plasma concentrates of drugs and as a result, reduce the therapeutic effect orincrease the toxicity. Every specialist should pay attention to DDIs. Professor Xie gave Chinese physicians three suggestions on how to manage the DDIs.

 

First of all, we should thoroughly enquirepatients’ medical history and the medicine they are taking. "Chinese physician are very likely to receive elderly patients with liver cirrhosis and other underlying disease like hypertension and diabetes. Usually, these patients concurrently take drugs to treat these underlying diseases, for example, cardiovascular drug, metabolic disorder drugs and even anti-tuberculoticdrugs. Before prescribing DAAs, we should know all the medications that patients are currently using.”

 

Secondly, understanding the different DDI profiles of various DAAs regimens. "We need to pay attention to whether the chosen DAA regimen would interact with the concomitant drugs that patientsare taking to treat his/her underlying disease or comorbidities.So, we should review the prescription information carefully, follow the related studies, read the guidelines and utilize our database, then we can learn some of the identified DDIs."

 

Last but not the least, we should modify the regimens. "When noticing some potential DDIs, in addition to limiting the impact on the basic therapy, we should try our best to choose the drug with lower risk of DDIs or reduce the dosage of relevant drugs, and to avoid or minimize the DDIs between the DAAs and the basic medicine. Additionally, physicians should know that some Chinese herbal medicines can interacted with DAAs."

 

"Our rule is to avoid using the drugs that are not necessary. If they need to be applied, we should keep our eyes open on preventing and monitoring the potential DDIs as well as the possible consequences related to the DDIs. And when needed, the dosage should be modified." Prof. Xie emphasized. 

 

The management of DDIs is no difficult in nowadays

 

Prof. Zeuzem shared some insights of managing the DDIs between three major DAAs. "There are very few drug-drug interactions with nucleus acidic NS5B inhibitors. Probably the most worth-noticing drug-drug interaction is amiodarone, which might lead to severe bradycardia and even cardiac mortality. The NS5A inhibitors generally are easy to manage, there are few drug-drug interactions need to be considered and they are reasonably safe drugs. Also, the DDIs of protease inhibitor has been improved a lot. Although several major DDIs are likely to occur to protease inhibitor, with the new drugs are being introduced, these issues have become less prominent. But when physicians including the protease inhibitors into the triple therapy, we must keep in mind that they interact with some statins, such as atorvastatin and some antiretroviral medication, especially efavirenz.” In addition, physicians should search the Liverpool drug-drug interaction database and be aware of the potential DDIs, emphasized by Prof. Zeuzem.

 

The above posting is sponsored by Gilead Sciences to support scientific and medical education, and with non-promotional intent.