人血白蛋白用于肝硬化治疗的快速建议指南计划书

摘 要为了促进人血白蛋白的临床合理应用,中国药学会医院药学专业委员会联合中华医学会肝病学分会共同制订首部基于循证的人血白蛋白用于肝硬化治疗的快速建议指南。本指南计划书将主要介绍该指南的制作方法和技术路线,如临床问题的收集及PICOS的确定,证据的获取和评价及推荐意见的形成等。     

2例PCI术后患者抗血小板治疗的药学监护

摘 要 目的：探讨临床药师参与抗血小板药物治疗的作用,以优化抗血小板药物治疗方案。方法：临床药师参与2例抗血小板治疗方案的分析,基于现有的指南和临床研究,考虑用药经济性,制定个体化抗血小板治疗方案。结果：临床药师基于循证证据,结合患者的具体情况,参与制定药物治疗方案可以提高药物治疗水平。结论：临床药师积极开展药学监护,优化抗血小板治疗方案,有利于用药有效性、经济性及安全性。     

中药临床药师肿瘤专业培训带教的经验体会

摘 要 目的：探讨中药临床药师培训的教学经验,为提高中药临床药师培训教学水平提供经验和参考。 方法: 总结我院1 年多中药临床药师肿瘤专业培训的带教经验,分别从医学、药学理论知识学习、药学文书书写讲授、中医诊疗方案和指南解读、药学查房、业务学习、作业完成等方面进行分析。 结果: 通过中药临床药师的知识培训,为临床开展工作做必要的知识储备。通过药学查房、指南解读、业务学习等教学手段提高中药临床药师的临床技能和思维,从而提高了中药临床药师培训的教学水平和效果。 结论: 不断积累理论教学和临床实践培训方面的经验,完善中药临床药师的培训带教模式,能够培养更多合格的中药临床药师,保障临床用药安全有效。     

《中国伏立康唑个体化用药指南》推荐意见的外审

摘 要 背景：《中国伏立康唑个体化用药指南》是基于GRADE系统制定的个体化用药指南。指南共识专家组和指导委员会分别于2016年7月1日和5日正式举行了推荐意见共识会议和审定会议,与会专家达成共识并批准了27 条推荐意见。目的：了解《中国伏立康唑个体化用药指南》推荐意见的科学性和可行性,以进一步修订推荐意见。方法：针对27 条推荐意见的赞成程度、表述清楚程度和可行程度,指南制定工作组以纸质问卷的形式开展外审工作,征求一线医务工作者（临床医师、临床药师）和患者代表的意见和建议,根据外审结果,由指南指导委员会对推荐意见进行修订和完善。 结果：来自4 家医院、7 个科室的12 名临床医师、8 名临床药师、1 名患者代表参与了外审工作。对推荐意见的总体赞成程度为80%,总体表述清楚程度为91%,总体可行程度为80%。所有推荐意见赞成程度、表述清楚程度和可行程度均超过30%。此外,共收到86 条主观建议。根据外审结果,指南指导委员会重新修订了14条（52%）推荐意见：修改了5条推荐意见的主体内容;修改了9 条推荐意见的表述,并将其中2 条推荐意见合并为1 条。最终指南包含了26 条推荐意见。结论：本次外审工作对《中国伏立康唑个体化用药指南》推荐意见的最终形成提供了依据,进一步完善了所有推荐意见的科学性、明晰性和可行性。     

临床药师参与外科术后耐药菌感染药物治疗的病例分析

摘 要 目的：通过参与外科术后耐药菌感染会诊的案例分析,探讨临床药师在外科抗感染药物治疗中的作用。方法: 临床药师根据指南及掌握的抗菌药物抗菌谱与药动学特点,协助临床医师参与患者术后抗感染方案的制定,开展药学监护。结果: 临床药师参与外科术后耐药菌感染会诊后,3例术后感染患者均获痊愈。结论: 临床药师在外科治疗团队中的药学监护作用不可忽视。     

临床药师参与多药耐药不动杆菌抗感染治疗的体会

目的 探讨临床药师参与药物治疗方案的制订与药学监护的方法。 方法 临床药师参与了1例患者的抗感染治疗,通过学习文献和指南,分析评价治疗方案,提出用药建议,开展药学服务。 结果 临床药师的建议被采纳,患者病情好转出院。 结论 临床药师可协助医师制订更为安全有效的治疗方案,对患者康复有促进作用。     

临床药师参与阿德福韦酯致低血磷性骨软化症治疗的实践

摘 要 目的：通过临床药师参与阿德福韦酯致低血磷性骨软化症的治疗实践案例,探讨其临床特征及诊治方法,以及临床药师在诊疗过程中所起的作用。方法：总结2 例低剂量阿德福韦酯致低血磷性骨软化症成功治疗案例,结合相关指南和文献报道,分析阿德福韦酯致低血磷性骨软化症的临床特征和诊治经过。结果：低剂量阿德福韦酯可导致低血磷性骨软化症,用药期间应定期监测肾功能、血磷、血碱性碱性磷酸酶等。结论：临床药师发挥专业知识技能,参与临床治疗实践,减少误诊,提高临床药物治疗水平。     

临床药师参与1例重症急性胰腺炎患者抗感染治疗的体会

目的 探讨临床药师参与胰腺炎抗感染治疗的方法。方法 通过查阅文献、学习相关指南,临床药师对1例重症急性胰腺炎患者的抗感染治疗提出药学建议,并进行药学监护。结果 药师建议被采纳,患者病情好转出院。结论 临床药师可协助医生,使药物治疗更安全有效,对患者康复有益。     

62例深静脉血栓患者华法林用药分析

摘 要 目的:了解我院深静脉血栓患者华法林用药情况及存在的问题并提出建议,促进临床合理用药。 方法：对2013年10月~2014年3月我院服用华法林治疗深静脉血栓的住院患者病历进行回顾性调查分析,调查内容包括在院期间华法林联合用药、用药期间国际标准化比值（INR）监测、华法林剂量调整等情况,并参照国内外指南进行综合评价和分析。结果：共收集62例患者病历,我院尚存在患者服用华法林期间联用药物种类多、INR监测不规范、华法林剂量调整不及时、住院期及出院前INR达标率低等问题。结论：目前我院华法林用药尚存在不足,需参照指南制定华法林用药规范,指导临床合理使用华法林进行抗凝治疗。     

依非韦仑在妊娠早期的安全性评价

目的 评价非核苷逆转录酶抑制剂依非韦仑（efavirenz,EFV）在妊娠早期抗逆转录病毒治疗（antiretroviral therapy,ART）中的安全性。方法 以代表性meta分析为依据,介绍EFV用于妊娠早期的文献资料及各国指南修订变化,对比各指南中妊娠期ART方案中EFV的推荐级别,阐述EFV的药动学和妊娠期用法。结果 EFV对HIV-1病毒有显著抑制作用,早期动物实验和少量人类临床数据显示EFV会导致胎儿神经管畸形,被列为妊娠早期禁用药物。随着样本量增加,数据显示妊娠早期使用EFV不增加整体出生缺陷风险,神经管缺陷风险概率不高于一般人群。但由于人类数据较为有限,仅部分指南推荐妊娠早期使用EFV。结论 针对不同个体的妊娠早期ART方案,仍需针对具体问题进行分析评估。     

Successful application of pharmacogenomic testing in the evaluation and management of a patient with human immunodeficiency virus and disseminated histoplasmosis

ObjectivesTo demonstrate the successful use of pharmacogenomic testing to specifically tailor antifungal treatment to the phenotype of a patient with human immunodeficiency virus (HIV) and disseminated histoplasmosis who had clinical progression while on itraconazole and subsequently had insufficient therapeutic drug levels of voriconazole.Case summaryWe present the case of a patient with HIV and disseminated histoplasmosis with a persistently elevated serum Histoplasma capsulatum antigen and subtherapeutic levels of voriconazole. Pharmacogenomic testing revealed he was a CYP2C19 rapid metabolizer, thus explaining his persistent, subtherapeutic levels of voriconazole and prompting a change in therapy.Practice implicationsOur case illustrates the importance of pharmacogenomic testing as a tool to evaluate subtherapeutic itraconazole or voriconazole levels, especially in patients with failed clinical or Histoplasmosis Ag response despite reporting full adherence to prescribed therapy.     

2018年郑州市第六人民医院伏立康唑致不良反应分析

目的了解郑州市第六人民医院应用伏立康唑所致药品不良反应(ADR)的特点、一般规律及预后,为临床安全合理使用伏立康唑提供参考。方法对2018年1~12月使用伏立康唑的162例病例进行回顾性分析,共计54例患者出现不良反应,按是否合并艾滋病(AIDS)、患者性别、年龄、给药方式、ADR发生时间、累及的器官或系统、转归等进行统计分析。结果 54例ADR中,AIDS患者42例,非AIDS患者12例;男性39例,女性15例;41~70岁的有39例。2~5 d内发生ADR的有27例,占50%;不良反应以神经系统损害最多,其余可涉及肝胆系统、皮肤及其附件、视觉系统等。1例肾损害患者留有后遗症,其余经过停药或对症处理后均好转。结论 AIDS患者使用伏立康唑不良反应发生率显著高于非AIDS患者,临床在合理用药的同时,对AIDS患者尤其应加强监测。     

Systematic review and network meta-analysis of clinical outcomes associated with isavuconazole versus relevant comparators for patients with invasive aspergillosis

Objectives: Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA.

Methods: Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model.

Results: Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3–5?mg/kg/day) with high-dose L-AmB (10?mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (?1.39 [?2.21, ?0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [?1.17, 1.53], 0.50 [?1.11, 2.13] and 0.32 [?0.19, 0.84], respectively) or overall response (?0.99 [?2.21, 0.29], ?0.89 [?2.41, 0.65] and 0.06 [?0.43, 0.57], respectively).

Conclusions: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.     

Voriconazole therapeutic drug monitoring: focus on safety

Importance of the field: Voriconazole has been widely used for the treatment of invasive fungal diseases, particularly invasive aspergillosis. Drug–drug interactions are, however, the main drawback associated with voriconazole use, since this drug suffers from extensive hepatic metabolism.

Areas covered in this review: This article reviews the current literature on voriconazole therapeutic drug monitoring, with a special focus on drug safety.

What the reader will gain: An update on voriconazole metabolism, drug interactions, toxicity and the relation of these with voriconazole drug concentrations.

Take home message: Therapy with voriconazole may be better guided by measuring voriconazole concentrations in the plasma.     

2013~2015年南京地区常用抗真菌药利用分析

摘 要 目的：了解南京地区抗真菌药的利用情况和发展趋势,为临床合理使用抗真菌药提供参考。方法: 采用限定日剂量法,对本地区34家医院2013~2015年抗真菌药的销售金额、用药频度（DDDs）和限定日费用（DDC）等进行回顾性分析。结果: 2013~2015年抗真菌药的销售金额逐年上升,增长率最高达41.13%;三唑类药物的销售金额连续三年居首位,占所有抗真菌药销售金额的60%以上;2013~2015年伏立康唑、氟康唑、伊曲康唑和卡泊芬净居销售金额的前4位;克霉唑外用剂型、伊曲康唑口服剂型保持DDDs的前2位;临床使用量较大的抗真菌药集中于唑类和烯丙胺类;DDC值居前三位的是卡泊芬净、米卡芬净和伏立康唑注射液。结论:2013~2015年抗真菌药的临床使用量持续攀升,侵袭性真菌感染是高危致命因素,合理使用抗真菌药是临床治疗的首要原则。     

Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: a multicentre,prospective, cluster randomised,crossover clinical trial

ObjectivesVoriconazole therapeutic drug monitoring (TDM) is recommended based on retrospective data and limited prospective studies. This study aimed to investigate whether TDM-guided voriconazole treatment is superior to standard treatment for invasive aspergillosis.MethodsA multicentre (n = 10), prospective, cluster randomised, crossover clinical trial was performed in haematological patients aged ≥18 years treated with voriconazole. All patients received standard voriconazole dose at the start of treatment. Blood/serum/plasma was periodically collected after treatment initiation of voriconazole and repeated during treatment in both groups. The TDM group had measured voriconazole concentrations reported back, with dose adjustments made as appropriate, while the non-TDM group had voriconazole concentrations measured only after study completion. The composite primary endpoint included response to treatment and voriconazole treatment discontinuation due to an adverse drug reaction related to voriconazole within 28 days after treatment initiation.ResultsIn total, 189 patients were enrolled in the study. For the composite primary endpoint, 74 patients were included in the non-TDM group and 68 patients in the TDM group. Here, no significant difference was found between both groups (P = 0.678). However, more trough concentrations were found within the generally accepted range of 1–6 mg/L for the TDM group (74.0%) compared with the non-TDM group (64.0%) (P < 0.001).ConclusionsIn this trial, TDM-guided dosing of voriconazole did not show improved treatment outcome compared with standard dosing. We believe that these findings should open up the discussion for an approach to voriconazole TDM that includes drug exposure, pathogen susceptibility and host defence.Clinical trial registrationClinicalTrials.gov registration no. NCT00893555.     

1例临床药师参与伊马替尼与伏立康唑联合用药的药学监护

目的 为伊马替尼与伏立康唑的联合用药提供药物用量调整思路。方法 对临床药师全程参与的１例费城染色体阳性的急性淋巴细胞白血病患者的治疗过程进行分析。该患者在伊马替尼治疗期间合并真菌感染，临床药师从药物的代谢特点、安全性等方面考虑，建议采用伏立康唑联合伊马替尼治疗，但需对伊马替尼进行剂量调整；结合患者病情将伊马替尼调整至每天0.2 g，后增加至每天0.3 g，并对伊马替尼进行血药浓度测定；联合用药期间评估和监测治疗过程中的药物不良反应。结果 医师采纳了临床药师的建议。采用伏立康唑联合伊马替尼联合用药期间，患者的感染得到了良好控制。伊马替尼血药浓度显示1 372.08 ng·mL^-1，监测患者肝功能、血常规等正常，病情平稳。结论 临床药师参与了该患者的治疗过程，为其制订了个体化的治疗方案并取得了良好的效果，为伊马替尼与伏立康唑的联合用药提供药物用量调整思路。     

临床药师参与处置伏立康唑致血液系统肿瘤患者视觉障碍的临床实践

目的 通过临床药师参与一例血液系统肿瘤并粒细胞缺乏患者长期服用伏立康唑片剂后出现视觉障碍不良反应的临床实践过程,探讨临床药师的服务模式、药学监护内容及临床药师应具备的基础知识和技能.方法 对病例的病史、用药史、当前用药进行全面系统回顾,利用药品不良反应因果关系判别方法分析患者反应与用药间相互关系,考察药物浓度影响因素,提出改进用药的建议.结果 医师接受药学建议,减少合并用药奥美拉唑的剂量以减轻肝药酶抑制,降低对伏立康唑浓度干扰.10 d后患者视觉障碍症状缓解.结论 临床药师应具备灵活运用所学药学知识的能力,能通过独立思考判断与评估用药后可能产生的效益及风险,制定药学监护计划,减少或避免药源性损伤.     

86例口服伏立康唑患者的不良反应观察与分析

目的:重点监测伏立康唑药品不良反应(ADR),进一步评价伏立康唑的安全性,为合理用药提供参考。方法:2012年1月—2013年12月,临床药师在呼吸科病房对86例应用伏立康唑的患者给予药学监护,重点监测ADR。对应用伏立康唑前后进行相关的实验室检查,参考我国药品ADR监测中心指定的药物ADR判断标准,对患者的用药情况,ADR发生时间、临床表现、处理方法及转归情况进行描述性分析。结果:86例患者中27例发生伏立康唑相关ADR,ADR发生率为31.40%,其中男性发生率高于女性;80岁以上老年患者伏立康唑ADR发生率最高;由于相互作用导致严重ADR 2例;ADR可发生在用药后的各个时间段,且累及多个系统-器官。结论:伏立康唑ADR较多,且易发生药物相互作用。通过重点监测,使医务人员对伏立康唑ADR的发生规律、临床特征及危险因素有了更加深入的认识,增加了伏立康唑ADR的暴露率,临床药师以此为切入点提供药学专业知识,促进临床合理用药。     

Pharmacoeconomics of voriconazole

Importance of the field: The recent increase in the use of antineoplastic and immune suppressive agents and the use of broad-spectrum antibiotics, prosthetic interventions, organ transplants and more aggressive surgery have been related to a greater prevalence of invasive fungal infections (IFI). Over the past few years, several new antifungal therapies have become available for these patients. Pharmacoeconomic data can play a useful role in comparing the relative benefits of treatment.

Areas covered in this review: This review summarizes all the available evidence regarding the pharmacoeconomics of voriconazole. A systematic review of pharmacoeconomic analyses through a non-restricted literature search was conducted (until May 2009).

What the reader will gain: The reader will gain a greater understanding of the pharmacoeconomics role of voriconazole.

Take home message: The majority of economic analyses have shown that voriconazole is a more cost-effective alternative in the treatment of invasive fungal infections than the antifungal drugs with which it was compared.