Clinical relevance of information in the Summaries of Product Characteristics for dose adjustment in renal impairment

Purpose

Information about dosing adjustments in patients with chronic kidney disease is important to avoid toxicity for several medicines. The aim of our study was to assess the clinical relevance of the instructions for dose adjustment in patients with renal impairment provided in the Summaries of Product Characteristics (SmPCs) approved by the European Medicines Agency (EMA).

Methods

SmPCs available on the EMA website on April 2011 were retrieved, and information on the elimination route and instructions for use in renal impairment was analysed independently by two of the authors. SmPCs were classified as containing ‘explicit’ or ‘poor’ information based on whether they presented (or not) instructions for use of the medicine in renal impairment. Information was considered ‘relevant’ if SmPCs provided clear instructions for dose adjustment.

Results

Of the 356 SmPCs analysed, 13.8 and 37.4 % were classified as providing poor information and explicit but not relevant information, respectively. Only 48.8 % SmPCs provided both explicit and relevant information on medicine use in renal impairment. No difference was found in the average time since last update among SmPCs classified as containing explicit or poor information, as well as those classified as containing relevant or not relevant information. Also, no association was found between the clinical relevance of the information and whether or not the medication was an orphan drug, and 80 % SmPCs did not provide information on the use of the medicine in patients undergoing haemodialysis.

Conclusions

Based on our analysis, current versions of SmPCs are characterised by several information deficits and by containing recommendations that are not relevant to clinical practice in terms of dose adjustment in renal impairment. These shortcomings might limit their usefulness for healthcare professionals and integration into clinical decision-making support systems.     

2015年煤炭总医院门诊处方中妊娠及哺乳期妇女中成药使用分析

目的 分析2015年煤炭总医院门诊处方中妊娠及哺乳期妇女中成药的使用情况,为特殊人群合理使用中成药提供依据.方法 从HIS系统提取相关数据,分析2015年煤炭总医院中成药的销售金额、品种、用药频度(DDDs)和日均费用(DDC)值;收集使用过的中成药说明书,并对其中涉及妊娠期及哺乳期妇女用药内容进行分析.结果 益气维血颗粒的DDDs值排名第1位,DDC最低,五加生化胶囊的DDC最高;妇产科计生门诊使用的中成药品种数共计56种;妊娠期贫血、上呼吸道感染是常见疾病;涉及妊娠期妇女慎用、忌用、禁用的品种占总数的比例分别为7.14%、5.36%、14.29%.用药辨证不当、用法用量不当、疗程不合理是不合理应用的主要原因.结论 2015年煤炭总医院妇产科中成药使用情况基本合理,然而说明书中关于妊娠期及哺乳期用药安全性的信息不全,处方书写不规范,哺乳期妇女尤为严重,药品监管部门应加强监督,保证妊娠期及哺乳期妇女用药安全.     

我国非处方药说明书范本中妊娠期和哺乳期女性用药信息调查分析

目的:评估国家药品监督管理局(NMPA)官网中非处方药说明书范本关于妊娠期和哺乳期女性用药信息标示的完整性和准确性。方法:收集截止到2018年11月11日NMPA官网中,非处方药化学药品说明书范本和非处方药中成药说明书范本,对范本的【禁忌】和【注意事项】中关于妊娠期和哺乳期女性用药信息标示情况进行统计分析。结果:我国非处方药说明书范本对妊娠期和哺乳期女性用药信息的标示情况仍存在较大空缺。非处方药化学药品说明书范本的用药信息标示率低于中成药(P<0.05),但其对妊娠期和哺乳期女性有指导意义的用药信息标示率明显高于中成药(P<0.01);对妊娠期女性有指导意义的用药信息标示率明显高于哺乳期女性(P<0.01)。结论:保障妊娠期和哺乳期女性用药的安全和有效,需要不断完善和规范说明书范本的用药信息,建立妊娠期和哺乳期女性用药信息数据库等措施。     

中国药典2020年版妊娠禁忌相关中成药的分析与思考

目的 整理和分析中国药典2020年版收载的妊娠期、哺乳期中成药，为临床药物咨询相关工作提供参考。方法 对中国药典2015年版及2020年版一部收载的中成药所涉及的妊娠禁忌相关描述及用药注意事项进行统计、比较、分类和归纳，明确中国药典2020年版收载的妊娠、哺乳期中成药变化情况。结果 中国药典2020年版较中国药典2015年版新增54种妊娠禁忌相关中成药，其中新增妊娠期患者慎用中成药14种，忌用中成药13种，禁用中成药20种，新增哺乳期患者禁忌用药7种；中国药典2020年版一部收载的含有禁用中药饮片但注意项下无禁忌说明的中成药共有134种，涉及的禁用中药饮片有22种；同一处方不同剂型的品种注意项下标注的妊娠禁忌不统一的中成药共有4种。结论 中国药典2020年版所收载的妊娠、哺乳期中成药较2015年版更加具体，但仍存在饮片、中成药及同一处方不同剂型中成药用药禁忌不统一的情况，建议有关部门尽量建立统一的妊娠、哺乳期用药禁忌标准，为中成药的合理运用提供法律依据。     

Health care providers’ requests to Teratogen Information Services on medication use during pregnancy and lactation

Background  Medication use during pregnancy and lactation is prevalent. However, current knowledge of the risks and benefits of medication use during pregnancy and lactation is incomplete as the best available evidence has been obtained from cohort studies of inadvertent exposures and registries. This situtation may partly explain health care providers’ (HCP) risk perceptions and thus the increasing number of calls to Teratogen Information Services (TIS). Objectives  The objectives of this study were (1) to identify the medication classes for which HCP are seeking counseling from the IMAGe center, a Quebec TIS; (2) to identify the medical conditions for which medication classes were used during pregnancy and lactation; (3) to identify and quantify predictors of medication information requests during pregnancy and lactation. Methods  A retrospective analysis of data was conducted within the population served by the IMAGe center, a TIS based at CHU Ste-Justine in Montreal, Quebec, Canada, that serves the French population of Canada. To be included, calls had to be received between January 1, 2004 and April 30, 2007, and the subject of the call had to be directly associated with the exposure, or not, of a pregnant or breastfeeding woman to medication. Multivariate generalized estimating equation (GEE) regression models were performed to identify the predictors of medication requests. Results  A total of 11, 076 requests regarding medication exposure during pregnancy, 12 055 requests regarding pregnant women before the exposure took place, and 13, 364 requests regarding lactation were included for analyses. Pregnant women were most frequently exposed to antidepressants (17.3), antibiotics (6.3%), and benzodiazepines (5.3%). Prior to drug exposure, the most frequent inquiries by HCP were on antibiotics (11.0%), anti-inflammatory drugs (6.0%), and antiemetics (5.1%). Inquiries concerning lactating women most frequently requested information on the drug classes of antidepressants (10.8%), antibiotics (9.1%), and anti-inflammatory drugs (7.8%). Depressive disorders were an indication of antidepressant, benzodiazepine and antipsychotic exposures reported to IMAGe. Associations were found between medication use and maternal age, previous pregnancies, trimester of pregnancy at the time of the call and lifestyle habits. Conclusions  The IMAGe received frequent inquiries on antidepressant, antibiotic, and benzodiazepine exposures, with depressive disorders being the most frequently declared indication. Predictors of medication requests were identified among exposed women during pregnancy, and breastfeeding women. These results emphasize the need for effective studies on drug use during pregnancy and lactation and for better knowledge transfer programs.     

我院药学门诊妊娠期用药咨询分析

目的分析医院药学门诊妊娠期用药咨询的基本情况。方法对医院2018年4月至2019年7月的药学门诊妊娠期用药咨询记录进行回顾性统计与分析。结果共提供妊娠期用药咨询525例,孕早期的用药咨询比例最高;咨询量最多的药物类别为中药/中成药(32.85%),其次为抗感染药物(20.33%)。结论中药中成药用药咨询是妊娠期用药咨询的重要内容,是提高药学服务水平、促进妊娠期中药/中成药合理应用的重要环节。     

Adherence to UK national guidance for discharge information: an audit in primary care

Aims

Poor communication of clinical information between healthcare settings is associated with patient harm. In 2008, the UK National Prescribing Centre (NPC) issued guidance regarding the minimum information to be communicated upon hospital discharge. This study evaluates the extent of adherence to this guidance and identifies predictors of adherence.

Methods

This was an audit of discharge summaries received by medical practices in one UK primary care trust of patients hospitalized for 24 h or longer. Each discharge summary was scored against the applicable NPC criteria which were organized into: ‘patient, admission and discharge’, ‘medicine’ and ‘therapy change’ information.

Results

Of 3444 discharge summaries audited, 2421 (70.3%) were from two teaching hospitals and 906 (26.3%) from three district hospitals. Unplanned admissions accounted for 2168 (63.0%) of the audit sample and 74.6% (2570) of discharge summaries were electronic. Mean (95% CI) adherence to the total NPC minimum dataset was 71.7% [70.2, 73.2]. Adherence to patient, admission and discharge information was 77.3% (95% CI 77.0, 77.7), 67.2% (95% CI 66.3, 68.2) for medicine information and 48.9% (95% CI 47.5, 50.3) for therapy change information. Allergy status, co-morbidities, medication history and rationale for therapy change were the most frequent omissions. Predictors of adherence included quality of the discharge template, electronic discharge summaries and smaller numbers of prescribed medicines.

Conclusions

Despite clear guidance regarding the content of discharge information, omissions are frequent. Adherence to the NPC minimum dataset might be improved by using comprehensive electronic discharge templates and implementation of effective medicines reconciliation at both sides of the health interface.     

Sweetening Inhaled Antibiotic Treatment for Eradication of Chronic Respiratory Biofilm Infection

One impediment to breastfeeding is the lack of information on the use of many drugs during lactation, especially newer ones. The principles of drug passage into breastmilk are well established, but have often not been optimally applied prospectively. Commonly used preclinical rodent models for determining drug excretion into milk are very unreliable because of marked differences in milk composition and transporters compared to those of humans. Measurement of drug concentrations in humans remains the gold standard, but computer modeling is promising. New FDA labeling requirements present an opportunity to apply modeling to preclinical drug development in place of conventional animal testing for drug excretion into breastmilk, which should improve the use of medications in nursing mothers.

     

乳汁中药物浓度测定的研究进展

母乳喂养对婴儿来说是一种非常健康及有营养的获取能量的方式，对母亲和婴儿都有益处。患有某些疾病的哺乳母亲在进行药物治疗时，需要考虑药物是否会进入乳汁而对婴儿产生一些不良反应或对母亲产生影响。由于许多药物的哺乳期用药安全性并不十分明确，因此在临床治疗中不推荐哺乳期妇女使用。测定乳汁中的药物浓度可以明确合理的给药时间和给药剂量，提高用药安全性，对临床用药具有非常重要的意义。但乳汁成分复杂，含有大量脂质和蛋白质等干扰物质，使乳药浓度测定有一定困难。本文综述了国内外乳药浓度测定方法，以期为哺乳期合理用药提供参考。     

Smoking in pregnancy and lactation: a review of risks and cessation strategies

Background  Despite documented evidence of harm to fetus and infant, a substantial number of women continue to smoke during pregnancy and lactation. Objective  To examine the literature regarding smoking during pregnancy and breastfeeding to ascertain adverse effects as well as the efficacy of interventions to enable women to stop smoking in the perinatal period. Study design  A comprehensive literature search was undertaken to identify all published studies reporting on smoking in pregnancy and lactation. MEDLINE, EMBASE, PUBMED, and Web of Science databases were searched for studies published in English from 1966 to 2008 that reported on smoking in pregnancy and breastfeeding, with information on adverse effects and on all forms of smoking cessation, including behavioral interventions, nicotine replacement therapy, and pharmacotherapy such as antidepressants. Results  There is evidence that smoking in pregnancy and lactation may cause many adverse affects in the perinatal period, childhood, and up to adulthood. These adverse effects include infertility, ectopic pregnancy, spontaneous abortion, placenta insufficiency, low birth weight, fetal growth restriction, preterm delivery, orofacial clefts, SIDS, craniosynostosis, clubfoot, childhood respiratory disease, attention deficit disorder, and some childhood cancers. A number of strategies have been developed to assist pregnant women in quitting smoking, including both behavioral interventions and pharmacological therapies, such as nicotine replacement and antidepressant therapy. Conclusions  Behavioral interventions report only modest success rates. Nicotine replacement therapy and antidepressants appear to be safe to use in pregnancy, but do not achieve a substantially higher success rate for quitting.     

我国儿童专用药品说明书调查与分析

目的：了解我国儿童专用药品（化学药品与生物制品）中药品说明书的标注情况及存在问题,为促进儿童用药信息的完善提供参考。方法：对儿童专用药品进行汇总,并依据药品说明书进行信息表的填写与统计,分析儿童专用药品说明书存在的问题。结果：共收集到儿童专用药品说明书1214份,其中国产药品1180个（占97.20%）,进口药品34个（占2.80%）;儿童专用药品数量最多的为呼吸系统用药（占42.01%）;儿童专用药品口服剂型1094个（占90.11%）,注射剂型57个（占4.70%）,外用剂型59个（占4.86%）,吸入剂型4个（占0.33%）;说明书中标注的剂量调整依据主要为年龄和体重（占45.80%）,只依据年龄进行剂量调整的占41.02%,而7.91%的药品未标注剂量调整依据;说明书中标有儿童用药最大剂量的占17.46%,标有儿童用药疗程的占28.01%,而标有儿童药代动力学的仅有16.72%。结论：我国儿童专用药品说明书存在标签撰写不规范、内容不完善、同一品规药品说明书差异大等问题,建议相关部门加强药品说明书的规范和管理,加大上市后的监管和数据监查,督促药品生产企业对儿童专用药品说明书中的内...     

Adverse Drug Reactions from Real-World Data in Inflammatory Bowel Disease Patients in the IBDREAM Registry

Introduction

Inflammatory bowel disease (IBD) frequently requires chronic immunosuppressive treatment and active involvement from patients during treatment decision making. Information about the risk of developing adverse drug reactions (ADRs) to IBD therapies is required in this process.

Objective

The aim of this study was to describe the ADRs reported in IBD patients from real-world data, using the Dutch nationwide IBDREAM registry, and compare the occurrence and cumulative incidences with the Summary of Product Characteristics (SmPC) of the associated drugs.

Methods

In this retrospective multicentre study, ADRs related to IBD medication were assessed. Only reports associated with the use of drugs used for the maintenance treatment of IBD were included. All ADRs were verified by healthcare professionals and coded by trained pharmacovigilance assessors.

Results

In total, 3080 ADRs were reported in 1179 patients. Twenty-three new drug–ADR associations related to the use of azathioprine, mercaptopurine, infliximab, oral mesalamine and thioguanine were reported in the IBDREAM registry that were not mentioned in the corresponding SmPCs. The most frequently reported new association was pyrexia for azathioprine (3.1%) and mercaptopurine (4.9%). In addition, there were seven ADRs with a higher cumulative incidence in IBDREAM compared with the SmPC, and included, among others, arthralgia during mercaptopurine use (2.5%), and diarrhoea (1.4%), alopecia (1.2%) and infections (1.6%) during azathioprine use.

Conclusions

Based on real-world data, ADR reporting demonstrated new ADRs and higher incidences of ADRs to IBD therapies. This information will contribute to drug safety by updating the SmPCs, allowing better risk assessment and communication towards patients.

     

Antihistamine use during breastfeeding with focus on breast milk transfer and safety in humans: A systematic literature review

Current data on use of antihistamines during breastfeeding and risks to the breastfed infant are insufficient. The aim of this systematic review was to provide an overview of studies measuring the levels of antihistamines in human breast milk, estimating the exposure for breastfed infants and/or reporting possible adverse effects on the breastfed infant. An additional aim was to review the antihistamine product labels available in the European Union (EU) and the United States. We searched seven online databases and identified seven human lactation studies that included 25 mother–infant pairs covering cetirizine, clemastine, ebastine, epinastine, loratadine, terfenadine and triprolidine. In addition, one study investigated the impact of chlorpheniramine or promethazine on prolactin levels among 17 women, and one study investigated possible adverse drug reactions in 85 breastfed infants exposed to various antihistamines. The relative infant dose was below 5% for all antihistamines, ranging from 0.3% for terfenadine to 4.5% for clemastine. Most product labels of the 10 antihistamines with available information in both the EU and the United States reported lack of evidence and recommended to avoid use during breastfeeding. The knowledge gap on antihistamines and lactation is extensive, and further human studies are warranted to ensure optimal treatment of breastfeeding women with allergy.     

FDA对药物临床哺乳期研究的建议

目前由于哺乳期用药的人体数据极其缺乏,对哺乳期药物治疗以及是否继续母乳喂养往往难以做出准确决策。美国食品药品管理局（FDA）于2019年5月发布了“临床哺乳期研究：研究设计考虑的因素”指导原则（草案）,对药物临床哺乳期研究的诸多方面提出了细致、具体的建议（如需要进行哺乳期研究的药物、研究类型、母乳取样方法、婴儿摄入母乳量的测量、药动学分析、婴儿剂量估算、婴儿安全数据的收集和药物对产乳量的影响等）,以期促进该方面研究,获得所需信息。中国尚无类似的指导原则,详细介绍FDA该指导原则主要内容,希望对我国开展这方面的研究工作及其监管有益,也对结合国情制定类似的指导原则有所启示。     

中医药在新型冠状病毒肺炎妊娠期患者治疗中的安全性分析

目的：分析中医药在新型冠状病毒肺炎（COVID-19）妊娠期患者治疗中的安全性，为临床合理用药提供参考。方法：全面地对《新型冠状病毒肺炎诊疗方案（试行第七版）》中推荐的中药处方及中成药中的药物在妊娠期使用是否安全进行分析和统计。结果：在诊疗方案中推荐的中药处方有10个，组方药物有68味中药，列入妊娠禁忌中药的有7味。推荐使用的中成药有14种，共有57味中药组成，列入妊娠禁忌中药的有15味。结论：COVID-19妊娠期患者中药的使用应权衡利弊，正确辨证，合理配伍并使用合适的剂量。     

Adverse effects on birth weight of parental illegal drug use during pregnancy and within two years before pregnancy

This study investigates possible links between maternal illegal drug use during pregnancy and up to two years before pregnancy with birth weight (BW), and explores the potential role of paternal illegal drug use on low birth weight. A population-based retrospective cohort study was conducted that linked four national databases in Taiwan. A total of 1,698 subjects with a criminal record of schedule I or II illegal drug use within two years before pregnancy were enrolled as the drug-exposed group, and 16,980 matched subjects were enrolled as the unexposed group. Multivariate analysis of BW found a decrease of 108.63 g (95% CI: −172.29, −44.96), 79.67 g (95% CI: −116.91, −42.43), and 69.78 g (95% CI: −106.71, −32.84) in newborns whose mothers used illegal drugs only during pregnancy (period I), only within one year before pregnancy (period II), and only within the second year before pregnancy (period III), respectively. Paternal use of illegal drugs before maternal pregnancy was significantly associated with low birth weight. The paternal effect on low birth weight was opposite the maternal effect. The adverse effect of illegal drug use on birth weight existed even if the mother did not use drugs during pregnancy but had ever used drugs during the two years before pregnancy. Paternal factors’ contribution to low birth weight persisted, and the decrement of BW was even greater than the maternal effect within one or two years before pregnancy. Maternal and paternal illegal drug use may have a lasting effect on their offspring’s birth weight.