Quality Issues in Caring for Older People
Doctoral Thesis - Tesis Doctoral Quality issues in caring for older people:
• Appropriateness of transition from long-term care facilities to acute hospital care
• Potentially inappropriate medication: development of a European list
Anna Renom Guiteras
Prof. Gabriele Meyer Prof. Ramón Miralles Basseda Martin Luther University Halle-Wittenberg Universitat Autònoma de Barcelona Halle (Saale) & Barcelona, Catalonia University of Witten/Herdecke Spain Witten Germany
Programa de doctorat en Medicina
Departament de Medicina, Facultat de Medicina Universitat Autònoma de Barcelona
Barcelona, 2015 13
Contents
15 1. Introduction
• Research context • Background of the research topics • P ese taio of the a i les
23 2. Summary and discussion of the results
31 3. Conclusions
37 4. References
47 5. Articles
• Article 1: Renom-Guiteras A, Uhrenfeldt L, Meyer G, Mann E. Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review. BMC Geriatr. 2014;14:80
• Article 2: Renom-Guiteras A, Meyer G, Thürmann PA. The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries. Eur J Clin Pharmacol. 2015;71(7):861-75
77 6. Annexes
• Annex 1.1 (article 1) - Additional file 1: Studies dealing with assessment tools for determining appropriateness of hospital admissions among residents of LTC facilities.
• Annex 1.2 (article 1) - Additional file 2: Characteristics of the assessment tools for determining appropriateness of hospital admissions among residents of LTC facilities.
• Annex 2.1 (article 2) - Appendix 1: Complete EU(7)-PIM list
• Annex 2.2 (article 2) - Appendix 2: Questionable Potentially Inappropriate Medications (Questionable PIM): results of the Delphi survey.
• Annex 2.3 (article 2) - Appendix 3: Non Potentially Inappropriate Medications (Non-PIM): results of the Delphi survey. 14 15
Introducion
1 16 QUALITY ISSUES IN CARING FOR OLDER PEOPLE INTRODUCTION 17
Introduction
Research context
This doctoral thesis should be put in the context of the first three years of a 5-year stay in Germany (2010-2015), when I worked as research fellow in the research team of Professor Gabriele Meyer, nursing scientist, in the Institute of Nursing Science at the University of Witten/ Herdecke in the city of Witten. This experience took place after specializing in geriatrics in Barcelona (Parc de Salut Mar). Professor Ramón Miralles, geriatrician in the Parc de Salut Mar (Universitat Autònoma de Barcelona), agreed with the idea of supervising my doctoral thesis within this context and so did Professor Gabriele Meyer, who gave me the opportunity to work in her team.
The main project I was involved in was the European project “RightTimePlaceCare”, a project which was carried out from January 2010 until September 2013 and in which eight European countries participated: England, Estonia, Finland, France, Germany, the Netherlands, Spain and Sweden (1, 2). The project was coordinated by the University of Witten/Herdecke in Germany, and led by Professor Gabriele Meyer. The aim of the RightTimePlaceCare project was to develop best practice recommendations for dementia care throughout Europe. The project included interviews with a European cohort of older people with dementia and their formal and informal caregivers. Several medical, nursing, and socio-economical aspects of dementia and dementia care were evaluated prospectively at two points of time, separated by 3 months (cross-sectional design).
As a research fellow, I participated in some design aspects of the study, in the selection of assessment tools, recruitment of participants, collection of data (interviews with participants), preparation of the statistical plan and database, and in the data analysis and interpretation. Several doctoral students were involved in the study and a publication plan was prepared in the early stages of the study. Together with my supervisors (Professor Ramón Miralles and Professor Gabriele Meyer) I decided to work on two research topics: hospital admission and use of potentially inappropriate medications. I had the opportunity to make suggestions on how to gather data on these two issues, in consensus with the RightTimePlaceCare Consortium members.
During this period of time, we planned two further research projects in the line of the mentioned research topics, which ended up constituting the core studies of my doctoral thesis: the preparation of a systematic review of the literature on assessment tools for determining the appropriateness of admission to acute care of persons transferred from long-term care (LTC) facilities and the development of a European list of potentially inappropriate medications for older people. 18 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Background of the research topics
This doctoral thesis covers two issues concerning the frail older population: hospital admission and prescription of medications.
The ageing process of the population is a known challenge in our society. By 2050 it is estimated that 21% of the population in the western industrialised states will be aged 60 years and older, and developing countries will also experience this tendency (3). Older people tend to be frail, showing higher comorbidity, cognitive and functional impairment. It is estimated that between 5-7% of the people older than 60 are affected by dementia (4) and more than half of the population aged 75 and older suffer from comorbidities (5, 6). Every year, people aged 70 and older may experience an increase in the limitation of their activities of daily living of between 1% and 2.5% in (7). Furthermore, older people may experience changes in their social and living situation such as admission to an LTC facility. In Europe, the percentage of people receiving care in institutions ranges between 1% and 7% for those people aged 65 years and older, and between 2% and 20% for those aged 80 and older, depending on the country (8).
Frail older people have an increased rate of hospital referral and hospital admission. Up to a quarter of all emergency department visits are accounted for by patients aged 65 and older (9). In nursing homes, the incidence of emergency department visits has been estimated to be approximately 30 transfers per 100 beds per year (10).
Older people have also a higher risk of being prescribed a high number of medications (polypharmacy). Between 34% and 59% of people aged 75 and older are exposed to five or more drugs (11-13) and the prescription of ten or more drugs to older people in nursing homes can reach 24% (14). Further, older people are also at risk of being inappropriately prescribed; for example, they may be prescribed duplicated active substances, doses of drugs not adjusted to renal function or drugs considered as “potentially inappropriate medications” (PIM) for this age group (15).
Hospital admission and the prescription of medications are often necessary and beneficial for older people, but they may also be inappropriate and associated with adverse consequences. Thus, inappropriate prescribing and/or the prescription of PIM for older people can be associated with adverse drug events (16-18), hospitalisation (19, 20) and death (21). Similarly, the admission of a frail old person to an emergency department or hospital represents a risk of distress, hospital-acquired nosocomial events (22), and deterioration of mobility and cognition (23, 24). Some older people who died in hospital after having been transferred to acute care may have benefited more from a palliative care approach at home or in the LTC facility (25).
For many years, several authors have been developing assessment tools to measure the appropriateness of hospital admission and the appropriateness of prescribing to older people. INTRODUCTION 19
These tools have been used for describing the current practices regarding these two issues, identifying areas of improvement and evaluating the effectiveness of the interventions aimed at improving the clinical practice. Nevertheless, important knowledge gaps still exist in the evidence regarding these measurement tools, and there is a need for further research, as is acknowledged by several authors. This doctoral thesis addresses these needs.
Presentation of the articles
The first article of this doctoral thesis is entitled “Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review”.
LTC facilities have high rates of hospital transfers and there is potential for the optimisation of working procedures. Therefore, a considerable number of studies have evaluated the appropriateness of hospital admission within this setting. International studies suggest that between 10% and 60% of hospital admissions among LTC residents may be inappropriate (26, 27). Variation may result from differences in the acute care settings, the nursing home populations, the facility characteristics, or the regional organisational aspects (e.g. incentives or procedures). However, part of the variation in the estimates of appropriate admissions can also be explained by the different assessment tools used.
So far, there is no agreement on which tool better evaluates the appropriateness of hospital admissions of older people transferred from LTC facilities. The terminology and definitions are not yet clarified, as claimed by some authors (28-31). Furthermore, there is no document available that provides an overview of the internationally existing assessment tools and that also describes them.
Systematic reviews are rigorous formats for synthesizing the evidence and play an important role in the disclosure of the knowledge available about a particular health issue. The performance of systematic reviews is characterized by stringency arising from a priori protocol development, transparency, comprehensive literature search, selection and appraisal of the evidence by independent reviewers, rigour in synthesis, and peer review at numerous stages during the conduction and reporting of the systematic review (32).
Thus, this article consists of a systematic review of the literature on the assessment tools for determining appropriateness of admission to acute care of persons transferred from LTC facilities. This systematic review has been published in BMC Geriatrics.
The second article of this doctoral thesis is entitled “The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries”. 20 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
The term “potentially inappropriate medications (PIM) for older people” refers to those drugs which should not be prescribed for this population because the risk of adverse events outweighs the clinical benefit, particularly when there is evidence in favour of a safer or more effective alternative therapy for the same condition (33, 34). The prevalence of inappropriate prescribing and/or use of potentially inappropriate medications has been estimated as being between 20% and 79%. This variation can be explained by the differences in the populations studied, the settings and the specific tools used for the evaluation (19, 34-38).
A recently published systematic review identified 46 tools or criteria for assessing inappropriate prescribing (39), and a prior systematic review identified 14 criteria specific for individuals aged 65 and older (40). No single ideal tool has been identified so far, but each tool seems to have its strengths and weaknesses, and the choice of a tool may depend on the purpose of use (i.e. daily practice, research) and availability of data (39). However, to the best of our knowledge, no assessment tool covers the drug markets of several European countries and could thus enable the analysis of European databases.
This article was conceived when planning to analyse the prescription of PIM among the European cohort of people with dementia participating in the RightTimePlaceCare study. None of the existing criteria could be applied to our cohort, either because they were too country- specific or because they required too much clinical information which was not available. Thus, we planned to develop a European list of PIM for older people consented by experts from seven European countries, namely the European Union (EU)(7)-PIM list. We had the opportunity to work together with two researchers who had been previously involved in the development of the PRISCUS list (41), a PIM list for older people covering the German drug market. We planned the development of the EU(7)-PIM list in two main phases. The first phase was the preparation of a preliminary PIM list based on the German PRISCUS list (41), PIM from other international PIM lists (33, 42-44) and a comprehensive literature search. The second phase was the expansion of the preliminary list with further drugs and the assessment of its appropriateness by means of a two-round Delphi survey by a group of experts on geriatric prescribing from the same European countries who participated in the RightTimePlaceCare project.
The Delphi technique is a research method that aims at obtaining information via an expert consensus. This method has been widely used for the development of PIM lists (33, 41, 45, 46) due to the lack of good quality evidence on drug efficacy and safety in older people, which makes it difficult to develop assessment tools based on evidence only (47).
The EU(7)-PIM list has been published in the European Journal of Clinical Pharmacology. INTRODUCTION 21 22 23
Summary and discussion of the results
2 24 QUALITY ISSUES IN CARING FOR OLDER PEOPLE SUMMARY AND DISCUSSION OF THE RESULTS 25
Summary and discussion of the results
The first article of this thesis entitled “Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review” aimed at systematically reviewing and describing the internationally existing assessment tools used for determining appropriateness of hospital admission among long- term care (LTC) residents. Twenty-nine articles assessing this issue were included in the systematic review, and 16 different assessment tools were identified among them. Mean age of the study samples ranged from 81 to 86, and the proportion of women varied from 62% to 80%. Studies varied regarding their designs (e.g. prospective vs. retrospective, observational vs. interventional), the population under study (e.g. residents of LTC facilities only vs. also older persons living in the community; all older people vs. only older people with dementia) and the acute care setting (e.g. only admission to emergency department vs. only in-patient hospitalisation vs. either emergency department or in-patient hospitalisation). The proportion of admissions considered as inappropriate varied widely, ranging from 2% to 77%.
Sixteen assessment tools were identified. Considerable heterogeneity among the tools was found regarding the concepts studied (e.g. inappropriate vs. avoidable vs. preventable admissions), the format of use (e.g. tool applied by study authors vs. expert panel or nursing staff) and data sources used for their application (e.g. administrative databases vs. resident’s hospital of LTC facility record vs. interview with residents or nursing staff). We agreed on a list of six aspects that were covered by the assessment tools’ items: specific medical diagnoses, acuteness or severity of symptoms at time of transition , resident’s characteristics prior to admission to hospital, resource availability/requirement, residents’/families’ wishes, and information on the existence of a care plan. However, not all assessment tools covered all aspects: most tools covered less than four of these aspects, and six of the tools covered four or more aspects. For example, one assessment tool consisted of a list of medical conditions called “Avoidable Hospital Conditions” (48) which judged appropriateness based on the specific medical diagnoses only; another tool consisted of an “Appropriateness Evaluation Protocol” (26) that judged appropriateness based on the acute symptoms (e.g. persistent fever, abnormally high or low pulse rate) and the resources available/needed (e.g. prescription of parenteral medications, vital sign monitoring). Only six assessment tools included some items on the residents’ characteristics prior to acute care admission, and only three assessment tools took the residents’/families’ wishes or the information about the existence of a care plan into consideration. For example, the “Quality Improvement Review tool” part of the INTERACT-II tool (49, 50) judged appropriateness based on a balance of issues: information about the resident’s characteristics, acute symptoms, and actions taken by staff before the transfer including presence of advanced care planning. The fact that many assessment tools did not include any items on any residents’ individual aspects is remarkable, considering that residents in LTC facilities often differ in terms of comorbidity, cognitive and functional status, and stage of their diseases, and considering the present advocacy towards person-centred care (51). 26 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
The results of this study are in the line with the results of a non-systematic review on tools used to identify preventable hospitalisations (including community-dwelling older people) (31, 52). The authors of that review emphasized the need for comprehensive measures to account for aspects such as medical comorbidities, clinical complexity or differences in resources in the care settings.
This systematic review did not include the assessment of the risk of bias of the original studies included. The reason is that we were interested in the concepts and tools identified, rather than in the internal validity of the studies. However, we described the study designs and most studies were secondary or retrospective routine data analyses, suggesting that the quality of the studies is limited.
This article provides an overview of the tools internationally used to assess the appropriateness of hospital admissions among LTC residents, and the study contexts where they were used. It provides some evidence about the lack of consideration of individual aspects and the lack of comprehensiveness of some assessment tools. It may contribute to the clarification of the concept “appropriateness of admission of LTC residents to acute care” and may support authors choosing an assessment tool to measure appropriateness of hospital admission. It may also be a first step towards the development of an evidence-based, comprehensive and generalizable tool. Authors aiming at developing interventions to reduce inappropriate hospital admissions may also benefit from this systematic review because the development of complex interventions requires studies that help to refine the design, identify suitable measures, and predict long term outcomes (53).
Unfortunately, we could not evaluate the appropriateness of hospital admission within the European cohort of older people with dementia participating in the RightTimePlaceCare project, because the data available were insufficient. However, we are currently evaluating the frequency, reasons and factors associated with hospital admission.
The second article of this thesis entitled “The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries” aimed at developing a European list of PIM for older people, which can be used for the analysis and comparison of prescribing patterns across European countries and for clinical practice. The European Union (EU)(7)-potentially inappropriate medication (PIM) list was developed based on the German PRISCUS list (41) and additional drugs from the French (33), American (42, 43, 46) and Canadian (44) lists. A preliminary PIM list was developed, expanded and assessed in a two-round Delphi survey with the collaboration of thirty experts in geriatric prescribing from seven European countries and from different professions. The experts were asked to assess appropriateness by using a 1-5 point Likert scale, and they were asked to provide suggestions for dose adjustments and safer therapeutic alternatives for those drugs judged as inappropriate. We calculated the means, the corresponding 95% confidence intervals and the medians of all Likert scores given to each drug and, depending on the scores, each drug was classified into PIM, non-PIM or questionable PIM. SUMMARY AND DISCUSSION OF THE RESULTS 27
The preliminary PIM list contained 184 drugs. Experts suggested 75 additional drugs. The participation of experts was moderate to high: 62% of the invited experts participated in the expansion phase, 90% in the first Delphi round and 86% in the second Delphi round. A last brief survey was carried out consisting of 11 questions with multiple-choice answers and covering issues regarding 13 drugs. The questions covered mostly dose-related issues commented by the experts during the survey and which remained open, and inconsistencies in the results identified after checking the literature. Experts reached consensus that 282 chemical substances or drug classes from 34 therapeutic groups are PIM for older people. Some PIM are restricted to a certain dose or duration of use or both; for example, the use of ibuprofen is considered to be potentially inappropriate if the dose prescribed is higher than 400mg, three times per day, or if the length of use is longer than one week. The level of agreement between experts in the Delphi survey varied and is reported in this article. Table 1 of this article displays an abbreviated version of the EU(7)-PIM list, with the 72 PIM most frequently identified among the participants of the RightTimePlaceCare survey (1, 2). Appendix 1 shows the complete EU(7)-PIM list, and Appendix 2 and 3 present the full lists of questionable PIM and non-PIM, respectively.
The EU(7)-PIM list can be seen as a screening tool or as a tool to draw attention to PIM among older people’s prescriptions. The main advantages of the EU(7)-PIM list are: 1) it can be applied both in the clinical practice and to databases where the amount of clinical information available is limited; 2) it covers the drug markets of seven different European countries; 3) it contains suggestions on dose adjustments and therapeutic alternatives.
The main limitations/considerations of use of the EU(7)-PIM list are: 1) the Delphi technique relies widely on the knowledge of the participating experts (54); 2) not all European countries were involved; 3) it cannot substitute the individual assessment of appropriateness of prescription, which should take into account other aspects such as the aims of the treatment, individual responses, and the older person’s functional level, values and preferences (55).
To the best of our knowledge, the EU(7)-PIM list is the first list that requires only a small amount of clinical data for its application and that has been developed taking into account several existing PIM lists and European markets. This list may allow the comparison of data on PIM use between different European countries, which was limited until now because the majority of the tools were country-specific (40, 56). The EU(7)-PIM list could represent one step towards the development of prescribing quality indicators which are useful for the electronic monitoring of the quality of prescribing in older people in Europe (57).
The EU(7)-PIM list is ready for use and has been applied for the first time to the RightTimePlaceCare data on older people with dementia. The results of this first application show that the use of certain PIM according to the EU(7)-PIM list differs between European countries. Furthermore, results suggest that, among people with dementia and according to the EU(7)-PIM list, those who are older than 80 years, have lower functional status and live in nursing homes may be 28 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
p es i ed PIMs o e ofte . Results also suggest that the use of ≥ PIM ight e asso iated with an increased risk for hospitalisation and falls (58).
Both topics of this doctoral thesis are public health concerns with economic implications. Lower hospital admission rate has been used as an indicator of the quality of care in nursing homes (59). Beyond adverse clinical effects, hospital transfers account for a high proportion of total healthcare costs (60, 61). In the United States, for example, potentially avoidable hospitalisations of nursing home residents have become a major focus of the proposed Medicare Pay for Performance Demonstration (60). Also inappropriate prescribing and/or the prescription of PIM to older people have been found associated not only with adverse events but also with increased health costs (62, 63), and attempts are being undertaken to develop prescribing quality indicators which are useful for the electronic monitoring of the quality of prescribing in older people in Europe (57).
Thus, research focussing on the improvement of the measurement tools for the assessment of these issues seems necessary, and this doctoral thesis is a contribution to this body of knowledge. The development of measurement tools which are applicable to different settings, regions or countries should facilitate the analysis and comparison of data and help learning from each other. Furthermore, such tools can help evaluating the efficiency of interventions aimed at improving the clinical practice. Nevertheless, tools cannot substitute the individual judgement on appropriateness at patient level, and this is the reason why some authors working in these fields often use the term “potentially inappropriate” or “potentially avoidable”, as the final judgement should be done for each individual case. SUMMARY AND DISCUSSION OF THE RESULTS 29 30 31
Conclusions
3 32 QUALITY ISSUES IN CARING FOR OLDER PEOPLE CONCLUSIONS 33
Conclusions
Article “Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review”:
• Twenty-nine studies were identified that assessed the prevalence of the appropriateness of acute care admissions among older people living in long-term care (LTC) facilities. The prevalence of inappropriate admissions ranged from 2% to 77%. This systematic review provides information about the study designs, populations and types of facilities analysed in each study.
• Sixteen different assessment tools were applied in the studies. This systematic review provides detailed information on each tool regarding the concepts analysed, how they were developed, their psychometric properties, their format of use and the aspects covered by their items.
• Six aspects were covered by the items of the assessment tools: “specific medical diagnoses”, “acuteness or severity of symptoms at time of transition”, “resident’s characteristics prior to admission to hospital”, “resource availability/requirement”, “residents’/families’ wishes” and “information on the existence of a care plan”.
• Five of the tools covered only one of the aspects, while six tools considered four or more. The aspects less covered were “resident’s characteristics prior to admission to hospital”, “residents’/families’ wishes” and “information on the existence of a care plan”. Thus, most assessment tools were not comprehensive and did not take into account individual aspects of the residents.
• This systematic review may be the basis for further research in this area which is needed to develop an evidence-based and comprehensive tool supported by quality assuring strategies to improve decisions on the appropriateness of hospital admissions among residents of LTC facilities.
Article “The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries”:
• This article describes the development process of the European Union (EU)(7)-PIM list, a tool for the assessment of potentially inappropriate medications (PIM) for older people. The list was consented by experts from seven European countries within a two-round Delphi survey.
• This article presents the complete EU(7)-PIM list, which contains 282 chemical substances or drug classes from 34 therapeutic groups. It contains suggestions for dose adjustments and therapeutic alternatives. 34 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
• The EU(7)-PIM list is a screening tool for PIM that can be applied to databases and to individual patient data. It is the first list focussing on chemical substances and requiring only a small amount of clinical data for its application that has been developed taking into account several existing PIM lists and European markets, and that has been consented by experts from different European countries.
• This list allows the description and comparison of PIM prescription between different European countries and may be used as a guide in the clinical practice. Its application is a first step towards the identification of areas of improvement and towards the harmonisation of the prescription quality throughout Europe.
• The EU(7)-PIM list has been already applied to the data of the European cohort of people with dementia participating in the RightTimePlaceCare project (Renom-Guiteras, 8th IAGG-ER Conference, Dublin 2015). Further research is needed to investigate the feasibility, applicability and the clinical benefits of the newly developed list.
Overall conclusions:
• This doctoral thesis covers two topics which belong to the area assessment tools for the evaluation of quality of medical care issues in older people: appropriateness of hospital admission and appropriateness of prescribing.
• The first article provides an overview of the available assessment tools for determining appropriateness of hospital admission, and the second article describes the development of a new assessment tool for the identification of inappropriate prescriptions.
• Both articles aim at enhancing the unification of concepts and the extent of consensus between professionals in different settings and countries. They are part of a wider research process towards the improvement of the evidence-based care of older people. CONCLUSIONS 35 36 37
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5 48 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 49
ARTICLE 1 50 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
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RESEARCHARTICLE Open Access Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review Anna Renom-Guiteras1,2,3*, Lisbeth Uhrenfeldt4, Gabriele Meyer1,5* and Eva Mann6
Abstract Background: Residents of long-term care facilities have a high risk of acute care admission. Estimates of the frequency of inappropriate transfers vary substantially throughout the studies and various assessment tools have been used. The purpose of this study is to systematically review and describe the internationally existing assessment tools used for determining appropriateness of hospital admissions among long-term care residents. Method: Systematic review of the literature of two databases (PubMed and CINAHL®). The search covered seven languages and the period between January 2000 and December 2012. All quantitative studies were included if any assessment tool for appropriateness of hospital and/or emergency department admission of long-term care residents was used. Two pairs of independent researchers extracted the data. Results: Twenty-nine articles were included, covering study periods between 1991 and 2009. The proportion of admissions considered as inappropriate ranged from 2% to 77%. Throughout the studies, 16 different assessment tools were used; all were based on expert opinion to some extent; six also took into account published literature or interpretation of patient data. Variation between tools depended on the concepts studied, format and application, and aspects evaluated. Overall, the assessment tools covered six aspects: specific medical diagnoses (assessed by n = 8 tools), acuteness/severity of symptoms (n = 7), residents’ characteristics prior to admission (n = 6), residents’ or families’ wishes (n = 3), existence of a care plan (n = 1), and availability or requirement of resources (n = 10). Most tools judged appropriateness based on one fulfilled item; five tools judged appropriateness based on a balance of aspects. Five tools covered only one of these aspects and only six considered four or more aspects. Little information was available on the psychometric properties of the tools. Conclusions: Most assessment tools are not comprehensive and do not take into account residents’ individual aspects, such as characteristics of residents prior to admission and wishes of residents or families. The generalizability of the existing tools is unknown. Further research is needed to develop a tool that is evidence-based, comprehensive and generalizable to different regions or countries in order to assess the appropriateness of hospital admissions among long-term care residents. Keywords: Nursing home, Patient transfer, Hospitalization, Systematic review
* Correspondence: [email protected]; [email protected] 3Institute of General Practice and Family Medicine, Faculty of Health, University of Witten/Herdecke, Alfred-Herrhausen-Str. 50, Witten D-58448, Germany 5Medical Faculty, Institute of Health and Nursing Science, Martin-Luther-University Halle-Wittenberg, Magdeburger Straße 8, Halle (Saale) D-06112, Germany Full list of author information is available at the end of the article
© 2014 Renom-Guiteras et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. ARTICLES 51
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Background claimed by some authors [11,15-17]. As a first step towards Residents of long-term care (LTC) facilities have a high clarification, it seems to be justified to systematically re- risk of being admitted to hospital. Internationally, the in- view all assessment instruments applied for judgement of cidence of visits to an emergency department has been appropriateness of transfers, to analyse their development, estimated to be approximately 30 transfers per 100 LTC their underlying concepts, the aspects included, their psy- beds per year [1]. LTC residents are often sent to emer- chometric properties, and to critically review them in the gency departments (ED) when they are in a highly acute context of the complexity of acute care admissions of frail condition, and are likely to be admitted to the hospital and vulnerable LTC residents. [2]. Common underlying diagnoses are pneumonia, urin- Thus, the aim of our systematic review is 1) to provide ary tract infection, congestive heart failure, chronic ob- an overview of the studies dealing with tools for asses- structive pulmonary disease, fall-related injuries, and sing appropriateness of hospital admissions in LTC resi- altered conscious state [3,4]. dents and 2) to describe the published assessment tools LTC residents are often frail and suffer from diseases in in detail, including information about their development advanced stages, have several comorbidities, high levels of and the aspects covered by the tools. dependency and take multiple medications. The referral or admission to an ED or acute hospital – although often Methods unavoidable and beneficial – represents an unfavourable Four researchers from Spain, Germany, Denmark and discontinuity of care and encompasses threats to the resi- Austria, all experienced in geriatric care and research, dents including distress, risk of iatrogenic events [5], and established a working group and developed a research deterioration of mobility and cognition [6,7]. Beyond ad- protocol (available from the authors on request). In verse clinical effects, hospital transfers account for a high January 2013, two reviewers conducted a literature proportion of total healthcare costs [8]. search. The search covered the databases Medline via Many authors have evaluated the appropriateness of PubMed and CINAHL® and was limited to studies pub- ED visits or hospitalisation among LTC residents. There lished between January 2000 and December 2012. The fol- is an on-going debate on how to define appropriateness lowing search strategy was used for Pubmed: (("Residential of admissions in order to reduce negative effects of in- Facilities"[MeSH]) OR (nursing homes) OR (homes for the appropriate transfers without withholding residents from aged) OR (aged care facilit*) OR (nursing facilit*) OR admission if acute care is needed. To distinguish be- ("Long-Term Care"[MeSH])) AND (("Emergency Service, tween admissions to acute care that are inappropriate Hospital"[MeSH]) OR hospital OR (acute care) OR (emer- and those that are not is of great interest not only for gency AND (medicine OR department* OR unit* OR the residents concerned but also for nursing home pro- ward* OR service* OR room*))) AND (appropriat* OR viders and policy makers alike. In international studies, suitable OR avoidable OR preventable) AND (("Patient between 10% and 60% of hospital admissions have been Transfer"[MeSH]) OR ("Hospitalization"[MeSH]) OR refer- classified as inappropriate [9,10]. So far, the reason for this ral* OR admission* OR transition*) AND (English[lang] high variability is not clarified. Variations may result from OR French[lang] OR German[lang] OR Spanish[lang] OR different study objectives, including different concepts Catalan[lang] OR Danish[lang] OR Norwegian[lang]) AND such as inappropriate, preventable, avoidable, or unneces- ("2000/01/01"[PDat]: "2010"[PDat])). The corresponding sary hospitalisation. Differences in acute care destinations search terms were used for CINAHL®. Articles pub- and nursing home populations included in the studies lished in English, German, French, Spanish, Catalan, may also affect the rates of inappropriate admissions. Sev- Danish and Norwegian were considered for inclusion. eral studies suggest that facility characteristics may be as Two reviewers independently checked titles and abstracts important as residents’ clinical characteristics [11,12]. In for relevance and, in a second step, eligible full-text addition, regional differences in terms of financial incen- articles for inclusion. Reference lists of the included arti- tives may also have an influence [13]. Interestingly, con- cles were checked manually. In addition, we followed siderable variations in inappropriate hospital admission PubMed-indexed related citations of two included articles rates were even found in studies including nursing homes which have been published recently and which focus on in well-defined areas only [14]. different acute care destinations [10,15]. It is also important to take into account that authors We included prospective and retrospective, experi- used different assessment tools to judge the appropriate- mental and non-experimental studies if they 1) investi- ness of acute care transfers. Up to now, there is no consen- gated residents from any type of LTC setting who were sus on which tool to use for assessment of appropriateness transferred to hospital emergency departments or hospital of residents’ hospital admission. Furthermore, there is no wards, 2) provided or assessed diagnostic and/or thera- agreement on the aspects to be covered by such a tool. peutic data on the process of transfer, 3) developed, ad- The terminology and definitions are not yet clarified, as ministered or derived a tool for assessing appropriateness 52 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
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of hospital admissions, including any list of aspects or any Results single question that could be used to distinguish between Twenty-nine articles met the inclusion criteria appropriate or inappropriate admissions. Studies using dif- [3,4,8-10,15,18-41]. Two articles reporting on the ferent terms (e.g. inappropriate, preventable, avoidable ad- same study were considered as one source [21,38]. A missions) and operational definitions of appropriateness list of studies excluded, along with the reason for exclu- were considered for inclusion. sion, is available from the authors on request. Figure 1 dis- Two pairs of independent researchers extracted infor- plays the process of identification of studies for inclusion mation on the study characteristics and the assessment in the systematic review. (Additional file 1: Table S1) pre- tools using a piloted data extraction form. Publications sents the characteristics of the included studies. The cited in the reference list were retrieved if necessary. Re- majority (n = 24) were retrospective. Five studies re- sults were discussed and, in the case of disagreement, a ported on an intervention or a strategy for reducing trans- third author was consulted to reach consensus. In case of fers to acute care (information not shown in the table) doubt, the authors of the primary study were contacted. [21,23,26,27,30,38]. Data extraction covered information about the type of The majority of the studies (n = 24) investigated resi- study, description of participants and settings, informa- dents of LTC facilities only; five studies also included older tion on which assessment tool was used, how and by persons living in the community [27,29,31,32,39]. Most whom it was used, number and proportion of inappro- studies (n = 25) considered the general population of LTC priate admissions to acute care reported, period of time residents; four studies focused on specific groups: resi- studied, and information on how the assessment tool dents with long-term neurological conditions [32], resi- was developed and which items were evaluated by the dents with advanced cognitive impairment [37], and tool. Once data extraction was finished, the research residents at the end-of-life [31,39]. Mean age of the study team agreed on a list of aspects that were covered by the samples ranged from 81 [31,41] to 86 years [37], and the items found in the assessment tools. proportion of women varied from 62% [15] to 80% [23]. We refrained from formal critical appraisal of the in- While types of LTC facilities seemed to be similar, the cluded studies, since we were interested in the concepts acute care destinations varied substantially: some studies and tools used for assessing appropriateness of hospital focused either on ED visits or in-patient hospitalisation admissions only, rather than the internal validity of the (n = 3), others included in-patient hospitalisation only, irre- studies. Assessment of risk of bias would not have pro- spective of a previous ED visit (n = 8), others included ED vided any substantial information with regard to the aim visits with consecutive in-patient hospitalisation (n = 2), ED of this review. visits with subsequent discharge to nursing homes (n = 1) Inter-rater reliability was not calculated because most or ED visits irrespective of subsequent in-patient hospital- information extracted was descriptive. All disagreements isation (n = 6). Some studies investigated hospitalisation could be solved after checking for accuracy and discussion. without any further specification (n = 9).
Records identified Records identified Records identified through PubMed through CINAHL® through other (n=266) (n=86) sources (n=1.762) Identification
Records screened (title and Records excluded abstract) (n=2.114) (n=2.052) Screening Full-text articles excluded (n=33). Full-text articles assessed Reasons: e.g. no for eligibility (n=62) assessment tool used or derived
Eligibility (only ideas or suggestions for improvement), LTC Studies included and population not analysed (n=29) Included
Figure 1 Identification of studies for inclusion in the systematic review. ARTICLES 53
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In eighteen studies the assessment tool used for deter- professionals directly engaged in the care of residents mining appropriateness was applied to administrative transferred (n = 2). databases. In eleven studies hospital or LTC facility re- As can be seen in Additional file 2: Table S2, some tools cords, or interviews with residents or nursing staff were (e.g. AEP; ACSC) comprised a list of conditions or dis- used as data sources. eases (e.g. congestive heart failure, hypoglycaemia) while Results regarding the rate of inappropriate hospital ad- others consisted of a short definition or question (e.g. tool missions varied substantially. Some studies reported low by Ong et al. [39], tool by Hammond et al. [32]). proportions of inappropriate admissions. For example, The assessment tools differed widely regarding the as- Bermejo et al. [35] and Finn et al. [3] reported on 1.6% pects considered as criteria for judgement of appropri- and 13.1% of inappropriate emergency department visits, ateness of acute care admissions. The six aspects are respectively; Becker et al. [33] reported on 18% of pre- summarized in Table 1. Eight tools considered specific ventable hospitalisation. Other studies documented high medical diagnoses as indicators for appropriate or in- proportions of inappropriate admissions. In the study by appropriate hospitalisation; seven tools considered the Saliba et al. [18], 36% of all ED visits were judged as in- acuteness or severity of the symptoms at the moment of appropriate; Walker et al. [19] and Ouslander et al. [30] hospital transfer or admission; six tools took into ac- reported on 55% and 77% of potentially avoidable hospi- count the resident’s characteristics prior to admission; talisation, respectively. three tools considered the residents’ or families’ wishes; Sixteen assessment tools determining appropriateness one tool assessed whether a nursing care plan had been of hospital admissions among residents of LTC facilities defined and adhered to; ten tools considered resource were identified throughout the included studies. Informa- availability or requirement. tion on their names, development, psychometric proper- While most tools judged appropriateness based on one ties, aim/concept studied, way of use, items included fulfilled item of the above mentioned aspects, five tools and aspects covered are displayed in (Additional file 2: determined appropriateness by considering a balance of Table S2). Those tools without an own name are given the issues, for example by asking the professionals applying name of the first author of the corresponding study (see the criteria to give their judgement on appropriateness column “Tool [corresponding studies]”). after considering all the aspects. The terms used for indicating “inappropriate” hospital- Some tools focused on one or two of the aspects (e.g. isation varied throughout the different assessment tools: ACSC; tool by Gonzalo et al. [37]), while others were while most of them favoured the term “appropriate”/ more comprehensive, i.e. covered a higher number of as- “inappropriate” (e.g., AEP), others used the terms “avoid- pects. Six tools covered four aspects or more (e.g. tool able” or “preventable” (e.g., ACSC; additional tool by by Abel et al. [31]; tool by Jensen et al. [15]; Quality Im- Finucane et al. [9]; AHC), and one study applied the term provement Review tool; SIR). “potentially burdensome” (tool by Gonzalo et al. [37]). Most tools (n = 10) were developed or adapted in the Most tools aimed at measuring appropriateness of context of the actual studies, providing no information hospital transfer, i.e., from the LTC facility to either ED about their use in other studies or generalizability. Other or hospital ward. Some of them focused on visits to ED tools had been used previously, but with an aim other (e.g., Modified AEP, tool by Jensen et al. [15]), while others than assessing appropriateness of admission to hospital focused on admissions to hospital (e.g., AEP), or on both (e.g. AEP). Finally, some tools had been developed or ED visits and hospital stay (e.g. Quality Improvement used only in one country or context (e.g. ACSC, Quality Review tool (INTERACT-II)). A smaller number of Improvement Review tool (INTERACT-II)). Moderate to tools aimed at determining those hospital transfers which good levels of inter-rater reliability were found for six could have been prevented by adequate ambulatory care tools (SIR; AEP; tool by Abel et al. [31]; tool by Ham- (e.g., ACSC, AHC), focusing therefore on the period pre- mond et al. [32]; tool by Codde et al. [34]. ceding the acute moment of transition. All assessment tools were developed and based upon Discussion expert opinion to different extents: two tools were com- We reviewed 29 studies applying 16 assessment tools piled using an expert consensus method, and six expert aimed at determining the appropriateness or prevent- groups also took into account the results of a literature ability of ED or hospital admissions of LTC residents. search or the interpretation of patient data. In all stud- The rates of admissions considered as inappropriate ies, tools were applied retrospectively, i.e., after hospital differed substantially throughout the studies from 2% [9] admission had already taken place. to 77% [30]. The studies included in our review, most of Assessment tools were applied by the investigators them retrospective in nature and thus susceptible for bias, themselves (n = 9), an external panel of experts (generally were distinctive in many aspects. They varied considerably with experience in LTC) looking for consensus (n = 5), or in study designs and objectives. Outcomes were defined in 54 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
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Table 1 Aspects covered by the assessment tools Aspect Examples of items included in the tools Number of tools covering the aspect Specific medical diagnoses Suspected fracture, ACSC (asthma, congestive heart failure, angina, grand mal 8 seizure disorder, hypoglycaemia, hypertension, etc.), death Acuteness or severity of symptoms Sudden onset of unconsciousness, incapacitating pain, tachycardia, gastrointestinal 7 at time of transition bleeding symptoms, signs of being systemically unwell Resident’s characteristics prior Resident’s baseline health status, level of functional ability, resident with advanced 6 to admission to hospital cognitive impairment, presence of a terminal illness Resource availability/requirement Requirement of intravenous antibiotics, laboratory, radiology, admission to hospital, 10 physician and nurse availability and expertise Residents’/families’ wishes Advance care directive in place, request of hospital admission or emergency 3 department visit by family Information on the existence Actions taken by staff before the transfer (including presence of advanced care planning) 1 of a care plan
different terms or even different concepts, e.g., inappropri- admission to hospital, resource availability/requirement, ate, avoidable, or preventable admissions. Besides, the residents’/families’ wishes, information on the existence acute care destinations varied, as well as the selection of of a care plan. Most tools covered less than four aspects, the LTC population and LTC facility-level factors. Further- and only six of them included four or more aspects and more, studies took place in different regions and coun- were therefore considered as more comprehensive. The tries, implicating different reimbursement policies and individual aspects “residents’ characteristics prior to ad- financial incentives. The impact of these varying aspects mission to hospital” and “residents’/families’ wishes” on the rate of hospital admissions has been a matter of were evaluated only by six and three tools, respectively. discussion for nearly 30 years. However, literature on this Some tools (e.g. ACSC, Modified ACSC) only evaluated issue is scarce. In a previous review, case mix differences aspects like “specific medical diagnoses” or “acuteness or representing LTC population-level factors turned out to severity of symptoms at transition time point”. Taking give only partial explanation for the variations in hospital into consideration that residents in LTC facilities often admission [42]. This was confirmed by a study published differ in terms of comorbidity, cognitive and functional by Wennberg et al., reporting that disparities in hospital status, and stage of their diseases, it is surprising that admissions remained in similar geographic areas even residents’ clinical characteristics prior to acute care ad- after adjusting for case mix [43]. A recently published re- mission were not acknowledged throughout as a neces- view of the literature confirmed that the propensity of be- sary dimension of the judgement process. The same ing referred to acute care was rather associated with applies to residents’ and relatives’ preferences which facility characteristics including nursing home ownership otherwise play an important role regarding the present and bed-hold requirements than with patient characteris- advocacy towards person-centred care [44]. It may also tics [11]. be seen as a weakness of the existing tools that they did Interestingly, to the best of our knowledge, the impact not consistently include facility-level characteristics as of assessment tools on the variability of inappropriate an indicator of the appropriateness of admissions. In re- hospital admissions has not been studied so far. spect to the frequently quickly changing conditions of In our review, we noticed considerable heterogeneity residents, the presence of skilled nursing staff and the among the tools regarding the aims of use and the con- availability of technical equipment including diagnostic cepts studied (e.g. assessment of appropriateness of ED and therapeutic procedures may greatly influence the de- visits vs. in-patient hospitalisation; focus on preventable cision on the appropriateness of acute care admission. nature of the admissions vs. appropriateness of hospital Finally, only 5 tools judged appropriateness based on a transfer), format of use (tool applied by study authors vs. balance of aspects. expert panel or nursing staff), data sources used (admin- All tools identified in this systematic review were de- istrative databases vs. resident’ hospital or LTC facility veloped based on expert opinion, at least to a great ex- record vs. interview with residents or nursing staff), and tent. Information on generalizability in other regions or aspects evaluated. countries is scarce. Our research team isolated six most prominent as- Our findings are supported by a non-systematic review pects considered by the assessment tools: specific med- [17,45]. Ouslander and Maslow did not focus on LTC resi- ical diagnoses, acuteness or severity of symptoms at dents only, but also included community-dwelling older per- transition time point, resident’s characteristics prior to sons. The review on preventable hospitalisations focusses on ARTICLES 55
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U.S. information sources and perspectives. The authors which varied widely throughout the studies. We found 16 emphasize, as we do, the need for comprehensive mea- different assessment tools used in the studies. Only six sures to account for aspects such as medical comorbidi- tools covered more than four aspects as criteria to deter- ties, clinical complexity or differences in resources in the mine the appropriateness of acute care admissions. Most care settings. They also criticize the lack of attention to assessment tools did not take into account residents' indi- how and where decisions about hospitalisation are made. vidual aspects, such as characteristics of residents prior to Our systematic review focussed on the assessment of admission and wishes of residents or families. Tools were appropriateness among LTC residents. The assessment of based mostly on expert opinion, and information on their appropriateness of hospital admission among community- generalizability is not provided. Further research is war- dwelling older persons may require the consideration of ranted to develop an evidence-based and comprehensive similar aspects, but adapted to the different setting. To tool supported by quality assuring strategies to improve the best of our knowledge, no systematic review covering decisions on the appropriateness of ED and hospital ad- international studies on this issue is available so far. missions among residents of LTC facilities. It may be seen as a limitation that we did not systemat- ically assess the risk of bias of the original studies included Additional files in our systematic review. However, we were interested in the concepts and tools used for assessing appropriateness Additional file 1: Table S1. Studies dealing with assessment tools for of hospital admissions, rather than in the internal validity determining appropriateness of hospital admissions among residents of LTC facilities. of the studies. Nevertheless, even without formal validity Additional file 2: Table S2. Characteristics of the assessment tools to assessment, it is obvious that the included studies suffer determine appropriateness of hospital admissions among residents of from methodological shortcomings, since many used sec- LTC facilities [46-52]. ondary or retrospective routine data analysis and are therefore more prone to bias. Competing interests Our review, which is the first to overview the tools The authors declare that they have no competing interests. internationally used to assess the appropriateness of hos- Authors’ contributions pital admissions among LTC residents, may contribute Review protocol: ARG, EM & GM. Literature search: ARG, EM, LU & GM. Data to the clarification of the concept “appropriateness of extraction: ARG, EM, LU & GM. Data interpretation: ARG, GM, EM, LU. Drafting ” of the manuscript: ARG. Critical revision of the manuscript with regard to admission of LTC residents to acute care . It also may important intellectual content: GM, EM & LU. Study supervision: EM & GM. present a first step towards the development of an All authors read and approved the final manuscript. evidence-based, comprehensive and generalizable tool. Such a tool may have a two-fold function: first as a qual- Acknowledgements We thank Mr Adriel Ortega, an exchange student from the USA at the ity indicator to assess the appropriateness of the deci- University of Witten/Herdecke, who contributed to the literature search. We sions made when admitting individual residents to acute also thank Ms Karin Velbek, hospital library service at Horsens Hospital, who care, considering that the resources available were not supported the literature search, and Ms Vivienne Krause, University of Witten/ Herdecke, who checked the manuscript for English language. We thank the modifiable at that time, and secondly to identify areas of Sociedad Española de Geriatría y Gerontología (Spanish Society of Geriatric improvement such as the need for training in palliative Medicine and Gerontology) for the grant which supported the work of the care or the need for more resources. The tool may at- first author of this study. tempt to assess appropriateness minimizing the effects Author details of the different rater perspectives (i.e. nursing staff of 1School of Nursing Science, Faculty of Health, University of Witten/Herdecke, 2 the LTC facility, ED professionals, and researchers). It Witten, Germany. Universitat Autònoma de Barcelona, Barcelona, Spain. 3Institute of General Practice and Family Medicine, Faculty of Health, may also be used to assess the effectiveness of new inter- University of Witten/Herdecke, Alfred-Herrhausen-Str. 50, Witten D-58448, ventions aimed at improving appropriateness of transi- Germany. 4Department of Research, Horsens Hospital, Department of Public 5 tion of LTC residents to acute care. Health, Aarhus University, Aarhus, Denmark. Medical Faculty, Institute of Health and Nursing Science, Martin-Luther-University Halle-Wittenberg, In the meanwhile, studies aiming at assessing appropri- Magdeburger Straße 8, Halle (Saale) D-06112, Germany. 6Institute of General ateness of admitting LTC residents to hospital are encour- Practice, Family Medicine and Preventive Medicine, Paracelsus Medical University, aged to use an assessment tool according to predefined Salzburg, Austria. aims and taking the different aspects into consideration. Received: 31 January 2014 Accepted: 11 June 2014 Studies should mention why a certain tool was chosen Published: 22 June 2014 and the limitations of not using a more comprehensive References tool should be clearly mentioned. 1. Arendts G, Howard K: The interface between residential aged care and the emergency department: a systematic review. Age Ageing 2010, Conclusions 39:306–312. 2. Wang HE, Shah MN, Allman RM, Kilgore M: Emergency department visits Our systematic review analysed 29 studies assessing the by nursing home residents in the United States. J Am Geriatr Soc 2011, prevalence of the appropriateness of acute care admissions, 59:1864–1872. 56 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
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doi:10.1186/1471-2318-14-80 Cite this article as: Renom-Guiteras et al.: Assessment tools for determining appropriateness of admission to acute care of persons transferred from long-term care facilities: a systematic review. BMC Geriatrics 2014 14:80.
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ARTICLE 2 60 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 DOI 10.1007/s00228-015-1860-9
PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
The EU(7)-PIM list: a list of potentially inappropriate medications for older people consented by experts from seven European countries
Anna Renom-Guiteras1,2,4 & Gabriele Meyer3,4 & Petra A. Thürmann5,6
Received: 20 February 2015 /Accepted: 29 April 2015 /Published online: 14 May 2015 # The Author(s) 2015. This article is published with open access at Springerlink.com
Abstract drugs and suggesting dose adjustments and therapeutic alter- Purpose The aim of the study was to develop a European list natives. Finally, twelve experts completed a brief final survey of potentially inappropriate medications (PIM) for older peo- to decide upon issues requiring further consensus. ple, which can be used for the analysis and comparison of Results Experts reached a consensus that 282 chemical sub- prescribing patterns across European countries and for clinical stances or drug classes from 34 therapeutic groups are PIM for practice. older people; some PIM are restricted to a certain dose or Methods A preliminary PIM list was developed, based on the duration of use. The PIM list contains suggestions for dose German PRISCUS list of potentially inappropriate medica- adjustments and therapeutic alternatives. tions and other PIM lists from the USA, Canada and France. Conclusions The European Union (EU)(7)-PIM list is a Thirty experts on geriatric prescribing from Estonia, Finland, screening tool, developed with participation of experts from France, the Netherlands, Spain and Sweden participated; eight seven European countries, that allows identification and com- experts performed a structured expansion of the list, suggest- parison of PIM prescribing patterns for older people across ing further medications; twenty-seven experts participated in a European countries. It can also be used as a guide in clinical two-round Delphi survey assessing the appropriateness of practice, although it does not substitute the decision-making process of individualised prescribing for older people. Further research is needed to investigate the feasibility and applicabil- Electronic supplementary material The online version of this article ity and, finally, the clinical benefits of the newly developed (doi:10.1007/s00228-015-1860-9) contains supplementary material, which is available to authorized users. list. . * Anna Renom-Guiteras Keywords Potentially inappropriate medication [email protected] Inappropriate prescribing [MeSH term] . Aged [MeSH term] . Screening . Europe [MeSH term]
1 Institute of General Practice and Family Medicine, Faculty of Health, University of Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany Background 2 Universitat Autònoma de Barcelona, Barcelona, Spain 3 Institute for Health and Nursing Science, Medical Faculty, Martin Appropriate prescribing for older people is a public health Luther University Halle-Wittenberg, Magdeburger Straße 8, concern, and several assessment tools are available for its 06112 Halle (Saale), Germany evaluation. Most of the tools focus on pharmacological appro- 4 School of Nursing Science, Faculty of Health, University of Witten/ priateness of prescribing [1]; they address various aspects of Herdecke, Witten, Germany appropriateness, including overprescribing of medications 5 Clinical Pharmacology, Faculty of Health, University of Witten/ that are clinically not indicated, omission of medications that Herdecke, Witten, Germany are needed, and incorrect prescriptions of medications that 6 Philipp Klee-Institute of Clinical Pharmacology, HELIOS Klinikum may be indicated [2]. The term Bpotentially inappropriate Wuppertal, Heusnerstraße 40, 42283 Wuppertal, Germany medications (PIM) for older people^ has been used to refer ARTICLES 61
862 Eur J Clin Pharmacol (2015) 71:861–875 to those drugs which should not be prescribed for this popu- inappropriate medications covering the drug markets of seven lation because the risk of adverse events outweighs the clinical European countries, which can be used for the analysis of benefit, particularly when there is evidence in favour of a potentially inappropriate prescription patterns in and across safer or more effective alternative therapy for the same con- several European countries. Additionally, the list should be dition [3, 4]. applicable in clinical practice to alert health care professionals The prevalence of inappropriate prescribing and/or use of to the likelihood of inappropriate prescribing, possible dose PIM has been analysed by several authors and ranges from 20 adjustments required and therapeutic alternatives. to 79 % depending on the population studied, the setting or country, and the specific tool used [5–10]. Inappropriate pre- scribing and use of PIM can be associated with adverse out- Methods comes such as adverse drug events [11–13], hospitalisation [6, 14] and death [15]. A research team consisting of a clinical pharmacologist, a A recently published systematic review identified 46 tools pharmacist, a nursing scientist and a geriatrician planned and or criteria for assessing inappropriate prescribing [16]. A prior coordinated the development of the European Union (EU)(7)- systematic review identified 14 criteria specific for individuals PIM list. Two members of the research team were developers aged 65 and older [1]. Generally, the assessment tools have of the German PRISCUS list [22]. The study comprised five been developed based on expert opinion due to the lack of consecutive phases: high-quality studies on the use of drugs in older people [17], although some tools have additionally used a literature search 1. Preparation of a preliminary PIM list. We prepared a [18, 19]. Criteria have been classified into explicit or implicit preliminary PIM list which contained 85 PIM (82 active or mixed approach [1]. Explicit criteria are generally lists of substances plus one combination of active substances and medications or criteria which can be applied with little or no two different preparations of one substance) from the Ger- clinical judgement but do not address individual differences man PRISCUS list [22] and 99 PIM from the French [3], between patients [2]. Implicit criteria are based on the judge- American [24, 25] and Canadian [26] lists. These tools ment of a professional and are person-specific [20], requiring have been used in research to evaluate the prescription of individual patient data for application, however, they are time- PIM and factors associated with PIM use [5, 6, 14, consuming and more dependent on the user [2]. No single 27–29]. The main reason for each drug being PIM was ideal tool has been identified so far, but each tool seems to formulated using the information provided by the original have its strengths and weaknesses, and the choice of a tool lists. This process was supported by a comprehensive lit- may depend on the purpose of use (i.e. daily practice, re- erature search. The anatomical therapeutic chemical search) and availability of data [16]. (ATC) code classification system was used (2011) [30]. Assessment tools are being used increasingly for the eval- 2. Recruitment of experts on geriatric prescribing/ uation of prescribing quality in older people, but their appli- pharmacotherapy. We established a collaboration with cation cannot substitute the individual assessment of prescrib- the Seventh Framework European project ing appropriateness [16]. One of the limitations of the tools is RightTimePlaceCare [23], a project aiming to develop the fact that the majority was developed following country- best practice recommendations for dementia care through- specific guidelines, national drug markets and prescribing out Europe. The consortium partners of this project sup- habits, hence, limiting their transferability to other countries ported the recruitment of experts on geriatric prescribing [1, 21]. For instance, the German PRISCUS list of potentially or pharmacotherapy in their respective countries. Thirty- inappropriate medications, a purely explicit list, defines 83 three experts from six European countries agreed to par- PIM drugs, of which twelve are not on the drug market in ticipate; they came from Finland (n=3), Estonia (n=9), France, the USA and Canada. However, there are 124 drugs the Netherlands (n=4), France (n=2), Spain (n=7) and on the PIM lists of these countries which are not part of the Sweden (n=8). The following professions were represent- German PRISCUS list, because seventy of them are not on the ed as follows: geriatricians (n=14), pharmacists (n=3), German drug market and many others are almost never used clinical pharmacologists (n=7) and other medical special- [22]. To the best of our knowledge, no assessment tool covers ists (n=9). Experts were sent information documents de- the drug markets of several European countries and could thus scribing the aims, concepts and steps of the study and enable the analysis of European databases. were asked whether they preferred to participate in the The present study was conceived when planning to expansion phase (phase 3), in the Delphi survey (phase analyse the prescription of PIM among a European cohort 4), or in both. of older people with dementia participating in the 3. Expansion of the preliminary PIM list. We asked thirteen RightTimePlaceCare study [23]. The primary aim of our experts representing the six countries to expand the pre- study was to develop an expert-consensus list of potentially liminary PIM list by adding drugs that they considered 62 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
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should be PIM and which were not represented, paying 12) was invited to participate in the last brief survey which special attention to those drugs available on their respec- took place in September 2013. tive countries’ markets. Expansion of the preliminary list was Internet-based and concluded in May 2012. 4. Two-round Delphi survey. A two-round Delphi survey Expert agreement and statistics was performed [31]. The first Delphi round took place between October and December 2012, and the second Several approaches have been suggested in the literature to Delphi round between March and May 2013. In the first define expert agreement within Delphi surveys [31]. In this round, we asked 29 experts to assess each drug of the study, after the first and second Delphi rounds, we calculated preliminary expanded list for appropriateness by using a the means, the corresponding 95 % confidence intervals (CI) 1–5 points Likert scale where B1^ represented BI strongly and the medians of all Likert scores given to each drug; expert agree that the drug is potentially inappropriate for older agreement was considered if the CI of the mean score for each people^; B2^, BI agree that the drug is potentially inappro- drug did not cross over the value 3. Thus, each drug was priate for older people^; B3^, Baverage/neutral/ classified into PIM (if both the mean value of the score and undecided^; B4^, BI disagree that the drug is potentially the upper limit of the CI were lower than 3), non-PIM (if both inappropriate for older people^; B5^, BI strongly disagree the mean value of the score and the lower limit of the CI that the drug is potentially inappropriate for older exceeded 3) and questionable PIM (if the CI was on both sides people^; and B0^, Bno answer; I do not feel qualified to of the value 3). Statistical calculations were performed with answer^. Experts were asked to provide suggestions for SPSS, version 21.0. dose adjustments and safer therapeutic alternatives for those drugs judged as inappropriate. Experts were free to insert additional comments and were invited to expand Results the list with any further drugs they considered to be PIM. In the second Delphi round, we asked 28 experts to The preliminary PIM list contained 184 drugs (including assess the appropriateness of those drugs classified as two combinations of two drugs) and preparations (e.g. questionable PIM during the first round (see BExpert sustained-release preparations of oxybutynine). Eight of the agreement and statistics^), as well as the further sugges- 13 invited experts (62 %) participated in the expansion tions for PIM made by the experts during the first Delphi phase and suggested 75 additional drugs and preparations. round, and also eight drugs appearing in the recently pub- Twenty-six out of the 29 invited experts (90 %) participated lished updated Beers list [18]. Some PIM concepts were in the first Delphi round, and 24 out of the 28 invited ex- adapted taking the experts’ suggestions made during the perts (86 %) participated in the second Delphi round. Two first Delphi round into account. The additional sugges- experts from Spain and three experts from Finland chose to tions for PIM were given a justification as to why they collaborate together in two teams to provide their assess- may be classified as PIM, taking published data into con- ments in both Delphi rounds. All the 12 experts invited sideration when necessary. Again, experts assessed the participated in the last brief survey. appropriateness of these drugs and were asked to provide Figure 1 shows the development process of the list. In the dose adjustments, therapeutic alternatives, and to insert first Delphi round, experts assessed 259 drugs and prepara- additional comments if necessary. Drugs were classified tions, of which the majority (n=234) were classified as PIM into PIM, non-PIM and questionable PIM (see BExpert and only one drug as non-PIM. In the second Delphi round, agreement and statistics^). experts assessed 79 drugs and preparations, comprising 23 5. Preparation of the final PIM list. Dose adjustments and questionable PIM, 47 further suggestions by experts, eight drug alternatives suggested by the experts during the Del- additional drugs from the updated Beers list [18] and one drug phi survey were compiled and included in the EU(7)-PIM (naproxen) judged as PIM for which the main reason for PIM list, prioritising in each case those made by the higher was adapted taking recent published data and experts’ com- number of experts. Suggestions were complemented, if ments into consideration. Again, 31 drugs and preparations necessary, with information available from the other remained as questionable PIM and 46 drugs were classified PIM lists and from Micromedex® [32], a commercially as PIM. Overall, after the third brief survey, 282 drugs and available database which contains comprehensive infor- preparations were classified as PIM, 29 as questionable PIM mation on drug use. We identified those drugs for which and three as non-PIM. some discussion issues raised by the experts still remained The level of agreement between experts varied in the as- open and those drugs where inconsistency in the results sessment of appropriateness. For example, experts reached was identified after checking the literature. In order to consensus for diazepam being PIM with a mean Likert score solve these problems, a reduced number of experts (n= of 1.61, confidence interval between 1.32 and 1.89, and ARTICLES 63
864 Eur J Clin Pharmacol (2015) 71:861–875
Fig. 1 The development process Preliminary PIM-List Expansion by experts of the EU(7)-PIM list (184 drugs) (75 drugs)
Preliminary expanded PIM- list (259 drugs) 1st Delphi round 26 expertsa
Non-PIM Questionable PIM PIM (1 drug) (23 drugs) (234 drugs)
+ 47 further suggestions by experts + 8 additional drugs from the updated Beers list [18] + 1 drug judged as PIM for which the main reason for PIM was adapted with experts‘ comments and literature. 2nd Delphi 79 drugs round 24 expertsa
Non-PIM Questionable PIM PIM (2 drugs) (31 drugs) (46 drugs) Last brief survey 2 drugs 12 expertsa
Non-PIM Questionable PIM PIM (3 drugs) (29 drugs) (282 drugs)
Final results
aThis number comprises two groups of 2 and 3 experts, respectively, doing joint assessments. median of 2. Consensus was reached also for digoxin being corrections in the PIM which needed experts’ approval (three PIM (mean Likert score 2.19; confidence interval 1.57–2.81; drugs). All of the issues could be solved. median 2), but in this case, the Likert scores ranged from 1 to Table 1 displays an abbreviated version of the EU(7)-PIM 5. No consensus was reached on the appropriateness of some list, with the 72 PIM most frequently identified among the drugs such as metamizole, which was classified as question- participants of the RightTimePlaceCare survey [23], a Euro- able PIM. For this drug, the disparity seemed to be in part due pean cohort of older people with dementia (data not shown). to the experts’ country of origin, since the majority of the Appendix 1 shows the complete EU(7)-PIM list, which Spanish experts considered metamizole to be appropriate comprises 275 chemical substances (i.e. 7-digit ATC codes; when used in adequate doses, whereas the majority of Finnish e.g. amitriptyline) including two combinations of two chemi- experts considered this drug to be clearly inappropriate. cal substances, plus seven drug classes (i.e. 5-digit ATC The last brief survey consisted of 11 questions with codes; e.g. triptans), belonging to 55 therapeutic classes (i.e. multiple-choice answers and covered issues regarding 13 4-digit ATC codes; e.g. antidepressants) and 34 therapeutic drugs. The questions covered mostly dose-related issues groups (i.e. 3-digit ATC codes; e.g. the nervous system). Some commented by the experts during the survey which remained PIM concepts are dose-related (e.g. zopiclone used at doses open (four drugs) and inconsistencies in the results identified higher than 3.75 mg/day) or defined by length of use (e.g. after checking the literature (three drugs). Additionally, the proton-pump inhibitors used longer than 8 weeks) or drug research group asked the experts to provide their opinion on regimen (e.g. insulin, sliding scale). Appendix 1 contains also the use of three drugs. Finally, the research group did minimal information on the number of experts who assessed each PIM, 64 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 865 . E, L b atives: macrogol, contraindications. E phloroglucinol. E gliclazide may be safer thanshort-acting the sulphonilureas. other E osmotically active lax lactulose. E, P low dose). E Domperidone (<30 mg/d) if no Non-pharmacological measures, e.g. diet; Diet; metformin (<2×850 mg/d); insulin; Clopidogrel; aspirin (<325 mg) When indication is appropriate, PPI (<8 weeks, Recommend proper dietary fibre and fluid intake; ations of use Alternative drugs and/or therapies vative titration scheme. d in palliative care. E 50 mL/min 150 mg q 24h (oral); 50 mg q 50 mL/min); reduce dose to 25 mg/d in cases of 24 h (iv). E – – each deposition until normalisation ofdo not bowel; exceed 16days; mg/d; may use be no useful longer innon-infectious than palliative diarrhoea. 2 care E for persisting mL/min 50 % ofdose normal 20 dose; mg/d; maximum may be use severe renal insufficiency (CrCl <30 mL/min). E, M 30 18 Titrate dose in increments ofevery 1 1 to to 2 2 mg weeks no based more on than individual response. M non-micronized glibenclamide; 0.75 mg/dmicronized for glibenclamide) and maintenance dose; not recommended if CrCl <50 mL/min. M renal failure and for1 older people, mg/d use followed initial by dose a of conser Lower doses to avoid hypoglycemia. E Basal insulin. E Start with a dose of 4 mg followed by 2 mg in Short-term use and dose reduction; CrCl <40 Reduce dose to 50 mg/d in cases of renal failure (CrCl 75 years ≥ de abdominal infection and hip fracture. se, may delay recovery adverse events include d anticholinergic effects, may spirin; risk of vasodilatation and ypoglycemia Adjust according to renal function. E For patients with pecially in people with difficult C. difficile ata available for adults aged ted hypoglycemia Use conservative initial dose (1.25 mg/d for ffects including confusion CrCl < monstrated in using sliding-scale Inappropriate if used >8 weekswithout in clear maximal indication dose increased risk of insulin. Might facilitate fluctuations inlevels glycemic pain and bloating. Rare dizziness. May precipitate toxic megacoloninflammatory in bowel disea in unrecognised gastroenteritis worsen peripheral arterial bloodintermittent flow claudication and precipitate pain, fluid and electrolyte imbalancehypoalbuminemia. and May exacerbate bowel dysfunction orthostatic hypotension. Proven beneficialpatients only with for artificial heart valves control of INR value old. Subjects aged 65 toconcentrations 80 than had younger higher subjects. plasmahypoglycemia, Risk dizziness, of headache andoedema peripheral a Long-term high dose PPI therapy is associated with an Main reason Dose adjustment/special consider IM according to the EU(7)-PIM list P pantoprazole Ranitidine CNS adverse e Insulin, sliding scaleGlibenclamide No benefits de Risk of protrac PPI (>8 weeks) e.g. omeprazole, Acenocoumarol Risk of bleeding, es MetoclopramideSodium picosulfate Loperamide (>2 days) Antidopaminergic an Risk of somnolence, constipation, nausea, abdominal Senna glycosides Stimulant laxative. Adverse events inclu GlimepirideSitagliptine Risk of protracted h Dipyridamole Limited safety d Less efficient than a Laxatives Propulsives Drugs for peptic ulcer and gastro-oesophageal reflux Insulins and analogues Blood glucose lowering drugs, excluding insulins Antithrombotic agents Antipropulsives Table 1 PIM ARTICLES 65
866 Eur J Clin Pharmacol (2015) 71:861–875 trial fibrillation: beta-blockers indication; exclude PIMs control yields better balance ofharms benefits than and rhythm controlpeople. for B most of older inhibitors, or other medication groups depending on comorbidity (exclude PIM). E inhibitors, or other medication groups depending on comorbidity (exclude PIM). E (except oxprenolol, pindolol, propranolol, sotalol, nadolol, labetalol). E,congestive P For heart failure: diuretics (except spironolactone >25 mg/d), ACE inhibitors. E Consider alternatives depending on the Other antihypertensive drugs, e.g. ACE For tachycardia/a Data suggest that for most older people rate Other antihypertensive drugs, e.g. ACE Intravenous iron. E 2/d; GFR – 50 mL/min), – ations of use Alternative drugs and/or therapies 25 mg/d; reduce dose if potassium nal function worsens. – 25 % of dose or every 48 h. E 75 % of dose or every 36 h; in – – 50 mL/min/1.73 m: initial dose ≥ 0.125 mcg/d; – 25 mg/d, increase up to 25 mg 1 8 mg/d (extended release). E – – 49 mL/min/1.73 m: initial dose 12.5 mg/d, – levels increase or re GFR <10 mL/min: avoid. M increase up to 12.5 30 cases of renal failure (CrCladminister <10 10 ml/min), body mass and maintenanceactual doses CrCl. using M M Use lower maintenance200 dose, e.g. mg/48 h. E body mass and maintenanceactual doses CrCl. using M For older0.0625 people, use dose in cases of renal failure (CrCl 10 administer 25 12.5 renal insufficiency. E P Start with 0.5or mg/d 4 (immediate release) E, M GFR (CrCl <15 mL/min). M, E Calculate digitalizing doses based on lean Start dose at the low end of the dosing range. Calculate digitalizing doses based on lean 20 mg twice per day for patients with moderate Start with half of usual dose, taper in and out. Reduce dose in cases of moderate renal insufficiency. Reduce dose in cases of renal failure thonia); caution in cases hypotension, bradycardia, amount absorbed but greatlyof increase constipation the incidence (women > men); risk of intoxication of provoking torsades de pointes of moderate renal failure and(>75 with years older old); people efficacytinnitus for or the dizziness treatment not of proven (tremor, akinesia, hyper urinary incontinence/ impaired micturition,side CNS effects (e.g. vertigo,somnolence) light-headedness, and cerebrovascular and cardiovascular disease older people, especially ifrequiring doses periodic >25 controls mg/d, syncope, CNS side effectscognitive (sedation, impairment) depression, Doses >325 mg/d do not considerably increase the Main reason Dose adjustment/special consider , peripherally acting ts, centrally acting (continued) (>325 mg/d) Digoxin Iron supplements / Ferrous sulfate DigitoxinAmiodarone Elevated glycoside sensitivity in older people Associated with QT interval problems and risk Trimetazidine Can cause or worsen parkinsonian symptoms Spironolactone (>25 mg/d) Higher risk of hyperkalaemia and hyponatremia in Rilmenidine Risk of orthostatic Doxazosin Higher risk of orthostatic hypotension, dry mouth, Iron preparations Cardiovascular system Cardiac glycosides Antiarrhythmics, classes I and III Other cardiac preparations Antiadrenergic agen Antiadrenergic agents Potassium-sparing agent Table 1 PIM 66 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 867 , b bitors, diuretics. E ckers, ACE inhibitors, ckers, ACE inhibitors, 3×400 mg/d or for ≤ e/naloxone, morphine e drugs (amlodipine, 2×250 mg/d or for a period shorter than r antihypertensive drugs (amlodipine, ≤ bisoprolol, carvedilol, atenolol). E beta-blockers, ACE inhi exercises, physical and behavioural therapy). E cardioselective beta-blo diuretics). E cardioselective beta-blo diuretics). E, L administration (i.e. vaginal application) considered safe and efficient. E, B a period shorter than one( week); naproxen one week). E Opiods withdelirium lower (e.g. risk tilidin of oxycodone, buprenorphine, hydromorphone). E, P Cardioselective beta-blockers (e.g. metoprolol, Depending on the indication: cardioselective Non-pharmacological treatment (pelvic floor Paracetamol; ibuprofen ( Other antihypertensiv Specific treatment for osteoporosis. E Local 60 mg/d. E – go slow for older ations of use Alternative drugs and/or therapies — nitial dose 40 mg three times 30 mL/min); avoid use if CrCl – slowly. P Reduce dose andof dosing renal interval failure. in M cases people and patients with renal failure. M times daily. E moderate renal failure andcases to of 400 severe mg renal oncetoxicities. failure; daily Avoid close in use monitoring if for CrCl <30 mL/min. M older people with 2.5 mg orally 2 or 3 times daily. M be reduced if combined with(use proton-pump <8 inhibitors weeks, low dose). E Initial dose 30 mg/d; maintenance dose 30 daily; sustained release tablets initialdaily; oral dose controlled 120 onset extended mg release100 initial mg/d. dose M postoperative pain: 50 mg/d infailure, case maximum dose of 50 renal or48 mg/8 hepatic h; h; the maximum risk length with of proton-pump bleeding inhibitors may (use be <8 reduced weeks, if low combined dose). E <10 mL/min. M impaired renal function. M failure (CrCl 10 Use 2 mg orally once daily in cases of severe renal 1 mg orally twice daily in cases of significantly Start at half or one third of the typical dose and increase Reduce dose or increase dosing interval. M 60 mg three Reduce dose to 400 mg twice daily in cases of 3 doses of 20 mg daily E start low Lower initial dose, half of usual dose, taper in and out. P Othe Start immediate-release oxybutynin chloride in frail 50 mg/d; start using low dose; the risk of bleeding may Lower initial dose, half of usual dose, taper in and out. P Dose reduction may be needed. M Start with lower dose, up to 50 mg/d in older people; in rofile; fatal; cardiovascular sk of bradycardia Immediate-release tablets: i orthostatic hypotension and fallwith risks most are vasodilators increased or cause respiratory depression; possibleadverse CNS events increased mortality (breast and endometrial cancer)cardioprotective and effect lack in of older women dry mouth, CNS side effects);(prolonged ECG QT) changes perforation, which may be contraindications Main reason Dose adjustment/special consider tic products, non-steroid (NSAID) (continued) xifylline No proven efficacy; unfavourable risk/benefit p Sotalol Diltiazem Pento Propranolol Non-selective beta-adrenergic blocker; may exacerbate Verapamil May worsen constipation; ri Nifedipine (non-sustained-release) Increased risk of hypotension; myocardial infarction; Nifedipine (sustained-release) Oxybutynine (non-sustained-release) Anticholinergic side effects (e.g. constipation, Oestrogen Evidence for carcinogenic potential Oxybutynine (sustained-release) Tolterodine (non-sustained-release) Tolterodine (sustained-release) Diclofenac Very high risk of GI bleeding, ulceration, or Solifenacin Dexketoprofen Oestrogens Peripheral vasodilators Beta blocking agents Selective calcium channel blockers with direct cardiac effects Selective calcium channel blockers with mainly vascular effects Other urologicals, including antispasmodics Anti-inflammatory and antirheuma Table 1 PIM ARTICLES 67
868 Eur J Clin Pharmacol (2015) 71:861–875 , b ; b ; lamotrigine b 3×400 mg/d or for a ≤ e/naloxone, morphine .E b ; gabapentin b .E b 2×250 mg/d or for a period shorter than ≤ (<6 weeks), olanzapine (<10haloperidol mg/d), (<2 mg singlequetiapine dose; < 5 mg/d); levodopa; irreversible inhibitor of monoamine oxidase as rasagiline. E one week). E Opioids withdelirium lower (e.g. risk tilidin of period shorter than one( week); naproxen valproic acid oxycodone, buprenorphine, hydromorphone). E, P Paracetamol; ibuprofen ( Bisphosphonates, vitamin D. E Levodopa; carbidopa-levodopa; benserazide Non-pharmacological treatment; risperidone ations of use Alternative drugs and/or therapies e; the risk of bleeding may reduced if combined with go slow. Not to be used in cases of severe go slow; use one third to one half the normal go slow; in persons older than 75 years, go slow; 0.5 mg/day. E Levetiracetam — — — — be reduced if combined with(use proton-pump <8 inhibitors weeks, low dose). E (CrCl <30 mL/min). M renal failure. E, M increase gradually by 0.25week mg for per four intake weeks, each upthe to dose 3 may be mg/d. increasedup Afterwards weekly to by 24 1.5 mg/d. mg/d E M Start with three intakesgradually of by 0.125 0.125 per mg day,days, per increase up intake to every 1.5 five to to 4.5 seven mg. E adult dose for debilitated oldermaintenance people; doses use of 300than mg 1 or g less; do dosesbe not greater responsible usually for offer an any increasedeffects. benefit, M incidence but of may adverse dose; the risk of bleedingwith may proton-pump be inhibitors (use reduced <8 if combined weeks, low dose). E proton-pump inhibitors (use <8 weeks, low dose). E daily doses over 300Start mg with are 12.5 not mg/8 recommended.12.5 M h mg/8 and progressive h; maximum increasesand 100 of extend mg/8 the h. dosing E intervalrenal Reduce for failure. dose patients M with severe Start low 11 mg/d; start with lower dos Avoid in cases of severe renal failure Start low Start with three intakes of 0.25 mg per day, Reduce dose in cases of moderate to severe renal failure. Start low Shortest possible duration of therapy. P Start with lower Adjust dose to the response and serum concentration. E The risk of bleeding may be risk of orthostatic th seizures or epilepsy nations, confusion, ntricular block and of SIADH-like syndrome; adverse inic-blocking drug; which may be fatal who are temporarily or permanentlyEvaluate immobilised. the need forover continued 80 therapy for years patients oldthromboembolism with increased risk of venous effects such as confusion, vertigo and nausea hypotension and falls; may lowerthresholds seizure in patients wi confusion, somnolence, nausea tract symptoms, halluci insomnia, peripheral oedema events like carbamazepine-induced confusion and agitation, atriove bradycardia complications at higher dosesespecially (>1200 in mg/d), case of previous cardiovascular disease Main reason Dose adjustment/special consider Risk of GI bleeding and increased risk of cardiovascular alization ture and miner (continued) period longer than one week) Etoricoxib Clonazepam Risk of falls, paradoxical reactions. Start low RopiniroleChlorpromazine Risk of orthostatic hypotension, hallucinations, Muscar MeloxicamIbuprofen (>3×400 mg/d or for a Strontium ranelate Very high risk of GI bleeding, ulceration, or perforation, Tramadol (sustained-release) Higher risk of venous thromboembolism in persons More adverse effects in older people; CNS side Carbamazepine Increased risk Tramadol (non-sustained-release) Pramipexole Side effects include orthostatic hypotension, GI Opioids Drugs affecting bone struc Antiepileptics Dopaminergic agents Antipsychotics Table 1 PIM 68 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 869 ; b ^ 3.75 mg/d), ≤ 0.125 mg/d); ≤ ). E, P If used as c es: see alternatives ses of short-acting 0.5 mg/d), brotizolam ≤ hypnotics and sedatives B 5 mg/d), zopiclon ( 5 mg/d); trazodone. E, P ≤ ≤ 0.125 mg/d); antidepressants with 0.5 mg/d), brotizolam ( ≤ ≤ short-acting benzodiazepines such as lormetazepam ( anxiolytic profile (SSRI ( hypnotics or sedativ proposed for passiflora, low do benzodiazepines such as lormetazepam ( zolpidem ( zaleplon ( Non-pharmacological treatment; low doses of Non-pharmacological treatment; mirtazapine go slow. — go slow; reduce dose ations of use Alternative drugs and/or therapies 1.5 mg/d) for the 2.5 mg once a day to – — – 1 mg/d. E – ded-release tablets: start ntegrating tablets): start s of renal failure; start with ully; administer in small 5 mg/d. M once-daily dosing desired, – cessary. E For geriatric severe renal failure shortest time period ne patients or in cases of (CrCl <30 mL/min), startincrease with doses 0.5 by mg 0.5 twice mgabove daily; twice 1.5 daily; mg increases twiceof daily at should least be 1 done week;For at slower geriatric intervals titration patients, may if beinitiate necessary. and titrate on a2 twice-daily to regimen 3 for days toonce-daily achieve dosing target thereafter. dose M and switch to in cases of significant renal failure. M doses of 5 to 10 mg in geriatric patients. M period possible. E twice a day. M taper in and out, shortest possible durationP, of M treatment. Use initial oral dose of 2 taper in and out, shortest possible durationP of Starting treatment. dose 0.25tablets mg/12 (including h. orally E disi Immediatewith release 0.25 mg administered twoand to titrate three as times tolerated; a exten with day 0.5 mg onceand daily, gradually tolerated. increase M as needed dose, taper in and outresponse, according shortest to possible individual duration of treatment. P, M taper in and out, shortest possible durationP of Reduce treatment. dose, e.g. 0.5 mg/d; start low E, M For induction ofpeople, anaesthesia titrate in dose older, caref poor-risk intravenous increments of 0.3 tointervals. 0.5 M mg, at 30-s Use the lowest dose required (0.5 Administer cautiously in case Use low oral doses of 2.5 Use the lowest possible dose, up to half of the usual Reduce dose; use doses of 0.25 Use oral doses of 0.75-1.5 mg; use for the shortest Start with 12.5 mg/d. E Start low Use the lowest possible dose, up to half of the usual dose, Use the lowest possible dose, up to half of the usual dose, Use the lowest possible dose, up to half of the usual dose, ion s effects (can also be paradoxical, acture, prolonged reaction time, sk-benefit profile for the treatment of behavioural symptoms ofmortality, dementia; with increased higher dose, in patients with dementia times; psychiatric reactions e.g. agitation, irritability, hallucinations, psychosis); cognitive impairment; depression (tardive dyskinesia); parkinsonism; hypotonia; sedation; risk of falling; increasedpersons with mortality dementia; in increased riskagranulocytosis of and myocarditis (tardive dyskinesia); parkinsonism; hypotonia; sedation; risk of falling; increasedpersons mortality with in dementia QTc-prolongation psychiatric reactions (which cane.g. be agitation, paradoxical, irritability, hallucinations, psychosis), cognitive impairment and depression Main reason Dose adjustment/special consider (continued) Diazepam Risk of falling with hip fracture; prolonged react Risperidone (>6 weeks) Problematic ri Clozapine Anticholinergic and extrapyramidal side effect LevomepromazineHaloperidol (>2 mg single dose; >5 mg/d) Zuclopenthixol Anticholinergic and extrapyramidal side Risk of hypotension, falls, extrapyramidal effects, Flunitrazepam Risk of falls and hip fr Lorazepam (>1 mg/d) Alprazolam Bromazepam Anxiolytics Hypnotics and sedatives Table 1 PIM ARTICLES 69
870 Eur J Clin Pharmacol (2015) 71:861–875 , c esterase, memantine. E esterase, memantine. E , trazodone. E b PIM: fluoxetine, paroxetine, fluvoxamine) pharmacotherapy of Alzheimer-type dementia: acetylcholin pharmacotherapy of Alzheimer-type dementia: acetylcholin mirtazapine Non-pharmacological treatment, SSRI (except Non-pharmacological treatment; consider Non-pharmacological treatment; consider ations of use Alternative drugs and/or therapies 50 % in cases of mild – pain may be considered 7 days as tolerated. E Reduce – 50 mg, two times per day and increase – 50 mg/d in divided doses. E, M Its use 1000 mg at bedtime. M – – reduce dose; start withand 10 20 mg mg 3 at timesneuropathic bedtime. per pain M, day may E, be P considered Itswith appropriate, use benefits for overweighting treating the risks. E start immediate-release tablets with 10(12.5 mg/d mg/d if controlled-release tablets),by increased 10 mg/d (12.5up mg/d to if 40 controlled-release mg/d tablets), tablets). (50 E, mg/d M if controlled-release also 20 mg/d; avoidE, administration M at bedtime. renal failure. M the total daily dose by 25 by 25 mg/dose; forstart extended-release with formulation 37.5 mg once37.5 daily mg and every increase 4 by to moderate renal failure. M usual dose, taper in andduration out, of shortest treatment. P possible Startand with watch 7.5 individual response. mg/d M dose, taper in and out,of shortest treatment. possible P duration usual dose, taper in andduration out, of shortest treatment. possible P 500 for treating neuropathic appropriate, with benefits overweightingrisks. the E Use the lowest possible dose, up to half of the usual Use the lowest possible dose, up to half of the Start at half the usual daily dose, increase slowly; For older people or for patients with renal failure, Reduce dose; start with 20 mg/d; maximum dose Reduce dose for older people and for patients with Start with 25 Use the lowest possible dose, up to half of the Use 30 ral anticholinergic side e mortality, attempted suicide, use mortality, higher risk n; unfavourable risk/benefit ticholinergic side effects (e.g. effects (drowsiness, inner unrest, confusion, other types of delirium); cognitiveincreased deficit; risk of falling constipation, dry mouth, orthostaticcardiac hypotension, arrhythmia); cent of seizures, falls andadverse fractures. effects Anticholinergic confusion); hyponatremia profile orthostatic hypotension and fall stroke, seizures, upper gastrointestinalfalls bleeding, and fracture Main reason Dose adjustment/special consider sed for ADHD and nootropics >0.5 mg/d) (continued) Amitriptyline Peripheral an Lormetazepam ( Temazepam Ginkgo biloba No efficacy proven; increased risk of Zopiclone (>3.75 mg/d) Zolpidem (>5 mg/d) Clomethiazole Risk of respiratory depression Reduce dose. E, M Use sedative dose FluoxetineParoxetine CNS side effects (nausea, insomnia, dizziness, Higher risk of all-ca Piracetam No efficacy prove Venlafaxine Higher risk of all-caus Nortriptyline Antidepressants Psychostimulants, agents u Anti-dementia drugs Table 1 PIM 70 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 871 ^ GI ADHD ^ is PIM). E Alternative anti-inflammatory and electrocardiographic, B like loratadine, cetirizine, but like loratadine, cetirizine, but d d ECG iuretic hormone secretion, every q hypnotics and sedatives drugs proposed for antirheumatic products, non-steroid (NSAID) antihistamines antihistamines not terfenadine (which is PIM).insomnia E see If alternatives used proposed for for B not terfenadine (which therapies depending on indication. E If used for pain management consider alternative Non-sedating, non-anticholinergic Non-sedating, non-anticholinergic evaluated millilitre, mL central nervous system, CNS minute, 1 min ations of use Alternative drugs and/or therapies syndrome of inappropriate antid SIADH milligram, go slow. M Reduce 12.5 mg for iv injection. M ], either by the experts or in Micromedex® – — mg 23 [ 50 mL/min and to 50 % if – angiotensin-converting enzyme, go slow; reduce dose to 75 % of the usual micrograms, — ACE ], mcg GFR <10 mL/min. M (especially in cases of renallow failure); start dose if GFR 10 for healthy younger people. E, M starting dose to 6.25 doses for younger people.maximum E Start dose of with 400 a levels mg/d; and monitor reduce serum doses ifolder needed; people for (>60 healthy years),is theophylline decreased clearance by an average of 30 %. M 18 Start treatment cautiously for older people Reduce dose to at least 50 % less than dose used see also EU(7)-PIM long version in Appendix RTPC RightTimePlaceCare intravenous, — iv n, Beers list (2012) [ B , this means that no suggestion was made ], ^ 3 iltration rate, proton-pump inhibitors, glomerular f PPI nts GFR Laroche et al. (2007) [ L ], oratadine was evaluated and judged to be questionable PIM; other drugs such as cetirizine were not day, 22 d sweating, constipation, vomiting, dizziness, sedation, respiratory depression). Avoid use for longer than 2constipation weeks without for concurrent persons use withand of chronic for laxatives persons with renal impairment dry mouth); impaired cognitive performance, confusion, sedation; electrocardiographic changes (prolonged QT) tion group were judged to be questionable PIM: citalopram, sertraline, and escitalopram Main reason Dose adjustment/special consider y used in the RTPC database are presented PRISCUS list [ Dose adjustment/special considerations of use P B ], creatinine clearance, 32 irway diseases CrCl potentially inappropriate medication, PIM Micromedex® [ M (continued) ystemic drugs for a Codeine (>2 weeks) Higher risk of adverse events (hypotensio Theophylline Higher risk of CNS stimulant effects Start with a 25 % reduction compared to the Promethazine Anticholinergic side effects (e.g. confusion, sedation) Reduce dose; start low Hydroxyzine Anticholinergic side effects (e.g. constipation, experts, Caution: this drug was judged to be questionable PIM In the group of non-sedating antihistamines, only l Only the details on the drugs most commonl The following drugs belonging to this medica Cough suppressants, excluding combinations with expectora Other s Antihistamines for systemic use Table 1 PIM Note: if nothing is stated under a b c d gastrointestinal, attention deficit hyperactivity disorder Dosage abbreviations: E ARTICLES 71
872 Eur J Clin Pharmacol (2015) 71:861–875 the mean, median and standard deviation of the scores given We expect the EU(7)-PIM list to be a sensitive tool because by experts to each drug (Likert scale), and the results of the of its inclusive development process. In contrast, other tools compilation and selection of suggestions for dose adjustments have been seen to be less sensitive, motivating some authors and therapeutic alternatives. Furthermore, Appendix 1 shows to use two or three assessment tools for the assessment of PIM two categories of those drugs (active substances characterised use in their populations in order to increase the sensitivity [5, by their ATC code) on the EU-PIM list that are included also 6, 35, 36]. on other PIM lists. Category A means that precisely this active We aimed at developing a list which can be used even if the substance is named as a PIM which should be avoided in older clinical information available is minimal. Therefore, we chose people. Category B means that (i) this active substance is to develop explicit PIM criteria, restricted to drugs or drug characterised as a PIM only in the case of certain clinical classes, in some instances restricted to high doses or conditions or co-morbidities or (ii) this active substance is prolonged treatment duration. Thus, the EU(7)-PIM list is not specifically named but considered as a PIM drug class suitable for pharmacoepidemiological applications using ad- (e.g. anticholinergics or long-acting benzodiazepines). This ministrative databases or surveys without any clinical infor- information refers to six international PIM lists or criteria [3, mation about the individuals concerned. 18, 19, 22, 26, 33] and shows that 24 drugs do not appear as To the best of our knowledge, this is the first list focusing PIM in any of the other lists, while the rest varies from on chemical substances and requiring only a small amount of appearing in one list only to appearing in all the lists. clinical data for its application that has been developed taking The full lists of questionable PIM and non-PIM and the into account several existing PIM lists and European markets, results of their assessments are presented in Appendix 2 and and that has been consented by experts from different Euro- 3, respectively. pean countries. This is also one of the few lists including suggestions for dose adjustments and therapeutic alternatives. Furthermore, the list enables a distinction between different drugs belonging to the same pharmacological subgroup and Discussion provides different suggestions for each of them. The recently published screening tool of older person’s prescriptions We developed the EU(7)-PIM list in order to analyse the pre- (STOPP)/screening tool to alert doctors to right treatment scription patterns of potentially inappropriate medication (START) criteria for potentially inappropriate prescribing for (PIM) across several European countries, and more specifical- older people (version 2) were developed also with the partic- ly among the people with dementia participating in the ipation of a European panel of experts [19]. However, these RightTimePlaceCare Seventh Framework European project criteria often consider as PIM the use of pharmacological sub- [23]. We also aimed to develop a list that would be applicable groups (e.g. thiazide diuretics) within specific clinical contexts in clinical practice. The development of the EU(7)-PIM list (e.g. history of gout, or current significant hypokalaemia). took several international PIM lists (i.e. the German PRISCUS Thus, the application of the START/STOPP criteria (both ver- list [22], the American Beers list [18, 24, 25], the Canadian list sions 1 and 2) [4, 19] requires clinical information, making [26], and the French list [3]) into consideration, as well as these criteria more suitable in the clinical context for a com- further drugs suggested by experts on geriatric prescribing prehensive drug review of individual patients. from seven European countries who belonged to different The development process of the EU(7)-PIM list resembles professions. those of most other PIM lists, such as the French list [3], the The EU(7)-PIM list can be seen as a screening tool for German PRISCUS list [22], the Austrian PIM list [37], but the identification of PIM for older people across many Eu- also the most recent Beers list [18]. One major aspect of crit- ropean countries. We have covered several regions of Eu- icism of all PIM lists is that the classification of PIM is usually rope including Finland and Sweden in Scandinavia, France done without using evidence derived from randomised, con- and Spain in southern Europe, Germany and the Netherlands trolled trials and relies on the expertise of the participants in in central Europe, and Estonia in eastern Europe. As shown the Delphi process [38]. However, this is partially justified by by Fialová et al. [5], the prevalence of PIM use in several the lack of evidence on drug efficacy and safety in older peo- European countries varies widely, depending on the PIM ple, due to their low enrolment in clinical trials [17]. In our criteria set. Thus, the creation of a PIM list suitable for study, we identified relevant literature and used it during the pharmacoepidemiological studies and clinical use in Europe development process, but we did not systematically review seems to be mandatory. Attempts are being undertaken to and report it, which may be seen as a limitation. develop prescribing quality indicators which are useful for The Delphi technique has also been criticised because of the electronic monitoring of the quality of prescribing in the lack of one standardised method, the difficulties in older people in Europe [34], and the EU(7)-PIM list could analysing the data, the difficulties in defining what an expert represent a part of this. is, the often heterogeneous expert group, and the vague 72 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Eur J Clin Pharmacol (2015) 71:861–875 873
concept of consensus [38]. In order to minimise the limitations In conclusion, the EU(7)-PIM list is an expert-consensus of the Delphi technique, in the present study, the characteris- list of potentially inappropriate medications for older people, tics of the survey were predefined (e.g. steps, consensus con- which was developed taking into consideration the medica- cept), and researchers provided experts with all necessary in- tions appearing in six country-specific PIM lists, as well as formation to favour their engagement and participation. Re- medications used in seven European countries. It is an explicit searchers compiled discussion issues raised by the experts and list of chemical substances and contains suggestions for dose took them into consideration for the consecutive steps of the adjustments and therapeutic alternatives. It can be applied as a development process. screening tool to identify potentially inappropriate medica- Only seven European countries participated in the devel- tions in databases where little clinical information is available opment of the EU(7)-PIM list (Estonia, Finland, France, Ger- and in individual data. It can also be used for international many, the Netherlands, Spain and Sweden). Furthermore, the comparisons of the prescription patterns of PIMs and may number of experts participating from some countries was lim- be used as a guide in the clinical practice. The application of ited. Certain drugs may not have been assessed for appropri- the EU(7)-PIM list is a first step towards the identification of ateness because they were neither included in the preliminary areas of improvement in both individual and population levels list nor were they suggested by the experts. Certain drugs were and towards the harmonisation of the prescription quality classified as PIM with a lower level of expert agreement than throughout Europe. others; some disagreements seemed related to the experts’ country of origin, which may show that there are international Acknowledgments We are very thankful to the following experts on differences in prescription patterns or attitudes. Regular up- geriatric prescribing and/or pharmacotherapy for their participation in the development process of the EU(7)-PIM list: Anti Kalda (University of dates of the list should take into consideration the inclusion of Tartu, Tartu, Estonia), Jana Lass (University of Tartu, Tartu, Estonia), Mai other European markets, the changes in the drug markets, the Rosenberg (University of Tartu, Tartu, Estonia), Peeter Saadla (Tartu prescribing tendencies, and above all, the new existing University Hospital, Tartu, Estonia), Kai Saks (University of Tartu, Tartu, evidence. Estonia), Gennadi Timberg (West-Tallinn Central Hospital and MedTIM Private Urological Clinic, Tallinn, Estonia), Tiina Uuetoa (East-Tallinn The application of the EU(7)-PIM list cannot substitute Central Hospital, Tallinn, Estonia), Risto Huupponen (University of Tur- the individual assessment of prescribing appropriateness, ku, Turku, Finland), Paula Viikari (Turku City Hospital, Turku, Finland), which should take into account other aspects such as the Matti Viitanen (University of Turku, Turku, Finland), François aims of the treatment, individual responses, and the older Montastruc (Toulouse University Hospital, Toulouse, France), Antoine ’ Piau (Toulouse University Hospital, Toulouse, France), Froukje Boersma person s functional level, values and preferences, among (University Medical Center Groningen, Groningen, the Netherlands), others [39]. This limitation has been recognised in the liter- Paul A. F. Jansen (Expertise Centre Pharmacotherapy in Old Persons ature with regard to most tools assessing appropriateness of (EPHOR) Utrecht, the Netherlands), Rob van Marum (Jeroen Bosch ‘ prescription [16]. Despite its limitations, the concept of PIM Hospital, s Hertogenbosch, VU University Medical Center, Amsterdam, the Netherlands), Jos M. G. A. Schols (University of Maastricht, Maas- suggests that their use should be associated with less tricht, the Netherlands), Eva Delgado-Silveira (University Hospital favourable outcomes. Indeed, the use of PIM has been found Ramón y Cajal, Madrid, Spain), Antonio Fernandez Moyano (San Juan associated with a higher rate of adverse drug reactions in de Dios del Aljarafe Hospital, Sevilla, Spain), Francesc Formiga (Univer- several studies, as reported in a systematic review [40], with sity Hospital of Bellvitge, Barcelona, Spain), Elisabet de Jaime (Parc de Salut Mar, Barcelona, Spain), Ramón Miralles (Parc de Salut Mar, Bar- some variations depending on the settings studied. Other celona, Spain), María Muñoz (University Hospital Ramón y Cajal, Ma- authors have suggested an association between PIM use drid, Spain), Olga Vázquez (Parc de Salut Mar, Barcelona, Spain), Robert and other adverse outcomes such as injuries [41] and Eggertsen (University of Gothenburg, Sahlgrenska Academy, Gothen- hospitalisation [6, 14]. A limited number of studies on inter- burg, Sweden), Peter Engfeldt (Örebro University, Örebro, Sweden), Tommy Eriksson (Lund University, Lund, Sweden), Johan Fastbom ventions involving the use of some of these tools have sug- (Karolinska Institute and Stockholm University, Stockholm, Sweden), gested benefits in terms or relevant outcomes [42–44]. How- Annika Kragh (Lund University, Lund, Sweden), Patrik Midlöv (Center ever, according to a recent systematic review, it is unclear for Primary Health Care Research, Lund University, Malmö, Sweden), whether such interventions result in clinically significant im- and Anders Wimo (Karolinska Institute, Stockholm, Sweden). We thank Dr Stefanie Holt-Noreiks and Dr Simone Bernard, Univer- provements, although benefits in terms of reducing inappro- sity of Witten/Herdecke, for their scientific contribution throughout the priate prescribing may exist [45]. project. We also thank Ms Vivienne Krause, University of Witten/ Future research should study whether the use of PIM ac- Herdecke, who checked the manuscript and the EU(7)-PIM list for the cording to the EU(7)-PIM list shows any association with English language; Ms Klaaßen-Mielke, Ruhr University Bochum, who contributed in the coding and plausibility checks of the list; and Ms Malin clinically relevant outcomes for older people, and whether Wörster, who contributed in comparing the EU(7)-PIM list with other the application of the list is associated with any benefits, both international lists. We are thankful to the RTPC Consortium partners in a population and on individual levels. The acceptability of who supported us to establish the contact to the experts. Finally, we thank the list among health professionals should also be investigat- the University of Witten/Herdecke for supporting the project and the Sociedad Española de Geriatría y Gerontología (Spanish Society of Ge- ed, including the usefulness of the suggestions for drug ad- riatric Medicine and Gerontology) for supporting the work of the first justments and therapeutic alternatives. author of this study with a grant. ARTICLES 73
874 Eur J Clin Pharmacol (2015) 71:861–875
Compliance with ethical standards patients admitted to six European hospitals. Eur J Clin Pharmacol 67(11):1175–1188 Conflict of interest The authors declare that they have no competing 9. Garcia-Gollarte F, Baleriola-Julvez J, Ferrero-Lopez I, Cruz-Jentoft interests. AJ (2012) Inappropriate drug prescription at nursing home admis- sion. J Am Med Dir Assoc 13(1):83 e9–83 e15 Funding This study was supported by a research grant of the Univer- 10. Mann E, Haastert B, Frühwald T, Sauermann R, Hinteregger M, sity of Witten/Herdecke. Hölzl D, Keuerleber S, Scheuringer M, Meyer G (2014) Potentially inappropriate medication in older persons in Austria: a nationwide prevalence study. Eur Geriatr Med 5(6):399–405 Contributions of authors’ statement Petra A Thürmann (PAT) and 11. Chang CM, Liu PY, Yang YH, Yang YC, Wu CF, Lu FH (2005) Gabriele Meyer (GM) conceptualised the study and applied for funding. Use of the Beers criteria to predict adverse drug reactions among Anna Renom-Guiteras (ARG) and PAT prepared the work documents first-visit elderly outpatients. Pharmacotherapy 25(6):831–838 during the development process. ARG recruited the experts and coordi- 12. Passarelli MC, Jacob-Filho W, Figueras A (2005) Adverse drug nated the expansion phase, the Delphi survey and the last brief question- reactions in an elderly hospitalised population: inappropriate pre- naire. PAT and ARG prepared the final version of the EU(7)-PIM list. scription is a leading cause. Drugs Aging 22(9):767–777 ARG drafted the manuscript, supported by GM and PAT. All the authors 13. Hamilton H, Gallagher P, Ryan C, Byrne S, O’Mahony D (2011) critically reviewed and approved the final manuscript. Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients. Arch Intern Med 171(11):1013–1019 14. Price SD, Holman CD, Sanfilippo FM, Emery JD (2014) Open Access This article is distributed under the terms of the Creative Association between potentially inappropriate medications from Commons Attribution 4.0 International License (http:// the Beers criteria and the risk of unplanned hospitalization in elder- creativecommons.org/licenses/by/4.0/), which permits unrestricted use, ly patients. Ann Pharmacother 48(1):6–16 distribution, and reproduction in any medium, provided you give 15. Gosch M, Wortz M, Nicholas JA, Doshi HK, Kammerlander C, appropriate credit to the original author(s) and the source, provide a link Lechleitner M (2014) Inappropriate prescribing as a predictor for to the Creative Commons license, and indicate if changes were made. long-term mortality after hip fracture. Gerontology 60(2):114–122 16. Kaufmann CP, Tremp R, Hersberger KE, Lampert ML (2014) Inappropriate prescribing: a systematic overview of published as- sessment tools. 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Annexes
6 78 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 79
ANNEX 1.1 A i le 80 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
(LTC (LTC
1
and data
(LTC facility
SIR Assessment tool used AEP + additional on question avoidability hospital and facility interview) records, AHC (administrative databases) ACSC (administrative databases) ACSCModified (administrative databases) and hospital hospital and records) source source (administrative databases, resident hospital / LTC records, facility interview)
to ially : all:
II 0.9 (<0.001) 0.9 II
hospitalisation
Outcome concept and number and Outcomeconcept %or inappropriate of admissions EDV: 36% the of Inappropriate IH: Inappropriate admissions; 40% all hospitalisation: Inappropriate NH (1%), 2/184 participants Potent (2%). 1/65 residents avoidable NH (10%), (26%) 19/184 17/65 2% of hospitalisation: Avoidable the IH (not specific data for NH reported) participants per hospitalisation Preventable month): per (rate 100 residents 0.8 I control 0.3; intervention control (p<0.001); due hospitalisation Preventable ACSC: (11%) n= 8.070
b
Acute care and destination number of facilities IH or EDV (n=10) EDV and IHconsecutive (n=1) (NNM) IH IH (excluding IH after EDV) (NNM) Hospitalisation (NNM)
Type of LTC of Type facilities and number NH (n=8) NH, rest hostels homes, (NNM) LTC settings (NNM) and Control intervention NH (n=44 pairs) NH (n=527)
home care a quarter - Sample Residents admitted to (n=458) hospital Residents admitted to (n=153), hospital (n=184) admissions Older persons, including (n=3.057) patients Residents: group intervention control (n=1.936), (n=2.868) groups Residents admitted to (n=72.319 hospital person observations)
Method Retrospective, analysis data secondary Prospective, study observational Retrospective, analysis data secondary Retrospective, routine analysis data Retrospective, analysis data secondary Studies dealing with assessment tools for determining appropriateness of hospital admissions among residents
- - - - Studied Studied period 1994 1995 1998 1992 1994 1998 2000 1991 1993
Country USA Australia USA USA USA
[22] [23] [24]
., 2000 ., Additional file 1: Table S1:
LTC facilities. Authors and publication year Saliba et al Finucane 2000 al., et [9] Murtaugh, 2002 Kaneet al., 2003 Carter, 2003 [18] ARTICLES 81
2
ACSC
ministrative ACSC (administrative databases) ACSC (administrative databases) ACSCModified (administrative databases) ACSC AEPModified hospital (resident records) Modified (administrative databases) ACSC (administrative databases) (ad databases)
; ;
c 6 %; n=3.137 n=3.137 (<0.001) 34 1
; control; I 0.9 4
ntervention 0.4; control I 0.7; 0.7; I control 0.4; ntervention Potentially preventable or or preventable Potentially avoidable hospitalisation: at hospitalised 8.450 of (37%) out once least per hospitalisation Preventable month): per (rate 100 residents 0. intervention 1. II control (p<0.001); per hospitalisation Preventable month): per (rate 100 residents i EDV 100 per Preventable month): per (rate residents 2. I control 1.7; intervention 2.3 II control or hospitalisation Avoidable ACSC: to due 41% hospitalisation with IH among residents the of ADRD; IH 43% among the of ADRD without those EDV: n=71 (13%) Inappropriate EDV avoidable and Potentially ICH ACSC with consecutive ACSC IH with 1999: in 32%; 33%; 2002: 2001: 2000: 29% 30%;32%; 2004: 2003: control II 0.6. 0.6. II control b b
Hospitalisation (NNM) IH (excluding IH after EDV) (NNM) IH or EDV (NNM) (NNM) IH EDV (n=1) EDV and IHconsecutive (NNM) IH (n=253)
-
289), 289),
-
(n=44 (n=44 NH (663) and Control intervention NH pairs) NH Control (n=181 intervention NH (n=110 studied (3 118) periods) NH (n=525) NH, hostels (NNM) NH (NNM) NH (n=690)
Residents (n=54.631) Residents Residents: group intervention control (n=1.936), (n=2.868) groups Residents: group intervention control (n=1.985), (n=3.970) groups Residents with ADRD residents (n=19.802), ADRD without (n=19.958) to Admissions from hospital care residential (n=541) institutions to Admissions NH from hospital (n=1.279) 1999 Residents: 2000 (n=167.452), 2001 (n=165.228), 2002 (n=162.946), 2003 (n=161.967), (n=161.726)
-
Prospective, cross observational, sectional Retrospective, routine analysis data Retrospective, routine analysis data Retrospective, analysis data secondary Retrospective, routine analysis data Retrospective, analysis data secondary Retrospective, routine analysis data - - - - - 1997 1998 2000 1997 2001 1991 1993 2002 2000 2002 1998 2004
US USA USA USA USA Australia USA
[26] [27] [28] [3]
Intratoret 2004 al., [25] Kaneet al., 2004 Kaneet al., 2005 Carter and Porell, 2005 Finn et al., 2006 Carter et 2006 al., [29] Grabowski 2007 al., et [8] 82 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
3
developed
house developed developed house house house developed house sidenthospital - - - In In (resident hospital hospital (resident records) ACSCModified (administrative databases) SIR Modified hospital (resident and LTC facility records) (re In hospital (resident and records structured interviews with residents) ACSC (administrative databases) SIR Modified (resident LTC facility records) records)
%) 4 n=2 (
Inappropriate EDV: Inappropriate Potentially avoidable the to according hospitalisation original US ACSC list: 47% according 8.885); of out (n=4.177 to the revised Canadian 55% list: of out (n=4.874 hospitalisation of 8.885) Potentially avoidable b) n=23 (77%); a) hospitalisation: n=32 (49%) the at staying of Appropriateness yes/maybeLTC facility (inappropriately transferred): NH RHn=53 (69%); n=27 (45%) admission: of Inappropriateness 25) of 12% out (3 EDV: 25% avoidable Potentially of all EDV avoidable definitely or Probably n=134 (67%) hospitalisation:
b b b b
EDV (n=3) Hospitalisation (NNM) Hospitalisation (NNM) IH (irrespective of EDV) (n=1) IH (n=2) (NNM) EDV Hospitalisation (NNM)
3)
LTC facilities (n=19) High intensity LTC facilities (n=150) NH (n= RH NH, (NNM) NH (NNM) NH (NNM) NH (n=20)
Residents admitted to (n=606) hospital (n=76.629); Residents Residents admitted to (n=8.885) hospital a) Residents admitted to hospital (n=30); b) Residents admitted to (n=65) hospital Residents admitted to NH from hospital RH and (n=77) (n=59) this in (who died care) of episode Residents with LTNC admitted to hospital (n=25) (n=64.589) Residents Residents admitted to (n=200) hospital
Retrospective, routine analysis data Retrospective, routine analysis data Retrospective, a) b) analysis; data routine prospective, interventional pilot study. arm single both of Comparison sets data Retrospective, routine analysis data Prospective Retrospective, analysis data secondary Retrospective, routine analysis data - - - - - 2000 1997 2002 2005 2007 2006 2007 2006 2007 2005 2005 2006
UK Canada Canada USA England Canada USA
[31]
Jensen et 2009 al., [15] Walker et 2009 al., [19] Ouslander 2009 al., et [30] Abel et al., 2009 Hammond 2009 al., et [32] Gruneiret 2010 al., [4] Ouslander 2010 al., et [10] ARTICLES 83
II)
- 4
house developed developed house developed house house developed developed house developed house - - - - In ACSC (administrative databases) from Adapted and II INTERACT sources other (administrative databases) In In hospital (resident and LTC facility records) AEPModified (administrative databases) In (administrative databases) Quality Improvement Review tool (INTERACT (resident hospital hospital (resident records) (administrative databases) (resident LTC and records, facility written questions to staff) nursing
hospitalisation
total transfers, % of % of the residents 1
6
% of all EDV 2
Preventable hospitalisation: 18% hospitalisation: Preventable (n=10.091 hospitalisation all of 8.382) of out Potentially preventable EDV: an with 40% among residents EDV EDV: 161 avoidable Potentially to discharged patients (69%) of NH; 31% the of including patients with IH suitable not or Inappropriate EDV: EDV: 22% all of Inappropriate EDV transition burdensome Potentially care: acute to with ACI avoidable possibly or Avoidable 24% of hospitalisation: hospitalisation (b) or avoidable Potentially inappropriate acute managed been have in to (likely homes): 4 care hospitalisation b b
Hospitalisation (NNM) (NNM) EDV EDV and NH to discharge (n=1) EDV (n=1) EDV (n=1) Hospitalisation (NNM) IH EDV, (NNM) IH (n=1)
; ;
NH (n=647) NH (n=1.500) NH (NNM) NH (n=1) RH NH, (n=15) NH (NNM) NHa) (n=25) NHb) (n=26) RH NH, a) (NNM); RH NH, b) (n=8)
;
;
Residents (n=72.251); (n=72.251); Residents to admitted residents 8.382) (n= hospital (n=14.017) Residents Residents admitted to and hospital NH to discharged (n=235) Residents admitted to (n=45); hospital hospital to admissions (n=62) Residents admitted to (n=4.149) hospital residents with EDV (n=423) Residents with ACI admitted to hospital (n=474.829) NH per Residents a) n=166) size (average NH per Residents b) n=174) size (average Residents admitted to RH from hospital NH and (n=223) (n=117)
-
Retrospective, routine analysis data Retrospective, analysis data secondary Retrospective, routine analysis data Retrospective, routine analysis data Retrospective, routine + analysis data qualitative interviews Retrospective, routine analysis data a) Prospective, single arm intervention; with comparison data; retrospective single prospective b) + one arm intervention hour calls conference Retrospective, a) + analysis data routine prospective b) qualitative analysis - - - - 2003 2006 2004 2007 2008 2008 2000 2007 2008 2009 2006 2005
USA USA Australia Spain Austria USA USA England
[20] [39]
;
21]
Becker et 2010 al., [33] Caffrey, 2010 Codde et 2010 al., [34] Bermejo et 2010 al., [35] Kadaet 2011 al., [36] et Gonzalo 2011 al., [37] a) Ouslander 2011 al., et [38] b) Lamb et 2011 al., [ Onget al., 2011 84 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 5
ACSC (administrative databases) ACSC (administrative databases) erm Care; LTNC: Long
days days -
iew.
ementias; AEP: Appropriateness Evaluation Evaluation AEP: Appropriateness ementias; Potentially preventable hospitalisation due to ACSC rate: resident 100.000 654 per Hospitalisation due to ACSC: than older 22% (among residents 65 years)
b b
Hospitalisation (NNM) Hospitalisation (NNM)
ient Hospitalisation; ISD: Intensive Service Days; LTC: Long T idential Home; SIR: Structured Implicit Rev Implicit Home; Structured SIR: idential pat - NH (n=147) Assisted living facilities
H: In
ve Conditions; ADRD:ve Conditions; Alzheimer’s Disease and Related D Residents (n=26.746) Residents (n=16.208); Residents 65 than older residents (n=7.991) years
d, if available. Retrospective, routine and analysis data analysis data secondary Retrospective, analysis data secondary - -
2006 2007 2002 2008
USA USA
Not specified if EDV or IH. Only data from LTC facilities are displaye are Only from data LTC facilities provided. not admissions Number inappropriate of
Protocol; AHC: Avoidable Hospital Conditions; EDV: Emergency Department Visit; I Young et 2011 al., [40] Becker et 2012 al., [41] ACI:Note: Advanced Impairment; Cognitive ACSC: Ambulatory Care Sensiti NH: Home; Nursing NNM: RH: Conditions; Res Number Mentioned; Not Term Neurological a b c ARTICLES 85 86 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 87
ANNEX 1.2 A i le 88 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 1 ment,vital riateness: 1)
) a
easing consciousness (A), requirement requirement (A), consciousness easing
Summary of the items evaluated Summary evaluated items the of covered (aspects between:Balance residents’ issues of advance (C), status health baseline directives (W), potential benefits of acute the in provided care the and (R), transfer NH changed status when residents’ the (R). approp indicating Items of onset sudden (e.g. illness of Severity low or high abnormally unconsciousness, pulse rate, persistent fever, incapacitating (A); abnormality) electrocardiogram pain, parenteral (e.g. service of Intensity 2) replace fluid and/or medications (R) monitoring) sign e.g. appropriateness, indicating Items a in performed be to unable procedure with trauma of history home (R), nursing suspectedfracture (D), difficult indwelling catheter insertion (R), PEG tube insertion with event cerebral of suspicion (R), decr admission (R), antibiotics intravenous for to hospital (R)
the
Format use the of in studies included Implicit criteria: of list trained for questions in (experienced reviewers LTC). Afterwards, they question the answer to had "was hospitalisation the avoidable?" with: "definitively not", "probably not", "probably yes" "definitively yes" or List of items applied to by the data residents' authors. Hospitalisations any if deemed appropriate criteria fulfilled. List of criteria applied by a to nurse study research of records medical of Records participants. patients not meeting the reviewed by a criteria clinical panel (consisting professionals different of and care acute both from LTC) to determine could episodes the whether
[18]
) and and )
8 a, 1981) 1981) a, Psychometric properties Reviewer 84%agreement: EDVagreement for 0.6 (kappa 89% for and hospitalisation Original AEP (German and Restucci agreement: Overall 92% 94% to specific (p<0.0001); for agreement rates the reviewer pairs: 73% 79% to provided No data
review review Refined by Refined
hospital [10]
[47] [46].
structuredinterviews with - Based on medical literature Based on medical literature
18]. Development 2000 al., et by Saliba Developed [ Original based. expert Mostly Restuccia, and by Gertman version assess to used 1981 (USA), unnecessary potentially between specific (not days care of NH care) and acute 1994 al., et Baggoley expert by an Defined multidisciplinaryclinical 2006 al., et by Finn Modified panel. [3] professionals and experts (e.g. (e.g. experts and professionals nursing facility administrators, geriatric nurse practitioners, family room physicians, emergency and physicians, medicine geriatricians). Modified by 2010 al., et Ouslander and semi
Characteristics of the assessment tools to determine appropriateness of hospital admissions among residents LTC Characteristics of the assessment tools and and
,
[10], [18]
[30]
Term(s), concept(s) and aim(s) of use To measure agreement between on reviewers the decisions of appropriateness to transfer NH residents to EDs hospital or for reasons and frequency avoidable potentially hospitalisations to strategies of efficacy avoidable potentially reduce hospitalisation To measure appropriateness hospital to admission of To measure appropriateness of EDV
[9]
Additional file 2: Table S2:
facilities. [correspo nding studies] Tool SIR [10,18,30] AEP Modified AEP [3,36] ARTICLES 89 2
(D)
[27] Kane (2005) Kane (2005)
na, grand mal mal grand na, : septicaemia: availability and [24];
preventable conditions, conditions, preventable - idential care setting (R) : timeliness,: availability of Availability of specialised care (e.g. (e.g. care specialised of Availability high drugs, parenteral fluid, parenteral supervision) nursing and medical of level within the res heart e.g. avoidability, indicating Items failure, urinary tract infection (D) asthma, e.g. avoidability, indicating Items angi failure, heart congestive hypoglycaemia, disorder, seizure hypertension. Modifications, e.g. Carter and pneumonia excluded (2003) failure heart congestive the to poisonings and accidents added emergency preventable services ACSC to added Two items deleted: conditions four falls/fractures; and immunization of balance a as defined Appropriateness issues (e.g., resources and treatment diagnostic intravenous, pharmaceuticals) (R), timely test results (R), physician and availability nursing (R), expertise (W), advanced (R), directives expertise nutritional deficiency, severe ear, nose and ear, severe deficiency, nutritional throat infections, tuberculosis (D)
on
reviewed reviewed homes.
dgment
have been managed within managed within been have nursing the to question Additional by authors. AEP. Applied involving conference Case seniorclinicians List of items applied to by the data residents' authors List of items applied by the authors to residents' data List of items applied to by the data residents' authors teamPhysician LTC) in (experienced independently made and cases resident clinical ju appropriateness of referral. Consensus meeting.
No data provided No data provided No data No explicit data found provided No data provided No data
[9].
dwelling Based AEP - Modified Modified
existing
- based - [49]. by a physician physician by a
considered. 1993 specified.
Literature review and Literature
Expert panel assessed panel Expert Defined
xperts. Originally
ped in the context of the the of context the in ped [22]. [19]. [15]. [48] [50,24]
Developed in the context of the the of context the in Developed to tool additional as study Methods not the of context the in Developed study of context the in Developed Billings et al., medical a including method Delphi and internists six of panel advisory paediatricians, including national e and local community for developed older adults. Several modifications exist Develo study applicability of the pre ACSC to an older institutionalised Canada and in population consensus developed setting the for appropriate revisions the of context the in Developed study team LTC experienced in health (a physicians) family and researcher on research from on Weissman research al., et 1992 expert opinion opinion expert
residents
preventable preventable
To identify potentially avoidable hospitalisation To identify potentially stays, hospital avoidable hospital as defined conditions for admissions inadequate suggesting ambulatory care To identify EDV or potentially of hospitalisation avoidable NH residents To identify potentially in hospitalisation avoidable LTC facilities and to identify for opportunities preventive in improvement and continuity provider care, management disease chronic of To assess appropriateness LTC EDV of
- [9]
by
[22]
b b
Additiona tooll AHC ACSC [4,11,23 29,33,40,4 1] Modified ACSC [19] Tool Jensen et 2009 al., [15] 90 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 3
W), : 1):
mstances mstances tory and medical medical and tory (C) used. Balance of of Balance used. (C) n the level of care required required care of level n the
premorbid health status (C) status health premorbid ; 2) The patient should have a a have should The patient 2) ;
e aspects, balance of issues of balance e aspects, ents as being in the last year of life, respect for patient and family wishes ( wishes family and patient for respect availability of his information, Thre deemed "admissions Working definition: whe appropriate e.g. hospital the at provided be only can equipment required, specialist to access treatment administration such as specialist urgent or antibiotics, intravenous (C), history on medical Data input". admitting problem (A), circu of level (A/R), admission the surrounding and dependence (C), ability functional cognitive status issues. been looked after at home, if the End of End of the if home, at after looked been recognising (includes Strategy Life pati of place concerning planning advance available care care, for anddeath priorities nursing day, per 24 hours notice short at of stages final home for at care available life) was implemented and services (R) available terminal illness as described in the Gold Framework Prognostic Standards of The cause 3) (C); Guidance Indication immediate require not should admission inpatient medical attention (A) Assumption that the patient could have have could patient the that Assumption
it wasit hospital s (as definition to of expert of One author (consultant for for (consultant One author palliative medicine) notes cases the reviewed tool. the applied and author Another a reviewed independently (10%). random sample Appropriateness coded as the was that clear it "no" if needed resident admission, "yes" if could have they that clear home and at stayed was"maybe" there a if uncertainty. of degree Panel neurological rehabilitation care an acute physician, general a and physician reviewed the practitioner) and notes usedcases the working on appropriateness. decide Consensus meeting.
90% - appa appa k 0.44,
2-
0.59, 0.70 0.59, rater
rater - - Level agreement of between consultants: range Inter of appropriateness admission: k 0.4 range Intra reliability referring agreement the to between individuals’ decision baseline panel overall and 79% decision: cases of reliability referring to agreement in the judging
ting
Methods not specified, specified, Methods not
[51] [32].
Developed by authors, based on a on a based by authors, Developed national developed previously Strategy” Life of “End strategy: 2008), Health of (Department exis best which the considers evidence the of context the in Developed study probably based on expert opinion on expert based probably
life - of -
measure the the measure the measure To at staying of appropriateness home (or LTC facility). end the for Specific phase. To of appropriateness IH and for admissions patients with LTNC. To management identify inappropriate for alternatives admissions
by by
[32] b b
Tool Abel et 2009 al., [31] Tool Hammon d et al., 2009 ARTICLES 91 4
ipitated the esident intravenous intravenous decision.
ria for potentially avoidable avoidable potentially for ria
toms (A), symptoms of mental status ayed in observation for more than 24 more than for observation in ayed Items indicating preventability, e.g. e.g. preventability, indicating Items symptoms fever chest general general (A), disease heart symptoms (A), pain symp bleeding gastrointestinal (A), changes infection tract urinary (A), symptoms disturbance metabolic (A), symptoms pneumonia of (D), diseases diseases (D), (D) skin the e.g. avoidability, indicating Items or wound dressing simple and assessment UTI uncomplicated (R), required closure (R), tube gastrostomy of replacement (D), (W); place in advance directive care Exclusion crite on one category as triaged e.g. conditions, arrival in ED (A), trauma with suspected or laboratory (D), fracture bone long being of signs (R), necessary radiology systemicallyunwell (A), significant (A), changes neurological requested family (R), required medication ED (W) between: r Balance issues of information (C), hospital transfer symptoms or including information, prec that condition in change transfer (A), actions taken by staff before of presence (including transfer the W); P, (R, planning) care advanced may that have factors of analysis transfer the influenced fulfilled: EDV criteria one if Appropriate 1) Patient admitted to a hospital ward or st hours (R); 2) Specialist visit or diagnostic
ur teamur
t oft items applied by List of items applied by data the to authors the Questionnaire to be filled Once they by NHin staff. the all have evaluated items they are required to "In question: the to answer yo does retrospect, think this transfer might have been prevented?" to and "yes" or "no" with for opportunities provide improvement. The reviewed the authors the and notes applied cases tool. the authors to the data the to authors the Lis
, 0.56) - rater - No data provided No data Inter reliability: 0.41 (95% 0.28 CI provided No data provided No data
Finn et et Finn n expert n expert [3]
Combination of expert expert of Combination
[34].
Authors took medical conditions conditions medical took Authors included at the INTERACT II tool other from conditions added and studies the of context the in Developed study Part of INTERACT II tool, based on data of on analyses as by experts rated hospitalisations o and avoidable potentially feasibility on the recommendations of variety a of importance and interventions using authors by the Developed studies prior from data opinion and prior work from prior and opinion al., 2006 (Modified AEP) 2006 (Modified al.,
potentially
To measure potentially To measure potentially EDV by NHpreventable residents To measure EDV by applying avoidable exclusion and indicators criteria of avoidability To measure NH residents of IH or EDV to NH the staff; to according assist NH staff in reasons the understanding for the transfer, identify improve to opportunities identification and in changes of management reduce and status, resident transfers care acute To measure the suitability or appropriateness of EDV
by by by
[20] [35]
b b b ., II)
-
21,38] Bermejo et al Tool Caffrey, 2010 Tool Codde et 2010 al., [34] Quality Improve ment Review tool (INTERA CT Tool 2011 [ 92 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 5
EDV: Emergency
test required, not available in the LTC the in available not required, test facility (R); 3) Requirement of a treatment not available in the LTC facility (R) transition: burdensome defining Condition a of hospital care acute to any transfer cognitive advanced with resident impairment (C) in the last 3 days of life (D) patients avoidability: defining Condition hospital after 3 days within dying inappropriately considered admission transferred; patients dying (D) after 7 days transferred appropriately considered CI: Confidence Interval; Interval; Confidence CI: s; D: specific medical diagnoses; P: existence of a care plan; R: plan; a care of existence P: medical diagnoses; D: specific ; G: Percutaneous Endoscopic Gastrostomy; RH: Residential Home; RH: Residential Gastrostomy; Endoscopic G: Percutaneous
The reviewed the authors the and notes applied cases tool. The reviewed the authors the and notes applied cases tool.
onditions; PE onditions; prior to admission to hospital to admission to prior eurological C eurological
ion Protocol; AHC: Avoidable Hospital Condition AHC: Hospital Avoidable Protocol; ion No data provided No data provided No data
2] [5
patients affected and affected patients
Developed in the context of the the of context the in Developed previously a of basis the on study with analysis narrative conducted families of opinion expert not development Method of specified
potentially To measure transitions burdensome with among NH residents and cognitive advanced impairment functional To measure or avoidable inappropriate acute NH of and hospitalisation RH residents
by by
[37] et
b b
2011
Tool without a specific name. a specific Tool without Aspects covered: A: acuteness/severity of the symptoms; the of characteristics Aspects A: covered: acuteness/severity C: resident's a Tool Gonzalo et al., 2011 Tool Ong al., [39] Evaluat AEP: Appropriateness Conditions; ACSC: Sensitive Care Note: Ambulatory SIR: Structured Implicit Review; UTI: Urinary Tract Infection. resource availability; W: residents’ or families’ wishes. Department Visits; NH: Home; Nursing LTC: Long LTNC: Term Care; Visits; Long TermDepartment N b ARTICLES 93 94 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 95
ANNEX 2.1 A i le 96 QUALITY ISSUES IN CARING FOR OLDER PEOPLE or
! ✴ E ! therapies !
E E dose) dose) Alternative drugs and
! ! ! osmotically Used as laxative: (macrogol, laxatives active lactulose) whenUsed indication as antacid, is appropriate: PPI (<8 weeks, low appropriate: is When indication low dose) weeks, (<8 PPI
! E M ! E !
special special ✴ 4 days). - ! considerations of use of considerations Dose adjustment PIM list ! ! ! Use for short periods (3 periods short Use for dose reduce Maximum 5 ml/8h; dose: failure. renal severe to moderate for failure. renal Adjust severe dose in - ! ! ! Main reason for PIM Main for reason ! ! ! Risk hypermagnesemia, of which is failure renal moderate severe in to higher aluminium of Renal decreases excretion in older individuals. Risk of CNS toxicity
; ; - - b ! ! ’ ! ! Appendix complete 1: EU(7) scale scale -
experts median) decisive decisive [95% CI]; answers at answers at (number of of (number mean value meanvalue Likert ! ! ! Results the of Delphi round Delphi Delphi survey [2.01 2.50 20; 2.00 2.99]; [1.72 2.09 23; 2.00 2.45];
3] : ! a [
! - (2010) (2010)
! ! containing containing -
[26] [22] !
(2014) [19] (2014) Potentially category A B) or category 2: McLeod 2: (1997) 6: STOPP/START6: include the specific 4: PRISCUS 4: 5: Beers (2012) [18] (2012) Beers 5: Lists or criteria which 1: Laroche (2007) Laroche 1: inappropriate drugs drugs inappropriate drug (following either either (following drug 3: Finnish (2013) [33] (2013) Finnish 3:
Alimentary and tract metabolism Drugs acid for disorders related Antacids Magnesium hydroxide In lists: 3 (A) Aluminium In lists: 3 (A); 6 (B)
antacids ! ! code - ! Code - ! ! ATC [30] (2011)) [30] (according to to (according ! WHO ATC A A02 A02A A02AA04 A02AB, A02AD ARTICLES 97 ! ! ! ! E E E E ! E pharmacological measures, measures, pharmacological - ! ! ! appropriate: is When indication low dose) weeks, (<8 PPI appropriate: is When indication low dose) weeks, (<8 PPI appropriate: is When indication low dose) weeks, (<8 PPI appropriate: is When indication low dose) weeks, (<8 PPI Non e.g. diet.
M 65 ≥ ! E ! E ! E ! ! 24 h (iv) 24 h (iv) - M 48 h. 48 h. - PIM list ! ! ! ! Use only for short periods. periods. short for Use only 300 mg or daily times 200 mg four renal due in a decrease to daily, twice aged adults in function hepatic and old. years (oral); 150 mg c/24h <50CrCl ml/min: 50 mg c/18 CrCl <50 ml/min: administer 50% of to interval dosing the increase or dose 36 every insufficiency. marked renal if Caution - ! ! ! ! C. ion ion ! infection and hip fracture.
term high dose PPI therapy is is therapy PPI dose high term - ! ! ! confusion including CNS effects adverse confusion CNS including adverse effects confusion CNS including adverse effects Long difficile >8 weeks in used if Inappropriate maximaldose withoutclear indicat insomnia, such dizziness, as Side effects anorexia associated with an increased risk of of risk with an increased associated - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 1.00 ! ! ! [1.18 1.43 23; 1.00 1.69]; [1.84 2.26 23; 2.00 2.68]; [1.84 2.17 23; 2.00 2.51]; [1.57 2.00 21; 2.00 2.43]; [1.16 1.60 20; 2.04]; ! ! ! I) (>8 ! ! !
c
-
! e.g. !
lists: 5lists: (B)
Drugs ulcer peptic for and gastro reflux oesophageal disease Cimetidine In lists: 1 (A); 2, 5 (B) Ranitidine In Famotidine In lists: 5 (B) pump Proton inhibitors (PP weeks) omeprazole, pantoprazole In lists: 6 (B) Drugs functional for gastrointestinal disorders Drugs functional for disorder bowel Mebeverine In lists: does not PIM appear as ! ! ! ! ! ! ! ! 02BA01 A02B A A02BA02 A02BA03 A02BC A03 A03A A03AA04 98 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 12h -
E
! ! ! ! L L E E, L E ! ! ! E E E E, McL E, McL E, McL E, McL
pharmacological measures, measures, pharmacological measures, pharmacological measures, pharmacological pharmacological measures, measures, pharmacological measures, pharmacological measures, pharmacological measures, pharmacological ------! Non Non Non e.g. diet. Phloroglucinol. Non e.g. diet. Phloroglucinol. Non e.g. diet. 20mg/6 Butylscopolamine in especially time, short a for palliative care. Phloroglucinol Non Butylscopolamine Non Phloroglucinol Phloroglucinol e.g. diet. e.g. diet. e.g. diet. e.g. diet. ! PIM list ! ! ! ! ! ! !
- ! ! ! ! ! ! ! antimuscarinic side anticholinergic, substantial toxic ! Anticholinergic and antimuscarinic side side and antimuscarinic Anticholinergic effects like agitation, sedation or efficacy no proven confusion; and Anticholinergic effects like agitation, sedation or efficacy no proven confusion; side and antimuscarinic Anticholinergic effects like agitation, sedation or efficacy no proven confusion; side and antimuscarinic Anticholinergic effects like agitation, sedation or efficacy no proven confusion; or such dizziness as Side effects esophageal ulceration Highly uncertain and adults older in effects no proven / efficacy effectiveness toxic substantial anticholinergic, Highly uncertain and adults older in effects no proven / efficacy effectiveness ------! ! ! ! ! ! ! Appendix complete 1: EU(7) 1.00 ! 19; 1.47 [1.07 1.47 19; 1.00 1.88]; [1.03 1.57 14; 1.00 2.11]; [1.07 1.50 18; 1.00 1.93]; [1.10 1.60 15; 1.00 2.10]; [1.07 1.50 18; 1.93]; [0.95 1.05 20; 1.00 1.29]; [0.98 1.14 22; 1.00 1.29]; ! !
! ! ! !
c ! ! Trimebutine In lists: 1, 2, 6 (B) Dihexyverine In lists: 1 (A); 2, 6 (B) bromide Otilonium In lists: 2, 6 (B) Tiemonium (iodide) In lists: 1 (A); 2, 6 (B) Pinaverium In lists: does not PIM appear as and Belladonna derivates, plain Hyoscyamine In lists: 5 (A); 1, 2, 5, 6 (B) alkaloids Belladonna In lists: 1, 5 (A); 2, 5, 6 (B) ! ! ! ! ! ! ! ! A03AA05 A03AA08 A03AB06 A03AB17 A03AX04 A03B A03BA03 A03BA04 ARTICLES 99 ! !
E E ! E, L ! E, McL E pharmacological measures, measures, pharmacological pharmacological measures, measures, pharmacological - - ! ! ! ! Non Phloroglucinol Non e.g. diet. no if mg/d) Domperidone (<30 contraindications. no if mg/d) Domperidone (<30 contraindications. e.g. diet. !
M ! E ! ! E term use and dose reduction; CrCl reduction; dose and use term - ! PIM list ! ! ! <40 ml/min: 50% of normal dose; dose; 50% normal of <40 ml/min: used may be mg/d; 20 maximumdose: in palliative care. 10 mg, chlordiazepoxide exceed Do not gradually increase 5 mg/d; clidinium and limit to the smallest effective dose. M Short the at Treatment should be initiated lowest possible dose and titrated cautiously. may recommended be Adjustment in failure. renal of cases - ! blocking blocking - ! intermittent claudication ! ! life in older adults (often - !
days), producing prolonged prolonged producing days), ! ! ! sedation and increasing the risk of falls falls of risk the increasing and sedation and fractures Long half several effects side Anticholinergic anticholinergic and Antidopaminergic effects; flow blood arterial peripheral mayworsen and precipitate ventricular serious of risk Increased in death cardiac sudden or arrhythmia adults older No muscarinic proven efficacy; and confusion as such effects side agents; sedation - - - - - ! ! ! ! ! Appendix complete 1: EU(7) ! ! ! [1.01 1.21 19; 1.00 1.41]; [1.55 2.00 18; 2.00 2.45]; [1.97 2.43 23; 2.00 2.90]; [1.70 2.11 18; 2.00 2.53]; [1.23 1.53 19; 1.00 1.82]; !
! ! ! not not
!
! -
c ! ! Antispasmodics in combination with psycholeptics Clidinium Chlordiazepoxide In lists: 1, 3, 5 (A); 2, 6 (B) Antispasmodics in combination with analgesics Pitofenone In lists: 3 (A); 1, 2, 6 (B) Propulsives Metoclopramide In lists: 3, 5 (A); 6 (B) Domperidone (>30 mg/d) In lists: does PIM appear as Alizapride In lists: 1 (A)
! ! ! ! ! ! ! ! A03C A03CA02 A03D A03DA02 A03F A03FA01 A03FA03 A03FA05 100 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! E E E ! ! ! E, P E, P E, P ! ! ! ! no if mg/d) Domperidone (<30 contraindications. no if mg/d) Domperidone (<30 contraindications. no if mg/d) Domperidone (<30 contraindications. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. ! E ! ! E PIM list ! ! ! ! ! ! ! ! enlarged with patients for Caution prostate. useful and may appropriate be 5 mg/4h; in palliative care. - ! ! ! diarrhoea. Maydiarrhoea. May bowel exacerbate ! ! ! ! ! ! ! effects side Anticholinergic no proven effects; side Anticholinergic efficacy blocking muscarinic No efficacy; proven and confusion as such effects side agent; sedation aspirated if Pulmonary effects side events Adverse laxative. softener Stool nausea, cramping, include bowelexacerbate disfunction Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. disfunction ------! ! ! ! ! ! Appendix complete 1: EU(7) ! ! ! ! [1.29 1.68 19; 1.00 2.08]; [1.36 1.68 22; 2.00 2.00]; [1.26 1.68 19; 1.00 2.11]; [1.88 2.43 21; 2.00 2.98]; [1.57 1.95 19; 2.00 2.32]; [1.59 1.90 21; 2.00 2.22]; ! !
!
! !
! ! ! !
!
Antiemetics and antinauseants Antiemetics and antinauseants Dimenhydrinate In lists: 1, 4 (A); 5, 6 (B) Scopolamine In lists: 1, 3 (A); 5 (B) Metopimazine In lists: 1(A) Laxatives Laxatives Viscous paraffin (=Liquid paraffin) In lists: 4, 5 (A) Docusate sodium (oral) In lists: 1 (A) days) (>3 Bisacodyl In lists: 1, 3 (A); 5 (B)
! ! ! ! ! g ! ! ! ! ! A04 A04A A04AB02 A04AD01 A04AD05 A06 A06A A06AA01 A06AA02 A06AB02 ARTICLES 101 motically ! ! ! ! ! ! E, P E, P E, P E, P E, P E, P Recommend proper dietary fibre fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper and fluid intake; osmotically active laxatives: macrogol, lactulose. fibre Recommend dietary proper os intake; fluid and active laxatives: macrogol, lactulose. E, ! ! PIM list ! ! ! ! ! in and adults older for dose Reduce (GFR<30 failure renal severe of cases over persons for dose starting ml/min); maximum 2 1 mg/d; dose: old: 65 years mg/d(1 mg/d severe if renal failure) M - ! dizziness May bowel exacerbate May bowel exacerbate May bowel exacerbate May bowel exacerbate May bowel exacerbate ! ! ! ! ! Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. disfunction Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. disfunction Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. disfunction Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. dysfunction Stimulant laxative. Adverse events and fluid pain, abdominal include imbalance and electrolyte hypoalbuminemia. disfunction abdominalAdverse can include effects headache, diarrhoea, pain, ------! ! ! ! ! ! Appendix complete 1: EU(7) 21; 2.24 [1.70 2.24 21; 2.00 2.77]; [1.79 2.35 23; 2.00 2.91]; [1.71 2.32 19; 2.00 2.92]; [1.82 2.32 22; 2.00 2.82]; [1.65 2.13 16; 2.00 2.60]; [1.46 2.09 11; 2.00 2.73];
! !
! ! ! !
Castor oil (=Ricinus =Neoloid) communis, In lists: 1 (A), 5 (B) glycosides Senna In lists: 3 (A) Cascara sagrada In lists: 1 (A); 5 (B) Sodium picosulfate In lists: 1, 3 (A) Aloe In lists: 1 (A) Prucalopride In lists: does not PIM appear as ! ! h ! g ! ! ! A06AB05 A06AB06 A06AB07 A06AB08 A06AB13 A06AX05 102 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E ! L ! E E pharmacological measures, measures, pharmacological measures, pharmacological measures, pharmacological - - - ! ! ! ! ! Non e.g. diet. Phloroglucinol Non e.g. diet; phloroglucinol. Non e.g. diet. ! E ! E ! eposition until n 7 days. n 7 days. infectious diarrhoea. - PIM list ! ! ! ! ! ! by 2 4 mg of followed dose a with Start d mgeach in exceed do not bowel; of normalisation may 2 days; than no longer use 16 mg/d; be useful in palliative care for persisting non Maximum maximum 100 mg/8h; dose duratio - ! ! ! ! ! ! ! ! blocking muscarinic No efficacy; proven agent nausea, constipation, somnolence, of Risk Rare bloating. and pain abdominal May dizziness. include events adverse in megacolon toxic precipitate inflammatory may bowel disease, delay gastroenteritis unrecognized in recovery of inhibitor selective No efficacy; proven the for enzyme responsible enkephalinase enkephalins, the of degradation by act which opioids endogenous lumen secretion intestinal the decreasing water andof electrolytes - - - ! ! ! Appendix complete 1: EU(7) ! ! ! ! ! [1.29 1.73 22; 1.00 2.16]; [1.47 1.81 21; 2.00 2.15]; [1.68 2.31 16; 2.00 2.95]; !
! - 5, 6 5, ! ! - ! ! -
!
! Antidiarrhoeal, intestinal anti inflammatory anti / infective agents Antipropulsives Diphenoxylate Atropine In lists: 1 (A); 2, (B) days) (>2 Loperamide In lists: does not PIM appear as Other antidiarrheals Racecadotril In lists: does not PIM appear as Drug used Diabetes in and Insulins analogues
! ! ! ! ! ! ! ! A07 A07D A07DA01 (Diphenoxylate) A03BA01 (Atropine) A07DA03 A07X A07XA04 A10 A10A ARTICLES 103 acting acting acting acting - - - - 2 x 850 mg/d); 2 x 850 mg/d); 2 x 850 mg/d); ! ! ! ! E E E E ! . E ! Basal insulin. Diet; metformin (< insulin; gliclazide may be safer short other the than sulphonilureas. x 850 mg/d); (<2 metformin Diet; insulin; gliclazide may be safer short other the than sulphonilureas x 850 mg/d); (<2 metformin Diet; insulin; gliclazide may be safer short other the than sulphonilureas. Diet; metformin (< insulin; gliclazide may be safer short other the than sulphonilureas.
! M
E ! M M, E ! E
E, M
M 5 mg/d at 1 to 2 week 1 to 5 mg/d at - ! !
E ! PIM list ! intervals. Lower doses to avoid hypoglycemia. hypoglycemia. avoid to Lower doses mg/d (1.25 dose initial Use conservative and glibenclamide nonmicronized for micronized mg/d for 0.75 and maintenance glibenclamide) dose; <50 CrCl ml/min. recommended if not M 125 mg/d. 100 to of doses Use initial (GFR >50 failure renal mild of cases In 50%. by dose decrease ml/min), renal severe to moderate of cases In failure (GFR <50 ml/min), avoid. function. renal to dose Adjust and Use initial conservative doses. maintenance mg/d 2.5 dose: Starting by 2.5 Increase - ! ! ! ! ! using using scaleinsulin. Might facilitate - ! sliding No benefits demonstrated in in demonstrated No benefits hypoglycemia protracted of Risk hypoglycemia protracted of Risk hypoglycemia protracted of Risk hypoglycemia protracted of Risk fluctuations in glycemic levels glycemic in fluctuations - - - - - ! ! ! ! ! Appendix complete 1: EU(7) ! 13; 2.00 [1.45 2.00 13; 2.00 2.55]; [1.55 2.00 23; 2.00 2.45]; [1.12 1.40 20; 1.00 1.68]; [1.61 2.06 16; 2.00 2.52]; [2.01 2.45 22; 2.00 2.90]; ! !
!
! !
! Insulin, sliding scale scale sliding Insulin, In lists: 5 (A) glucose Blood excl. drugs, lowering insulins Glibenclamide In lists: 1, 5 (A); 6 (B) Chlorpropamide In lists: 5 (A); 1, 6 (B) Carbutamide In lists: 1 (A), 6 (B) Glipizide In lists: 1 (A) ! ! ! ! ! ! no ATC, concept treatment PIM A10B A10BB01 A10BB02 A10BB06 A10BB07 104 QUALITY ISSUES IN CARING FOR OLDER PEOPLE acting acting acting acting - - - - 2 x 850 mg/d); 2 x 850 mg/d); <2 x 850 mg/d); <2 x 850 mg/d); ! ! ! ! E E E E onilureas. Diet; metformin ( insulin; gliclazide may be safer short other the than sulphonilureas. Diet; metformin (< insulin; gliclazide may be safer short other the than sulphonilureas. x 850 mg/d); (<2 metformin Diet; insulin; gliclazide may be safer short other the than sulphonilureas. x 850 mg/d); (<2 metformin Diet; insulin; gliclazide may be safer short other the than sulph
E 50 ml/min); - ! ! E, M ! PIM list ! ! Adjust according to renal function. function. renal to according Adjust M of cases 50 mg/d in to dose Reduce renal failure (CrCl 30 of cases 25 mg/d in to dose reduce severerenal insufficiency(CrCl <30 ml/min). For patients with renal failure and for for and failure renal with patients For 1 mg/d of dose initial use adults, older titration conservative by a followed 1 of increments in dose Titrate scheme. 2 weeks 1 to 2 mg every to no more than response. glycemic on individual based - ! ! ! may ! year has been associated with an has beenyear associated 75 years old. Subjects aged 65 to 65 to aged Subjects old. 75 years ≥ related risks include bladder cancer, cancer, bladder include risks related - Risk of protracted hypoglycemia protracted of Risk No proven efficacy Age adults for available is data safety Limited aged fractures and heart failure. Use for more Use for failure. heart and fractures one than May cancer. bladder of risk increased the of fractures of incidence the increase female upper in hands arms, and feet oral other to (compared diabetics Can cause fluid agents). antidiabetic which adults, older in retention 80 years had higher plasma plasma higher had 80 years subjects. younger than concentrations dizziness, hypoglycemia, of Risk oedemaheadache and peripheral exacerbate or precipitate heart failure heart precipitate or exacerbate - - - - ! ! ! ! Appendix complete 1: EU(7) 21; 2.05 [1.71 2.05 21; 2.00 2.38]; [1.68 2.22 23; 2.00 2.75]; [1.42 1.71 21; 2.00 2.01]; [1.44 1.94 17; 2.00 2.44]; ! ! ! !
Glimepiride In lists: 3 (A); 6 (B) Acarbose In lists: does not PIM appear as Pioglitazone In lists: 5, 6 (B) Sitagliptine In lists: does not PIM appear as ! ! ! ! A10BB12 A10BF01 A10BG03 A10BH01 ARTICLES 105 . . . d d d acting - ! E ! ! ! ! ! ! ! Diet; metformin (<2 x 850 mg/d); x 850 mg/d); (<2 metformin Diet; insulin; gliclazide may be safer short other the than sulphonilureas. (<325mg) aspirin Clopidogrel; (<325mg) aspirin Clopidogrel; (<325mg) aspirin Clopidogrel; E, L E, L E, L ! E, M ! M ! PIM list ! ! ! ! ! ! Reduce dose to 50 mg/d in cases of of cases 50 mg/d in to dose Reduce failure. renal severe or moderate in may required be Dose reductions failure. renal of cases - ! 70 ! ≥ ! ! 40 years). 40 years). risk of -
profile, !
! ! ! Limited safety data available in older older in available data safety Limited ( adults older healthy In subjects. vildagliptin of exposure overall the years) by was increased mg(100 daily) once peak in 18% an 32%, with increase compared as plasma concentration to (18 subjects young healthy population) (general events Adverse dizziness, hypoglycemia, of risk include oedemaheadache and peripheral people in especially bleeding, of Risk INR of value control difficult with counts blood altered of Risk aspirin; than Less efficient orthostatic and vasodilatation hypotension with patients for only beneficial Proven artificial heart valves risk/benefit Unfavourable older 75 and aged adults for especially - - - - - ! ! ! ! ! Appendix complete 1: EU(7) ! ! ! 15; 1.87 [1.21 1.87 15; 2.00 2.52]; [1.84 2.35 17; 2.00 2.87]; [1.36 1.70 20; 2.00 2.04]; [1.70 2.14 22; 2.00 2.58]; [1.41 2.00 18; 2.00 2.59]; ! ! ! !
!
!
! ! Vildagliptine In lists: does not PIM appear as andBlood blood forming organs Antithrombotic agents Antithrombotic agents Acenocoumarol In lists: 6 (B) Ticlopidine In lists: 1, 4, 5, 6 (A); 6 (B) Dipyridamole In lists: 1, 2, 3, 5 (A); 6 (B) Prasugrel In lists: 4 (A); 6 (B) ! ! ! ! ! ! ! ! A10BH02 B B01 B01A B01AA07 B01AC05 B01AC07 B01AC22 106 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E ! ! ! ! !
iron Intravenous
to : :
(E)) CrCl <30CrCl
60 kg, or or 60 kg, 50 (110 mg50 (110 ≤ - ! M 1.5 mg/dL. 1.5 ≥ ! (1 of the following following the of (1
! (M) E, M
! E 80 years old, body weight body weight old, 80 years PIM list ! ! ! ≥ Reduce aged >75 dose adults years for 30 CrCl and mg/d) (150 old twice per day); contraindicated CrCl if <30. Reduce aged >65 dose adults years for with persons for use avoid and ml/min. twice mg 2.5 orally to dose Reduce the 2 of any with patients for daily following creatinine serum 15 mL/min than less CrCl if use Do not dose reduce dialysis; undergoing if or mg2.5 severe of day cases per twice in renal failure (CrCl 15 mL/min to 29 adjustment dosage no mL/min); 51 to (CrCl mild of cases in necessary 50 30 to (CrCl moderate or 80 mL/min) mL/min)renal failure. - ! ! ! reversal agent is is agent reversal
! ! ! Limited information on use for older older for on use information Limited events bleeding of risk on the and adults no population; this in overdose of case in available older for on use information Limited no events; bleeding of risk adults; of case in available agent reversal may higher be bleeding of risk overdose; failure renal severe of cases in older for on use information Limited no events; bleeding of risk adults; of case in available agent reversal overdose considerably Doses >325 mg/d do not greatly but absorbed amount the increase constipation of incidence the increase - - - - ! ! ! ! Appendix complete 1: EU(7) ! ! 22; 2.45 [2.01 2.45 22; 2.00 2.90]; [2.02 2.42 19; 2.00 2.82]; [1.75 2.25 16; 2.00 2.75]; [1.68 2.22 23; 2.00 2.75]; !
! ! ! ! ! c
c
c
Dabigatran In lists: 6 (B) Rivaroxaban In lists: 6 (B) Apixaban In lists: 6 (B) Antianemic preparations preparations Iron / supplements Iron (>325 sulfate Ferrous mg/d) In lists: 6 (B)
! ! ! g, h g, i ! ! ! B01AE07 B01AF01 B01AF02 B03 B03A B03AA ARTICLES 107 ! ! ! E E E
E, P E, P E, P rt failure:rt inhibitors. inhibitors. inhibitors. - - - blockers (except oxprenolol, oxprenolol, (except blockers oxprenolol, (except blockers oxprenolol, (except blockers - - - ! ! ! For tachycardia/atrial fibrillation: beta hea congestive For spironolactone (except diuretics ACE>25 mg/d), For tachycardia/atrial fibrillation: beta failure: heart For congestive spironolactone (except diuretics ACE>25 mg/d), For tachycardia/atrial fibrillation: beta failure: heart For congestive spironolactone (except diuretics ACE>25 mg/d), pindolol, propranolol, sotalol, sotalol, propranolol, pindolol, nadolol, labetalol). sotalol, propranolol, pindolol, nadolol, labetalol). sotalol, propranolol, pindolol, nadolol, labetalol). - - ! !
M M M ! 25% of dose or every 48 every 25% or dose of - ure (CrCl <10 ml/min), 50 ml/min), administer 25 - ! E PIM list ! ! ! doses based on digitalizing Calculate doses maintenance body mass and lean using actual CrCl. doses based on digitalizing Calculate doses maintenance body mass and lean using actual CrCl. doses based on digitalizing Calculate doses maintenance body mass and lean using actual CrCl. 0.0625 dose use adults, older For failure renal of cases in 0.125mcg/d; (CrCl 10 cases in 36 hours; every 75% or dose of of renal fail administer 10 hours. hours. - ! ! ! ! ! ! older in sensitivity glycoside Elevated of (women risk >men); adults intoxication older in sensitivity glycoside Elevated of (women risk >men); adults intoxication older in sensitivity glycoside Elevated of (women risk >men); adults intoxication - - - ! ! ! Appendix complete 1: EU(7) ! ! ! [1.47 2.14 14; 2.00 2.82]; [1.57 2.19 16; 2.00 2.87]; [1.92 2.35 23; 2.00 2.77]; ! !
! !
! ! Cardiovascular Cardiovascular system therapy Cardiac Cardiac glycosides Acetyldigoxin In lists: 4 (A) Digitoxin In lists: does not PIM appear as Digoxin In lists: 4, 5 (A); 1, 6 (B) ! ! ! ! ! ! C C01 C01A C01AA02 C01AA04 C01AA05 108 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E
E, P E, P E, P E, P inhibitors. - ia/atrial fibrillation: blockers (except oxprenolol, oxprenolol, (except blockers oxprenolol, (except blockers oxprenolol, (except blockers blockers (except oxprenolol, oxprenolol, (except blockers - - - - ! For tachycard beta failure: heart For congestive spironolactone (except diuretics ACE>25 mg/d), Beta sotalol, propranolol, pindolol, nadolol, labetalol). Beta sotalol, propranolol, pindolol, nadolol, labetalol). Beta sotalol, propranolol, pindolol, nadolol, labetalol). pindolol, propranolol, sotalol, sotalol, propranolol, pindolol, nadolol, labetalol). ! ! ! - ing ing ! ! M M
nister every 6 nister
M !
M ! 50 ml/min admi 50 ml/min - E 24 h. 24 h. PIM list ! ! Calculate digitalizing doses based on digitalizing Calculate doses maintenance body mass and lean using actual CrCl. and failure heart with adults old In maintenance oral function, renal normal times 1.4 is digoxin of requirement dose metildigoxin. than higher patient individual the to dose Adjust longer or Lower doses response. between doses mayintervals be required. 10 CrCl every administer <10 CrCl ml/min 12 h; 8- dos the of end lower the at dose Start maximum upward to titrate and range antiarrhythmic for required as dose and based on CrCl. effects - ! ! ! B B B
! inotrope; anticholinergic ! Elevated glycoside sensitivity (women sensitivity glycoside Elevated >men); risk of intoxication mortality. increased CNS effects; side most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits interactions. drug of risk High most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits negative Potent failure; heart may induce effects; side death. cardiac maysudden cause most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits - - - - ! ! ! ! Appendix complete 1: EU(7) ! 15; 2.20 [1.57 2.20 15; 2.00 2.83]; [1.22 1.48 23; 1.00 1.73]; [1.41 1.76 21; 2.00 2.11]; [1.18 1.43 23; 1.00 1.69]; ! ! !
! !
Metildigoxin In lists: 4 (A) Antiarrhythmics, Class I and III Quinidine In lists: 3, 4, 5 (A) Procainamide In lists: 5 (A) Disopyramide In lists: 1, 2, 5 (A) ! ! ! ! ! C01AA08 C01B C01BA01 C01BA02 C01BA03 ARTICLES 109
E, P E, P E, P blockers (except oxprenolol, oxprenolol, (except blockers oxprenolol, (except blockers oxprenolol, (except blockers - - - ! Beta sotalol, propranolol, pindolol, nadolol, labetalol). Beta sotalol, propranolol, pindolol, nadolol, labetalol). Beta sotalol, propranolol, pindolol, nadolol, labetalol). ! ! ! ! ! M M onset onset -
M ing recent ing ! ! E
M PIM list ! dosing the of end lower the at dose Start gradually. increase and range may dose 600 mg loading oral A single convert for be effective atrial fibrillation to sinus rhythm in without 60 years than older persons signsor symptomsof heart failure. failure. renal Adjust cases of dose in dosing the of low end the at dose Start range. Use 200 lower maintenance e.g. dose, mg/48h. - ! ! !
!
B B B B
CNS mortality. and increased effects side interactions. drug of risk High most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits especially adverse of effects, Higher rate in older adults. most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits problemsAssociated QT with interval pointes. de torsades provoking of risk and most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits Data suggest that for most older adults most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits - - - - ! ! ! ! Appendix complete 1: EU(7) 22; 1.36 [1.15 1.36 22; 1.00 1.58]; [1.44 1.89 19; 1.00 2.35]; [1.66 2.14 22; 2.00 2.62]; [1.81 2.30 23; 2.00 2.80]; ! ! ! !
3, 4, 5 (A) 4, 3, lists: 4lists: (A)
Quinidine in in Quinidine with combination verapamil In Propafenone In lists: 3, 5 (A) Flecainide In lists: Amiodarone In lists: 3, 5 (A); 6 (B) ! ! ! ! C01BA51 C01BC03 C01BC04 C01BD01 110 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! ! ! !
! E ! . M !
PIM list ! ! ! ! with patients for day per 20 mg twice insufficiency. renal moderate adults; older for dose Lower initial years. >75 in mg/d 2.5 x 2 dose starting M, E CrCl with patients for caution Use with less than 15 mL/min - ! B 10% of - degree AV -
! extrasystoles, dizziness ! cause or worsen parkinsonian parkinsonian worsen or cause ! ! ! Frequent drug interactions; prolonged QT prolonged interactions; drug Frequent permanent recommended in not interval; atrial fibrillation; increased mortality due causes. cardiovascular to most adults for older Data that suggest of balance better yields control rate control rhythm than harms and benefits Can hypertonia); akinesia, (tremor, symptoms failure moderate of renal cases in caution old); years (>75 adults older with and efficacy for the treatment of tinnitus or proven not dizziness Common (1 adverse events ventricular block, vision blurred and patients) may include first - - - ! ! ! Appendix complete 1: EU(7) ! ! ! 21; 1.57 [1.23 1.57 21; 2.00 1.91]; [1.22 1.62 13; 2.00 2.01]; [1.61 2.13 16; 2.00 2.64]; ! !
! !
!
centrally ! Dronedarone Dronedarone In lists: 3, 5 (A) Other cardiac preparations Trimetazidine In lists: does not PIM appear as Ivabradine In lists: does not PIM appear as Antihypertensives Antiadrenergic agents, acting ! ! ! ! ! ! C01BD07 C01E C01EB15 C01EB17 C02 C02A ARTICLES 111 ! ! ! ! !
E E E E E depending on depending Other antihypertensive drugs, e.g. e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups mediation PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups mediation PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, groups medication PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity
- M ! M ! er every er M, E release; start - 60 ml/min): -
! P P
! ! M M, E ! E 50 ml/min administer every 8 every administer 50 ml/min M, P - 24 h. 24 h. - PIM list 12 Low initial dose, half of usual dose, dose, usual of half dose, Low initial out. and in taper normal to mg/d) (0.05 Lower doses recommended. are mg/d) (0.25 doses Avoid if CrCl <10 ml/min. dose, usual of half dose, Low initial out. and in taper 250 mg of is dose daily initial Suggested dose daily maximal a with methyldopa 1000 mg. of 8 h; every administer >50CrCl ml/min 10 CrCl administ <10 CrCl ml/min 12 h; of treatment Lower initial doses for in taper dose, usual of half hypertension; out. and guanfacine when using dosing Cautious immediate hydrochloride range. the of low end the at dosing moderate cases of in Caution renal insufficiency (CrCl 30 CrCl if avoid mg/d; 0.4 maximumdoses <30ml/min. - ! ! ! ! ! Risk of orthostatic hypotension, hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 20; 1.25 [1.04 1.25 20; 1.00 1.46]; [1.11 1.38 21; 1.00 1.65]; [1.04 1.36 22; 1.00 1.69]; [1.13 1.42 19; 1.00 1.71]; [1.34 1.77 22; 1.50 2.20]; ! !
! ! ! Reserpine In lists: 1, 2, 4, 5 (A); 6 (B) Methyldopa In lists: 1, 4, 5 (A); 6 (B) Clonidine In lists: 1, 3, 4, 5 (A); 6 (B) Guanfacine In lists: 1, 5 (A); 6 (B) Moxonidine In lists: 1, 3 (A); 6 (B) ! ! ! ! ! C02AA02 C02AB01 C02AC01 C02AC02 C02AC05 112 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! !
E E E E antihypertensive drugs, e.g. e.g. drugs, antihypertensive ! Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIM). (exclude comorbidity 2 - ! ! M E ! M, E ! M
P P ! E 8 mg/d (extended release). 8 mg/d release). (extended - PIM list ! Reduce dose in cases of renal failure Reduce failure renal cases of dose in (CrCl <15 ml/min), Lower dose for initial treatment of hypertension. Start with half of usual dose, taper in out. and First dose given at bedtime: initial 1 mg/d. Start with half of usual dose, taper in out. and Start with 0.5mg/d (immediate release) or 4 and adults older for dose Reduce patients with renal insufficiency. - ! ! ! headedness, headedness, headedness, headedness, - - - disease
! ! Risk of orthostatic hypotension, hypotension, orthostatic of Risk syncope, CNS bradycardia, effects side cognitive depression, (sedation, impairment) hypotension, orthostatic of risk Higher incontinence/ urinary mouth, dry impaired micturition, CNS side effects light vertigo, (e.g. and cerebrovascular and somnolence) disease cardiovascular hypotension, orthostatic of risk Higher incontinence/ urinary mouth, dry impaired micturition, CNS side effects light vertigo, (e.g. and cerebrovascular and somnolence) disease cardiovascular hypotension, orthostatic of risk Higher incontinence/ urinary mouth, dry impaired micturition, CNS side effects light vertigo, (e.g. and cerebrovascular and somnolence) cardiovascular - - - - ! ! ! ! Appendix complete 1: EU(7) ! 17; 1.53 [1.16 1.53 17; 1.00 1.90]; [1.27 1.55 20; 1.50 1.83]; [1.61 1.95 22; 2.00 2.30]; [1.29 1.68 19; 1.00 2.08]; ! ! !
(A); 6 (B)
! ! Rilmenidine In lists: 1 (A); 6 (B) Antiadrenergic agents, peripherally acting Prazosin In lists: 1, 3, 4, 5 (A); 6 (B) Doxazosin In lists: 4, 5 Urapidil In lists: 1 (A); 6 (B) ! ! ! ! ! C02AC06 C02C C02CA01 C02CA04 C02CA06 ARTICLES 113 ! !
E alternatives depending depending alternatives ! ! ! ! ! Other antihypertensive drugs, e.g. e.g. drugs, antihypertensive Other other or ACE inhibitors, on depending groups medication PIMs). (exclude comorbidity Consider PIMs. exclude indication; on the
- 25 mg/d; 25 mg/d; - !
M
! E, M ! go slow; go slow; ! – – 49 mL/min/1.73 m: initial dose - M M, E
50 mL/min/1.73 m: initial dose
≥ 25 mg/d, increase up to 25 mg up to 1 increase 25 mg/d, - PIM list ! ! ! ! Start low renal of cases in interval dose Increase failure. Start low renal of cases in interval dose Increase failure. Reduce moderate cases of dose in renal insufficiency. GFR 2x/d; GFR 30 increase levels potassium if dose reduce worsens. function renal or GFR <10 avoid. mL/min: 12.5 mg/d, increase up to 12.5 up to increase mg/d, 12.5 12.5 - ! ! headedness, headedness, - ! ! ! ! ! Higher risk of orthostatic hypotension, hypotension, orthostatic of risk Higher incontinence/ urinary mouth, dry impaired micturition, CNS side effects light vertigo, (e.g. and cerebrovascular and somnolence) disease cardiovascular hypotension orthostatic of Risk and hyperkalaemia of risk Higher if especially adults, older in hyponatremia periodic requiring >25 mg/d, doses controls - - - ! ! ! Appendix complete 1: EU(7) ! ! ! ! 19; 1.58 [1.25 1.58 19; 1.00 1.91]; [1.73 2.33 21; 2.00 2.93]; [1.99 2.50 20; 2.00 3.01]; ! !
!
! sparing sparing - ! !
c ! lists: 6lists: (B)
Guanethidine Guanethidine In lists: does not PIM appear as on acting Agents Arteriolar Smooth muscle Hydralazine In Diuretics Potassium (>25 Spironolactone mg/d) In lists: 5 (A); 6 (B) Peripheral vasodilators agent ! ! ! ! ! ! ! C02CC02 C02D C02DB02 C03 C03D C03DA01 C04 114 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! ! ! ! ! !
! M ! ! M s. Avoid use if CrCl <30 <30 CrCl if use Avoid s. PIM list ! ! ! ! ! ! in daily 400 mg to twice dose Reduce and to failure moderate of renal cases severe of cases in 400 mg daily once for monitoring close failure; renal toxicitie ml/min. renal cases of Reduce dose in daily >2 mg/dl). creatinine (serum failure - increased increased ! ! ! ! ! ! ! profile; orthostatic ! unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit increased are risks fall and hypotension with most vasodilators ------! ! ! ! ! ! ! Appendix complete 1: EU(7) ! 1.95[1.42 21; 2.00 2.48]; [1.12 1.63 19; 1.00 2.15]; [1.05 1.42 19; 1.00 1.79]; [0.99 1.33 18; 1.00 1.67]; [1.04 1.33 18; 1.00 1.63]; [1.12 1.53 17; 1.00 1.94]; [1.12 1.53 17; 1.00 1.94]; !
! ! ! !
!
!
- !
Dihydroergocristine Dihydroergocristine Peripheral Peripheral vasodilators Pentoxifylline In lists: 1, 2, 3, 4 (A); 6 (B) Nicergoline In lists: 1, 4 (A); 6 (B) Dihydroergocristine In lists: 1 (A), 6 (B) Raubasine In lists: 1 (A); 6 (B) Cyclandelate (=Cyclospasmol) In lists: 6 (B) Vincamine In lists: 1 (A); 6 (B) Moxisylyte In lists: 1 (A); 6 (B)
! ! ! ! ! ! ! ! C04A C04AD03 C04AE02 C04AE04 C04AE54 C04AX01 C04AX07 C04AX10 ARTICLES 115 ! ! ! ! E E E E ! ! ! ! ! . stocking Compression . stocking Compression . stocking Compression . stocking Compression ! PIM list ! ! ! ! ! ! ! ! !
- are increased increased are ! ! ! ! ! ! ! ! ! No proven efficacy; unfavourable unfavourable No efficacy; proven risk/benefit profile; orthostatic risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators unfavourable No efficacy; proven risk/benefit profile; orthostatic increased are risks fall and hypotension with most vasodilators ------! ! ! ! ! ! ! Appendix complete 1: EU(7) ! 17; 1.53 [1.12 1.53 17; 1.00 1.94]; [1.08 1.69 16; 1.00 2.29]; [1.11 1.59 17; 1.00 2.07]; [1.41 1.82 17; 2.00 2.24]; [1.37 1.83 18; 2.00 2.29]; [1.34 1.75 16; 2.00 2.16]; [1.33 1.81 16; 2.00 2.30];
!
! ! !
!
! ! !
Rutoside Rutoside Vincamine
- - stabilizing (A); 6 (B) ! Vinburnine Vinburnine In lists: 1 (A); 6 (B) Buflomedil In lists: 6 (B) Naftidrofuryl In lists: 1, 4 (A); 6 (B) Vasoprotectives Capillary Hidrosmin In lists: 6 (B) Escin (=Aescin) In lists: 6 (B) Vincamine In lists: 1 (A); 6 (B) Troxerutin In lists: 1 agents ! ! ! ! g ! ! ! ! ! C04AX17 C04AX20 C04AX21 C05 C05C C05CA05 C05CA07 C05CA51 C05CA54 116 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E ! ! ! ! ! blockers blockers blockers blockers blockers blockers blockers, blockers, E E E E E ------selective beta selective beta selective beta selective beta selective beta selective selective beta selective - - - - - ilol, atenolol). - ! ! ! Cardio bisoprolol, metoprolol, (e.g. carvedilol, atenolol). Cardio bisoprolol, metoprolol, (e.g. carvedilol, atenolol). indication: on the Depending cardio ACE inhibitors, diuretics. Cardio bisoprolol, metoprolol, (e.g. carvedilol, atenolol). Cardio bisoprolol, metoprolol, (e.g. carved Cardio bisoprolol, metoprolol, (e.g. carvedilol, atenolol). ! E, M 60 h. 60 h. ! -
M P
! E 200 mg once or 200 mg or once - M 48h; if CrCl <10 CrCl if 48h; 30 ml/min: - - ! ! M 50 ml/min: administer every go slow for older adults and and adults older for go slow - – 36 h; if CrCl 10 CrCl if 36 h; - PIM list ! ! ! ! ! Start low 20 mg of daily 3 doses Start at half or one third of the typical slowly. increase and dose in interval dosing and dose Reduce failure. renal of cases If CrCl 31 24 24 every administer ml/min:administer every 40 day. per twice 100 mg or dose once Start E 100 dose Maintenance day. per twice patients with renal failure. - ! ! ! ! CNS adverse events adrenergic blocker; blocker; adrenergic blocker; adrenergic blocker; adrenergic blocker; adrenergic blocker; adrenergic blocker; adrenergic ------! ! selective beta selective beta selective beta selective beta selective beta selective beta selective exacerbate or cause respiratory cause respiratory or exacerbate ------! ! ! may exacerbate or cause respiratory respiratory cause or mayexacerbate CNS events adverse possible depression; respiratory cause or mayexacerbate possible depression; respiratory cause or mayexacerbate CNS events adverse possible depression; respiratory cause or mayexacerbate CNS events adverse possible depression; may depression respiratory cause or mayexacerbate depression Non Non Non Non Non Non ------! ! ! ! ! ! Appendix complete 1: EU(7) 1.86 [1.64 1.86 7]; 2.00 7]; ! ! [1.79 2.25 16; 2.00 2.71]; [1.91 2.40 20; 2.00 2.89]; [1.94 2.33 21; 2.00 2.72]; 21; 2.0 [1.89 2.44 16; 2.00 2.99]; [1.87 2.30 20; 2.00 2.73]; ! ! ! ! ! ! !
5 (A); 2, 6 2, 5 (A);
!
blocking agents blocking blocking agents blocking - - ! Beta Beta Oxprenolol In lists: 2, 6 (B) Pindolol In lists: 3 (A); 2, 6 (B) Propranolol In lists: 3 (A); 6 (B) Sotalol In lists: 4, (B) Nadolol In lists: 2, 6 (B) Labetalol In lists: 2, 6 (B) channel Calcium blockers ! ! ! ! ! ! ! ! ! C07 C07A C07AA02 C07AA03 C07AA05 C07AA07 C07AA12 C07AG01 C08 ARTICLES 117 - - - - drugs drugs
! ! ! ! E, L E, L E, L E ! ! ! drugs antihypertensive Other beta cardioselective (amlodipine, blockers, ACE inhibitors, diuretics). drugs antihypertensive Other beta cardioselective (amlodipine, blockers, ACE inhibitors, diuretics). drugs antihypertensive Other beta cardioselective (amlodipine, blockers, ACE inhibitors, diuretics). antihypertensive Other beta cardioselective (amlodipine, blockers, ACE inhibitors, diuretics). ! E ! M ! ! P P M ! ! times daily. E
60 mg/d. -
PIM list ! ! Lower initial dose. dose, usual of half dose, Lower initial out. and in taper dose, usual of half dose, Lower initial out. and in taper dose: maitenance 30 mg/d; dose: Initial 30 40 dose initial tablets: release Immediate release sustained daily; times mgthree tablets: initial dose 120 mg daily; oral controlled onset extended release: initial 100 mg/d. dose Reduce dosing interval. dose increase or M 60 mg three - ! ! ! ! ! ! ! hypotension, orthostatic of Risk stroke or infarction myocardial myocardial hypotension; of risk Increased infarction; increased mortality myocardial hypotension; of risk Increased infarction; increased mortality of risk May constipation; worsen bradycardia of risk May constipation; worsen bradycardia - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 2.00 ! ! [1.38 2.00 19; 1.00 2.62]; [1.28 1.74 23; 1.00 2.19]; [1.51 1.95 21; 2.00 2.40]; [1.98 2.39 23; 2.80]; [2.18 2.57 23; 2.00 2.95]; ! ! - !
- 2, 6 (B) 2,
release) release)
-
! ! !
release) release) Selective calcium Selective channel blockers with vascular mainly effects Nicardipine In lists: 1 (A); 2, 6 (B) (non Nifedipine sustained In lists: 1, 4, 5 (A); 2, 6 (B) (sustained Nifedipine In lists: 1 (A); calcium Selective channel blockers with effects cardiac direct Verapamil In lists: 3, 5 (A); 2, 6 (B) Diltiazem In lists: 3, 5 (A); 2, 6
! ! ! ! ! ! ! C08C C08CA04 C08CA05 C08CA05 C08D C08DA01 C08DB01 118 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E E, B
pharmacological treatment treatment pharmacological - ! ! ! ! ! ! ! ! for treatment Specific osteoporosis. Local administration (i.e. vaginal and safe considered application) efficient. Non (pelvic floor exercises, physical physical exercises, floor (pelvic ! PIM list ! ! ! ! ! ! ! ! ! !
- ! ! ! ! ! ! ! ! ! ! ineffective effects; Moderate side of risk dementia of treatment the for potential carcinogenic for Evidence lack and cancer) endometrial and (breast women older in effect cardioprotective of to leading flow, urinary May decrease retention urinary - - - ! ! ! Appendix complete 1: EU(7) ! ! ! ! ! ! ! [1.28 1.77 22; 1.00 2.26]; [1.21 1.52 21; 1.00 1.83]; [1.22 1.75 16; 1.00 2.28]; ! !
① ! ! ! ! ! !
urinary - !
!
hormones system and se and system (B) Lipid modifiying agents Lipid modifiying agents, plain Niacin (=Nicotinic acid) In lists: 2 (A) Genito Sex hormones and the of modulator genital system Oestrogens Oestrogen (oral) In lists: 5 (A); 6 (B) Urologicals Other urologicals, incl. antispasmodics Flavoxat ! ! ! ! ! ! ! ! ! ! C10 C10A C10AD02 G G03 G03C G03C G04 G04B G04BD02 ARTICLES 119 ! ! ! ! ! ! E E E E E E apy). apy). pharmacological treatment treatment pharmacological treatment pharmacological treatment pharmacological treatment pharmacological treatment pharmacological - - - - - and behavioural therapy). therapy). behavioural and Non Non Non Non Non (pelvic floor exercises, physical physical exercises, floor (pelvic therapy). behavioural and physical exercises, floor (pelvic therapy). behavioural and physical exercises, floor (pelvic therapy). behavioural and physical exercises, floor (pelvic therapy). behavioural and physical exercises, floor (pelvic ther behavioural and ! M ! M ! 30 -
M release oxybutynin oxybutynin release - ! ! M PIM list ! Start immediate mg 2.5 with adults older frail in chloride orally 2 or 3 times daily. of cases in daily twice 1 mg orally function. renal impaired significantly Use cases of in 2 mg once daily orally severerenal failure(CrCl 10 <10 CrCl if use avoid mL/min); mL/min. may needed. be Dose reduction - ! ! ! ! ! mouth, CNS side CNS side mouth, CNS side mouth, Anticholinergic side effects (e.g. (e.g. effects side Anticholinergic dry constipation, QT) ECG (prolonged changes effects); (e.g. effects side Anticholinergic CNS mouth, dry side constipation, QT) ECG (prolonged changes effects); (e.g. effects side Anticholinergic dry constipation, QT) ECG (prolonged changes effects); (e.g. effects side Anticholinergic CNS mouth, dry side constipation, QT) ECG (prolonged changes effects); (e.g. effects side Anticholinergic CNS mouth, dry side constipation, QT) ECG (prolonged changes effects); - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 23; 1.43 [1.78 1.43 23; 1.00 1.69]; [1.16 1.57 23; 1.00 1.97]; [1.27 1.59 22; 1.00 1.92]; [1.32 1.77 22; 1.00 2.23]; [1.34 1.81 21; 1.00 2.28];
- - !
release) release) release) - - release) release) release) - - ! ! ! ! ! 6 (B)
sustained In lists: 5, 6 (B) (non Oxybutynine In lists: 1, 3, 4, 5 (A); 6 (B) 5, Oxybutynine (sustained In lists: 1, 3, 4, 5 (A); 6 (B) 5, (non Tolterodine sustained In lists: 1, 3, 4, 5 (A); 6 (B) 5, Tolterodine (sustained In lists: 1, 3, 5 (A); 5, 6 (B) Solifenacin In lists: 1, 3, 4, 5 (A); 5,
! ! ! ! ! G04BD04 G04BD04 G04BD07 G04BD07 G04BD08 120 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! E E E blockers, calcium blockers, - ! armacological treatment treatment armacological E ph treatment pharmacological pharmacological treatment treatment pharmacological - - - ! Non Non Non physical exercises, floor (pelvic therapy). behavioural and other antihypertensive, as used If ACE agents: antihypertensive inhibitors, beta (exclude diuretics antagonists, PIM). (pelvic floor exercises, physical physical exercises, floor (pelvic therapy). behavioural and (pelvic floor exercises, physical physical exercises, floor (pelvic therapy). behavioural and !
M ! E
M P 75 years old, the dose dose the old, 75 years ! ≥ ! ose: 1 mg at bedtime; up to 10 up to bedtime; 1 mg at ose: M PIM list ! ! CrCl <30 mL/min: 20 mg/d (immediate 20 mg/d <30 (immediate CrCl mL/min: extended of use the avoid release); trospium. release aged adults In maximum <30CrCl mL/min: 4 dose mg/d. dose, usual of half dose, Low initial out. and in taper Initial d required. may be mg/d frequency of trospium immediate immediate trospium of frequency 20 mg/d. to may reduced be release - ! ! ! headedness, headedness, - ! ! Anticholinergic side effects (e.g. (e.g. effects side Anticholinergic CNS mouth, dry side constipation, effects) antimuscarinic of Higher incidence mouth, dry (e.g., events adverse increased dyspepsia, constipation, tract urinary and dizziness) urine, residual and 75 years aged persons in infection patients younger with compared older antimuscarinic of Higher incidence mouth, dry (e.g., events adverse increased dyspepsia, constipation, tract urinary and dizziness) urine, residual and 75 years aged persons in infection patients younger with compared older hypotension, orthostatic of risk Higher incontinence/ urinary mouth, dry impaired micturition, CNS side effects light vertigo, (e.g. and cerebrovascular and somnolence) disease cardiovascular - - - - ! ! ! ! Appendix complete 1: EU(7) 1.79 [2.27 1.79 ! 18; 1.94 [1.42 1.94 18; 2.00 2.47]; 14; 2.00 2.30]; 14; 1.71 [1.24 1.50 2.19]; [1.25 1.52 21; 1.00 1.80]; ! ! !
! ! Trospium Trospium In lists: 5 (A); 5, 6 (B) Darifenacin In lists: 3, 5 (A); 5, 6 (B) Fesoterodin In lists: 3, 5 (A); 5, 6 (B) benign in used Drug hypertrophy prostatic Terazosin In lists: 4, 5 (A); 6 (B) ! ! ! ! ! G04BD09 G04BD10 G04BD11 G04C G04CA03 ARTICLES 121 ! ! E E ! ! ! ! ! ! ! accordance in Other antibiotics and resistance sensitivity with testing. accordance in Other antibiotics and resistance sensitivity with testing. ! M ! ! E 100 mg/8h; use shorter than one one than shorter use 100 mg/8h; - PIM list ! ! ! ! ! ! ! Reduce dosing dose and increase interval renal if failure. 50 week. - ! use ! term - life may be prolonged with with may prolonged be life - ! ! ! ! ! ! ! Its half ratio, risk/benefit Unfavourable particularly with long damage, liver effects, side (pulmonary renal severe if contraindicated etc.); and excretion decreased to due failure increased risk of toxicity elevated serum concentrations in older older in concentrations serum elevated de torsade of risk increased adults; rupture tendon or tendinitis and pointes - - ! ! Appendix complete 1: EU(7) ! ! ! ! ! ! ! [1.70 2.23 22; 2.00 2.76]; [1.59 2.00 21; 2.00 2.41]; ! ! ! steroid ! - ! !
eletal ❦
s rheumatic rheumatic rheumatic ! - ! - - !
inflammatory inflammatory - - and anti and anti Antiinfectives for for Antiinfectives systematicuse Antibacterial for systemic use Quinolone antibacterials Ofloxacin In lists: does not PIM appear as Other antibacterials (>1 Nitrofurantoin week) In lists: 1, 4, 5 (A) Musculo system Anti products Anti non products, (NSAID)
! ! ! ! ! ! ! ! ! J J01 J01M J01MA01 J01X J01XE01 M M01 M01A 122 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤ period shorter than than shorter period
oxycodone, oxycodone, E E E , oxycodone, oxycodone, , oxycodone, , , d d d ! ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine hydromorphone). buprenorphine, E, P mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P P P M
inhibitors reduced if if reduced ! ! !
E E E . pump inhibitors pump inhibitors pump inhibitors pump - - - ! PIM list Use for the shortest period possible. possible. period Use shortest the for may be bleeding of The risk proton with combined dose) low <8 weeks, (use by 25%. reduction dose Reduce possible. period Use shortest the for if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use low dose; using start 50 mg/d; if may reduced be bleeding of risk the proton with combined dose). low <8 weeks, (use -
! fatal; ! ! Very high risk of GI bleeding, ulceration, ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or dyscrasia blood of risk ulceration, GI bleeding, of risk Very high may which be perforation, or CNS of disturbances risk ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular - - - ! ! ! Appendix complete 1: EU(7) 19; 1.21 [1.01 1.21 19; 1.00 1.41]; [1.08 1.39 23; 1.00 1.70]; [1.59 2.00 23; 2.00 2.41];
1, 2, 5,
! ! ! Phenylbutazone Phenylbutazone In lists: 1, 2, 4 (A); 5, 6 (B) Indometacin In lists: 1, 3, 4, 5 (A); 6 (B) 5, 2, Diclofenac In lists: 5 (A); 6 (B) ! ! ! M01AA01 M01AB01 M01AB05 ARTICLES 123 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ of 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤
h lower risk of of risk h lower oxycodone, oxycodone, E E E , oxycodone, oxycodone, , oxycodone, , , d d d ! ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). Opioids wit delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). Opioids with lower risk delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine hydromorphone). buprenorphine, E, P mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P P M ! ! E E 6 hours, 6 hours, - pump inhibitors pump inhibitors pump inhibitors - - ! E ! pump inhibitors (use <8 (use pump inhibitors - risk of bleeding may be reduced if if may reduced be bleeding of risk PIM list weeks, low dose). Use for the shortest period possible. possible. period Use shortest the for The proton with combined dose). low <8 weeks, (use advanced cases of in Contraindicated as indicated not dose oral failure; renal recommended continuation dose; initial intramuscular or intravenous after dose 4 10 mg every is dosing days. 5 for and maximummg/d 40 if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use of risk the low dose; using Start combined if may reduced be bleeding proton with - ! ! ! mayfatal be Very high risk of GI bleeding, ulceration, ulceration, GI bleeding, of risk Very high may which fatal be perforation, or ulceration, GI bleeding, of risk Very high which perforation, or ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular - - - ! ! ! Appendix complete 1: EU(7) 16; 1.50 [1.22 1.50 16; 1.50 1.78]; [1.44 1.76 21; 2.00 2.08]; [1.50 1.85 20; 2.00 2.20]; !
! ! Acemetacin In lists: 4 (A); 1, 2, 4, 6 (B) 5, Ketorolac In lists: 5 (A); 1, 2, 5, 6 (B) Aceclofenac In lists: 1, 2, 5, 6 (B) ! ! ! M01AB11 M01AB15 M01AB16 124 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤ period shorter than than shorter period
lower risk of E E E , oxycodone, oxycodone, , oxycodone, , oxycodone, , d d d ! ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). Opioids with delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P
P P M ! ! ! E E E e). ! pump inhibitors (use <8 (use pump inhibitors <8 (use pump inhibitors <8 (use pump inhibitors - - - PIM list Start with lower dose; the risk of combined if may reduced be bleeding proton with weeks, low dose). weeks, low dose). dos low weeks, Doses >20 mg with associated are increased GI toxicity and ulceration, especially in older adults. possible. period Use shortest the for 10 mg/d; start with lower dose; the risk combined if may reduced be bleeding of proton with possible. period Use shortest the for 11 mg/d; start with lower dose; the risk combined if may reduced be bleeding of proton with - ! ! ! fatal; high risk of GI bleeding, ulceration, ulceration, GI bleeding, of risk high
Very may which fatal be perforation, or ulceration, GI bleeding, of risk Very high may which be perforation, or contraindications cardiovascular ulceration, GI bleeding, of risk Very high may which fatal be perforation, or - - - ! ! ! Appendix complete 1: EU(7) 22; 1.55 [1.28 1.55 22; 1.50 1.81]; [1.35 1.74 19; 2.00 2.13]; [1.34 1.65 23; 2.00 1.96]; !
(A); 1, 2,
! ! Piroxicam In lists: 4, 5 (A); 1, 2, 6 (B) 5, Lornoxicam In lists: 1, 2, 5, 6 (B) Meloxicam In lists: 4, 5 6 (B) 5, ! ! ! M01AC01 M01AC05 M01AC06 ARTICLES 125 x 400 3 x 400 3 x 400 3 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤
E E E , oxycodone, oxycodone, , oxycodone, , oxycodone, , d d d ! ! ! week); naproxen ( naproxen week); Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine mg/d or for a period shorter than than shorter period a for or mg/d one than shorter period a for or mg/d ( naproxen week); one mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P
P M M ! ! ! E E E go slow in older older in go slow pump inhibitors pump inhibitors pump inhibitors pump inhibitors – 20 mL/min; start - - - ! PIM list The risk of bleeding may be reduced if if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use low Reduce start dose; if may reduced be bleeding of The risk proton with combined low dose). <8 weeks, (use Reduce CrCl dose < if reduced use and dose lower with adults. older in dose maintenance possible. period Use shortest the for if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use adults; avoid if CrCl <30 mL/min. - r ! ! ! Risk of GI bleeding and increased risk of of risk increased and GI bleeding of Risk highe at complications cardiovascular cases in especially mg/d), (>1200 doses disease cardiovascular previous of GI bleeding of Risk ulceration, GI bleeding, of risk Very high may which fatal be perforation, or - - - ! ! ! Appendix complete 1: EU(7) 21; 2.43 [1.98 2.43 21; 2.00 2.87]; [1.62 2.04 23; 2.00 2.47]; [1.45 1.87 23; 2.00 2.29];
! ! c c
one week) ! Ibuprofen (>3 x 400 (>3 Ibuprofen period a for or mg/d week) one than longer In lists: 5 (A); 5, 6 (B) x 250 (>2 Naproxen period a for or mg/d than longer In lists: 5 (A); 5, 6 (B) Ketoprofen In lists: 4, 5 (A); 1, 2, 6 (B) 5, ! ! ! M01AE01 M01AE02 M01AE03 126 QUALITY ISSUES IN CARING FOR OLDER PEOPLE than than 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤ eriod shorter than than shorter eriod
oxycodone, oxycodone, E E E , oxycodone, oxycodone, , oxycodone, , , d d d ! ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine hydromorphone). buprenorphine, E, P ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one p a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P maximum maximum
! ! E E ! ! pump inhibitors (use <8 (use pump inhibitors <8 (use pump inhibitors - - E pump inhibitors (use <8 weeks, <8 weeks, (use pump inhibitors - PIM list Start with lower dose; the risk of combined if may reduced be bleeding proton with 50 mg/d in up to dose, lower with Start 50 pain: postoperative in adults; older failure, hepatic or renal of case mg/din mg/8h; 50 maximumdose bleeding of risk the 48 hours; length with combined if reduced maybe proton Start with lower dose; the risk of combined if may reduced be bleeding proton with low dose). low dose). weeks, low dose). weeks, low dose). - ! ! ! ulceration, or perforation, which may be fatal; may which fatal; be perforation, or contraindications cardiovascular Very high risk of GI bleeding, ulceration, ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular GI bleeding, of risk Very high - - - ! ! ! Appendix complete 1: EU(7) 19; 1.84 [1.41 1.84 19; 2.00 2.28]; [1.50 1.91 23; 2.00 2.32]; [1.35 1.72 18; 2.00 2.10]; ! !
! Flurbiprofen Flurbiprofen In lists: 1, 2, 5, 6 (B) Dexketoprofen In lists: 1, 2, 5, 6 (B) Mefenamic acid In lists: 5 (A); 1, 2, 5, 6 (B) ! ! ! M01AE09 M01AE17 M01AG01 ARTICLES 127 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤
E E E , oxycodone, oxycodone, , oxycodone, , oxycodone, , d d d etamol; ibuprofen ( ibuprofen etamol; ! ! ! week). ! Parac than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; than shorter period a for or mg/d one of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, E, P
P ! ! E E pump inhibitors pump inhibitors pump inhibitors - - ! E ! M pump inhibitors (use <8 (use pump inhibitors - PIM list ! weeks, low dose). The risk of bleeding may be reduced if if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use therapy. of duration possible Shortest moderateAdjust cases of dose in or maximum starting failure; renal severe 750 mg 500 exceed or not should dose mg 1500 and maximum a of to mg/d, receive should adults older 1000 mg/d; dose 1000mg; of doses daily single low recommended, consider reduction startingdose. if may reduced be bleeding of The risk proton with combined dose). low <8 weeks, (use Start with lower dose; the risk of combined if may reduced be bleeding proton with -
! ! ! ! Very high risk of GI bleeding, ulceration, ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular ulceration, GI bleeding, of risk Very high may which fatal; be perforation, or contraindications cardiovascular - - - ! ! ! Appendix complete 1: EU(7) 21; 1.67 [1.28 1.67 21; 1.00 2.06]; [1.34 1.73 22; 1.50 2.12]; [1.33 1.70 20; 1.50 2.08]; ! ! 6 (B)
! ! Celecoxib Celecoxib In lists: 1, 2, 5, Etoricoxib In lists: 4 (A); 1, 2, 5, 6 (B) Nabumetone In lists: 5 (A); 1, 2, 5, 6 (B) Muscle relaxants ! ! ! ! M01AH01 M01AH05 M01AX01 M03 128 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! ! ! ! ! Rehabilitation; botulinum toxin. E Rehabilitation; botulinum toxin. E Rehabilitation; botulinum toxin. E Rehabilitation; botulinum toxin. E Rehabilitation; botulinum toxin. E M, go slow go slow – ! E ! M 3 times daily and and daily 3 times - M ! 10 mg 3 times daily. daily. 10 mg 3 times
! PIM list ! ! ! ! in may required be Dose reductions low start failure; renal of cases in older adults. Start with 5 mg 2 needed; as maximum gradually increase dose: in may required be Dose reductions failure. renal of cases failure. renal cases of dosing in Cautious M adults. older for dosing Conservative E - ! ! ! ! ! ! including orthostatic hypotension, hypotension, orthostatic including sedation, weakness, confusion, confusion, weakness, sedation, ! CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNSand side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk hypotension, orthostatic including effects falls, amnesia ------! ! ! ! ! ! Appendix complete 1: EU(7) ! [1.15 1.62 13; 1.00 2.08]; [1.15 1.62 13; 1.00 2.08]; [1.11 1.38 16; 1.00 1.64]; [1.72 2.14 22; 2.00 2.55]; [1.37 1.94 18; 2.00 2.52]; [1.37 1.80 15; 2.00 2.23]; ! ! ! ! !
! 5 (B)
! Muscle relaxants, centrally acting agents Carisoprodol In lists: 5 (A); Methocarbamol In lists: 1, 2, 5 (A) Orphenadrine In lists: 3, 5 (A); 5 (B) Baclofen In lists: 1, 3, 4 (A) Tizanidine In lists: 3 (A), 5 (B) Tetrazepam In lists: 1, 4 (A) ! ! ! ! ! ! ! M03B M03BA02 M03BA03 M03BC01 M03BX01 M03BX02 M03BX07 ARTICLES 129 a !
! E E 3 x 400 mg/d or for 3 x 400 mg/d or 2 x 250 mg/d or for a a for 2 x 250 mg/d or ≤ ≤ ! ! ! ! ! ! ( Ibuprofen D. Vitamin Bisphosphonates, period shorter than one week); week); one than shorter period ( naproxen period shorter than one week). one than shorter period E, ! ! M M
M ! go slow. go slow. – ! PIM list ! ! ! ! ! Start low adults by 50% older dose Reduce in old). years (>70 Reduce failure. renal cases of dose in M failure Avoid renal severe cases of in (CrCl <30 mL/min). - ! ! mbolism ! ! ! ! ! ! Risk of anticholinergic and CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia adults, older in toxicity of risk Higher particularly in cases of existing renal, GI disease cardiac or thromboembolism venous of risk Higher or who temporarily are persons in permanently immobilised. Evaluate the patients for therapy continued for need of risk increased with old 80 years over thromboe venous - - - ! ! ! Appendix complete 1: EU(7) 2.11 [1.66 2.11 ! ! ! ! ! 16; 1.69 [1.22 1.69 16; 1.00 2.15]; 18; 2.00 2.56]; [1.35 1.72 18; 2.00 2.10]; ! ! !
! ! ! !
skeletal - does not not does ! Cyclobenzaprine Cyclobenzaprine In lists: 2, 5 (A); 5 (B) preparations Antigout preparations Antigout Colchicin In lists: 6 (B) Drugs treatment for bone diseases of Drugs bone affecting and structure mineralization Strontium ranelate In lists: PIM appear as Other drugs for disorders of the musculo system ! ! ! ! ! ! ! ! M03BX08 M04 M04A M04AC01 M05 M05B M05BX03 M09 130 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 3 x 400 3 x 400 ≤ ≤ 2 x 250 2 x 250 ( ≤ ≤ eriod shorter than than shorter eriod
E E , oxycodone, oxycodone, , oxycodone, , d d ! ! ! ! ! ! ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine mg/d or for a p a for or mg/d ( naproxen week); one mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P hydromorphone). buprenorphine, !
M P
E ! M, P M 50 mL/min); use 50% use 50 mL/min); ! - 6 hours. ! M - go slow. go slow. – PIM list ! ! ! ! failure. renal Adjust cases of dose in Start low 4 50 mg every usual the at dose Use normal 75% the of intervals in cases of moderate renal failure (GFR 10 GFR with 10 and between patients For reduced be should dose 50 mL/min the GFR with less patients by 25% for and be should dose the 10 mL/min, than by 50%. decreased of the normal dose at the usual intervals intervals usual the at dose normal the of in cases of severe renal failure (GFR <10 mL/min). Use for the shortest period possible. possible. period Use shortest the for - ! ! ! ! ! ! ! adverse and idiosyncratic Risk cardiac of effects confusion, fractures, Risk falls, of syndrome withdrawal and dependency Risk of delirium and agitation - - - ! ! ! Appendix complete 1: EU(7) ! ! ! ! [1.44 2.13 15; 2.00 2.82]; [1.24 1.50 22; 1.00 1.77]; [1.05 1.28 18; 1.00 1.51]; ! !
2, 6 (B) 2, !
! skeletal - ! ! !
Other drugs for disorders of the musculo system and Quinine derivatives In lists: does not PIM appear as Nervous system Analgesics Opioids Pethidine (=Meperidine) In lists: 4, 5 (A); 2, 6 (B) Pentazocine In lists: 5 (A);
! ! ! ! ! ! ! M09A M09AA N N02 N02A N02AB02 N02AD01 ARTICLES 131 than than 3 x 400 3 x 400 ≤ ≤ 2 x 250 2 x 250 ≤ ≤
ibuprofen ( ibuprofen oxycodone, oxycodone, E E , oxycodone, oxycodone, , , d d ! ! ! E, P Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine ( ibuprofen Paracetamol; ( naproxen week); one than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine hydromorphone). buprenorphine, E, P mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one shorter period a for or mg/d buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P are are
M !
! E ! go slow. go slow. than older persons in go slow;
– – E, M M PIM list Not to be used in cases of severe renal Not be renal severe cases of used to in failure. 300 mg over doses daily 75 years, Start low Start low recommended. not progressive mg/8h and 12.5 with Start maximum mg/8h; 12.5 of increases 100mg/8h. dosing the extend and dose Reduce interval for patients with severe renal failure. - ! ! More adverse effects in older adults; CNS adults; older More in effects adverse vertigo confusion, as such effects side nausea and CNS adults; older More in effects adverse vertigo confusion, as such effects side nausea and - - ! ! Appendix complete 1: EU(7) 23; 1.83 [1.44 1.83 23; 2.00 2.21]; [1.77 2.33 21; 2.00 2.90]; -
! ! - release) release) -
adol (sustained adol
sustained Tram In lists: 5, 6 (B) (non Tramadol In lists: 5, 6 (B) release) release)
! ! N02AX02 N02AX02 132 QUALITY ISSUES IN CARING FOR OLDER PEOPLE e). 3 x 400 3 x 400 3 x 400 ≤ ≤ ≤ 2 x 250 2 x 250 2 x 250 ≤ ≤ ≤ risk of pharmacological pharmacological -
ibuprofen ( ibuprofen ! E E E , oxycodone, oxycodone, , oxycodone, , d d ! ! ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine E, P ( ibuprofen Paracetamol; than shorter period a for or mg/d one week). Opioids with lower delirium (e.g., tilidine/naloxone, morphine Paracetamol; than shorter period a for or mg/d non week); one treatment (silence, rest, darkness). mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d ( naproxen week); one buprenorphine, hydromorphon buprenorphine, hydromorphone). buprenorphine, E, P E
! go slow. go slow. – ! PIM list ! ! ! ! Lowest possible dose. Lowest dose. possible Start low with dose methadone Lower initial are intervals dosing longer dose slower a with recommended, along titration for patients with renal failure. M - ! ! ! prolongated clotting time, acting especially in the elderly - ! ! elevation of INR values or inhibition of of inhibition or INR of values elevation platelet aggregation Very long May or GI ulcers existing exacerbate of risk increased new GI ulcers; produce to due bleeding profile risk/benefit Unfavourable - - - ! ! ! Appendix complete 1: EU(7) ! ! 22; 1.82 [1.47 1.82 22; 2.00 2.17]; [1.33 1.83 23; 1.00 2.33]; [1.08 1.55 20; 1.00 2.02]; ! ! !
!
!
Methadone Methadone In lists: 6 (B) Other and analgesics antipyretics acid Acetylsalicylic mg)(>325 In lists: 3, 5 (A); 2, 5, 6 (B) Antimigraine preparations Ergotamine In lists: 4 (A) ! ! ! ! ! N07BC02 N02B N02BA01 N02C N02CA02 ARTICLES 133 !
E ; ; . d d 3 x 400 ≤ 2 x 250 ≤ pharmacological pharmacological - ; gabapentin ; d ! ; valproic; acid d E ! ! Paracetamol; ibuprofen ( ibuprofen Paracetamol; than shorter period a for or mg/d non week); one treatment (silence, rest, darkness). Levetiracetam mg/d or for a period shorter than than shorter period a for or mg/d ( naproxen week); one lamotrigine ! M
P renal renal
E, M
M term therapy. -
16 hours in cases cases in 16 hours - M 40 mg; maximum dose: - ! or short or go slow. go slow. – ! the lowest possible dose, taper taper dose, possible lowest the M PIM list ! !
Eletriptan Hydrobromide: initial dose of of dose initial Hydrobromide: Eletriptan 2 hours; after 20 mg, may repeated be 20 of dose usual Start low cases of in contraindicated Naratriptan: severerenal failure(CrCl <15 mL/min). moderate to mild of cases In be should dose starting lower a failure, 2.5 maximum is the and dose considered mg/d. Use dose. possible lowest 12 every Administer (GFR failure <10 renal severe of acting longer Avoid ml/min). of cases in use term long for barbiturates doses Decrease failure. renal significantlyf 40 mg for older adults. adults. older 40 mg for Start at dose. usual the of down half to - ! d risk of decreased decreased of d risk
! M ! ! Safety and efficacy in older adults have adults older in andSafety efficacy established been not older for use sumatriptan and Naratriptan has an increase adults and reduced function clearance hepatic for risk higher dysfunction, renal to due in and increases disease, coronary artery pressure blood excitation paradoxical Risk sedation, of - - ! ! Appendix complete 1: EU(7) ! ! 23; 2.13 [1.78 2.13 23; 2.00 2.48]; [1.24 1.50 22; 1.00 1.77]; !
!
! !
Triptanes (e.g. Sumatriptan, Eletriptan, Naratriptan, Zolmitriptan) In lists: does not PIM appear as Antiepileptics Antiepileptics Phenobarbital In lists: 4, 5 (A); 5 (B) ! ! ! ! N02CC N03 N03A N03AA02 134 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! E E E ; ; ; ; . . . d d d d d d ; gabapentin ; gabapentin ; gabapentin ; d d d ; valproic; acid valproic; acid valproic; acid d d d Levetiracetam Levetiracetam Levetiracetam lamotrigine lamotrigine lamotrigine 7 - 500 mg/d ! - E dose is 300 is dose
100 mg/d every 5 100 mg/d every g/day, in divided divided in g/day, - !
! E . M ! go slow; E – 7 mg / kg / d in 2 doses. 2 doses. d in 7 mg kg / / - PIM list Lower doses or less frequent dosing dosing frequent less or Lower doses to due adults older for necessary maybe or hypoalbuminemia clearance, reduced disease renal Start with 3 mg/k to according dosage the adjust doses, and concentrations hydantoin serum the guide a as use response; patient dose in the increase plasma levels, increments of 50 the dose; an achieve effective days to maintenanceusual or 4 Start low serum and response the to dose Adjust concentration. 0.5 mg/d. mg/d. 0.5 - ! ! - ! like syndrome; syndrome; like - Narrow window; increased therapeutic CNS (e.g. adults older in toxicity of risk toxicity) hematologic and reactions paradoxical Risk falls, of SIADH of risk Increased carbamazepine like events adverse agitation, and confusion induced bradycardia and block atrioventricular - - - ! ! ! Appendix complete 1: EU(7) 22; 2.18 [1.76 2.18 22; 2.00 2.61]; [1.45 1.70 23; 2.00 1.94]; [1.71 2.17 23; 2.00 2.64]; ! ! !
Phenytoin Phenytoin In lists: 3 (A); 5 (B) Clonazepam In lists: 3, 5 (A); 5 (B) Carbamazepine In lists: 5 (A); 5 (B) ! ! ! N03AB02 N03AE01 N03AF01 ARTICLES 135
! E ; ; . d d levodopa; levodopa; levodopa; levodopa; - - - ; gabapentin ; d ; valproic; acid inhibitor of d ! ! ! ! ! Levetiracetam carbidopa Levodopa; rasagiline. as oxidase monoamine carbidopa Levodopa; carbidopa Levodopa; benserazide levodopa; levodopa; benserazide irreversible levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine lamotrigine E E E ! E
M 200 mg/d. 200 mg/d. - ! M ! half the usual dose. dose. usual the half - go slow. go slow. – PIM list ! ! ! ! Dosage may adjustment in be indicated function renal extent the to adults older impaired evident of cases In reduced. is <70 mL/min/1.73 (CrCl function renal one use m), dose 25 of mg/d and increase Use initial 100 up to 25 mg/d weekly Start low - ! hypotension, hypotension, related dysfunction dysfunction related - ! ! ! ! ! (e.g., confusion, psychomotor slowing) psychomotor confusion, (e.g., Risk of cognitive of Risk CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk effects including orthostatic confusion, weakness, sedation, falls, amnesia - - - - ! ! ! ! Appendix complete 1: EU(7) ! ! 19; 2.53 [2.12 2.53 19; 2.00 2.93]; [1.08 1.53 17; 1.00 1.98]; [1.78 1.50 20; 1.00 1.82]; [1.05 1.40 15; 1.00 1.75]; ! !
2, 5, !
! ! ! Topiramate In lists: 5 (B) drugs Antiparkinson Anticholinergic agents Trihexyphenidyl In lists: 1, 5 (A); 6 (B) Biperiden In lists: 1, 3 (A); 2, 6 (B) Tropatepin In lists: 1 (A); 2, 6 (B) ! ! ! ! ! ! N03AX11 N04 N04A N04AA01 N04AA02 N04AA12 136 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
levodopa; levodopa; levodopa; levodopa; levodopa; levodopa; - - - - - ! ! ! ! ! ! Levodopa; carbidopa Levodopa; carbidopa Levodopa; carbidopa Levodopa; E carbidopa Levodopa; carbidopa Levodopa; E benserazide levodopa; levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine E E E ! M ! go slow. go slow. – ! E PIM list ! ! ! ! Start low daily 2 divided 100 mg/d in with Start doses. - ! dystonia, dystonia, ! ! ! ! ! Risk of anticholinergic and CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia CNS and side anticholinergic of Risk hypotension, orthostatic including effects confusion, weakness, sedation, falls, amnesia Risk CNS of effects side Adverse dyskinesia, include events dizziness, hallucinations, insomnia, somnolence, confusion, nausea anxiety, profile risk/benefit Unfavourable - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 2.00 ! 14; 1.14 [0.93 1.14 14; 1.00 1.35]; [1.39 1.70 20; 2.00 2.00]; [1.38 1.86 22; 1.50 2.34]; [1.45 1.88 16; 2.00 2.30]; [1.42 2.15 13; 2.89]; ! !
! !
!
!
Benzatropine Benzatropine In lists: 2, 6 (B) agents Dopaminergic Amantadine In lists: does not PIM appear as Bromocriptine In lists: 3 (A); 6 (B) Pergolide In lists: 6 (B) Dihydroergocryptine In lists: 1, 4 (A); 6 (B) ! ! ! ! ! ! B N04AC01 N04 N04BB01 N04BC01 N04BC02 N04BC03 ARTICLES 137
levodopa; levodopa; levodopa; levodopa; levodopa; levodopa; - - - - - ! ! ! ! ! Levodopa; Levodopa; carbidopa Levodopa; carbidopa carbidopa Levodopa; E carbidopa Levodopa; E carbidopa Levodopa; benserazide levodopa; levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine levodopa; benserazide irreversible inhibitor of rasagiline. as oxidase monoamine E E E ! E
M ! ! E e or akinetic crisis. ! E PIM list ! ! Start with three intakes of 0.25 mg 0.25 per of intakes three with Start mg by 0.25 per gradually increase day, 3 up to weeks, four week each for intake may be dose the Afterwards mg/d. 24 mg/d up to by 1.5 weekly increased mg/d. Reduce moderate cases of dose in to failure. renal severe day, per 0.125 of intakes three with Start mg by 0.125 per gradually increase up to days, seven to five every intake mg. 4.5 to 1.5 2 at started One usually day, per patch by weekly titrated and mg/24h increments in size patch the increasing do not 6 mg/24h; up to 2 mg/24h, of sudden abruptly: treatment the stop syndrome a may produce withdrawal malignant neuroleptic resembling syndrom - ! ! ! confusion, insomnia, insomnia, confusion, ! ! Risk of orthostatic hypotension, hypotension, orthostatic of Risk somnolence, confusion, hallucinations, nausea Side effects include orthostatic symptoms, GI tract hypotension, hallucinations, oedemaperipheral CNS effects side falls and hypotension orthostatic of Risk Side effects include orthostatic fatigue, nausea, headache, hypotension, sleep, of onset sudden disorder, sleep somnolence - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 17; 2.47 [1.92 2.47 17; 2.00 3.02]; [1.86 2.32 19; 2.00 2.77]; [1.25 1.78 18; 1.50 2.31]; [1.29 1.73 11; 2.00 2.16]; [1.68 2.33 15; 2.00 2.98]; ! ! !
! !
c c
c
Ropinirole In lists: 6 (B) Pramipexole In lists: 6 (A) Cabergoline In lists: 3 (A); 6 (B) Piribedil In lists: 1 (A); 6 (B) Rotigotine In lists: 6 (B) ! ! ! ! ! N04BC04 N04BC05 N04BC06 N04BC08 N04BC09 138 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
agiline. ! ! ! E E E levodopa; levodopa; . . . - d d d ! E ). e pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - ! ! ! Levodopa; carbidopa Levodopa; Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non antidepressant with anxiolytic profile (SSRI Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); benserazide levodopa; levodopa; benserazide irreversible inhibitor of ras as oxidase monoamine E - ! ! E M to 10 mg to in third to one to third - for an increased increased an for ! M ! go slow; use one use go slow; – PIM list ! ! ! ! half the normal adult dose for debilitated debilitated for dose adult normal the half of doses maintenance use adults; older 1 than greater doses 300 mg less; or benefit, any offer usually gram do not may responsible be but Do not use at doses >10 mg/d; 6mg/24h >10 mg/d; doses at use Do not recommended;patch dose increase changes to attention paying cautiously, pressure. blood orthostatic in Start low adverse effects. of incidence renal cases of in Administer cautiously failure; start with doses of 5 geriatric patients. - ! patients with ! ! ! ! blocking drug; risk of of risk drug; blocking drug blocking - - dizziness ! ! Increased risk of orthostatic hypotension hypotension orthostatic of risk Increased and Muscarinic seizures or epilepsy side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia effects adverse of risk activity; Protracted suchas drowsinessand falls Muscarinic orthostatic hypotension and falls; may falls; and hypotension orthostatic lower seizure thresholds in - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 1.58 [1.08 1.58
! ! 2.09]; 1.00 2.09]; 21; 2.29 [1.78 2.29 21; 2.00 2.79]; [1.11 1.38 21; 1.00 1.65]; [1.15 1.36 22; 1.00 1.58]; [1.08 1.57 14; 1.00 2.06]; 12; ! !
!
! ! -
! ! lists: 1lists: (A); 6 (B)
Selegiline In lists: 3 (A) Psycholeptics Antipsychotics Chlorpromazine In lists: 1, 5 (A); 2, 5, 6 (B) Levomepromazine In lists: 1, 3, 4 (A); 5, 6 (B) Clorazepate Acepromazine In Cyamemazine In lists: 1 (A); 5, 6 (B) ! ! ! ! ! ! ! N04BD01 N05 N05A N05AA01 N05AA02 N05AA04 N05BA05 N05AA06 ARTICLES 139 ! ! ! ! !
E E E E E . . . . . d d d d d pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - - operidol (<2 mg single dose; dose; mg (<2 single operidol Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine hal quetiapine <5mg/d); ! - ! M E, M
third to one to third ! - M 2.5 mg/day. mg/day. 2.5 - go slow. – ! M ! go slow; use one use go slow; – PIM list ! half the usual adult dose. dose. adult usual the half Start with oral dose of 1 Start low low Reduce start dose; Start low go slow. - ! prolongation - dyskinesia); dyskinesia); ! ! ! ! Anticholinergic and extrapyramidal side side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia side extrapyramidal and Anticholinergic (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia effects, side Risk anticholinergic of sedation,falls, QTc neuromuscular and hypotension of Risk reactions side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 2.00
21; 1.43 [1.09 1.43 21; 1.00 1.77]; [1.05 1.40 20; 1.00 1.75]; [1.10 1.47 17; 1.00 1.84]; [1.37 1.80 15; 2.00 2.23]; [1.32 1.79 14; 2.25]; !
! ! ! !
Fluphenazine Fluphenazine In lists: 1, 4, 5 (A); 5, 6 (B) Perphenazine In lists: 1, 3, 4, 5 (A); 6 (B) 5, Prochlorperazine In lists: 3, 5 (A); 5, 6 (B) Trifluoperazine In lists: 5 (A); 5, 6 (B) Propericiazine (=Periciazine) In lists: 1, 3 (A); 5, 6 (B) ! ! ! ! ! N05AB02 N05AB03 N05AB04 N05AB06 N05AC01 140 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! ! ! E E E E E . . . . . d d d d d pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - - Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); ! E 1.5 mg; use for for mg; use 1.5 - ! ! M ! ! M M ! E ral doses of 0.75 of doses ral PIM list Reduce dose. doses with less of Reduce start dose; 25 mg. than Use o and Reduce failure renal cases of dose in in older adults. 10 mg/d. the shortest period possible. possible. period shortest the - - ! ! ! ! ! blocking drug blocking - increased mortality in persons Anticholinergic and extrapyramidal side side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; falling; with dementia Muscarinic side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia QTc falls, hypotension, of Risk prolongation - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 19; 1.37 [1.08 1.37 19; 1.00 1.65]; [1.06 1.50 14; 1.00 1.94]; [1.33 1.59 22; 2.00 1.85]; [1.20 1.73 15; 1.00 2.27]; [1.20 1.63 16; 1.00 2.05]; ! !
!
! ! Thioridazine Thioridazine In lists: 4, 5 (A); 5, 6 (B) Pipotiazine In lists: 1 (A); 5, 6 (B) (>2 mg Haloperidol >5mg/d) dose; single In lists: 4, 5 (A); 5, 6 (B) Droperidol In lists: 5, 6 (B) Sertindole In lists: 3 (A); 5, 6 (B)
! ! ! ! ! N05AC02 N05AC04 N05AD01 N05AD08 N05AE03 ARTICLES 141 ! ! ! ! E E E E ngle dose; dose; ngle . . . . d d d d pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine mg (<2 si haloperidol quetiapine <5mg/d); ! ! M M 5 mg/d. 5 mg/d. - ! E ! M ! go slow. – PIM list Starting dose 20 mg/d. 20 mg/d. dose Starting Dose may adjustment be required. Start low Use doses low 2.5 of oral - ! isperidone related related - ! ! ! prolongation, torsades de de torsades prolongation, - prolongation - effects like tiredness, dizziness, prolongation - Risk of QTc of Risk and insomnia sedation, pointes, for Not approved hypotension. orthostatic the treatment of dementia mortality, increased of Risk psychosis. when used doses, higher with increased dementia in problems behavioural for maybe similar to the risk for r Adverse QTc Lower threshold seizure extrapyramidal falls, hypotension, of Risk QT effects, - - - - ! ! ! ! Appendix complete 1: EU(7) 16; 2.13 [1.51 2.13 16; 2.00 2.74]; [1.27 1.71 17; 2.00 2.14]; [1.24 1.87 15; 2.00 2.49]; [1.07 1.50 12; 1.00 1.93]; ! ! !
!
lists: 3lists: (A); 5, 6 (B) Ziprasidone Ziprasidone In lists: 5, 6 (B) Flupentixole In lists: 3 (A); 5, 6 (B) Chlorprothixen In Zuclopenthixol In lists: 3 (A); 5, 6 (B) ! ! ! ! N05AE04 N05AF01 N05AF03 N05AF05 142 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! E E E . . . d d d 6 weeks), pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); Non (< risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); E, ! M
E . ! go slow; reduce dose in cases cases in dose reduce go slow; – ! PIM list ! Recommended initial dose of 1 mg/d. 1 mg/d. of dose Recommended initial M Start with 12.5 mg/d Start low of significant renal failure. - ! - ! ! More rarely: neuroleptic neuroleptic More rarely: malignant syndrome and QT and syndrome malignant Anticholinergic and extrapyramidal side side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; of risk and mortality increased falling; with persons in accident cerebrovascular dementia. prolongation side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; of risk increased dementia; with myocarditis and agranulocytosis side extrapyramidal and Anticholinergic dyskinesia); (tardive effects of risk sedation; hypotonia; parkinsonism; persons in mortality increased falling; with dementia - - - ! ! ! Appendix complete 1: EU(7) 14; 1.57 [1.27 1.57 14; 2.00 1.87]; [1.28 1.55 22; 1.50 1.81]; [1.29 1.64 22; 1.50 1.99]; ! (A); 5, 6
! ! Pimozide In lists: 5, 6 (B) Clozapine In lists: 3, 4, 5 (A); 5, 6 (B) (>10 Olanzapine mg/d) In lists: 4, 5 (B)
! ! ! N05AG02 N05AH02 N05AH03 ARTICLES 143 ! E ! ! E E . . d d , trazodone. trazodone. , d quetiapine , mirtazapine e pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - ! Non SSRI Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol <5mg/d); Non weeks), (<6 risperidone mg/d), (<10 olanzapine dose; mg (<2 single haloperidol quetiapine <5mg/d); ! - E M, 30 1.5 1.5 - 12mg/d) 12mg/d) - 50 - daily - ! M tiate and titrate on a 50% of the usual dose dose usual 50% the of - E ! For geriatric patients or in
75% of the usual dose; GFR dose; usual 75% the of - E go slow; it may be necessary may necessary be it go slow; – daily regimen for 2 to 3 days to to 3 days 2 to for regimen daily - 600 mg/d. 600 mg/d. - ! PIM list ! Start low mg/d) for the shortest time period period time shortest the for mg/d) necessary. necessary. period time shortest the for cases of severe renal failure (CrCl < failure renal severe of cases <10 ml/min, 25 once to switch and dose target achieve 300 ml/min,50 Use (0.5 dose lowest required the mL/min), startwith 0.5 mg twice daily; daily; mg by 0.5 twice doses increase above mg 1.5 increases daily twice 1 least at of intervals at done be should may be necessary. week; slower titration For geriatric patients, if once ini desired, dosing twice thereafter. dosing daily Use (7 dose lowest required the to decrease dosage by as much 50% by as as dosage decrease to for compensate to adults older in in reduction dose clearance; reduced GFR 10 failure: renal of cases given at the normal dosage interval. interval. dosage normal the at given E - ! ! symptoms of of symptoms benefit profile for the the for profile benefit - ! ! Narrow therapeutic window; cumulation cumulation window; Narrow therapeutic in renal failure Problematic risk treatment of behavioural dementia; increased mortality, with dementia with patients in dose, higher when for used mortality increased of Risk dementia in problems behavioural - - - ! ! ! Appendix complete 1: EU(7) ! 22; 2.27 [1.80 2.27 22; 2.00 2.75]; [1.96 2.45 20; 2.00 2.94]; [1.46 2.60 16; 2.00 2.66]; ! ! !
!
Lithium In lists: 3 (A); 5, 6 (B) (>6 Risperidone weeks) In lists: 5 (A); 5, 6 (B) Aripiprazole In lists: 5 (A); 5, 6 (B) Anxiolytics
! ! ! ! N05AN01 N05AX08 N05AX12 N05B 144 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! as
acting acting acting - - t- 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 E, P E, P E, P ≤ ≤ ≤ ). ). ). 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 e e e ≤ ≤ ≤ pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non shor of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs . 2.5 mg2.5 out, -
! ! M M ! west possible dose, up to half half up to dose, possible west ! seinitial oral dose of 2 M
PIM list P Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P, M U once a day. a day twice to up half dose, to Use possible lowest the and in taper dose, usual the of treatment. of duration possible shortest P daily use adults older for dose; Reduce a times 5 mg four of two to dose oral failure renal severe of cases in day; by dose decrease <10 ml/min), (CrCl 50%. Use lo the for and adults older for dose Reduce patients with renal failure. of the usual dose, taper in and out, out, and in taper dose, usual the of treatment of duration possible shortest - ! ! ! Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression - - - ! ! ! Appendix complete 1: EU(7) 23; 1.61 [1.32 1.61 23; 2.00 1.89]; [1.08 1.37 19; 1.00 1.66]; [1.12 1.50 14; 1.00 1.88];
4 (A); 2, 5, 6 5, 2, 4 (A); ! ! ! Diazepam In lists: 1, 4, 5 (A); 2, 6 (B) 5, Chlordiazepoxide In lists: 1, 4, 5 (A); 5, 6 (B) Medazepam In lists: (B) ! ! ! N05BA01 N05BA02 N05BA03 ARTICLES 145 ! ! !
acting acting acting - - - 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 0.5 mg/d), mg/d), 0.5 E, P E, P E, P ≤ ≤ ≤ ). ). ). 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 e e e ≤ ≤ ≤ zepam ( pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - otizolam ( br Non short of low doses suchbenzodiazepines as lormetazepam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormeta brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs
1 mg/d. - dose, up to half half up to dose, ! 20 mg/d; maximum20 mg/d; - E ! ! ! PIM list Use the lowest possible Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P Use doses 10 of up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P Reduce use doses dose; 0.25 of E dose: 30 mg/d. 30 mg/d. dose: - ! ! ! Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression - - - ! ! ! Appendix complete 1: EU(7) 1.00 22; 1.50 [1.20 1.50 22; 1.00 1.80]; [0.99 1.40 15; 1.81]; [1.23 1.67 21; 1.00 2.11];
! ! ! (B) Oxazepam mg/d) (>60 In lists: 1, 4, 5 (A); 5, 6 Dipotassium clorazepate In lists: 1, 4 (A); 2, 5, 6 (B) mg/d) (>1 Lorazepam In lists: 1, 4, 5 (A); 5, 6 (B)
! ! ! N05BA04 N05BA05 N05BA06 146 QUALITY ISSUES IN CARING FOR OLDER PEOPLE atives: ! !
acting acting - - 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 E, P E, P ≤ ≤ ). ). 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 e e ≤ ≤ (SSRI pharmacological treatment; treatment; pharmacological treatment; pharmacological - - Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sed / hypnotics as used If for proposed alternatives see N05C. with coded drugs ! lf lf ay M . 40 mg/d, 40 mg/d, - ! dose; start with 5 mg/d orally
20 mg/d in 2 divided doses, doses, 2 divided 20 mg/d in P -
! PIM list Use the lowest possible dose, up to ha up to dose, possible lowest Use the P up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest E, Reduce to 7 days every than no faster titrate and 10 tolerated, well If on weight. depending further titrate necessary if starting on maximum a 20 21 to day of m adults older on weight; depending dose adult usual the of half receive of the usual dose, taper in and out, out, and in taper dose, usual the of treatment. of duration possible shortest - ! ! Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression - - ! ! Appendix complete 1: EU(7) 19; 1.63 [1.30 1.63 19; 2.00 1.96]; [1.09 1.41 17; 1.00 1.73];
! ! Bromazepam In lists: 1, 4 (A); 5, 6 (B) Clobazam In lists: 1, 3, 4 (A), 5, 6 (B) ! ! N05BA08 N05BA09 ARTICLES 147
! ! !
acting acting acting - - - 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 E, P E, P E, P ≤ ≤ ≤ ). ). ). 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 e e e nts with anxiolytic ≤ ≤ ≤ pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - metazepam ( Non short of low doses suchbenzodiazepines as lor brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressa profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs -
lf lf 15 ! - M
E erated; extended erated; ! ! M !
PIM list P Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest or adults older for dose; Reduce debilitated patients, start with 10 doses). divided (in orally mg/d ha up to dose, possible lowest Use the out, and in taper dose, usual the of treatment. of duration possible shortest P 0.25mg/12h. dose Starting (including tablets release Immediate orally disintegrating tablets): start with times three two to mg0.25 administered a day, and titrate as tol mg 0.5 once with start tablets: release needed as and increase gradually daily, tolerated. 20 mg or with once start dose; Reduce twice daily for patients 70 years or response. to according dose adjust older; M, E - psychiatric ! ! ! Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression - - - ! ! ! Appendix complete 1: EU(7) 16; 1.31 [0.99 1.31 16; 1.00 1.63]; [1.40 1.91 22; 2.00 2.42]; [1.33 2.00 9; 2.00 2.67]; !
! ! Prazepam In lists: 1, 4 (A); 2, 5 (B) Alprazolam In lists: 1, 3, 4, 5 (A); 6 (B) 5, Halazepam In lists: 6 (B) ! ! ! N05BA11 N05BA12 N05BA13 148 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! !
acting acting acting - - - 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 E, P E, P E, P ≤ ≤ ≤ ). ). ). 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 e e e ≤ ≤ ≤ epines such as epines pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non short of low doses benzodiaz lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs ! ! ! ! M M M PIM list Reduce dose. Reduce dose. Reduce dose. - fracture; be paradoxical, e.g. e.g. be paradoxical,
! ! ! prolonged reaction times; psychiatric psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged e.g. paradoxical, be also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip fracture; psychiatric times; reaction prolonged also (can reactions agitation, irritability, hallucinations, impairment; cognitive psychosis); depression Risk of falling with hip - - - ! ! ! Appendix complete 1: EU(7) 12; 1.75 [1.20 1.75 12; 1.50 2.30]; [1.20 1.75 12; 1.50 2.30]; [1.17 1.56 16; 1.00 1.95]; ! !
) Loflazepate ) -
! Nordazepam In lists: 1 (A); 2, 5, 6 (B) (Ethyl In lists: 1 (A); 5, 6 (B) Clotiazepam (>5 mg/d) In lists: 1 (A); 5, 6 (B)
! ! ! N05BA16 N05BA18 N05BA21 ARTICLES 149 5 5 ! ≤ ≤ ! !
acting E, P E, P - 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 E, P ≤ ≤ ≤ acting acting ). - - 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 e ; passiflora,; low passiflora,; low ≤ ≤ ≤ 5 mg/d), zopiclon zopiclon 5 mg/d), zopiclon 5 mg/d), d d ≤ ≤ pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ≤ ≤ ! Non short of low doses suchbenzodiazepines as lormetazepam ( brotizolam ( antidepressants with anxiolytic profile (SSRI sedatives: / hypnotics as used If for proposed alternatives see N05C. with coded drugs Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); doses of short of doses short of doses
go slow; go slow; – ! ! M M failure (10 to 50 ml/min)
! ! M
PIM list ! P P Reduce dose; start low Reduce start dose; up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest in insomnia management of the For geriatric patients, use initial oral dose of 250 mg/d. up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest Start with 15 mg/d. and every 12 to 18 hours in cases of of cases in 18 hours 12 to every and failure. renal severe increase dosage interval in cases of renal renal of cases in dosage interval increase in 6 hours every administer failure; (GFR>50 failure mild renal of cases of cases in hours 12 to 9 every ml/min), renal moderate - ! ! ! paradoxical, e.g. agitation, ! Risk of drowsiness, confusion drowsiness, of Risk and Risk dizziness of risk Higher changes. electrocardiographic in cases of renal failure prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction be can (which irritability, hallucinations, psychosis), depression and impairment cognitive - - - ! ! ! Appendix complete 1: EU(7) 1.33 [1.09 1.33 18; 18; 1.00 1.57]; [1.21 1.53 17; 1.00 1.85]; [1.04 1.25 20; 1.00 1.46]; ! !
! ! Meprobamate In lists: 1, 5 (A) and Hypnotics sedatives Chloralhydrate In lists: 4, 5 (A); 5 (B) Flurazepam In lists: 4, 5 (A); 5, 6 (B) ! ! ! ! N05BC01 N05C N05CC01 N05CD01 150 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 5 5 5 ≤ ≤ ≤ ! ! ! mg/d),
E, P E, P E, P 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 0.5 ≤ ≤ ≤ acting acting acting - - - 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 ; passiflora,; low passiflora,; low passiflora,; low ≤ ≤ ≤ 5 mg/d), zopiclon zopiclon 5 mg/d), zopiclon 5 mg/d), zopiclon 5 mg/d), d d d ≤ ≤ ≤ pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ≤ ≤ ≤ Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); doses of short of doses short of doses short of doses – ! ! M out, E, M risk adults, - ! ntervals. M ! For induction of of induction For
second i second - E, M 5 mg/d at bedtime. -
PIM list Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P Use 2.5 up half dose, to Use possible lowest the and in taper dose, usual the of treatment. of duration possible shortest low start mg/d; 0.5 e.g. P Reduce dose, go slow. poor older, in anaesthesia titrate dose carefully; administer in to 0.3 of increments intravenous small 30 mg, at 0.5 or debilitated who are adults older For dose initial consider low weight, a have bedtime. mg 0.5 at of - ! ! ! fracture, prolonged prolonged fracture,
nt and depression depression and nt impairment and depression and impairment Risk of falls and hip fracture, prolonged prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), cognitive impairme hip and falls of Risk prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), cognitive reaction time, psychiatric reactions reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive - - - ! ! ! Appendix complete 1: EU(7) 20; 1.40 [1.12 1.40 20; 1.00 1.68]; [1.03 1.32 22; 1.00 1.60]; [0.99 1.42 12; 1.00 1.84];
! ! ! Nitrazepam In lists: 1, 3, 4 (A); 2, 6 (B) 5, Flunitrazepam In lists: 1, 4 (A); 5, 6 (B) Estazolam In lists: 1, 5 (A); 5, 6 (B) ! ! ! N05CD02 N05CD03 N05CD04 ARTICLES 151
5 5 5 5 ≤ ≤ ≤ ≤ ! ! ! ! zopiclon zopiclon E, P E, P E, P E, P 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 ≤ ≤ ≤ ≤ aleplon ( aleplon acting acting acting acting - - - - 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 ; passiflora,; low passiflora,; low passiflora,; low passiflora,; low ≤ ≤ ≤ ≤ 5 mg/d), 5 mg/d), 5 mg/d), zopiclon zopiclon 5 mg/d), zopiclon 5 mg/d), zopiclon 5 mg/d), d d d d ≤ ≤ ≤ ≤ short pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 z mg/d), 3.75 ( zaleplon mg/d), 3.75 otizolam ( ≤ ≤ ≤ ≤ ( br Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); doses of short of doses short of doses of doses short of doses 1 - ment. ! E, M ! 0.25 mg/d at mg/d at 0.25 - M go slow. go slow. – adults; start with 0.5 ! ! M
E
! PIM list P Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treat of duration possible shortest 0.125 dose: Reduce bedtime Start low up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P individual watch mg/d and 7.5 with Start response. in used dose 50% the to of dose Reduce younger healthy mg/d. (CrCl failure renal severe of cases In be should dose the <10 ml/min), by 50%. decreased - ! ! ! ! reactions reactions psychiatric reactions reactions psychiatric Risk of falls and hip fracture, prolonged prolonged fracture, hip and falls of Risk time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive - - - - ! ! ! ! Appendix complete 1: EU(7) 18; 1.67 [1.18 1.67 18; 1.00 2.15]; [1.15 1.47 17; 1.00 1.79]; [1.34 1.88 17; 2.00 2.42]; [1.93 2.45 22; 2.50 2.98]; ! !
! ! Triazolam 5 4, 3, 2, 1, lists: In (A); 5, 6 (B) Lormetazepam (>0.5 mg/d) In lists: 1, 4 (A); 5, 6 (B) Temazepam In lists: 1, 4, 5 (A); 5, 6 (B) Midazolam In lists: 3 (A); 5, 6 (B)
! ! ! ! N05CD05 N05CD06 N05CD07 N05CD08 152 QUALITY ISSUES IN CARING FOR OLDER PEOPLE 5 5 5 5 ≤ ≤ ≤ ≤ ! ! ! ! E, P E, P E, P E, P 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 ≤ ≤ ≤ ≤ acting acting acting acting mg/d), zopiclon zopiclon mg/d), - - - - 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 ; passiflora,; low passiflora,; low passiflora,; low passiflora,; low ≤ ≤ ≤ ≤ 5 5 mg/d), zopiclon zopiclon 5 mg/d), zopiclon 5 mg/d), zopiclon 5 mg/d), d d d d ≤ ≤ ≤ ≤ pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological - - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 rmetazepam ( rmetazepam ≤ ≤ ≤ ≤ ( Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lo brotizolam ( ( zolpidem ( trazodone. mg/d); doses of short of doses short of doses short of doses short of doses ! E E
go slow. go slow. go slow. go slow. go slow. – – – ! ! E ! ; ! hortest possible duration of treatment. treatment. of duration possible hortest PIM list Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of Reduce dose; start low Reduce start dose; s P low Reduce start dose; low Reduce start dose; P up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P - ! ! ! ! psychosis), psychosis), l, e.g.l, agitation, psychiatric reactions reactions psychiatric impairment and depression and impairment Risk of falls and hip fracture, prolonged prolonged fracture, hip and falls of Risk time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction paradoxica be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), cognitive - - - - ! ! ! ! Appendix complete 1: EU(7) 15; 1.73 [1.29 1.73 15; 2.00 2.18]; [1.31 1.82 11; 2.00 2.32]; [1.24 1.63 16; 1.50 2.01]; [1.82 2.27 22; 2.00 2.73]; ! ! (>3.75 (>3.75
c ! !
Brotizolam (>0.125 (>0.125 Brotizolam mg/d) In lists: 4 (A); 5, 6 (B) Quazepam In lists: 5 (A); 2, 5, 6 (B) (>0.5 Loprazolam mg/d) In lists: 1 (A); 5, 6 (B) Zopiclone In lists: 1, 4, 5, 6 (A); 5 (B) mg/d)
! ! ! ! N05CD09 N05CD10 N05CD11 N05CF01 ARTICLES 153 5 5 5 5 ≤ ≤ ≤ ≤ ! ! ! ! E, P E, P E, P E, P 0.5 mg/d), mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 mg/d), 0.5 ≤ ≤ ≤ ≤ acting acting acting acting passiflora, low - - - - 0.125 mg/d); mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 mg/d); 0.125 ; ; passiflora,; low passiflora,; low passiflora,; low ≤ ≤ ≤ ≤ 5 mg/d), zopiclon zopiclon 5 mg/d), zopiclon 5 mg/d), zopiclon 5 mg/d), zopiclon 5 mg/d), d d d d ≤ ≤ ≤ ≤ razodone. razodone. mg/d), zaleplon ( zaleplon mg/d),
pharmacological treatment; treatment; pharmacological treatment; pharmacological treatment; pharmacological treatment; pharmacological odiazepines such as odiazepines - - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 ( zaleplon mg/d), 3.75 3.75 ≤ ≤ ≤ ≤ Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( mg/d);t Non mirtazapine benz lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); Non mirtazapine short of doses suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem ( trazodone. mg/d); doses of short of doses short of doses short of doses 1000 mg at 1000 mg at -
! E, M ! ossible duration of treatment. M ! ! PIM list ! Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of shortest p P up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P Reduce dose. bedtime. Use dose 500 sedative - ! ! ! prolonged prolonged psychosis), psychosis), ! Risk of falls and hip fracture, fracture, and hip Risk falls of reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, psychosis), depression and impairment cognitive prolonged fracture, hip and falls of Risk reactions psychiatric time, reaction agitation, e.g. paradoxical, be can (which irritability, hallucinations, depression and impairment cognitive depression Risk respiratory of sedation effects, Risk antimuscarinic of mouth and dry hypotension, and reactions extrapyramidal - - - - ! ! ! ! Appendix complete 1: EU(7) 22; 2.09 [1.66 2.09 22; 2.00 2.52]; [1.56 1.94 17; 2.00 2.33]; [1.53 2.23 13; 2.00 2.94]; [0.90 1.20 10; 1.00 1.50];
!
! ! ! Zolpidem (>5 mg/d) (>5 Zolpidem In lists: 1, 4, 5, 6 (A); 5 (B) mg/d) (>5 Zaleplone In lists: 3, 4, 5, 6 (A); 5 (B) Clomethiazole In lists: 5 (B) Propiomazine In lists: 5, 6 (B) ! ! ! ! N05CF02 N05CF03 N05CM02 N05CM06 154 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! , , 5 e e E E ≤ ! zopiclon zopiclon E, P 0.5 mg/d), mg/d), 0.5 ≤ acting - 0.125 mg/d); mg/d); 0.125 , trazodone. trazodone. , trazodone. , ; passiflora,; low ≤ 5 mg/d), 5 mg/d), d d d ≤ pharmacological treatment; treatment; pharmacological treatment, pharmacological treatment, pharmacological - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ≤ ! ! ( Non mirtazapine suchbenzodiazepines as lormetazepam ( brotizolam ( ( zolpidem trazodone. mg/d); Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine doses of short of doses
P ! E ! 50 mg/d at bedtime; bedtime; 50 mg/d at 100 mg/d; maximum100 mg/d; M - - ! PIM list ! ! ! Use doses 25 of Start at half the usual daily dose, reduce dose. slowly; increase Use doses 25 of maximum dose: 100 mg/d. mg/d. 100 maximumdose: dose: 150 mg/d. 150 mg/d. dose: -
! blocking drug, risk of of risk drug, blocking - ! ! alling ! ! Muscarinic effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, of types other confusion, unrest, inner delirium); cognitive deficit; increased risk of f effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, of types other confusion, unrest, inner delirium); cognitive deficit; increased risk of falling cognitve impairment cognitve - - - ! ! ! Appendix complete 1: EU(7) 1.00 ! 14; 1.64 [1.21 1.64 14; 1.50 2.07]; [1.12 1.50 14; 1.00 1.88]; [1.14 1.50 20; 1.86]; ! ! ! !
! Aceprometazine In lists: 1 (A); 6 (B) Psychoanaleptics Antidepressants Desipramine In lists: 2, 5, 6 (B) Imipramine In lists: 1, 4, 5 (A); 2, 6 (B) 5, ! ! ! ! ! No ATC No N06 N06A N06AA01 N06AA02 ARTICLES 155 ! ! ! , , , e e e E E E xetine, , trazodone. trazodone. , trazodone. , trazodone. , d d d pharmacological treatment, treatment, pharmacological treatment, pharmacological treatment, pharmacological - - - Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluo fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine
E, M, P M, P ! E y and 20 mg at 20 mgy and at 20 mg/d, max. 250 max. 20 mg/d,
- ! ! M ! M, E, P E PIM list Start with half the usual daily dose, reduce dose. slowly; increase 10 dose Starting mg/day. Start at half the usual daily dose, reduce dose. slowly; increase exceed do not 50 mg/d and with Start 100 mg/d. Start at half the usual daily dose, increase slowly; reduce dose; start with da per 10 mg 3 times bedtime. may pain neuropathic treating for use Its benefits with appropriate, considered be risks. the overweighing - arrhythmia); central confusion, other types of of types other confusion,
! ! ! alling Peripheral anticholinergic side effects effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, of types other confusion, unrest, inner delirium); cognitive deficit; increased risk of f effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, inner unrest, effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. cardiac hypotension, anticholinergic side effects (drowsiness, of types other confusion, unrest, inner delirium); cognitive deficit; increased risk of falling delirium); cognitive deficit; increased risk of falling - - - ! ! ! Appendix complete 1: EU(7) 21; 1.48 [1.14 1.48 21; 1.00 1.82]; [1.10 1.44 16; 1.00 1.77]; [1.26 1.68 22; 1.00 2.10];
! ! ! mipramine Clomipramine In lists: 1, 3, 4, 5 (A); 6 (B) 5, 2, 1, Tri In lists: 1, 3, 4, 5 (A); 6 (B) 5, 2, Amitriptyline In lists: 1, 3, 4, 5 (A); 6 (B) 5, 2, ! ! ! N06AA04 N06AA06 N06AA09 156 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! ! ! ! , , , , e e e e E E E E , trazodone. trazodone. , trazodone. , trazodone. , , trazodone. trazodone. , fluvoxamine) d d d d pharmacological treatment, treatment, pharmacological treatment, pharmacological treatment, pharmacological treatment, pharmacological - - - - Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine !
M ! M . E, M !
M ! E E, M 3x/d. 3x/d. -
P ! 75 mg/d. 75 mg/d. - E 50 mg/d in divided doses divided 50 mg/d in - PIM list Use 30 Start at half the usual daily dose, increase slowly. mg/d. 0.5 maximum 6 mg/d. 3 mg/d, dose: Start with 50 three two to 25 mg with given Start times per day; by the end of the first two 50 mg to to given increase week, three times per day. 2 Its use for treating neuropathic pain may pain neuropathic treating for use Its benefits with appropriate, considered be risks. the overweighing Reduce dose in cases of renal failure. Reduce failure. renal cases of dose in - ! ! blocking agents with with agents blocking with agents blocking - - ! ! unrest, confusion, other types of of types other confusion, unrest, alling Peripheral anticholinergic side effects effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, inner delirium); cognitive deficit; increased risk of falling effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, of types other confusion, unrest, inner delirium); cognitive deficit; increased risk of f Muscarinic Muscarinic cardiotoxicity when overdosed cardiotoxicity when overdosed cardiotoxicity - - - - ! ! ! ! Appendix complete 1: EU(7) 21; 2.10 [2.52 2.10 21; 2.00 2.67]; [1.05 1.40 20; 1.00 1.75]; [1.05 1.29 17; 1.00 1.54]; [1.12 1.50 14; 1.00 1.88];
! (A); 2, 5, 6
! ! ! Nortriptyline In lists: 3 (A); 2, 5, 6 (B) Doxepin In lists: 1, 3, 4, 5 (A); 6 (B) 5, 2, Dosulepin In lists: 1 (B) Amoxapine In lists: 1 (A); 2, 5, 6 (B) ! ! ! ! N06AA10 N06AA12 N06AA16 N06AA17 ARTICLES 157 ! ! ! ! ! ! , , , , , , e e e e e e E E E E E E treatment, odone. odone. azodone. azodone. , trazodone. trazodone. , , traz , trazodone. trazodone. , trazodone. , , tr trazodone. , d d d d d d pharmacological pharmacological treatment, pharmacological treatment, pharmacological treatment, pharmacological treatment, pharmacological treatment, pharmacological ------Non mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, -
release release - ! ! ! M ! P, E release release - E, M . E, M E, M
75 mg/d. 75 mg/d. - slowly.
! ! release tablets), increased by increased tablets), release tablets) release ! - -
E M trolled PIM list 10 mg/d (12.5 mg/d if controlled mg/d if 10 mg/d (12.5 Start at half the usual daily dose, reduce dose. slowly; increase by 25 mg increase 25 mg/d, with Start 50 up to increments 20 mg/d; with start dose; Reduce avoid mg/d; 20 also maximumdose administration at bedtime. with patients for or adults older For renal failure, start immediate mg/d if 10 mg/d (12.5 with tablets con mg/d if 40 mg/d (50 up to tablets), controlled and adults older for dose Reduce patients with renal failure; start with 50 100 mg/d; titrate maximum 30 mg/d; dose: dose: Reduce 60 mg/d. for frequency dosing and dose Reduce renal with patients and adults older failure. - ! - ! ! ! ! cause mortality, higher cause mortality, self - - ! unrest, confusion, other types of of types other confusion, unrest, harm, falls, fractures and hyponatraemia fractures harm, falls, Peripheral anticholinergic side effects effects side anticholinergic Peripheral orthostatic mouth, dry constipation, (e.g. central arrhythmia); cardiac hypotension, anticholinergic side effects (drowsiness, inner delirium); cognitive deficit; increased risk of falling insomnia, CNS (nausea, effects side hyponatremia confusion); dizziness, all of risk Higher fractures. and falls seizures, of risk adverse effects Anticholinergic all of risk Higher Irreversible MAO inhibitor. Risk of hemorrhage cerebral crises, hypertensive hyperthermia malignant and May threshold lower seizure ------! ! ! ! ! ! Appendix complete 1: EU(7) 21; 1.43 [1.09 1.43 21; 1.00 1.77]; [1.80 2.27 22; 2.00 2.75]; [1.99 2.29 21; 2.00 2.58]; [1.69 2.05 20; 2.00 2.41]; [1.06 1.73 15; 1.00 2.41]; [1.77 2.30 20; 2.00 2.83]; ! !
! !
! ! Maprotiline In lists: 1, 4 (A); 2, 5, 6 (B) Fluoxetine In lists: 3, 4 (A); 2, 5, 6 (B) Paroxetine In lists: 2, 5, 6 (B) Fluvoxamine In lists: 2, 5, 6 (B) Tranylcypromine In lists: 4 (A) Bupropion In lists: 5 (B) ! ! ! ! ! ! N06AA21 N06AB03 N06AB05 N06AB08 N06AF04 N06AX12 158 QUALITY ISSUES IN CARING FOR OLDER PEOPLE . d d ! ! , , e e E E , trazodone. trazodone. , trazodone. , d d type dementia: type dementia: - - pharmacotherapy of of pharmacotherapy pharmacological treatment, treatment, pharmacological treatment, pharmacological treatment; pharmacological treatment; pharmacological - - - - ! ! ! ! acetylcholinesterase, memantine acetylcholinesterase, memantine acetylcholinesterase, Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non SSRI (except PIM: fluoxetine, fluvoxamine) paroxetine, mirtazapine Non consider Alzheimer E Non of pharmacotherapy consider Alzheimer E 50%
- E !
! M M rate renal renal rate 6 mg/d. 6 mg/d. - two times per day in
! 50 mg, two times per day day per 50 mg, two times - 7 days as tolerated. 7 days tolerated. as - ! release formulation start with - M PIM list ! ! ! 37.5 mg once daily and increase by 37.5 by 37.5 increase and mg daily 37.5 once cases of renal failure; for older adults, adults, older for failure; renal of cases 4 to dose reduce Start with 25 by 25 dose daily total the Reduce mode to mild of cases in failure. Reduce failure; renal cases of dose in startwith 2 mg for and adults older for dose Reduce patients with renal failure. mg every 4 mgevery and increase by 25 mg/dose; for for by 25 mg/dose; increase and extended - !
supressingeffects - altering effects; - ! ! cause mortality, - ! ! ! Higher risk of all of risk Higher attempted suicide, stroke, seizures, upper gastrointestinal bleeding, falls and fracture constipation, mouth, (dry effects Side dizziness, headache, drowsiness, Higher insomnia). and sweating excessive disturbances, conduction of risk and atrial occasional tachycardia, ectopy ventricular insomnia; worsen or May cause CNS to due concern appetite to due concern unfavorable proven; No efficacy risk/benefit profile - - - - ! ! ! ! Appendix complete 1: EU(7) 21; 2.43 [2.06 2.43 21; 2.00 2.80]; [1.46 1.87 15; 2.00 2.28]; [1.14 1.63 19; 1.00 2.12]; [1.40 2.05 19; 2.00 2.70]; ! ! !
! !
!
dementia drugs dementia - Venlafaxine In lists: does not PIM appear as Reboxetine In lists: does not PIM appear as Psychostimulants, for used agents ADHD and nootropics Methylphenidat In lists: 2 (A); 5 (B) Piracetam In lists: 1, 4 (A) Anti ! ! ! ! ! ! N06AX16 N06AX18 N06B N06BA04 N06BX03 N06D ARTICLES 159 . . d d type dementia: type dementia: - - pharmacotherapy of of pharmacotherapy pharmacological treatment; treatment; pharmacological pharmacological treatment; treatment; pharmacological - - ! ! Non ! ! ! ! ! ! ! acetylcholinesterase, memantine acetylcholinesterase, memantine acetylcholinesterase, Non of pharmacotherapy consider Alzheimer E E consider consider Alzheimer ! M ! PIM list ! ! ! ! ! ! ! ! 1 mg three times daily. - ! ! ! ! ! ! ! ! ! No efficacy proven; increased risk of of risk No increased proven; efficacy fall and hypotension orthostatic unfavourable proven; No efficacy risk/benefit profile; increased risk of fall and hypotension orthostatic may relaxants bladder Anticholinergic benign with persons in obstruction cause hyperplasia prostatic pressure blood of elevation of risk Higher activity sympathomimetic to secondary - - - - ! ! ! ! Appendix complete 1: EU(7) ! ! ! ! 20; 2.05 [1.42 2.05 20; 1.50 2.68]; [1.03 1.48 21; 1.00 1.92]; [1.24 1.71 14; 1.50 2.19]; [1.56 2.05 21; 2.00 2.54];
! !
! ! !
! !
(A)
!
!
Ginkgo biloba Ginkgo In lists: 1 mesylate Ergoloid (dihydroergotoxine) In lists: 1, 4 (A); 6 (B) Other nervous system drugs Parasympathomimeti cs Bethanechol In lists: does not PIM appear as Respiratory system preparations Nasal Nasal decongestants for systemic use Norephedrine In lists: 3 (A) (=Phenylpropanolami ne)
! ! ! ! ! ! ! ! ! N06DX02 C04AE01 N07 N07A N07AB02 R R01 R01B R01BA01 160 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ! E ! ! ! ! ! ! form. Inhaled - 50 - ! dults M
E ! M ! ! M PIM list ! ! ! ! Adjust dose in cases of renal failure; 15 failure; renal Adjust cases of dose in the for day per times 30 mg three treatment of urinary incontinence in older adults. patients for dose Use usual 50% the of (GFR moderate failure with 10 renal renal severe of cases in avoid ml/min); failure (GFR <10 ml/min). to compared 25% a with reduction Start adults. younger for doses the maximum a 400 with of dose Start reduce and levels serum monitor mg/d; a older healthy for needed; if doses is clearance theophylline years), (>60 bydecreased an 30%. average of - ! ! ! ! ! ! ! Higher risk of elevation of blood pressure pressure blood of elevation of risk Higher activity sympathomimetic to secondary as adverse of effects Higher risk form inhaled the to compared CNS of Higher risk effects stimulant - - - ! ! ! Appendix complete 1: EU(7) ! ! ! ! 21; 2.00 [1.52 2.00 21; 2.00 2.48]; [1.25 1.75 20; 1.00 2.25]; [1.76 2.27 22; 2.00 2.79]; ! !
! !
! ! ! Pseudoephedrine In lists: 5 (B) Drugs obstructive for diseases airway Adrenergics for systemic use Terbutaline (oral) In lists: does not PIM appear as Other drugs systemic diseases airway for Theophylline In lists: 3 (A); 5, 6 (B) Cough and cold preparation ! ! ! ! ! ! ! R01BA02 R03 R03C R03CC03 R03D R03DA04 R05 ARTICLES 161 3 x 400
≤ 2 x 250 ≤
E , oxycodone, oxycodone, , d ! ! ! ! ! ! management pain for used If drugs alternative consider analgesics: for proposed ( ibuprofen paracetamol; than shorter period a for or mg/d ( naproxen week); one than shorter period a for or mg/d one week). of risk lower with Opioids delirium (e.g., tilidine/naloxone, morphine buprenorphine, hydromorphone). hydromorphone). buprenorphine, E, P
go slow; reduce reduce go slow; – ! ! M 50 ml/min and to 50% if GFR 50% to and if <1050 ml/min se to 75% of the usual dose if GFR if dose usual the 75% of to se - PIM list ! ! ! ! ! Start treatment cautiously of cases in (especially adults older for renal failure); start low 10 ml/min. do - Avoid use for longer than 2 than longer for use Avoid ! ! ! ! ! ! of treatment the No in evidence clear coughacute adverse of events Higher risk constipation, sweating, (hypotension, vomiting, dizziness, sedation, respiratory depression). chronic with persons weeks for of use concurrent without constipation laxatives and for persons with renal failure of treatment No the evidence in clear coughacute - - - ! ! ! Appendix complete 1: EU(7) 2.00 ! ! ! [1.43 1.90 21; 2.38]; [1.68 2.00 21; 2.00 2.32]; [1.55 2.10 20; 2.00 2.65];
!
! ! ! ! ! Cough suppressants, excl. combinations with expectorants Ethylmorphine In lists: 3 (A) Codeine (>2 weeks) In lists: 6 (B) Dextrometorphan In lists: 3 (A) Antihistamines for systemic use Antihistamines for systemic use ! ! ! ! ! ! R05D R05DA01 R05DA04 R05DA09 R06 R06A 162 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
f f f
! ! E E E - 5 mg/d) 5 mg/d) - ! ≤ , d - - - 0.5 mg/d), mg/d), 0.5 ≤ non hich is PIM). 0.125 mg/d); mg/d); 0.125
≤ 5 mg/d), zopiclon zopiclon 5 mg/d), E ≤ sedating, non sedating, non sedating, - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ≤ ormetazepam ( Non like loratadine, cetirizine, but not terfenadine (which is PIM). non insomnia: for used If treatment, pharmacological passiflora, mirtazapine trazodone. short of doses low Consider such benzodiazepines as acting l brotizolam ( ( zolpidem ( to aternatives (suggested drugs) hypnotic/sedative Non like loratadine, cetirizine, but not terfenadine (w Non like loratadine, cetirizine, but not terfenadine (which is PIM). anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines – 18 hours in in 18 hours - 12 hours in in 12 hours - ! M !
! M ! go slow. go slow. M M – 50 ml/min), and every 12 every and 50 ml/min), -
PIM list Reduce dose for older adults; start low start Reduce adults; dose older for up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest P 6 every to interval dosing the Increase failure renal mild of cases in hours 6 every (GFR >50 ml/min), (GFR failure moderate of renal cases 10 (GFR failure <10 renal severe of cases ml/min). Reduce dose. Start low go slow. go slow. - ! sedation,
! blocking drug; higher risk of of risk higher drug; blocking - ! Anticholinergic side effects, effects, side Anticholinergic changes electrocardiographic dizziness; (e.g. effects side Anticholinergic impaired mouth); dry constipation, performance; cognitive (prolonged changes electrocardiographic QT) Muscarinic sedation, drowsiness sedation, - - - ! ! ! Appendix complete 1: EU(7) 21; 1.48 [1.20 1.48 21; 1.00 1.75]; [1.37 1.77 22; 2.00 2.18]; [1.16 1.64 14; 1.00 2.13];
! Diphenhydramine In lists: 1, 4, 5 (A); 5, 6 (B) Clemastine In lists: 4 (A); 5, 6 (B) Carbinoxamine In lists: 1 (A); 5, 6 (B) ! ! ! R06AA02 R06AA04 R06AA08 ARTICLES 163
f f f f ! ! ! E E E E - 5 mg/d) 5 mg/d) - ! ≤ , d - - - - ia: non 0.5 mg/d), mg/d), 0.5 antihistamines ≤
0.125 mg/d); mg/d); 0.125
≤ 5 mg/d), zopiclon zopiclon 5 mg/d), E ≤ ed aternatives to to ed aternatives sedating, non sedating, non sedating, non sedating, non sedating, - - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ≤ Non like loratadine, cetirizine, but not terfenadine (which is PIM). insomn for used If treatment, pharmacological passiflora, mirtazapine trazodone. short of doses low Consider such benzodiazepines as acting lormetazepam ( brotizolam ( ( zolpidem ( (suggest drugs) hypnotic/sedative Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). anticholinergic antihistamines anticholinergic antihistamines anticholinergic anticholinergic antihistamines
! M ! E ! PIM list ! ! Reduce dose. P 5 mg/d. Use the lowest possible dose, up to half up half dose, to Use possible lowest the out, and in taper dose, usual the of treatment. of duration possible shortest - !
! ! blocking drug; higher risk of of risk higher drug; blocking - ! Anticholinergic side effects, dizziness; dizziness; effects, side Anticholinergic changes electrocardiographic Muscarinic (e.g. effects side Anticholinergic sedation) confusion, (e.g. effects side Anticholinergic impaired mouth); dry constipation, performance; cognitive (prolonged changes electrocardiographic QT) sedation, drowsiness sedation, - - - - ! ! ! ! Appendix complete 1: EU(7) 16; 1.38 [1.05 1.38 16; 1.00 1.70]; [1.14 1.60 15; 1.00 2.06]; [1.10 1.47 17; 1.00 1.84]; [1.13 1.56 16; 1.00 2.00];
! Doxylamine Doxylamine In lists: 1, 4, 5 (A); 5, 6 (B) Brompheniramine In lists: 1 (A); 5, 6 (B) Dexchlorpheniramine In lists: 1, 4, 5 (A); 5, 6 (B) Dimetindene In lists: 4 (A); 6 (B) ! ! ! ! R06AA09 R06AB01 R06AB02 R06AB03 164 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
f f f f f ! ! ! ! ! E E E E E - - - - - non sedating, non sedating, sedating, non sedating, non sedating, non sedating, - - - - - Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines ! M go slow. go slow. – ! PIM list ! ! ! ! low Reduce start dose; - ! blocking blocking -
! ! ! blocking drug; higher risk of of risk higher drug; blocking of risk higher drug; blocking - - ! Anticholinergic side effects (e.g. (e.g. effects side Anticholinergic impaired mouth); dry constipation, performance; cognitive (prolonged changes electrocardiographic QT) No muscarinic proven efficacy; sedation confusion, of risk higher agents; Muscarinic (e.g. effects side Anticholinergic sedation) confusion, Muscarinic sedation, drowsiness drowsiness sedation, drowsiness sedation, - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 17; 1.41 [1.05 1.41 17; 1.00 1.78]; [1.12 1.40 15; 1.00 1.68]; [0.99 1.31 16; 1.00 1.63]; [1.22 1.75 16; 1.00 2.28]; [1.02 1.31 13; 1.00 1.60]; -
(A); 5, 6
Chlorpheniramine Chlorpheniramine (=Chlorphenamine) In lists: 1, 4 (B) Pheniramine In lists: 1 (A); 6 (B) Dexchlorpheniramine Betamethason In lists: 1, 5 (A); 5, 6 (B) Tripelennamine In lists: 6 (B) Alimemazine In lists: 1 (A); 6 (B) ! ! ! ! ! R06AB04 R06AB05 R06AB52 R06AC04 R06AD01 ARTICLES 165
f f f f f
! ! ! ! E E E E E 5 mg/d) 5 mg/d) - 0.5 0.5 ! ≤ , ≤ d 0.125 mg/d); mg/d); 0.125 ≤ - - - - -
5 mg/d), zopiclon zopiclon 5 mg/d), E ≤ rotizolam ( sedating, non sedating, non sedating, non sedating, non sedating, non sedating, - - - - - 3.75 mg/d), zaleplon ( zaleplon mg/d), 3.75 ≤ Non like loratadine, cetirizine, but not terfenadine (which is PIM). non insomnia: for used If treatment, pharmacological passiflora, mirtazapine trazodone. to short of doses low Consider benzodiazepines intermediate ( lormetazepam as such mg/d),b ( zolpidem ( to aternatives (suggested drugs) hypnotic/sedative Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines
M 12.5 mg12.5 - go slow. go slow. – ! M ! PIM list ! ! ! ! Reduce dose; start low Reduce start dose; for iv injection. Reduce starting dose to 6.25 to dose starting Reduce - ! ! ! blocking blocking blocking blocking blocking blocking - - - muscarinic ! ! sedation)
higher risk of confusion, sedation confusion, of risk higher proven efficacy; muscarinic proven efficacy; Anticholinergic side effects (e.g. (e.g. effects side Anticholinergic sedation) confusion, (e.g. effects side Anticholinergic confusion, No muscarinic proven efficacy; agents; No efficacy; proven No agents; higher risk of confusion, sedation confusion, of risk higher agents; agents; higher risk of confusion, sedation confusion, of risk higher agents; - - - - - ! ! ! ! ! Appendix complete 1: EU(7) 18; 1.44 [1.14 1.44 18; 1.00 1.75]; [0.92 1.33 12; 1.00 1.75]; [0.91 1.36 11; 1.00 1.82]; [0.92 1.33 12; 1.00 1.75]; [1.21 1.53 17; 1.00 1.85];
(A); 5, 6
Promethazine In lists: 1, 5 (B) Mequitazine In lists: 1 (A); 6 (B) Oxomemazine In lists: 1 (A); 6 (B) Buclizine In lists: 1 (A); 6 (B) Cyclizine In lists: 3 (A); 6 (B) ! ! ! ! ! R06AD02 R06AD07 R06AD08 R06AE01 R06AE03 166 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
f f f f f f f ! ! ! ! ! ! E E E E E E E ------! non E sedating, non sedating, non sedating, non sedating, non sedating, non sedating, sedating, non sedating, ------Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). Non like loratadine, cetirizine, but not terfenadine (which is PIM). depending therapies Alternative on indication. anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines anticholinergic antihistamines E, ! ! ! M M ! PIM list ! ! ! ! Administer one tablet daily if CrCl <40 ml/min. renal severe Avoid reduce dose if / failure. 50% Reduce than least less at dose to adults. younger healthy for used dose M - ! ! ! blocking blocking blocking - -
! ! ! events include impaired impaired include events ! No muscarinic proven efficacy; sedation confusion, of risk higher agents; (e.g. effects side Anticholinergic sedation) confusion, (e.g. effects side Anticholinergic impaired mouth); dry constipation, performance; cognitive (prolonged changes electrocardiographic QT) QT prolonged include effects Adverse interval, tachyarrhythmia, weakness, anxiety, agitation Adverse 50 mg with or performance psychomotor fatigue somnolence, tachycardia, greater, No muscarinic proven efficacy; sedation confusion, of risk higher agents; (e.g. effects side Anticholinergic impaired mouth); dry constipation, confusion, performance, cognitive changes electrocardiographic sedation; QT) (prolonged ------! ! ! ! ! ! ! Appendix complete 1: EU(7) [1.05
1.83]; 1.00 1.83]; 16; 1.44 16; [0.99 1.28 18; 1.00 1.56]; [0.99 1.43 14; 1.00 1.87]; [1.52 1.88 17; 2.00 2.24]; [1.84 2.26 19; 2.00 2.68]; [0.91 1.36 11; 1.00 1.82]; [1.12 1.40 20; 1.00 1.68];
!
1, 4, 5 (A); 5, 1, 5 (A); 5, 6 5, 5 (A); 1,
Meclozine In lists: 1, 3 (A); 6 (B) Cyproheptadine In lists: Triprolidine In lists: 6 (B) Terfenadine In lists: does not PIM appear as Ebastine In lists: does not PIM appear as Pimethixene In lists: 1 (A); 6 (B) Hydroxyzine In lists: 1, 3, 4, 5 (A); 5 (B) (B) ! ! ! ! ! ! ! R06AE05 R06AX02 R06AX07 R06AX12 R06AX22 R06AX23 N05BB01 ARTICLES 167 - ATC i ed and and ed Delphi round: round: Delphi sity of of sity ! Converting . - ® Decisive Decisive b code website 2013; 2013; website code - The following drugs belonging belonging drugs The following Angiotensin e s comprise two groups of 2 and 3 3 and 2 of groups two comprise s . European Journal of Clinical Pharmacology. Pharmacology. Clinical of Journal European . estinal; PIM: Potentially Inappropriate acting benzodiazepines). benzodiazepines). acting - ated; these number these ated; as a PIM only in the case of certain clinical conditions or or conditions clinical certain of case the PIM a in as only ATC according to WHO to ATC according ATC h !
: Beers: (2012) list [18]. ACE: sedating antihistamines, only loratadine was evaluat was loratadine only antihistamines, sedating - B
osing abbreviations: CrCl: Creatinine Clearance; d: day; GFR: day; d: Clearance; Creatinine CrCl: abbreviations: osing PIM list - ound: 24 experts particip 24 experts ound: . xperts from seven European countries European seven from xperts In the group of non of group the In f wh.de Caution, this drug was judged to be questionable PIM. questionable be to was judged drug this Caution, - d ive substance is characterized characterized is substance ive : McLeod: et al (1997) [26]; McL r: Faculty of Health, Institute of General Medicine and Family Medicine, Univer Medicine, Family and Medicine General of Institute Health, of Faculty r: ATC according to WIDO to ATC [46]; (2013) according g , this means that no suggestion was made either by the experts or in Micromedex in or experts by the was made either no suggestion means that this , in: minute; mL: millilitre; q: every. ” vous GI: Gastroint System; ECG: Electrocardiographic; Anna.Renom@uni t considered as a PIM drug class (e.g. anticholinergics or long or anticholinergics (e.g. PIM a class as drug considered t : Laroche: et al (2007) [3]; L Appendix complete 1: EU(7) Drug reevaluated during the last brief survey. survey. brief last the during Drug reevaluated c
be questionable PIM: citalopram, sertraline, escitalopram. Straße 50, 58448 Witten, Germany. 58448 Witten, 50, Straße - adjustment / special considerations of use of considerations special / adjustment : PRISCUS: [22]; list P Dose “ [32]; ® Herrhausen - code website 2014. website code Pump Inhibitors; SIADH: Syndrome of Inappropriate Antidiuretic Hormone secretion. D Hormone secretion. Antidiuretic SIADH: Inappropriate Syndrome of Pump Inhibitors; - - Alfred Guiteras*, Gabriele Meyer, Petra A Thürmann. *Corresponding autho A *Corresponding Thürmann. Petra Meyer, Gabriele Guiteras*, - : Micromedex: PIM list: a list of potentially inappropriate medications for older people consented by e consented people older for medications inappropriate potentially of list a PIM list: - M : Experts;: The EU(7) Anna Renom Witten/Herdecke. Category A (A): precisely this active substance is named substance is active act as a PIM. this Category this Category A B i) precisely (A): (B): comorbidities or ii) this active substance is not specifically named bu a r 2nd Delphi participated; 26 experts round: Delphi (1st was reached consensus which in round Delphi experts, respectively, doing joint assessments). to were judged group medication this to evaluated. were not cetirizine as such drugs PIM; other questionable be to judged WHO to according ATC Enzyme; ADHD: CNS: Disorder; Hyperactivity Ner Deficit Central Attention Medication; PPI: Proton under stated is nothing if Note: Glomerular Filtration Rate; iv: intravenous; mcg: micrograms; mg: milligram; m E ! ! ! 168 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 169
ANNEX 2.2 A i le 170 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
Appendix 2: Questionable Potentially Inappropriate Medications (Questionable PIM): results of the Delphi survey.
✛ ✜ ✚ ✢✖ ✣ ❘✖ ✗✘ ✙✚✗ -point Likert Questionable PIM scale
a
✝✞ ☎✟✠ ☎✆✡ ☛ ☞ ✌ ☛✍ ☎✆☛ ✌✡ ✎ ☎✏ ✑☛✑ ✒☎ ✓ ☎✔✠✕ ✑ Drug ATC ✭ ✁✂✄ ☎✆ Mean [95% roundb) Median confidence interval] A Alimentary tract and metabolism A06 Laxatives A06A Laxatives A06AC01 Plantago ovate (=Ispaghula, =Psylla seed) (17) 3 2.82 [2.27 - 3.38] A10 Drug used in Diabetes A10B Blood glucose lowering drugs, excl. insulins A10BA02 Metformin (>2 x 850 mg/d) (21) 2 2.57 [2.10 - 3.04] B Blood and blood forming organs B01 Antithrombotic agents B01A Antithrombotic agents Aspirin low dose in primary prevention of B01AC06 2 2.71 [2.23 - 3.19] cardiovascular disease (21) C Cardiovascular system C07 Beta-blocking agents C07A Beta-blocking agents C07AG02 Carvedilol (21) 3 3.00 [2.50 - 3.50] C08 Calcium channel blockers Selective calcium channel blockers with mainly C08C vascular effects C08CA01 Amlodipine (21) 3 3.33 [2.85 - 3.82] C08CA02 Felodipine (18) 3 2.78 [2.22 - 3.33] G Genito urinary system and sex hormones G04 Urologicals G04C Drug used in benign prostatic hypertrophy G04CA02 Tamsulosin (19) 3 3.00 [2.55 - 3.45] J Anti-infectives for systematic use J01 Antibacterial for systemic use J01M Quinolone antibacterials J01MA02 Ciprofloxacin (21) 3 3.29 [2.83 - 3.74] ARTICLES 171
J01MA12 Levofloxacin (20) 3.5 3.20 [2.73 - 3.67] N Nervous system N02 Analgesics N02A Opioids N02AA01 Morphine sulfate (non-sustained-release) (21) 3 3.33 [2.89 - 3.77] N02B Other analgesics and antipyretics N02BB02 Metamizole (16) 1.5 2.25 [1.14 - 3.09] N03 Antiepileptics N03A Antiepileptics N03AF02 Oxcarbazepine (20) 2 2.65 [2.12 - 3.18] N03AG01 Valproic acid (20) 2.5 2.95 [2.48 - 3.42] N03AX09 Lamotrigine (19) 3 2.84 [2.35 - 3.33] N03AX12 Gabapentin (21) 3 2.95 [2.53 - 3.37] N03AX14 Levetiracetam (18) 4 3.17 [2.59 - 3.74] N03AX15 Zonisamide (11) 2 1.82 [1.16 - 2.48] N03AX16 Pregabalin (21) 2 2.81 [2.36 - 3.26] N04 Antiparkinson drugs N04B Dopaminergic agents N04BX01 Tolcapone (15) 2 2.60 [1.94 - 3.26] N04BX02 Entacapone (16) 2.5 2.81 [2.22 - 3.40] N05 Psycholeptics N05A Antipsychotics N05AH04 Quetiapine (18) 2 2.67 [2.10 - 3.23] N06 Psychoanaleptics N06A Antidepressants N06AB04 Citalopram (21) 3 2.95 [2.51 - 3.40] N06AB06 Sertraline (21) 3 2.95 [2.53 - 3.37] N06AB10 Escitalopram (21) 3 2.86 [2.42 - 3.30] N06AX11 Mirtazapine (21) 2 2.62 [2.20 - 3.04] N06D Anti-dementia drugs N06DX01 Memantine (20) 3 3.15 [2.54 - 3.76] R Respiratory system R03 Drugs for obstructive airway diseases Other drugs for obstructive airway diseases, R03B inhalants 172 QUALITY ISSUES IN CARING FOR OLDER PEOPLE
R03BB01 Ipratropium bromide (inhaled) (21) 3 2.81 [2.34 - 3.28] R03BB04 Tiotropium bromide (inhaled) (20) 2 2.70 [2.17 - 3.23] R06 Antihistamines for systemic use R06A Antihistamines for systemic use R06AX13 Loratadine (19) 3 2.74 [2.32 - 3.16] aAccording to WHO ATC-code list 2011 [30]; bDecisive Delphi round: Delphi round in which the results presented were obtained (1st Delphi round: 26 experts participated; 2nd Delphi round: 24 experts participated; these numbers comprise two groups of 2 and 3 experts, respectively, doing joint assessments). !
!
The!EU(7)*PIM!list:!a!list!of!potentially!inappropriate!medications!for!older!people!consented!by!experts!from! seven!European!countries.!European!Journal!of!Clinical!Pharmacology.!Anna!Renom*Guiteras*,!Gabriele!Meyer,! Petra!A!Thürmann.!*Corresponding!author:!Faculty!of!Health,!Institute!of!General!Medicine!and!Family! Medicine,!University!of!Witten/Herdecke.!Alfred*Herrhausen*Straße!50,!58448!Witten,!Germany.! Anna.Renom@uni*wh.de.! ARTICLES 173 174 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 175
ANNEX 2.3 A i le 176 QUALITY ISSUES IN CARING FOR OLDER PEOPLE ARTICLES 177
Appendix 3: Non Potentially Inappropriate Medications (Non-PIM): results of
the Delphi survey.
✼✽ ✻✾ ✷ ✿ ♣ ✼❀❁ ✻ ❂❀❃ ✷❄✻ ✸❅❆✺ ✷ Non-potentially inappropriate ✶ ✷✸✹✺ ✻✸ - drugs
Drug ATCa Mean [95%
✫✬ ✩✮✯ ✩✪ ✰✱✲ ✳ ✥ ✱✵✩✪ ✱ ✳ ✰ ✤ ✥✦✧★ ✩✪ Median confidence b decisive Delphi round ) interval] Alimentary tract and A metabolism A06 Laxatives A06A Laxatives A06AD15 Macrogol (2) 3.5 3.45 [3.03 - 3.87] A06AD11 Lactulose (21) 4 3.71 [3.36 - 4.07] Blood and blood forming B organs B01 Antithrombotic agents B01A Antithrombotic agents B01AC04 Clopidogrel (23) 4 3.74 [3.23 - 4.25] aAccording to WHO ATC-code list 2011 [30]; bDecisive Delphi round: Delphi round in which the results presented were obtained (1st Delphi round: 26 experts participated; 2nd Delphi round: 24 experts participated; these numbers comprise two groups of 2 and 3 experts, respectively, doing joint assessments).
!
!
The!EU(7)*PIM!list:!a!list!of!potentially!inappropriate!medications!for!older!people!consented!by!experts!from! seven!European!countries.!European!Journal!of!Clinical!Pharmacology.!Anna!Renom*Guiteras*,!Gabriele!Meyer,! Petra!A!Thürmann.!*Corresponding!author:!Faculty!of!Health,!Institute!of!General!Medicine!and!Family! Medicine,!University!of!Witten/Herdecke.!Alfred*Herrhausen*Straße!50,!58448!Witten,!Germany.! Anna.Renom@uni*wh.de.!
!