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Official websites use. Share sensitive information only on official, secure websites. Explicit criteria for potentially inappropriate medications PIMs developed for other countries are difficult to apply to a specific territory. This study aimed to update the PIM-Taiwan criteria from a qualitative review of several published PIM criteria, followed by consensus among regional experts in Taiwan. The intraclass coefficient ICC was used to examine the reliability of the modified Delphi method. Overall, two categories of PIMs were established: individual drugs and 9 drugs with combinations that should generally be avoided; and 9 chronic diseases with their corresponding PIMs that have drug—disease interactions. The version of PIM-Taiwan criteria was established and several modifications were made to keep the criteria updated and relevant. Clinicians can use them to reduce polypharmacy and PIMs among older patients. Keywords: modified Delphi method, older people, potentially inappropriate medications. National Health Insurance in Taiwan is well known worldwide and has a high coverage rate. When people live longer, they frequently have a higher chance of having chronic diseases. In current clinical practice, under the assumption of one guideline that is applied to all adults, 2 multiple medications are more likely to be prescribed for multimorbid patients, because each guideline might recommend an average of three medications. However, it has been updated 9 and applied to clinical practice and many clinical studies to find the associations between PIMs and outcomes over the past two decades. Establishing a new set of criteria is time-consuming, particularly during the literature review process, and relatively few studies have enrolled older people with multiple comorbidities in clinical trials. The PIM-Taiwan criteria have been established and have proven their applicability in several cross-sectional studies among older Taiwanese adults. PIM users had higher health resource utilization and higher costs of medications 20 , 21 than non-PIM users. As technology advanced and new results from clinical studies emerged, many new medications were developed after , and some of the statements in the PIM criteria were considered irrelevant or inaccurate. In addition, some older drugs are not available in the market. The initial literature review was conducted on PubMed from studies published from 1 January to 1 January We selected this time limit for literature inclusion because our PIM-Taiwan criteria were published in As an initial step for the development of PIM criteria in Taiwan, we identified nine sets 9 , 11 , 13 , 15 , 17 , 23 — 26 of explicit criteria published in the English language. After criteria were omitted that were developed based on other published criteria, we selected four sets of criteria to develop a preliminary list Figure 1. A research team was convened, including three geriatricians, one psychiatrist, and two clinical pharmacists, to create a list of preliminary PIMs from the four published criteria. The research team reviewed the concerns regarding these PIMs and approved a preliminary list that consisted of individual drugs and 9 drugs with combinations to be generally avoided and 9 statements for drug—disease interactions. The availability of medications in Taiwan listed in the preliminary PIM list was confirmed using the medication database from the National Health Insurance Administration. When a set of medication classes, rather than an individual medication, was considered potentially inappropriate, we identified all available medications in Taiwan belonging to this set of medication classes. A group of 24 experts from different specialties geriatricians, neurologists, psychiatrists, cardiologists, pulmonologists, gastroenterologists, urologists, and clinical pharmacists was invited to develop a consensus using the modified Delphi methods from the preliminary PIM list. Briefly, this method is a form of communication among these experts with a structured questionnaire to reach a consensus decision. All nongeriatric experts were selected because they are experienced and skilled in the principles of prescribing for older people and have reputations in their specialties in Taiwan. Hard copies of the questionnaire were mailed to all of the experts. A brief introduction of the modified Delphi method and scoring methodology was also given. Then, the experts were asked to rank each statement according to its degree of inappropriateness using a 5 point Likert scale that ranged from 5 points strongly agree to 1 point strongly disagree. In addition, the experts could add suggestions for PIMs that were not listed originally or remove PIMs in the preliminary list. The first round of the questionnaires was scored by each expert by October During round two, we also gave the mean score for each statement, and all experts could find the opinion of other experts in round one. We also welcomed the suggestions of new statements or alternative therapies from the experts. We welcomed the suggestions of new statements or alternative therapies from the experts, and the alternative therapies or suggestions for each PIM to be generally avoided were finalized by four clinical pharmacists. The resulting data generated by the hard copies of the survey were imported into Microsoft Excel Microsoft Office for analysis. Descriptive statistics were used to measure the consistency of each measurement. Therefore, this study was not human subject research. In the legislation of the Research Ethics Committee of National Taiwan University Hospital, the study did not need ethical approval as it was not human subject research. The objectives of the Delphi method were presented to all experts, their agreement and availability to participate were obtained consisted of replying positively by email to the invitation sent by the research team. The information that this study generated was used for consensual quality criteria only and can be publicly accessible and there is no reasonable expectation of privacy. A total of 29 individual drugs were not available in After two rounds of the modified Delphi method, the final PIM-Taiwan criteria included individual drugs, 9 drugs with combinations to be avoided generally Table 1 , and 9 statements for drug—disease interaction. When an entire medication class was considered to be PIMs, all individual drugs available in the class are listed in Table 1. When there was no optimal alternative medication for certain PIMs, we recommended other nonpharmacological therapies. For example, antipsychotics for behavioral problems of dementia or delirium should be avoided among older adults because the mortality rate is higher for antipsychotic users. Therefore, nonpharmacological options e. Table 2 summarizes drug—disease interactions, which included individual medications or medication classes that should be avoided in patients with corresponding chronic diseases. The entire medication class should be considered inappropriate if patients have a corresponding chronic disease. Table 3 lists individual drugs in 10 medication classes overall. The statements and drugs have been removed since the version of PIM-Taiwan were enumerated Table 4. The entire medication class of muscle relaxants was removed from PIM-Taiwan. Chlordiazepoxide is classified as a benzodiazepine, and it is available in Taiwan by combining clidinium, anticholinergics or antacid as a single pill for gastrospasm or gastritis. Hydroxyzine is classified as a first-generation antihistamine, but it can be used for sedation and anxiolysis. Individual medication list for medication classes in Table 2 for drug—condition interactions that may cause the exacerbation of chronic diseases. For drug—disease interactions, the entire criterion was removed, including blood clotting disorders or anticoagulant therapy, chronic constipation, glaucoma, sleep apnea syndrome, and urinary incontinence. Statements were removed for benzodiazepines for patients with chronic obstructive pulmonary disease and benzodiazepines for patients with cognitive impairment or dementia. Summary of interrater reliability statistics for medications considered to be potentially inappropriate. Explicit criteria with a listing of potentially inappropriate criteria have been established since These criteria have been applied to discourage the use of high-risk drugs among older people and have been used as indicators for prescription quality. The first version of the PIM-Taiwan criteria was published in Our methodology has been used as a reference to develop regional PIM lists because the literature review processes were dynamic and complex. After the PIM-Taiwan criteria were updated, many medication classes and drugs that are newly available in Taiwan have been added to the version. In contrast, some medications and drug—disease interaction statements were removed Table 4. The experts who participated in the establishment of the most frequently published PIM criteria were geriatricians, psychiatrists, and clinical pharmacists. In this study, we invited many experts from other specialties including gastroenterology, cardiology, pulmonary medicine, neurology, and urology, to reflect the multidisciplinary perspectives. With a multidisciplinary approach, the rating of some PIMs in the preliminary list can be more heterogeneous, particularly for medications commonly prescribed in certain specialties. In Table 1 , the quetiapine and insulin sliding scale was not considered to be potentially inappropriate. Quetiapine has a less negative influence on mortality than do other antipsychotics. In addition, the majority of its adverse drug events were preventable. Although we did not regard it as a PIM in the PIM criteria, physicians still need to monitor its adverse events and avoid long-term use. For the sole use of sliding scale insulin, we could not conclude from current systemic reviews that using other strategies can reduce hyperglycemia and prevent hypoglycemia. Therefore, we did not include this statement as PIM. In Table 2 , all experts agreed that these medication classes were potentially inappropriate in their corresponding chronic comorbidities. After we published our strategy to establish a new country- or region-specific PIM criteria, 29 several sets of criteria were established using a similar methodology. If we use all the newly published sets of criteria to establish our preliminary lists, we find that some of the PIMs are duplicated, because they may be derived from other criteria, such as the Beers criteria. Therefore, we only selected those established based on the results of a literature review and a subsequently modified Delphi method. As a result of this strategy, in Table 1 , two classes of medications barbiturates and muscle relaxants that were regarded as PIMs in the first version of our criteria were removed. In Table 2 , five chronic diseases blood clotting disorders or anticoagulant therapy, chronic constipation, glaucoma, sleep apnea syndrome, and urinary incontinence were removed, because these diseases were not restricted to older adults. These disease—medication interactions should be considered among the general population without regard to age. Polypharmacy has been shown to be associated with adverse outcomes, high healthcare costs, and poor quality of life. The avoidance of potentially inappropriate medication is an important strategy to prevent adverse drug events and to deprescribe for older adults. In the systemic review, deprescribing seems to be an effective strategy to reduce mortality in nonrandomized studies. However, when studies aim to investigate the effect of implicit and explicit tools on the outcome of reducing PIMs, the benefit of interventions was not clear. When using implicit criteria, pharmacists or other clinicians need more knowledge and clinical experiences to identify target medications for deprescribing. In addition, clinicians may identify different targets for deprescribing without a clear reference. In contrast, the use of explicit criteria is straightforward and simple. With the assistance of e-prescribing or computerized physician order entry systems, the positive effect of reduced PIMs has been demonstrated in several studies. The first disadvantage of this tool was that PIMs were derived from existing criteria, and new findings from recent clinical trials were not fully reviewed. Our criteria only listed drugs to be avoided and not those that should be initiated among older adults. Second, for ease of application in clinical practice, we did not use the complex classification system adopted by the version of the Beers criteria including PIMs to be used with caution, drug—drug interactions, and dose consideration with varying levels of kidney function in older adults. Third, all medications listed in these criteria were available in the medication database from the National Health Insurance Administration in Taiwan. Therefore, the criteria should be modified before applying them in other countries. In conclusion, a version of the PIM-Taiwan criteria was developed through a systemic method that could be replicated by other groups. Several important modifications were made to maintain the relevance and usefulness of the criteria. Its user-friendly characteristics will help clinicians to reduce polypharmacy and PIMs among older patients. As a library, NLM provides access to scientific literature. Ther Adv Chronic Dis. Find articles by Chirn-Bin Chang. Find articles by Hsiu-Yun Lai. Find articles by Shinn-Jang Hwang. Find articles by Shu-Yu Yang. Find articles by Ru-Shu Wu. Find articles by Lo-Yu Chang. Find articles by I-Shan Lee. Find articles by Hsing-Cheng Liu. Find articles by Ding-Cheng Chan. Received Jan 16; Accepted Aug 19; Collection date Open in a new tab. Use other diuretics or regularly monitor serum potassium. Antiarrhythmic Amiodarone C01BD01 With greater toxicities than other antiarrhythmics used in atrial fibrillation. Use other rhythm control medications for atrial fibrillation. Use other first-line antihypertensive as suggested by guidelines. When it has been used for heart failure, higher dosages were associated with higher mortality. Use medications for rhythm control, except amiodarone for atrial fibrillation. Peripheral alpha-1 blockers Prazosin C02CA01 High risk of orthostatic hypotension; not first-line treatment for hypertension. Avoid use unless absolutely indicated. Testosterone G03BA03 Estrogens including combination Estradiol G03CA03 Carcinogenic potential breast and endometrium ; lack of cardiovascular or cognitive protective effects in older women. Vaginal estrogens for treatment of vaginal dryness are safe, but those with history of breast cancer are advised to discuss the risk-benefits ratio of low-dose vaginal estrogen therapy with their health provider. Use other oral hypoglycemic agents. Use other oral hypoglycemic agents when patients have heart failure or osteoporosis. Domperidone, mosapride. Avoid long-term use. Use other drugs with less anticholinergic activity. Increased risk of skin and mucosa bleeding and hyponatremia. Use other antidepressants, except TCAs. Use other antidepressants, except paroxetine. Use other antiparkinsonian drugs. Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options e. Avoid as possible; low-dose and short-term use as needed. Increased risk of acute kidney injury. Second-generation antihistamine. NSAID, nonsteroidal anti-inflammatory drug. CI, confidence interval; PIM, potentially inappropriate medication. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel. With greater toxicities than other antiarrhythmics used in atrial fibrillation. High risk of adverse central nervous system effects; may cause orthostatic hypotension and bradycardia. Should not be used for atrial fibrillation because it may be associated with higher mortality. High risk of orthostatic hypotension; not first-line treatment for hypertension. Potentially increased risk of cardiac problems; contraindicated in men with malignancy of prostate. Carcinogenic potential breast and endometrium ; lack of cardiovascular or cognitive protective effects in older women. Can lead to osteoporosis and fractures in women; exacerbation of heart failure. Central nervous system adverse effects with potential to induce or worsen delirium. High anticholinergic effects that may lead to risk of confusion, urinary retention, constipation, dry mouth, etc. High anticholinergic effects that may lead to sedation, urinary retention, and orthostatic hypotension. High anticholinergic effects that may lead to confusion, urinary retention, constipation, dry mouth, etc. Increased risk of cognitive impairment, confusion, falls, fractures, and motor vehicle accidents. Increased risk of gastrointestinal bleeding or peptic ulcer disease; concurrent use of proton-pump inhibitor or misoprostol reduces but does not fully prevent the risk.