2018 AGS Beers Criteria - For Review Period 8.13.18 PDF

CONFIDENTIAL DRAFT - American Geriatrics Society 2018 Updated Beers Criteria® for Potentially
Inappropriate Medication Use in Older Adults

1 American Geriatrics Society 2018 Updated Beers Criteria® for Potentially
2 Inappropriate Medication Use in Older Adults
3
4 By the American Geriatrics Society 2018 Beers Criteria® Update Expert Panel
5
6 INTRODUCTION
7 The American Geriatrics Society (AGS) Beers Criteria® for Potentially Inappropriate
8 Medication (PIM) Use in Older Adults is widely used by clinicians, educators,
9 researchers, and healthcare administers and regulators. Since 2011, the AGS has been the
10 steward of the criteria and has produced updates on a 3-year cycle that began in 2012.1,2
11 The AGS Beers Criteria® are an explicit list of PIMs that are typically best avoided by
12 older adults in most circumstances or under specific situations, such as in certain diseases
13 or conditions.
14
15 For the 2018 update, an interdisciplinary expert panel reviewed the evidence published
16 since the last update (2015) to determine if new criteria should be added or if existing
17 criteria should be removed or undergo changes to their recommendation, rationale, level
18 of evidence, or strength of recommendation. Each of the 5 types of criteria in the 2015
19 update (ie, medications that are potentially inappropriate in most older adults, those that
20 should typically be avoided in older adults with certain conditions, drugs to use with
21 caution, drug-drug interactions, and drug dose adjustment based on kidney function) were
22 retained in this 2018 update.
23
24 OBJECTIVES
25 The specific aim was to update the 2015 AGS Beers Criteria® using a comprehensive,
26 systematic review and grading of the evidence on drug-related problems and adverse
27 events in older adults. The strategies to achieve this aim were to:
28
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AGS REVIEW DRAFT – DO NOT CITE OR QUOTE


29  Incorporate new evidence on PIMs included in the 2015 criteria and evidence
30 regarding new criteria or modifications of existing criteria being considered for the
31 2018 update.
32  Grade the strength and quality of each PIM statement based on the level of evidence
33 and strength of recommendation.
34  Convene an interdisciplinary panel of 13 experts in geriatric care and
35 pharmacotherapy who would apply a modified Delphi method, informed by the
36 systematic review and grading, to reach consensus on the 2018 update.
37  Incorporate needed exceptions in the criteria that the panel deemed clinically
38 appropriate. These exceptions would be designed to make the criteria more
39 individualized to clinical practice and be more relevant across settings of care.
40
41 INTENT OF CRITERIA
42 The primary target audience for the AGS Beers Criteria® is practicing clinicians. The
43 criteria are intended for use in populations 65 years old and older in all ambulatory,
44 acute, and institutionalized settings of care, except for the hospice and palliative care
45 settings. Consumers, researchers, pharmacy benefits managers, regulators, and
46 policymakers also widely use the AGS Beers Criteria®. The intentions of the criteria are
47 to improve medication selection; educate clinicians and patients; reduce adverse drug
48 events; and serve as a tool for evaluating quality of care, cost, and patterns of drug use of
49 older adults.
50
51 As for previously published AGS Beers Criteria®, the goal of the 2018 update continues
52 to be improving the care of older adults by reducing their exposure to PIMs that have an
53 unfavorable balance of benefits and harms compared with alternative treatment options.
54 This is accomplished by using the criteria as both an educational tool and a quality
55 measure—two uses that are not always in agreement—and the panel considered and
56 vigorously deliberated both. These criteria are not meant to be applied in a punitive
57 manner. Prescribing decisions are not always clear-cut, and clinicians must consider
58 multiple factors, including discontinuation of medications no longer indicated. Quality
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59 measures must be clearly defined, easily applied, and measured with limited information
60 and, thus, although useful, cannot perfectly distinguish appropriate from inappropriate
61 care. The panel’s review of evidence at times identified subgroups of individuals who
62 should be exempt from a given criterion or to whom a specific criterion should apply.
63 Such a criterion may not be easily applied as a quality measure, particularly when such
64 subgroups cannot be easily identified through structured and readily accessible electronic
65 health data. In these cases, the panel thought that a criterion should not be expanded to
66 include all adults 65 years old and older when only certain subgroups have an adverse
67 balance of benefits versus harms for the medication, or conversely when a sizable
68 subgroup of older adults may be appropriate candidates for a medication that is otherwise
69 problematic.
70
71 Despite past and current efforts to translate the criteria into practice, some controversy
72 and myths about their use in practice and policy continue to prevail. The panel addressed
73 these concerns and myths by writing a companion paper to the 2015 update of the
74 criteria, which remains the best way to advise patients, providers, and health systems on
75 how to use (and not use) the 2018 AGS Beers Criteria®.3
76
77 METHODS
78 Methods used for the 2018 update of the AGS Beers Criteria® were similar to those used
79 in the 2015 update, with additional emphasis on extending the rigor of the evidence
80 review and synthesis process.2 These methods were based on the Grading of
81 Recommendations Assessment, Development, and Evaluation (GRADE) guidelines for
82 clinical practice guideline development and are consistent with recommendations from
83 the National Academy of Medicine.4,5
84
85 Panel Composition
86 The AGS Beers Criteria® expert update panel comprised 13 clinicians that included
87 physicians, pharmacists, and nurses, each of whom had participated in the 2015 update.
88 Panelists had experience in different practice settings, including ambulatory care, home
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89 care, acute hospital care, skilled-nursing facility, and long-term care. In addition, the
90 panel included ex-officio representatives from the Center for Medicare and Medicaid
91 Services, the National Committee for Quality Assurance, and the Pharmacy Quality
92 Alliance. Potential conflicts of interest were disclosed at the beginning of the process and
93 before each full panel call and are listed in the disclosures section of this paper. Panelists
94 were recused from discussion in areas in which they had a potential conflict of interest.
95
96 Literature Review
97 Literature searches were conducted in PubMed and the Cochrane Library from January 1,
98 2015, to September 30, 2017. Search terms for each criterion included individual drugs,
99 drug classes, specific conditions, and combinations thereof, each with a focus on
100 “adverse drug events” and “adverse drug reactions.” Searches targeted controlled clinical
101 trials, observational studies, and systematic reviews and meta-analyses, with filters for
102 human participants, 65 years old and older, and English language. Clinical reviews and
103 guidelines were also included to provide context. Case reports, case series, letters to the
104 editor, and editorials were excluded.
105
106 Searches identified 17,627 references; 5,403 abstracts were sent to panelists for review,
107 of which 1,422 references were selected for full-text review. Among these, 377
108 manuscripts were abstracted into evidence tables, including 67 systematic reviews and/or
109 meta-analyses, 29 controlled clinical trials, and 281 observational studies.
110
111 Development Process
112 Between February 2016 and May 2018, the full panel convened for a series of conference
113 calls and one full-day, in-person meeting. In addition, the panel divided into 4
114 workgroups, each assigned a subset of the criteria. Each workgroup led the review and
115 synthesis of evidence for its subset of the criteria, convening via conference calls and
116 electronically via email.
117
118 The development process began by soliciting ideas from the panelists about criteria that
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119 should be explored for addition, modification, or removal. Suggestions from others were
120 also welcomed. To guide the evidence selection, review, and synthesis process, each
121 workgroup then undertook an exercise to identify a priori which clinical outcomes,
122 indications, and comparison groups were most relevant when considering evidence for
123 each criterion, ie, the “desired evidence” for reviewing each criterion. These discussions
124 were not considered binding but provided guidance for keeping the evidence review and
125 synthesis focused on what was most clinically relevant.
126
127 Each workgroup reviewed abstracts from the literature searches for the criteria in their
128 purview and collectively selected a subset for full-text review. This selection process
129 considered the methodologic quality of each study, its relevance to older adults, and its
130 concordance with the desired evidence noted above. After reviewing the full text of each
131 selected article, the workgroup then decided by consensus which manuscripts represented
132 the best available evidence, based on a balance of these same 3 key criteria
133 (methodologic quality, relevance to older adults, and concordance with desired evidence).
134 Special emphasis was placed on selecting systematic reviews and meta-analyses when
135 available, because resource constraints precluded the panel from conducting these types
136 of comprehensive analyses. In general, a study was considered relevant to older adults if
137 the mean or median age of participants was over 65 years old, and especially relevant if
138 most or all participants were older than this age threshold.
139
140 Manuscripts comprising the best available evidence were abstracted by AGS staff into
141 evidence tables. These tables summarized the design, population, and findings of each
142 study, and identified markers of methodologic quality highlighted by the GRADE criteria
143 for clinical trials and observational studies, and by the AMSTAR criteria for systematic
144 reviews and meta-analyses.6–8 Each workgroup then synthesized evidence for each
145 criterion from the 2015–2017 literature reviews based on GRADE recommendations and
146 the American College of Physicians’ evidence grading framework.6,9
147
148 Using evidence from the 2015–2017 literature review, evidence findings from previous
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149 updates in 2012 and 2015, and clinical judgment, each workgroup presented to the full
150 panel their findings and suggestions for changes (or no change) to the criteria, with
151 ensuing discussion. For most criteria a consensus emerged, either to leave an existing
152 criterion from the 2015 update unchanged, to modify it, to remove it entirely, or to add a
153 new criterion. Potential modifications included the drug(s) included in the criterion, the
154 recommendation, the rationale, the quality of evidence, and the strength of
155 recommendation. As noted in the GRADE criteria, strength of recommendation ratings
156 incorporate a variety of considerations, including expert opinion and clinical judgment
157 and context, and thus do not always align with quality of evidence ratings.
158
159 After discussion of proposed changes, an anonymous Delphi process was used to
160 ascertain panel consensus, using a 5-point Likert scale with anchors of “strongly
161 disagree” and “strongly agree.” As a general rule, criteria receiving “agree” or “strongly
162 agree” ratings from more than 90% of panelists were included. The remainder were
163 brought back for group discussion, with final decisions resolved through consensus.
164
165 In addition to changes made on the basis of evidence, the panel decided on several
166 modifications to improve clarity and usability of the criteria. These included removing a
167 number of medications that are used only rarely. These removals do not condone use of
168 these medications but rather are intended to “declutter” the criteria and not distract from
169 more commonly used medications. In selected cases, the panel changed the wording of
170 certain criteria, recommendations, and rationale statements to improve clarity and avoid
171 potential misinterpretations.
172
173 The final set of criteria was reviewed by the AGS Executive Committee and Clinical
174 Practice and Models of Care Committee and subsequently released for public comment.
175 [Add details after public comment period]
176
177 RESULTS
178 Noteworthy Changes to PIMS for Older Adults
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179 Tables 2 through 6 show the 2018 criteria. Compared with the 2015 criteria, several drugs
180 were removed from Table 2 (medications that are potentially inappropriate in most older
181 adults), Table 3 (medications that are potentially inappropriate in older adults with certain
182 conditions), and Table 4 (medications that should be used with caution). These removals
183 are summarized in Table 8 and included removal of drugs no longer available in the
184 United States (eg, ticlopidine, oral pentazocine) or that likely have low utilization (eg, the
185 antihypertensive agents guanabenz, guanfacine, methyldopa and reserpine >0.1 mg/day,
186 and the anxiolytic meprobamate). In other cases, the recommendation was removed
187 entirely because the panel decided the drug-related problem was not sufficiently unique
188 to older adults, eg, using stimulating medications in patients with insomnia, or avoiding
189 medications that can lower the seizure threshold in patients with a seizure disorder. These
190 removals do not imply that these medications are now considered safe for older adults;
191 rather, they were made to help keep the criteria streamlined and focused on medications
192 that are commonly used by and particularly problematic for older adults.
193
194 The H2-receptor antagonists were removed from the “avoid” list in patients with
195 dementia or cognitive impairment. This is because evidence for adverse cognitive effects
196 in these conditions is weak, and because the panel expressed concern that the intersection
197 of this criterion with another criterion that discourages chronic use of proton-pump
198 inhibitors in the absence of strong indications would overly restrict therapeutic options
199 for older adults with dementia who have gastroesophageal reflux or similar issues.
200 However, H2-receptor antagonists remain on the criteria as “avoid” in patients with
201 delirium. In addition, wording of this criterion was modified to affirm that
202 nonbenzodiazepine, benzodiazepine receptor agonists (ie, the “Z drugs” zolpidem,
203 eszopiclone, and zaleplon) should be avoided in older adults with delirium.
204
205 Two drugs with strong anticholinergic properties, pyrilamine and methscopolamine, were
206 added to the list of anticholinergic drugs to avoid. Changes to criteria on cardiovascular
207 drugs include minor updates to the rationale and a minor change to clarify the
208 recommendation for avoiding digoxin as first-line therapy for atrial fibrillation and heart
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209 failure (Table 2). The rationale to avoid sliding scale insulin has been revised to clarify its
210 meaning and intent (Table 2). Glimepiride has been added to the list of sulfonylureas
211 with a greater risk of severe prolonged hypoglycemia (Table 2). The duration of use of
212 metoclopramide has been added to be consistent with FDA labeling (Table 2).
213
214 The serotonin-norepinephrine reuptake inhibitors (SNRIs) have been added to the list of
215 drugs to avoid in patients with a history of falls or fractures (Table 3). Following a
216 principle that applies to all criteria, the panel recognizes there may be situations when
217 SNRIs, other antidepressants, and other medications listed in this criterion may be
218 appropriate for people with falls or fracture, based on potential benefits and the
219 availability of safer alternatives. After reviewing and discussing the evidence on
220 antipsychotics to treat psychosis in patients with Parkinson disease, the panel decided to
221 remove aripiprazole as acceptable and add pimavanserin. Thus, the 2018 criteria
222 recognize quetiapine, clozapine, and pimavanserin as exceptions to the general
223 recommendation to avoid all antipsychotics in older adults with Parkinson disease (Table
224 3). However, none of these 3 excepted drugs is close to ideal in either efficacy or safety,
225 each having its own limitations and concerns.
226
227 The criteria on drugs to avoid in older adults with heart failure were reorganized to add
228 clinical nuance based on evidence, other guideline recommendations, and clinical
229 considerations. The updated recommendations are that nondihydropyridine calcium
230 channel blockers should be avoided in older adults who have heart failure with reduced
231 ejection fraction; that NSAIDs, COX-2 inhibitors, thiazolidinediones (“glitazones”), and
232 dronedarone should be used with caution in older adults with heart failure who are
233 asymptomatic (ie, excellent control of heart failure signs and symptoms, with or without
234 use of medications) and avoided in older adults who are symptomatic; and that cilostazol
235 should continue to be avoided in older adults with heart failure of any type.
236
237 Drugs to Be Used with Caution
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238 Table 4 contains drugs to be used with caution in older adults. The purpose of this table is
239 to identify drugs for which there is some cause for concern, but for which the evidence
240 and/or clinical context is as of yet insufficient to merit inclusion in the main tables.
241 Compared with the previous update, the following changes and additions were made:
242  The age threshold beyond which extra caution is advised for using aspirin for primary
243 prevention of cardiovascular disease was lowered to ≥70 years from ≥80 years. This
244 criterion was also expanded to cover use of aspirin as primary prevention of
245 colorectal cancer. Note that this criterion does not apply to use of aspirin for
246 secondary prevention of either disease.
247  In addition to the existing caution about dabigatran, the updated criteria highlight
248 caution about use of rivaroxaban for treatment of venous thromboembolism or atrial
249 fibrillation in adults ≥75 years old.
250  The use of dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with heart failure was
251 added because of concerns of potentially increased risk of hospitalization for heart
252 failure.
253  Tramadol was added to the list of drugs associated with hyponatremia or SIADH. The
254 chemotherapeutic agents carboplatin, cyclophosphamide, cisplatin, and vincristine
255 were removed from this list because the panel thought the prescribing of these highly
256 specialized drugs fell outside the scope of the criteria.
257  Vasodilators were removed, because syncope is not unique to older adults.
258  The combination dextromethorphan and quinidine was added to the “use with
259 caution” table on the basis of limited efficacy in treating patients with neurocognitive
260 disorders while potentially increasing the risk of falls and drug-drug interactions.
261  The combination trimethoprim-sulfamethoxazole (TMP-SMZ) should be used with
262 caution by patients with reduced kidney function and taking an angiotensin-
263 converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) because
264 of an increased risk of hyperkalemia.
265
266 Drug-Drug Interactions
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267 Table 5 contains potentially clinically important drug-drug interactions to be avoided in
268 older adults. New recommendations include avoiding use of opioids concurrently with
269 benzodiazepines and avoiding use of opioids concurrently with gabapentinoids (except
270 when transitioning from the former to the latter). Other additions to the table are
271 interactions involving TMP-SMZ, macrolide antibiotics, and ciprofloxacin. TMP-SMZ in
272 combination with phenytoin or warfarin increases the risk of phenytoin toxicity and
273 bleeding, respectively. Macrolides, excluding azithromycin, or ciprofloxacin in
274 combination with warfarin increase bleeding risk. Ciprofloxacin in combination with
275 theophylline increases risk of theophylline toxicity. The concurrent use of a combination
276 of three or more CNS agents (antidepressants, antipsychotics, benzodiazepines,
277 nonbenzodiazepine benzodiazepine receptor agonists, antiepileptics, and opioids) and
278 increased falls risk has been collapsed into one recommendation instead of separate
279 recommendations for each drug class. The recommendation on avoiding concurrent use
280 of medications that increase serum potassium has been expanded to encompass a broader
281 range of these medications.
282
283 PIMS Based on Kidney Function
284 Table 6 contains a list of medications that should be avoided or have their dosage reduced
285 based on kidney function. Two antibiotics have been added, ciprofloxacin and TMP-
286 SMZ, over concerns of increased CNS effects and tendon rupture, and worsening renal
287 function and hyperkalemia, respectively. Dofetilide was also added because of concerns
288 of QTC prolongation and torsade de pointes. The lower limit creatinine clearance at
289 which to avoid edoxaban has been reduced to <15 mL/min.
290
291 DISCUSSION
292 The 2018 AGS Beers Criteria® update contributes to the critically important evidence
293 base and discussion of medications to avoid in older adults and the need to improve
294 medication use in older adults. The 2018 criteria include 30 individual criteria of
295 medications or medication classes to be avoided in older adults (Table 2) and 16 criteria
296 specific to more than 40 medications or medication classes that should be used with
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297 caution or avoided in certain diseases or conditions (Tables 3 and 4). As in past updates,
298 there were several changes to the 2018 criteria, including criteria that were modified or
299 dropped, a few new criteria, and some changes in the level of evidence grading and
300 clarifications in language and rationale.
301
302 The 2018 AGS Beers Criteria® for PIMs is the third such update by the AGS and the
303 fifth update of the criteria since their original release.1,2,10–12 The criteria were first
304 published almost 30 years ago in 1991, making them the longest running criteria for
305 PIMs in older adults.
306
307 Compared with the 2015 update, the 2018 update has a similar number of changes but
308 fewer than the 2012 update. This is likely because, with the support of the AGS and the
309 expert panel, the criteria have been regularly updated about every 3 years since 2012. In
310 2018, 18 medications or medication classes to be avoided outright or in a disease
311 condition were dropped from the criteria (see Table 8). A few were also moved to a new
312 table category or modified (see Table 10). For medications to be removed from the
313 criteria, the panel had to have new evidence or a strong rationale, for reasons such as the
314 medications are rarely used anymore (eg, ergoloid mesylates), or the literature showed a
315 change in evidence that cast new doubt on their “avoid” status. Finally, some drugs or
316 drug-disease combinations were omitted because they are not disproportionately relevant
317 to the older adult population; this included the criteria on drugs to avoid in adults with
318 chronic seizures or epilepsy and in adults with insomnia. In general, the vast majority of
319 existing criteria dropped in this 2018 update were removed because the medications are
320 rarely used or are not of special relevance to older (versus younger) populations, rather
321 than a change in evidence that suggested the drugs in question are in fact safe.
322
323 Four new medications or medication classes were added to the list of drugs to be used
324 with caution (Table 4; additions are also summarized in Table 9). The DPP-4 inhibitors
325 were added because of their potential to increase the risk of hospitalization for heart
326 failure. Dextromethorphan/quinidine was added because of its limited efficacy, concerns
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327 for clinically significant drug interactions, and potentially increased risk for falls in older
328 adults. Trimethoprim-sulfamethoxazole was placed in the caution table because of
329 increased risk of hyperkalemia when used concurrently with an ACEI or ARB in the
330 presence of decreased creatinine clearance.13,14 Rivaroxaban was also added to be used
331 with caution in persons ≥75 years old. Other important changes in the caution table
332 included lowering the age threshold in the aspirin for primary prevention
333 recommendation from ≤80 years old to ≤70 years old on the basis of emerging evidence
334 of a major increase in the risk of bleeding with advancing age.15 In a few instances, the
335 level of evidence was revised based on new literature and the improved modified grading
336 methodology. For instance, H2-receptor antagonists were removed from the list of drugs
337 to avoid in dementia, and the evidence level for H2-receptor antagonists was decreased to
338 low (from moderate in 2015) for drugs to avoid in delirium.16 Again in 2018, the panel
339 clarified the language in sliding scale insulin because this continues to be an area of
340 confusion for clinicians.
341
342 Importantly, several drugs were added to the drug-disease and drug-drug interactions
343 tables (Tables 3 and 5). Notably, SNRIs were added to list of antidepressant drug
344 classes to avoid in persons with a history of falls or fractures,17,18 and for this criterion
345 the level of evidence for opioids was changed to moderate with all others staying as a
346 high level of evidence. Importantly, two new drug-drug interactions involving opioids
347 were added, reflecting evidence of substantial harms that can occur when opioids are
348 used concurrently with benzodiazepines or gabapentinoids. Several drug-drug
349 interactions involving antibiotics were also added to Table 5, and the recommendation
350 to avoid concurrent use of 3 or more CNS-active medications was reformatted to clarify
351 and bring further attention to the increased risk of falls and other harms that can occur
352 when multiple CNS-active medications are combined.19
353
354 Potentially inappropriate medication use continues to be a serious problem in older adults
355 and especially in vulnerable older adults with multiple chronic conditions. Thus, these
356 criteria continue to be useful and necessary as a clinical tool; an educational tool at the
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357 bedside; and a public health tool to improve medication safety in older adults, to increase
358 awareness of polypharmacy, and to aid decision making for choosing drugs to avoid in
359 older adults. In a 2017 study using Medical Expenditure data (n=16,588) in adults 65 and
360 older, poor health status was associated with increased PIM use. In another study, the use
361 of PIMs in persons with dementia as measured by the 2015 criteria was 11% higher after
362 diagnosis than in the year of diagnosis.20,21 Benzodiazepine use remains common in older
363 adults, especially in older women, despite the fact that older adults are highly vulnerable
364 to harms associated with their use.22 The challenge of decreasing PIM use and improving
365 the overall quality of medication use in older adults remains, and The AGS Beers
366 Criteria® is one part of the solution.
367
368 The AGS Beers Criteria® are an essential evidence-based tool that should be used as a
369 guide for drugs to avoid in older adults. However, they are not meant to supplant clinical
370 judgment or an individual patient’s preferences, values, care goals, and needs. These
371 criteria were developed to be used in conjunction with a person-centered team approach
372 (physicians, nurses, pharmacists, therapists, the older adult, family, and others) to
373 prescribing and monitoring adverse effects.23 In 2015, a companion paper published to
374 that update of the AGS Beers Criteria® entitled How to Use the Beers Criteria – A Guide
375 for Patients, Clinicians, Health Systems, and Payors remains an important guide for
376 using the AGS Beers Criteria® and reminds clinicians to read the rationale and
377 recommendation statements for each medication to avoid because these statements
378 provide important guidance.3 A 2012 paper gives a case example for how nurses can use
379 the criteria to improve medication use in older adults.24
380 As in previous years, the panel recognizes the need to offer older adults and their
381 clinicians pharmacological and non-pharmacological alternatives to medications included
382 in the AGS Beers Criteria®. Alternatives to some of the most commonly implicated
383 medications listed in the 2015 update were published in a companion paper that
384 accompanied that update. Readers are encouraged to review these suggestions, although
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385 we acknowledge that further work needs to be done to keep pace with updates to the
386 criteria and the changing landscape of drug and non-drug therapies.
387 Of particular note is the potential role for non-pharmacologic approaches to manage
388 common conditions in older adults. The evidence base for specific nonpharmacologic
389 approaches with a person-centered approach to care is small but growing.25-28 One
390 example of the growing evidence for non-drug alternatives is in the area of care for
391 persons with dementia and delirium. Scales and colleagues published a 2018
392 comprehensive review of evidence-based nonpharmacologic approaches for behavioral
393 and psychological symptoms of dementia. They evaluated 197 articles that included
394 sensory practices (eg, massage, light therapy), psychosocial practices (eg, music, pet
395 therapy, reminiscence), and structured care protocols (eg, mouth care, bathing). Though
396 they had recommendations for improving the evidence base, they concluded most
397 practices were acceptable to patients, had no harmful effects, and required minimal to
398 moderate investment.29 Online resources for some of these approaches can be found at
399 www.nursinghometoolkit.com and www.hospitalelderlifeprogram.org.
400 While the AGS Beers Criteria® can be a valuable tool, they should be viewed within the
401 larger context of tools and strategies for improving pharmaceutical care for older adults.
402 Specifically, the AGS Beers Criteria® are one component of what should be a
403 comprehensive approach to medication use in older adults, and should be used in
404 conjunction with other tools and management strategies for improving medication safety
405 and effectiveness. Moreover, other explicit criteria for evaluating potentially
406 inappropriate medications in older adults, including the STOPP/START criteria, can be
407 valuable resources for improving medication therapy.30
408 The 2018 AGS Beers Criteria® have several limitations. Evidence about the benefits and
409 harms of medications in older adults is often limited, particularly in randomized clinical
410 trials, and so decisions on the composition of the criteria were often made in context of
411 best-available, rather than definitive, evidence. Moreover, evidence assessment
412 frameworks are not perfectly tuned to drug safety evaluation, particularly for
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413 observational studies from which much of the relevant evidence derives. [ADD
414 REFERENCES: Neyarapally GA, Hammad TA, Pinheiro SP, Iyasu S. Review of quality
415 assessment tools for the evaluation of pharmacoepidemiological safety studies. BMJ
416 Open 2012;2:e001362; AND Hilmer SN, Gnjidic D, Abernethy DR.
417 Pharmacoepidemiology in the postmarketing assessment of the safety and efficacy of
418 drugs in older adults. J Gerontol MS 2012;67A:181–188).”] The criteria are unable to
419 account for the complexity of all individuals and patient subpopulations, and thus should
420 be taken as guidance to support clinical decision-making and not as “the final word” of
421 whether a specific drug is appropriate or inappropriate for an individual patient. In
422 addition, the criteria are not meant to apply to end-of-life and palliative care, when risk-
423 benefit considerations of drug therapy can be different. Medications considered for
424 inclusion in the criteria were generally those available in the United States, and the
425 criteria do not include agents available in other countries that may be equally
426 problematic. Finally, the update literature search was comprehensive but may have
427 missed certain sources of evidence, such as papers written in languages other than
428 English, white papers, technical reports, and other evidence published in the “grey
429 literature.”
430 Notwithstanding these limitations, the guideline update process had a number of
431 important strengths. The expert panel included members from multiple clinical
432 disciplines, backgrounds, and types of clinical experience. The inclusion of ex-officio
433 members from the Centers for Medicare and Medicaid Services, the Pharmacy Quality
434 Alliance, and the National Committee for Quality Assurance added depth to considering
435 the opportunities and pitfalls of translating recommendations into quality measures. In
436 addition, the panel used a rigorous process for identifying, reviewing, and synthesizing
437 the available evidence to inform the guideline update process, and benefited from the
438 close support of the AGS.
439 In conclusion, the 2018 update has several important revisions, including the addition of
440 nearly 70 modifications of the 2015 AGS Beer Criteria, including new medications,
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441 clarifications of some of the criteria language and rationale, and the addition of selected
442 drug-drug interactions.
443
444 We hope that the criteria will be used thoughtfully and widely. To facilitate this process,
445 we encourage healthcare professionals, patients, payors, and health systems to access
446 resources with information on the criteria, including patient-oriented information on the
447 Health In Aging Foundation website (www.healthinaging.org/medications-older-adults/),
448 and guidance for all on the proper use of the criteria.3. Ongoing support from the AGS
449 will facilitate future evidence-based updates, with a goal of keeping the criteria useful,
450 relevant, and a valuable tool for improving the health and well-being of older adults.
451
452 ACKNOWLEDGEMENTS
453 Financial Disclosure:
454 Conflict of Interest:
455 Author Contributions:
456 Sponsor’s Role:
457
458 DRAFT References
459 1. American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American
460 Geriatrics Society updated Beers Criteria for potentially inappropriate medication
461 use in older adults. J Am Geriatr Soc. 2012;60(4):616–631.
462 2. American Geriatrics Society Beers Criteria Update Expert Panel. American
463 Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate
464 Medication Use in Older Adults. J Am Geriatr Soc. 2015;63(11):2227–2246.
465 3. Steinman MA, Beizer JL, DuBeau CE, et al. How to Use the American Geriatrics
466 Society 2015 Beers Criteria - A Guide for Patients, Clinicians, Health Systems, and
467 Payors. J Am Geriatr Soc. 2015;63(12):e1–e7.
468 4. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction-GRADE
469 evidence profiles and summary of findings tables. J Clin Epidemiol.
470 2011;64(4):383–394.
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471 5. Institute of Medicine (U.S.). Committee on Standards for Developing Trustworthy
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546
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CONFIDENTIAL DRAFT - American Geriatrics Society 2018 Updated Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults

Table 1. Designations of Quality of Evidence and Strength of Recommendations

Quality of Evidence
Quality of evidence ratings for each criterion are based on synthetic assessment of 2 complementary approaches to evaluating the quality of evidence.
ACP-based approach [ACP ref – Qaseem et al] GRADE-based approach [GRADE ref – Guyatt et al]
High-quality evidence “Evidence…obtained from 1 or more well-designed and well- Consider the following 5 factors for the studies that
executed randomized, controlled trials (RCTs) that yield consistent comprise the best-available evidence for a given
and directly applicable results. This also means that further criterion:
research is very unlikely to change our confidence in the estimate
of effect.” [ACP ref – Qaseem et al] 1. Risk of bias: Severity of threats to studies’
Moderate-quality evidence “Evidence…obtained from RCTs with important limitations…. In internal validity (e.g., randomized vs
addition, evidence from well-designed controlled trials without observational design, potential for
randomization, well-designed cohort or case-control analytic confounding, bias in measurement, etc.)
studies, and multiple time series with or without intervention are 2. Inconsistency: Do different studies provide
in this category. Moderate-quality evidence also means that further similar or different estimates of effect size
research will probably have an important effect on our confidence 3. Indirectness: How relevant are the studies to
in the estimate of effect and may change the estimate.” [ACP ref – the clinical question at hand (e.g., nature of
Qaseem et al] study of population, comparison group, type
of outcomes measured, etc.)
Low-quality evidence ”Evidence obtained from observational studies would typically be 4. Imprecision: Precision of estimates of effect
rated as low quality because of the risk for bias. Low-quality 5. Publication bias: Risk of bias due to
evidence means that further research is very likely to have an selective publication of results
important effect on our confidence in the estimate of effect and
will probably change the estimate. However, the quality of
evidence may be rated as moderate or even high, depending on
circumstances under which evidence is obtained from
observational studies.” [ACP ref – Qaseem et al]


Overall quality of evidence that supports a given criterion: high, moderate, low
Strength of Evidence
Strength of evidence ratings for each criterion are based on synthetic integration of the quality of evidence, the frequency and severity of potential adverse
events and relationship to potential benefits, and clinical judgment.
Strong Harms, adverse events, and risks clearly outweigh benefits.
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Weak Harms, adverse events, and risks may not outweigh benefits.
Adapted from:
Qaseem A, Snow V, Owens DK, et al. The development of clinical practice guidelines and guidance statements of the American College of Physicians: Summary of methods. Ann
Intern Med. 2010;153:194–199.
Guyatt G, Oxman AD, Sultan S, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. J Clin
Epidemiol. 2013;66(2):151–157.
Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation’s direction and strength. J
Clin Epidemiol. 2013;66(7):726–735.
21
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Table 2. 2018 American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults
Organ System, Quality

Therapeutic Category, of Strength of
Drug(s) Rationale Recommendation Evidence Recommendation
Anticholinergics *
First-generation Highly anticholinergic; clearance reduced with Avoid Moderate Strong
antihistamines advanced age, and tolerance develops when used
Brompheniramine as hypnotic; risk of confusion, dry mouth,
Carbinoxamine constipation, and other anticholinergic effects or
Chlorpheniramine toxicity
Clemastine
Cyproheptadine Use of diphenhydramine in situations such as
Dexbrompheniramine acute treatment of severe allergic reaction may
Dexchlorpheniramine be appropriate.
Dimenhydrinate
Diphenhydramine (oral)
Doxylamine
Hydroxyzine
Meclizine
Promethazine
Pyrilamine
Triprolidine
Antiparkinsonian agents Not recommended for prevention or treatment of Avoid Moderate Strong
Benztropine (oral) extrapyramidal symptoms with antipsychotics;
Trihexyphenidyl more effective agents available for treatment of
Parkinson disease
Antispasmodics Highly anticholinergic, uncertain effectiveness Avoid Moderate Strong
Atropine (excludes
ophthalmic)
Belladonna alkaloids
Clidinium-
chlordiazepoxide
Dicyclomine
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Hyoscyamine
Methscopolamine
Propantheline
Scopolamine
Antithrombotics
Dipyridamole, oral short- May cause orthostatic hypotension; more Avoid Moderate Strong
acting (does not apply to effective alternatives available; IV form
the extended-release acceptable for use in cardiac stress testing
combination with aspirin)
Anti-infective
Nitrofurantoin Potential for pulmonary toxicity, hepatoxicity, Avoid in Low Strong
and peripheral neuropathy, especially with long- individuals with
term use; safer alternatives available creatinine
clearance <30
mL/min or for
long-term
suppression
Cardiovascular
Peripheral alpha-1 High risk of orthostatic hypotension and Avoid use as an Moderate Strong
blockers for treatment of associated harms, especially in older adults; not antihypertensive
hypertension recommended as routine treatment for
Doxazosin hypertension; alternative agents have superior
Prazosin risk/benefit profile
Terazosin
Clonidine for first-line High risk of adverse CNS effects; may cause Avoid as first-line Low Strong
treatment of hypertension bradycardia and orthostatic hypotension; not antihypertensive
recommended as routine treatment for
hypertension
Disopyramide May induce heart failure in older adults because Avoid Low Strong
of potent negative inotropic action; strongly
anticholinergic; other antiarrhythmic drugs
preferred
Dronedarone Worse outcomes have been reported in patients Avoid in High Strong
taking dronedarone who have permanent atrial individuals with
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fibrillation or severe or recently decompensated permanent atrial

heart failure. fibrillation or
severe or recently
decompensated
heart failure
Digoxin for first-line Use in atrial fibrillation: should not be used as a Avoid this rate Atrial Atrial fibrillation:
treatment of atrial first-line agent in atrial fibrillation, because there control agent as fibrillatio strong
fibrillation or of heart are safer and more effective alternatives for rate first-line therapy n: low
failure control supported by high-quality evidence. for atrial
fibrillation
Use in heart failure: Evidence for benefits and
harms of digoxin is conflicting and of lower Avoid as first-line Heart Heart failure:
quality; most but not all of the evidence therapy for heart failure: strong
concerns use in heart failure with reduced failure low
ejection fraction (HFrEF). There is strong
evidence for other agents as first-line therapy to If used for atrial Dosage >0.125
reduce hospitalizations and mortality in adults fibrillation or heart Dosage mg/d: strong
with HFrEF. In heart failure, higher dosages are failure, avoid >0.125
not associated with additional benefit and may dosages >0.125 mg/d:
increase risk of toxicity. mg/d moderate
Decreased renal clearance of digoxin may lead

to increased risk of toxic effects; further dose
reduction may be necessary in those with Stage
4 or 5 chronic kidney disease.
Nifedipine, immediate Potential for hypotension; risk of precipitating Avoid High Strong
release myocardial ischemia
Amiodarone Effective for maintaining sinus rhythm but has Avoid as first-line High Strong
greater toxicities than other antiarrhythmics used therapy for atrial
in atrial fibrillation; may be reasonable first-line fibrillation unless
therapy in patients with concomitant heart patient has heart
failure or substantial left ventricular hypertrophy failure or
if rhythm control is preferred over rate control substantial left
ventricular
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hypertrophy
Central nervous system
Antidepressants, alone or Highly anticholinergic, sedating, and cause Avoid High Strong
in combination orthostatic hypotension; safety profile of low
Amitriptyline dose doxepin (≤6 mg/d) comparable with that of
Amoxapine placebo
Clomipramine
Desipramine
Doxepin >6 mg/d
Imipramine
Nortriptyline
Paroxetine
Protriptyline
Trimipramine
Antipsychotics, first- Increased risk of cerebrovascular accident Avoid, except for Moderate Strong
(conventional) (stroke) and greater rate of cognitive decline and schizophrenia,
and second- (atypical) mortality in persons with dementia. bipolar disorder, or
generation short-term use as
Avoid antipsychotics for behavioral problems of antiemetic during
dementia or delirium unless nonpharmacological chemotherapy
options (e.g., behavioral interventions) have
failed or are not possible and the older adult is
threatening substantial harm to self or others
Barbiturates High rate of physical dependence, tolerance to Avoid High Strong
Amobarbital sleep benefits, greater risk of overdose at low
Butabarbital dosages
Butalbital
Mephobarbital
Pentobarbital
Phenobarbital
Secobarbital
Benzodiazepines Older adults have increased sensitivity to Avoid Moderate Strong
Short- and intermediate- benzodiazepines and decreased metabolism of
acting: long-acting agents; in general, all
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Alprazolam benzodiazepines increase risk of cognitive

Estazolam impairment, delirium, falls, fractures, and motor
Lorazepam vehicle crashes in older adults
Oxazepam
Temazepam May be appropriate for seizure disorders, rapid
Triazolam eye movement sleep behavior disorder,
benzodiazepine withdrawal, ethanol withdrawal,
Long-acting: severe generalized anxiety disorder, and
Chlordiazepoxide (alone periprocedural anesthesia
or in combination with
amitriptyline or
clidinium)
Clonazepam
Clorazepate
Diazepam
Flurazepam
Quazepam
Nonbenzodiazepine, Nonbenzodiazepine benzodiazepine receptor Avoid Moderate Strong
benzodiazepine receptor agonist hypnotics (i.e., “Z drugs”) have adverse
agonists (i.e., “Z-drugs”) events similar to those of benzodiazepines in
Eszopiclone older adults (eg, delirium, falls, fractures);
Zaleplon increased emergency room
Zolpidem visits/hospitalizations; motor vehicle crashes;
minimal improvement in sleep latency and
duration
Endocrine
Androgens Potential for cardiac problems; contraindicated Avoid unless Moderate Weak
Methyltestosterone in men with prostate cancer indicated for
Testosterone confirmed
hypogonadism
with clinical
symptoms
Desiccated thyroid Concerns about cardiac effects; safer alternatives Avoid Low Strong
available
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Estrogens with or without Evidence of carcinogenic potential (breast and Avoid oral and Oral and Oral and patch:
progestins endometrium); lack of cardioprotective effect topical patch patch: strong
and cognitive protection in older women. high
Vaginal cream or Topical vaginal
Evidence indicates that vaginal estrogens for the vaginal tablets: Vaginal cream or tablets:
treatment of vaginal dryness are safe and acceptable to use cream or weak
effective; women with a history of breast cancer low-dose vaginal
who do not respond to nonhormonal therapies intravaginal tablets:
are advised to discuss the risks and benefits of estrogen for moderate
low-dose vaginal estrogen (dosages of estradiol management of
<25 mcg twice weekly) with their healthcare dyspareunia,
provider recurrent lower
urinary tract
infections, and
other vaginal
symptoms
Growth hormone Impact on body composition is small and Avoid, except as High Strong
associated with edema, arthralgia, carpal tunnel hormone
syndrome, gynecomastia, impaired fasting replacement after
glucose pituitary gland
removal
Insulin, sliding scale Higher risk of hypoglycemia without Avoid Moderate Strong
(The sole use of short- or improvement in hyperglycemia management
rapid-acting insulin in the regardless of care setting. Refers to sole use of
absence of basal or long- short- or rapid-acting insulins to manage or
acting insulin to manage avoid hyperglycemia without concurrent use of
or avoid hyperglycemia.) basal or long-acting insulin. Does not apply to
titration of basal insulin or use of additional
short- or rapid-acting insulin in conjunction with
basal or long-acting insulin.
Megestrol Minimal effect on weight; increases risk of Avoid Moderate Strong
thrombotic events and possibly death in older
adults
Sulfonylureas, long-acting Chlorpropamide: prolonged half-life in older Avoid High Strong
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Chlorpropamide adults; can cause prolonged hypoglycemia;

Glimepiride causes SIADH
Glyburide (also known as
glibenclamide) Glimepride and glyburide: higher risk of severe
prolonged hypoglycemia in older adults
Gastrointestinal
Metoclopramide Can cause extrapyramidal effects, including Avoid, unless for Moderate Strong
tardive dyskinesia; risk may be greater in frail gastroparesis with
older adults and with prolonged exposure duration of use not
to exceed 12
weeks except in
rare cases
Mineral oil, given orally Potential for aspiration and adverse effects; safer Avoid Moderate Strong
alternatives available
Proton-pump inhibitors Risk of C difficile infection and bone loss and Avoid scheduled High Strong
fractures use for >8 weeks
unless for high-
risk patients (eg,
oral corticosteroids
or chronic NSAID
use), erosive
esophagitis,
Barrett’s
esophagitis,
pathological
hypersecretory
condition, or
demonstrated need
for maintenance
treatment (eg,
because of failure
of drug
discontinuation
trial or H2-receptor
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antagonists)
Pain medications
Meperidine Not effective oral analgesic in dosages Avoid Moderate Strong
commonly used; may have higher risk of
neurotoxicity, including delirium, than other
opioids; safer alternatives available
Non-cyclooxygenase- Increased risk of gastrointestinal bleeding or Avoid chronic use, Moderate Strong
selective NSAIDs, oral: peptic ulcer disease in high-risk groups, unless other
Aspirin >325 mg/d including those >75 years old or taking oral or alternatives are not
Diclofenac parenteral corticosteroids, anticoagulants, or effective and
Diflunisal antiplatelet agents; use of proton-pump inhibitor patient can take
Etodolac or misoprostol reduces but does not eliminate gastroprotective
Fenoprofen risk. Upper gastrointestinal ulcers, gross agent (proton-
Ibuprofen bleeding, or perforation caused by NSAIDs pump inhibitor or
Ketoprofen occur in ~1% of patients treated for 3–6 months misoprostol)
Meclofenamate and in ~2–4% of patients treated for 1 year;
Mefenamic acid these trends continue with longer duration of
Meloxicam use.
Nabumetone
Naproxen
Oxaprozin
Piroxicam
Sulindac
Tolmetin
Indomethacin Indomethacin is more likely than other NSAIDs Avoid Moderate Strong
Ketorolac, includes to have adverse CNS effects. Of all the NSAIDs,
parenteral indomethacin has the most adverse effects.
Increased risk of gastrointestinal bleeding/peptic

ulcer disease, and acute kidney injury in older
adults
Skeletal muscle relaxants Most muscle relaxants poorly tolerated by older Avoid Moderate Strong
Carisoprodol adults because some have anticholinergic
Chlorzoxazone adverse effects, sedation, increased risk of
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Cyclobenzaprine fractures; effectiveness at dosages tolerated by

Metaxalone older adults questionable
Methocarbamol
Orphenadrine
Genitourinary
Desmopressin High risk of hyponatremia; safer alternative Avoid for Moderate Strong
treatments treatment of
nocturia or
nocturnal polyuria
The primary target audience is the practicing clinician. The intentions of the criteria include 1) improving the selection of prescription drugs by
clinicians and patients; 2) evaluating patterns of drug use within populations; 3) educating clinicians and patients on proper drug usage; and 4)
evaluating health-outcome, quality-of-care, cost, and utilization data.
CNS=central nervous system; NSAIDs=nonsteroidal anti-inflammatory drugs; SIADH=syndrome of inappropriate antidiuretic hormone
* See also criterion on highly anticholinergic antidepressants.
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Table 3. 2018 American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults Due to Drug–Disease or
Drug–Syndrome Interactions That May Exacerbate the Disease or Syndrome
Disease or Quality of Strength of

Syndrome Drug(s) Rationale Recommendation Evidence Recommendation
Cardiovascular
Heart failure Avoid: Potential to promote As noted, avoid or
Cilostazol fluid retention and/or use with caution Cilostazol: low Cilostazol: strong
exacerbate heart failure
Avoid in heart failure (NSAIDs and COX-2
with reduced ejection inhibitors, non-
fraction: dihydropyridine CCBs,
Non-dihydropyridine thiazolidinediones); Non- Non-
CCBs (diltiazem, potential to increase dihydropyridine dihydropyridine
verapamil) mortality in older CCBs: moderate CCBs: strong
adults with heart failure
Use with caution in (cilostazol and
patients with heart dronedarone)
failure who are
asymptomatic; avoid in
patients with
symptomatic heart
failure:
NSAIDs and COX-2 NSAIDs: moderate NSAIDs: strong
inhibitors
COX-2 inhibitors: COX-2 inhibitors:
low strong
Thiazolidinediones Thiazolidinediones: Thiazolidinediones

(pioglitazone, high : strong
rosiglitazone)
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Dronedarone Dronedarone: high Dronedarone:

strong
Syncope Acetylcholinesterase AChEIs cause Avoid AChEIs: high AChEIs: strong
inhibitors (AChEIs) bradycardia and should
be avoided in older Non-selective Non-selective
Non-selective adults whose syncope peripheral alpha-1 peripheral alpha-1
peripheral alpha-1 may be due to blockers: high blockers: weak
blockers (ie, doxazosin, bradycardia. Non-
prazosin, terazosin) selective peripheral
alpha-1 blockers cause
orthostatic blood
pressure changes and
should be avoided in
older adults whose
syncope may be due to
orthostatic hypotension.
Central nervous system
Delirium Anticholinergics (see Avoid in older adults Avoid H2-receptor Strong
Table 7 in full criteria with or at high risk of antagonists: low
available on delirium because of
www.geriatricscareonlin potential of inducing or All others:
e.org.) worsening delirium moderate
Antipsychoticsa
Benzodiazepines Avoid antipsychotics
Corticosteroids (oral for behavioral
and parenteral)b problems of dementia
H2-receptor antagonists and/or delirium unless
Cimetidine nonpharmacologic
Famotidine options (eg, behavioral
Nizatidine interventions) have
Ranitidine failed or are not
Meperidine possible and the older
Nonbenzodiazepine, adult is threatening
benzodiazepine receptor substantial harm to self
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agonist hypnotics: or others.

eszopiclone, zaleplon, Antipsychotics are
zolpidem associated with greater
risk of cerebrovascular
accident (stroke) and
mortality in persons
with dementia.
Dementia or Anticholinergics (see Avoid because of Avoid Moderate Strong
cognitive Table 7 in full criteria adverse CNS effects
impairment available on
www.geriatricscareonlin Avoid antipsychotics
e.org) for behavioral
problems of dementia
Benzodiazepines and/or delirium unless
nonpharmacologic
Nonbenzodiazepine, options (eg, behavioral
benzodiazepine receptor interventions) have
agonist hypnotics failed or are not
Eszopiclone possible and the older
Zaleplon adult is threatening
Zolpidem substantial harm to self
or others.
Antipsychotics, chronic Antipsychotics are
and as-needed usea associated with greater
risk of cerebrovascular
accident (stroke) and
mortality in persons
with dementia.
History of falls Antiepileptics May cause ataxia, Avoid unless safer Opioids: moderate Strong
or fractures impaired psychomotor alternatives are not
Antipsychoticsa function, syncope, available; avoid All others: high
Benzodiazepines additional falls; antiepileptics
Nonbenzodiazepine, shorter-acting except for seizure
benzodiazepine receptor benzodiazepines are and mood
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agonist hypnotics not safer than long- disorders.

Eszopiclone acting ones.
Zaleplon Opioids: avoid
Zolpidem If one of the drugs except for pain
must be used, consider management in the
TCAs reducing use of other setting of severe
SSRIs CNS-active acute pain, eg,
SNRIs medications that recent fractures or
increase risk of falls joint replacement.
Opioids and fractures (ie,
antiepileptics, opioid-
receptor agonists,
antipsychotics,
antidepressants,
nonbenzodiazepine and
benzodiazepine
receptor agonist
hypnotics, other
sedatives/hypnotics)
and implement other
strategies to reduce fall
risk
Parkinson All antipsychotics Dopamine-receptor Avoid Moderate Strong
disease (except quetiapine, antagonists with
clozapine, potential to worsen
pimavanserin) parkinsonian symptoms
Antiemetics Pimavanserin and

Metoclopramide clozapine appear to be
Prochlorperazine less likely to precipitate
Promethazine worsening of Parkinson
disease. Quetiapine has
only been studied in
low quality clinical
trials with efficacy
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comparable to that of
placebo in 5 trials and
to that of clozapine in 2
others.
Gastrointestinal
History of Aspirin >325 mg/d May exacerbate Avoid unless other Moderate Strong
gastric or Non-COX-2 selective existing ulcers or cause alternatives are not
duodenal ulcers NSAIDs new/additional ulcers effective and
patient can take
gastroprotective
agent (ie, proton-
pump inhibitor or
misoprostol)
Kidney/Urinary tract
Chronic kidney NSAIDs (non-COX and May increase risk of Avoid Moderate Strong
disease Stage 4 COX-selective, oral and acute kidney injury and
or higher parenteral, non- further decline of renal
(creatinine acetylated salicylates) function
clearance <30
mL/min)
Urinary Estrogen oral and Lack of efficacy (oral Avoid in women Estrogen: high Estrogen: strong
incontinence transdermal (excludes estrogen) and
(all types) in intravaginal estrogen) aggravation of
women incontinence (alpha-1
Peripheral alpha-1 blockers) Peripheral alpha-1 Peripheral alpha-1
blockers blockers: moderate blockers: strong
Doxazosin
Prazosin
Terazosin
Lower urinary Strongly anticholinergic May decrease urinary Avoid in men Moderate Strong
tract symptoms, drugs, except flow and cause urinary
benign prostatic antimuscarinics for retention
hyperplasia urinary incontinence
(see Table 7 in full
35
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criteria available on
www.geriatricscareonli
ne.org)
The primary target audience is the practicing clinician. The intentions of the criteria include 1) improving the selection of prescription drugs by
clinicians and patients; 2) evaluating patterns of drug use within populations; 3) educating clinicians and patients on proper drug usage; and 4)
evaluating health-outcome, quality of care, cost, and utilization data.
AChEI=acetylcholinesterase inhibitor; CCBs=calcium channel blockers; CNS=central nervous system; COPD=chronic obstructive pulmonary
disease; COX=cyclooxygenase; NSAIDs=nonsteroidal anti-inflammatory drugs; SSRIs=selective serotonin reuptake inhibitors; TCAs=tricyclic
antidepressants
a
May be required to treat concurrent schizophrenia, bipolar disorder, and other selected mental health conditions but should be prescribed in the
lowest effective dose and shortest possible duration.
b
Excludes inhaled and topical forms. Oral and parenteral corticosteroids may be required for conditions such as exacerbation of COPD but should be
prescribed in the lowest effective dose and for the shortest possible duration.
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Table 4. 2018 American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medications to Be Used with Caution in
Older Adults
Quality
of Strength of
Drug(s) Rationale Recommendation Evidence Recommendation
Aspirin for primary Risk of major bleeding from aspirin increases Use with caution in Moderate Strong
prevention of markedly in older age. Several studies suggest lack of adults ≥70 years old.
cardiovascular net benefit when used for primary prevention in older
disease and adult with cardiovascular risk factors, but evidence is
colorectal cancer not conclusive. Aspirin is generally indicated for
secondary prevention in older adults with established
cardiovascular disease.
Dabigatran Increased risk of gastrointestinal bleeding compared Use with caution for Moderate Strong
Rivaroxaban with warfarin and other direct oral anticoagulants treatment of VTE or
when used for long-term treatment of venous atrial fibrillation in
thromboembolism (VTE) or atrial fibrillation in adults ≥75 years old.
adults ≥75 years old; lack of evidence for efficacy
and safety of dabigatran in individuals with CrCl <30 Avoid dabigatran in
mL/min adults with CrCl <30
mL/min.
Avoid rivaroxaban in
adults with CrCl <30
mL/min for VTE
treatment or for VTE
prophylaxis with hip
or knee replacement.
Dipeptidyl Potential to increase risk of hospitalization for heart Use with caution. Low Weak
peptidase 4 failure. Studies are not conclusive about nature of
inhibitors (DPP-4 risk and if potential risk is drug specific or applies to
inhibitors) in older all drugs in this class.
37
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adults with heart

failure:
Alogliptin
Lanagliptin
Saxagliptin
Sitagliptin
Prasugrel Increased risk of bleeding in older adults; benefit in Use with caution in Moderate Weak
highest-risk older adults (eg, those with prior adults ≥75 years old.
myocardial infarction or diabetes mellitus) may
offset risk when used for its approved indication of
acute coronary syndrome to be managed with
percutaneous coronary intervention.
Antipsychotics May exacerbate or cause SIADH or hyponatremia; Use with caution. Moderate Strong
Diuretics monitor sodium level closely when starting or
Carbamazepine changing dosages in older adults
Mirtazapine
Oxcarbazepine
SNRIs
SSRIs
TCAs
Tramadol
Dextromethorphan/ Limited efficacy in patients with neurocognitive Use with caution. Moderate Strong
quinidine disorders; may increase the risk of falls and concerns
with clinically significant drug interactions
Trimethoprim- Increased risk of hyperkalemia when used Use with caution in Low Strong
sulfamethoxazole concurrently with an ACEI or ARB in the presence patients on ACEI or
of decreased creatinine clearance ARB and decreased
creatinine clearance.
38
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The primary target audience is the practicing clinician. The intentions of the criteria include 1) improving the selection of prescription
drugs by clinicians and patients; 2) evaluating patterns of drug use within populations; 3) educating clinicians and patients on proper
drug usage; and 4) evaluating health-outcome, quality-of-care, cost, and utilization data.
ACEI= angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; CrCl=creatinine clearance; SIADH= syndrome
of inappropriate antidiuretic hormone; SNRIs=serotonin-norepinephrine reuptake inhibitors; SSRIs=selective serotonin reuptake
inhibitors; TCA=tricyclic antidepressant; VTE=venous thromboembolism
39
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Table 5. 2018 American Geriatrics Society Beers Criteria® for Potentially Clinically Important Drug–Drug Interactions That Should
Be Avoided in Older Adults
Object Drug Interacting Drug Risk Quality of Strength of

and Class and Class Rationale Recommendation Evidence Recommendation
RAS inhibitor Another RAS Increased risk Avoid routine use Moderate Strong
(ACEIs, ARBs, inhibitor (ACEIs, of in those with
aliskiren) or ARBs, aliskiren) hyperkalemia chronic kidney
potassium- disease Stage 3a or
sparing diuretics higher
(amiloride,
triamterene)
Opioids Benzodiazepines Increased risk Avoid Moderate Strong
of overdose
Opioids Gabapentin, Increased risk Avoid, except Moderate Strong
pregabalin of overdose when transitioning
from opioid
therapy to
gabapentin and
pregabalin
Anticholinergic Anticholinergic Increased risk Avoid, minimize Moderate Strong
of cognitive number of
decline anticholinergic
drugs (Table 7)
Antidepressants Any combination Increased risk Avoid total of ≥3 Combinati Strong
(TCAs, SSRIs, of ≥3 of these of falls (all) CNS-active drugsa; ons
and SNRIs) CNS-active and of fracture minimize number including
drugsa (benzodiazepin of CNS-active benzodiaze
Antipsychotics es and drugs pines and
nonbenzodiaze nonbenzod
Antiepileptics pine, iazepine,
benzodiazepin benzodiaze
40
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Benzodiazepines e receptor pine

and agonist receptor
nonbenzodiazepi hypnotics) agonist
ne, hypnotics
benzodiazepine or opioids:
receptor agonists high
(i.e., “Z-drugs”)
All other
Opioids combinatio
ns:
moderate
Corticosteroids, NSAIDs Increased risk Avoid; if not Moderate Strong
oral or parenteral of peptic ulcer possible, provide
disease or gastrointestinal
gastrointestinal protection
bleeding
Lithium ACEIs Increased risk Avoid; monitor Moderate Strong
of lithium lithium
toxicity concentrations
Lithium Loop diuretics Increased risk Avoid; monitor Moderate Strong
of lithium lithium
toxicity concentrations
Peripheral alpha- Loop diuretics Increased risk Avoid in older Moderate Strong
1 blockers of urinary women, unless
incontinence in conditions warrant
older women both drugs
Phenytoin Trimethoprim- Increased risk Avoid Moderate Strong
sulfamethoxazole of phenytoin
toxicity
Theophylline Cimetidine Increased risk Avoid Moderate Strong
of theophylline
toxicity
Theophylline Ciprofloxacin Increased risk Avoid Moderate Strong
41
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of theophylline
toxicity
Warfarin Amiodarone Increased risk Avoid when Moderate Strong
of bleeding possible; if used
together, monitor
INR closely
Warfarin Ciprofloxacin Increased risk Avoid when Moderate Strong
together, monitor
INR closely
Warfarin Macrolides Increased risk Avoid when Moderate Strong
(excluding of bleeding possible; if used
azithromycin) together, monitor
INR closely
Warfarin Trimethoprim- Increased risk Avoid when Moderate Strong
sulfamethoxazole of bleeding possible; if used
together, monitor
INR closely
Warfarin NSAIDs Increased risk Avoid when High Strong
together, monitor
closely for bleeding
a
Central nervous system (CNS)-active drugs: antiepileptics, antipsychotics; benzodiazepines; nonbenzodiazepine, benzodiazepine
receptor agonist hypnotics; tricyclic antidepressants (TCAs); selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine
reuptake inhibitors (SNRIs); and opioids
ACEIs=angiotensin-converting enzyme inhibitors; ARBs=angiotensin receptor blockers; NSAIDs=nonsteroidal anti-inflammatory

drugs; RAS=renin-angiotensin system
42
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Table 6. 2018 American Geriatrics Society Beers Criteria® for Medications That Should Be Avoided or Have Their Dosage Reduced
with Varying Levels of Kidney Function in Older Adults
Creatinine
Clearance
(mL/min) at
Which Strength of
Medication Class Action Quality of Recommend
and Medication Required Rationale Recommendation Evidence ation
Anti-infective
Ciprofloxacin <15 Increased risk of Reduce dose Moderate Strong
CNS effects (eg,
seizures,
confusion) and
tendon rupture
Trimethoprim- <30 Increased risk of Reduce dose if CrCl 15-29 Moderate Strong
sulfamethoxazole worsening of renal mL/min
function and
hyperkalemia Avoid if CrCl <15 mL/min
Cardiovascular or hemostasis
Amiloride <30 Increased Avoid Moderate Strong
potassium and
decreased sodium
Apixaban <25 Increased risk of Avoid Moderate Strong
bleeding
Dabigatran <30 Increased risk of Avoid Moderate Strong
bleeding
Dofetilide <60 QTC prolongation Reduce dose if CrCl 20-59 Moderate Strong
and torsades de mL/min
pointes
Avoid if CrCl <20 mL/min
Edoxaban 15–50 Increased risk of Reduce dose if CrCl 15– Moderate Strong
43
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<15 or >95 bleeding 50 mL/min

Avoid if CrCl <15 or >95
mL/min
Enoxaparin <30 Increased risk of Reduce dose Moderate Strong
bleeding
Fondaparinux <30 Increased risk of Avoid Moderate Strong
bleeding
Rivaroxaban <50 Increased risk of Nonvalvular atrial Moderate Strong
bleeding fibrillation: Reduce dose if
CrCl 15–50 mL/min;
avoid if CrCl <15 mL/min
Venous thromboembolism
treatment and for VTE
prophylaxis with hip or
knee replacement: Avoid
if CrCl <30 mL/min
Spironolactone <30 Increased Avoid Moderate Strong
potassium
Triamterene <30 Increased Avoid Moderate Strong
potassium and
decreased sodium
Central nervous system and analgesics
Duloxetine <30 Increased Avoid Moderate Weak
gastrointestinal
adverse effects
(nausea, diarrhea)
Gabapentin <60 CNS adverse Reduce dose Moderate Strong
effects
Levetiracetam ≤80 CNS adverse Reduce dose Moderate Strong
effects
Pregabalin <60 CNS adverse Reduce dose Moderate Strong
effects
44
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Tramadol <30 CNS adverse Immediate release: reduce Low Weak

effects dose
Extended release: avoid
Gastrointestinal
Cimetidine <50 Mental status Reduce dose Moderate Strong
changes
Famotidine <50 Mental status Reduce dose Moderate Strong
changes
Nizatidine <50 Mental status Reduce dose Moderate Strong
changes
Ranitidine <50 Mental status Reduce dose Moderate Strong
changes
Hyperuricemia
Colchicine <30 Gastrointestinal, Reduce dose; monitor for Moderate Strong
neuromuscular, adverse effects
bone marrow
toxicity
Probenecid <30 Loss of Avoid Moderate Strong
effectiveness
CNS=central nervous system; CrCl=creatinine clearance
45
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Table 7. Drugs with Strong Anticholinergic Properties

Antiarrhythmic Promethazine
Disopyramide Pyrilamine
Triprolidine
Antidepressants
Amitriptyline
Amoxapine
Clomipramine Antimuscarinics
Desipramine (urinary incontinence)
Doxepin (>6 mg) Darifenacin
Imipramine Fesoterodine
Nortriptyline Flavoxate
Paroxetine Oxybutynin
Protriptyline Solifenacin
Trimipramine Tolterodine
Trospium
Antiemetics
Prochlorperazine Antiparkinsonian agents
Promethazine Benztropine
Trihexyphenidyl
Antihistamines (first-generation)
Brompheniramine Antipsychotics
Carbinoxamine Chlorpromazine
Chlorpheniramine Clozapine
Clemastine Loxapine
Cyproheptadine Olanzapine
Dexbrompheniramine Perphenazine
Dexchlorpheniramine Thioridazine
Dimenhydrinate Trifluoperazine
Diphenhydramine (oral)
Doxylamine Antispasmodics
Hydroxyzine Atropine (excludes ophthalmic)
Meclizine Belladonna alkaloids
46
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Clidinium-chlordiazepoxide Scopolamine (excludes ophthalmic)

Dicyclomine
Homatropine (excludes ophthalmic) Skeletal muscle relaxants
Hyoscyamine Cyclobenzaprine
Methscopolamine Orphenadrine
Propantheline
47
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Table 8. Medications/Criteria Removed Since 2015 American Geriatrics Society Beers Criteria®
Medication/Criterion Reason for Removal
Independent of Diagnosis or Condition (Table 2)
Ticlopidine No longer on U.S. market; low use
CNS antihypertensives Low use
Guanabenz
Guanfacine
Methyldopa
Reserpine >0.1 mg/d
Meprobamate Low use
Ergoloid mesylates Low use
Isoxsuprine
Pentazocine Oral no longer on U.S. market
Considering Disease and Syndrome Interactions (Table 3)
Syncope Not unique to older adults
TCAs
Chlorpromazine
Thioridazine
Olanzapine
Chronic seizures or epilepsy Not unique to older adults
Bupropion
Chlorpromazine
Clozapine
Maprotiline
Olanzapine
Thioridazine
Thiothixene
Tramadol
Dementia Weak evidence and to avoid overly restricting therapeutic options
H2-receptor antagonists for older adults with dementia who have gastroesophageal reflux
or similar issues (given a coexisting criterion advising against
chronic use of PPIs except in specific circumstances.)
48
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Insomnia Not unique to older adults

Oral decongestants
Pseudoephedrine
Phenylephrine
Stimulants
Amphetamine
Armodafinil
Methylphenidate
Modafinil
Theobromines
Theophylline
Caffeine
Parkinson disease Removed as a preferred antipsychotic in older adults with
Aripiprazole Parkinson disease because of safety and efficacy concerns
Use with Caution (Table 4)
SIADH/hyponatremia Highly specialized drugs that fell outside the scope of the criteria
Carboplatin
Cyclophosphamide
Cisplatin
Vincristine
Syncope Not unique to older adults
Vasodilators
CNS=central nervous system; SIADH= syndrome of inappropriate antidiuretic hormone; TCAs=tricyclic antidepressants
49
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Table 9. Medications/Criteria Added Since 2015 American Geriatrics Society Beers Criteria®
Medication/Criterion Reason for Addition
Glimepiride Severe, prolonged hypoglycemia in older adults
Methscopolamine Strong anticholinergic
Pyrilamine
History of falls or fractures Associated with increased risk in older adults
SNRI
Parkinson disease Unlike most other antipsychotics, the revised criteria consider
(Pimavanserin) pimavanserin acceptable for treatment of psychosis in Parkinson
disease
Rivaroxaban Risk of bleeding
Dipeptidyl peptidase 4 (DPP-4) inhibitors in patients with Increased risk of hospitalization for heart failure
preexisting heart failure
Alogliptin
Lanagliptin
Saxagliptin
Sitagliptin
Tramadol Risk of SIADH/hyponatremia
Dextromethorphan/quinidine Limited efficacy in treating patients with neurocognitive
disorders while potentially increasing risk of falls and drug-drug
interactions
Trimethoprim-sulfamethoxazole (TMP-SMZ) Increased risk of hyperkalemia in combination with ACEIs and
ARBs in patients with reduced kidney function
Clinically Important Drug-Drug Interactions (Table 5)
Opioids + Benzodiazepines Increased risk of overdose
Opioids + Gabapentin/pregabalin Increased risk of overdose
Phenytoin + TMP-SMZ Increased risk of phenytoin toxicity
Theophylline + Ciprofloxacin Increased risk of theophylline toxicity
Warfarin + Ciprofloxacin Increased risk of bleeding
50
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Warfarin + Macrolides (excluding azithromycin) Increased risk of bleeding

Warfarin + TMP-SMZ Increased risk of bleeding
Medications That Should be Avoided or Have Their Dosage Reduced with Reduced Kidney Function (Table 6)
Ciprofloxacin Increased risk of CNS effects
TMP-SMZ Increased risk of worsening of renal function and hyperkalemia
ACEIs=angiotensin-converting enzyme inhibitors; ARBs=angiotensin receptor blockers; CNS=central nervous system; SIADH=
syndrome of inappropriate antidiuretic hormone; SNRI=serotonin-norepinephrine reuptake inhibitor
51
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Table 10. Medications/Criterion Modified Since 2015 American Geriatrics Society Beers Criteria®
Medication/Criterion Modification
Peripheral alpha-1 blockers For treatment of hypertension
CNS alpha blocker – Clonidine Dropped other CNS antihypertensives from a shared criterion
(see Table 8); clonidine now the only medication listed in this
criterion.
Digoxin for atrial fibrillation and heart failure Added wording to Drug column; modified rationale; QE for
atrial fibrillation changed to Low
Estrogen with or without progestin Added “recurrent” urinary tract infections
Sliding-scale insulin Clarified definition of sliding-scale insulin
Metoclopramide Added duration of use to recommendation
Meperidine Removed caveat from recommendation
Heart failure Reorganized recommendations; separated COX-2 inhibitors
from other NSAIDs; added QE and SR for COX-2 inhibitors;
changed recommendation for NSAIDs, COX-2 inhibitors, and
thiazolidinediones to use with caution in asymptomatic heart
failure and avoid in symptomatic heart failure; modified
rationale.
Syncope Specified “non-selective peripheral alpha-1 blockers”; separated
rationales, QE, and SR for AChEIs and non-selective peripheral
alpha-1 blockers
Delirium Changed “Sedative/hypnotics” to Nonbenzodiazepine,
benzodiazepine receptor agonists; changed H2-receptor
antagonists’ QE to low
History of fractures and falls Changed opioid SR to strong
Parkinson disease Added rationale for quetiapine, clozapine, and pimavanserin
Chronic kidney disease and NSAIDs Changed wording (minor) of criterion title
Aspirin as primary prevention Modified age, indication, rationale, and QE
Dabigatran Modified rationale and recommendation
52
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Clinically Important Drug-Drug Interactions (Table 5)

Title Dropped “Non-anti-infective”
ACEIs/ARBs and hyperkalemia Changed to renin-angiotensin system (RAS) inhibitors
Combination of 3 or more CNS agents (antidepressants, Replaced individual criteria with a single criterion
antiepileptics, antipsychotics, benzodiazepines, and opioids)
Medications That Should be Avoided or Have Their Dosage Reduced with Reduced Kidney Function (Table 6)
Edoxaban Changed lower limit of CrCl
ACEIs= angiotensin-converting enzyme inhibitors; AChEIs=acetylcholinesterase inhibitors; ARBs=angiotensin receptor blockers;
CNS=central nervous system; COX=cyclooxygenase; NSAIDs=nonsteroidal anti-inflammatory drugs; QE=quality of evidence;
SR=strength of recommendation
53
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CONFIDENTIAL DRAFT - American Geriatrics Society 2018 Updated Beers Criteria® for Potentially

Inappropriate Medication Use in Older Adults

Table 1. Designations of Quality of Evidence and Strength of Recommendations

Organ System, Quality

fibrillation or severe or recently decompensated permanent atrial

Decreased renal clearance of digoxin may lead

Alprazolam benzodiazepines increase risk of cognitive

Chlorpropamide adults; can cause prolonged hypoglycemia;

Increased risk of gastrointestinal bleeding/peptic

Cyclobenzaprine fractures; effectiveness at dosages tolerated by

evaluating health-outcome, quality-of-care, cost, and utilization data.

* See also criterion on highly anticholinergic antidepressants.

Drug–Syndrome Interactions That May Exacerbate the Disease or Syndrome

Disease or Quality of Strength of

Thiazolidinediones Thiazolidinediones: Thiazolidinediones

Dronedarone Dronedarone: high Dronedarone:

agonist hypnotics: or others.

agonist hypnotics not safer than long- disorders.

Antiemetics Pimavanserin and

evaluating health-outcome, quality of care, cost, and utilization data.

adults with heart

of inappropriate antidiuretic hormone; SNRIs=serotonin-norepinephrine reuptake inhibitors; SSRIs=selective serotonin reuptake

inhibitors; TCA=tricyclic antidepressant; VTE=venous thromboembolism

Be Avoided in Older Adults

Object Drug Interacting Drug Risk Quality of Strength of

Benzodiazepines e receptor pine

reuptake inhibitors (SNRIs); and opioids

ACEIs=angiotensin-converting enzyme inhibitors; ARBs=angiotensin receptor blockers; NSAIDs=nonsteroidal anti-inflammatory

with Varying Levels of Kidney Function in Older Adults

<15 or >95 bleeding 50 mL/min

Tramadol <30 CNS adverse Immediate release: reduce Low Weak

Table 7. Drugs with Strong Anticholinergic Properties

Clidinium-chlordiazepoxide Scopolamine (excludes ophthalmic)

Insomnia Not unique to older adults

Warfarin + Macrolides (excluding azithromycin) Increased risk of bleeding

Clinically Important Drug-Drug Interactions (Table 5)

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