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CLINICAL INVESTIGATION American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults By the 2019 American Geriatrics Society Beers Criteria® Update Expert Panel* The American Geriatrics Society (AGS) Beers Criteria® (AGS Beers Criteria®) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used by clinicians, educators, researchers, healthcare administrators, and regulators. Since 2011, the AGS has been the steward of the criteria and has produced updates on a 3-year cycle. The AGS Beers Criteria® is an explicit list of PIMs that are typically best avoided by older adults in most circumstances or under speciﬁc situations, such as in certain diseases or conditions. For the 2019 update, an interdisciplinary expert panel reviewed the evidence published since the last update (2015) to determine if new criteria should be added or if existing criteria should be removed or undergo changes to their recommendation, rationale, level of evidence, or strength of recommendation. J Am Geriatr Soc 00:1– 21, 2019. Key words: medications; drugs; older adults; Beers list; Beers Criteria he American Geriatrics Society (AGS) Beers Criteria® (AGS Beers Criteria®) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used by clinicians, educators, researchers, healthcare administrators, and regulators. Since 2011, the AGS has been the steward of the criteria and has produced updates on a 3-year cycle that began in 2012.1,2 The AGS Beers Criteria® are an explicit list of PIMs that are typically best avoided by older adults in most circumstances or under speciﬁc situations, such as in certain diseases or conditions. T From the *American Geriatrics Society, New York, New York. Address correspondence to Mary Jordan Samuel, American Geriatrics Society, 40 Fulton St, 18th Floor, New York, NY 10038. E-mail: [email protected] See related editorial by Michael Steinman et al. DOI: 10.1111/jgs.15767 JAGS 00:1–21, 2019 © 2019 The American Geriatrics Society For the 2019 update, an interdisciplinary expert panel reviewed the evidence published since the last update (2015) to determine if new criteria should be added or if existing criteria should be removed or undergo changes to their recommendation, rationale, level of evidence, or strength of recommendation. Each of the ﬁve types of criteria in the 2015 update were retained in this 2019 update: medications that are potentially inappropriate in most older adults, those that should typically be avoided in older adults with certain conditions, drugs to use with caution, drug-drug interactions, and drug dose adjustment based on kidney function. OBJECTIVES The speciﬁc aim was to update the 2015 AGS Beers Criteria® using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse events in older adults. The strategies to achieve this aim were to: • Incorporate new evidence on PIMs included in the 2015 AGS Beers Criteria® and evidence regarding new criteria or modiﬁcations of existing criteria being considered for the 2019 update. • Grade the strength and quality of each PIM statement based on the level of evidence and strength of recommendation. • Convene an interdisciplinary panel of 13 experts in geriatric care and pharmacotherapy who would apply a modiﬁed Delphi method, informed by the systematic review and grading, to reach consensus on the 2019 update. • Incorporate exceptions in the AGS Beers Criteria® that the panel deemed clinically appropriate. These exceptions would be designed to make the criteria more individualized to clinical practice and be more relevant across settings of care. INTENT OF CRITERIA The primary target audience for the AGS Beers Criteria® is practicing clinicians. The criteria are intended for use in adults 65 years and older in all ambulatory, acute, and institutionalized settings of care, except for the hospice and palliative care settings. Consumers, researchers, pharmacy beneﬁts managers, regulators, and policymakers also widely use the AGS Beers Criteria®. The intention of the AGS Beers Criteria® is to improve medication selection; 0002-8614/18/$15.00 2 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL educate clinicians and patients; reduce adverse drug events; and serve as a tool for evaluating quality of care, cost, and patterns of drug use of older adults. As with previously published AGS Beers Criteria®, the goal of the 2019 update continues to be improving the care of older adults by reducing their exposure to PIMs that have an unfavorable balance of beneﬁts and harms compared with alternative treatment options. This is accomplished by using the AGS Beers Criteria® as both an educational tool and a quality measure—two uses that are not always in agreement—and the panel considered and vigorously deliberated both. The AGS Beers Criteria® are not meant to be applied in a punitive manner. Prescribing decisions are not always clear-cut, and clinicians must consider multiple factors, including discontinuation of medications no longer indicated. Quality measures must be clearly deﬁned, easily applied, and measured with limited information and, thus, although useful, cannot perfectly distinguish appropriate from inappropriate care. The panel’s review of evidence at times identiﬁed subgroups of individuals who should be exempt from a given criterion or to whom a speciﬁc criterion should apply. Such a criterion may not be easily applied as a quality measure, particularly when such subgroups cannot be easily identiﬁed through structured and readily accessible electronic health data. As an exle, the panel thought that a criterion should not be expanded to include all adults 65 years and older when only certain subgroups have an adverse balance of beneﬁts vs harms for the medication, or conversely when a sizable subgroup of older adults may be appropriate candidates for a medication that is otherwise problematic. Despite past and current efforts to translate the criteria into practice, some controversy and myths about their use in practice and policy continue to prevail. The panel addressed these concerns and myths by writing a companion article to the 2015 update of the AGS Beers Criteria® and an updated 2019 short piece, which remains the best way to advise patients, providers, and health systems on how to use (and not use) the 2019 AGS Beers Criteria®.3 METHODS Methods used for the 2019 update of the AGS Beers Criteria® were similar to those used in the 2015 update, with additional emphasis on extending the rigor of the evidence review and synthesis process.2 These methods were based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for clinical practice guideline development and are consistent with recommendations from the National Academy of Medicine.4,5 Panel Composition The AGS Beers Criteria® expert update panel comprised 13 clinicians and included physicians, pharmacists, and nurses, each of whom had participated in the 2015 update. Panelists had experience in different practice settings, including ambulatory care, home care, acute hospital care, skilled-nursing facility, and long-term care. In addition, the panel included ex-ofﬁcio representatives from the Centers for Medicare and Medicaid Services, the National MONTH 2019–VOL. 00, NO. 00 JAGS Committee for Quality Assurance, and the Pharmacy Quality Alliance. Potential conﬂicts of interest were disclosed at the beginning of the process and before each full panel call and are listed in the disclosures section of this article. Panelists were recused from discussion in areas in which they had a potential conﬂict of interest. Literature Review Literature searches were conducted in PubMed and the Cochrane Library from January 1, 2015, to September 30, 2017. Search terms for each criterion included individual drugs, drug classes, speciﬁc conditions, and combinations thereof, each with a focus on “adverse drug events” and “adverse drug reactions.” Medications believed to have low utilizations (eg, meprobamate and central α-agonist antihypertensives other than clonidine) or no longer available in the United States were excluded from the literature search. Searches targeted controlled clinical trials, observational studies, and systematic reviews and meta-analyses, with ﬁlters for human participants, 65 years and older, and English language. Clinical reviews and guidelines were also included to provide context. Case reports, case series, letters to the editor, and editorials were excluded. Searches identiﬁed 17,627 references; 5403 abstracts were sent to panelists for review, of which 1422 references were selected for full-text review. Among these, 377 articles were abstracted into evidence tables, including 67 systematic reviews and/or meta-analyses, 29 controlled clinical trials, and 281 observational studies. Development Process Between February 2016 and May 2018, the full panel convened for a series of conference calls and 1 full-day, inperson meeting. In addition, the panel divided into four work groups, each assigned a subset of the criteria. Each work group led the review and synthesis of evidence for its subset of the criteria, convening via conference calls and electronically via e-mail. The development process began by soliciting ideas from the panelists about criteria that should be explored for addition, modiﬁcation, or removal. Suggestions from others were also welcomed. To guide the evidence selection, review, and synthesis process, each work group then undertook an exercise to identify a priori which clinical outcomes, indications, and comparison groups were most relevant when considering evidence for each criterion (ie, the “desired evidence” for reviewing each criterion). These discussions were not considered binding but provided guidance for keeping the evidence review and synthesis focused on what was most clinically relevant. Each work group reviewed abstracts from the literature searches for the criteria in its purview and collectively selected a subset for full-text review. This selection process considered the methodologic quality of each study, its relevance to older adults, and its concordance with the desired evidence noted above. After reviewing the full text of each selected article, the work group then decided by consensus which articles represented the best available evidence, based on a balance of these same three key criteria (methodologic quality, relevance to older adults, and concordance with JAGS MONTH 2019–VOL. 00, NO. 00 desired evidence). Special emphasis was placed on selecting systematic reviews and meta-analyses when available, because resource constraints precluded the panel from conducting these types of comprehensive analyses. In general, a study was considered relevant to older adults if the mean or median age of participants was older than 65 years, and especially relevant if most or all participants were older than this age threshold. Articles comprising the best available evidence were abstracted by AGS staff into evidence tables. These tables summarized the design, population, and ﬁndings of each study, and identiﬁed markers of methodologic quality highlighted by the GRADE criteria for clinical trials and observational studies and by A MeaSurement Tool to Assess Systematic Reviews (AMSTAR).6–8 Each work group then synthesized evidence for each criterion from the 2015 to 2017 literature reviews based on GRADE guidelines and the American College of Physicians’ evidence grading framework (Table 1).6,9 Using evidence from the 2015 to 2017 literature review, evidence ﬁndings from previous updates in 2012 and 2015, and clinical judgment, each work group presented to the full panel its ﬁndings and suggestions for changes (or no change) to the criteria, with ensuing discussion. For most criteria, a consensus emerged, to leave an existing criterion from the 2015 update unchanged, to modify it, to remove it entirely, or to add a new criterion. Potential modiﬁcations included the drug(s) included in the criterion, the recommendation, the rationale, the quality of evidence, and the strength of recommendation. As noted in the GRADE guidelines, strength of recommendation ratings incorporate a variety of considerations, including expert opinion and clinical judgment and context, and thus do not always align with quality of evidence ratings. After discussion of proposed changes, an anonymous Delphi process was used to ascertain panel consensus, using a ﬁve-point Likert scale with anchors of “strongly disagree” and “strongly agree.” As a general rule, criteria receiving “agree” or strongly agree ratings from more than 90% of panelists were included. The remainder were brought back for group discussion, with ﬁnal decisions resolved through consensus. In addition to changes made on the basis of evidence, the panel decided on several modiﬁcations to improve clarity and usability of the AGS Beers Criteria®. These included removing a number of medications that are used only rarely. These removals should not be interpreted as condoning use of these medications but rather are intended to “declutter” the AGS Beers Criteria® and not distract from information on more commonly used medications. In selected cases, the panel changed the wording of certain criteria, recommendations, and rationale statements to improve clarity and avoid potential misinterpretations. The ﬁnal set of criteria was reviewed by the AGS Executive Committee and Clinical Practice and Models of Care Committee and subsequently released for public comment. Comments were solicited from the general public and sent to 39 organizations. Comments were accepted over a 3-week period from August 13, 2018, until September 4, 2018. A total of 244 comments were received from 47 individuals (79 comments), 6 pharmaceutical companies (10 comments), and 22 peer organizations (155 comments). All comments were reviewed and discussed by the panel 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL 3 cochairs. All comments along with proposed changes to the criteria were shared with the entire panel for ﬁnal approval. RESULTS Noteworthy Changes to PIMs for Older Adults Tables 2 through 6 show the 2019 criteria. Table 7 lists those drugs with strong anticholinergic properties that are sometimes referenced in Tables 2 through 6. Compared with the 2015 criteria, several drugs were removed from Table 2 (medications that are potentially inappropriate in most older adults), Table 3 (medications that are potentially inappropriate in older adults with certain conditions), and Table 4 (medications that should be used with caution). These removals are summarized in Table 8 and include removal of drugs no longer available in the United States (ticlopidine, oral pentazocine). In other cases, the recommendation was removed entirely because the panel decided the drug-related problem was not sufﬁciently unique to older adults (eg, using stimulating medications in patients with insomnia or avoiding medications that can lower the seizure threshold in patients with a seizure disorder). These removals do not imply that these medications are now considered safe for older adults; rather, they were made to help keep the AGS Beers Criteria® streamlined and focused on medications particularly problematic for older adults. The H2-receptor antagonists were removed from the “avoid” list in patients with dementia or cognitive impairment. This is because evidence for adverse cognitive effects in these conditions is weak, and because the panel expressed concern that the intersection of this criterion with another criterion that discourages chronic use of protonpump inhibitors in the absence of strong indications would overly restrict therapeutic options for older adults with dementia who have gastroesophageal reﬂux or similar issues. However, H2-receptor antagonists remain on the criteria as “avoid” in patients with delirium. In addition, wording of this criterion was modiﬁed to afﬁrm that nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (ie, the “Z drugs”: zolpidem, eszopiclone, and zaleplon) should be avoided in older adults with delirium. Two drugs with strong anticholinergic properties, pyrilamine and methscopolamine, were added to the list of anticholinergic drugs to avoid. Changes to criteria on cardiovascular drugs include minor updates to the rationale and a minor change to clarify the recommendation for avoiding digoxin as ﬁrst-line therapy for atrial ﬁbrillation and heart failure (Table 2). The rationale to avoid slidingscale insulin has been revised to clarify its meaning and intent (Table 2). Glimepiride has been added to the list of sulfonylureas with a greater risk of severe prolonged hypoglycemia (Table 2). The duration of use of metoclopramide has been added to be consistent with US Food and Drug Administration labeling (Table 2). The serotonin-norepinephrine reuptake inhibitors (SNRIs) have been added to the list of drugs to avoid in patients with a history of falls or fractures (Table 3). Following a principle that applies to all criteria, the panel recognizes there may be situations when SNRIs, other antidepressants, and other medications listed in this criterion may be appropriate for people with a history of falls 4 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL MONTH 2019–VOL. 00, NO. 00 JAGS Table 1. Designations of Quality of Evidence and Strength of Recommendationsa Quality of Evidence Quality of evidence ratings for each criterion are based on synthetic assessment of two complementary approaches to evaluating the quality of evidence. ACP-based approach9 GRADE-based approach4 Consider the following ﬁve factors for the studies High-quality evidence “Evidence…obtained from 1 or more wellthat comprise the best-available evidence for a designed and well-executed randomized, controlled trials (RCTs) that yield consistent and given criterion: directly applicable results. This also means that 1. Risk of bias: Severity of threats to studies’ internal validity (eg, randomized vs further research is very unlikely to change our observational design, potential for conﬁdence in the estimate of effect.” Moderate-quality evidence “Evidence…obtained from RCTs with important confounding, bias in measurement) limitations…. In addition, evidence from well2. Inconsistency: Do different studies provide designed controlled trials without randomization, similar or different estimates of effect size well-designed cohort or case-control analytic 3. Indirectness: How relevant are the studies to studies, and multiple time series with or without the clinical question at hand (eg, nature of intervention are in this category. Moderatestudy of population, comparison group, type quality evidence also means that further of outcomes measured) research will probably have an important effect 4. Imprecision: Precision of estimates of effect on our conﬁdence in the estimate of effect and 5. Publication bias: Risk of bias due to selective may change the estimate.” publication of results Low-quality evidence “Evidence obtained from observational studies would typically be rated as low quality because of the risk for bias. Low-quality evidence means that further research is very likely to have an 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.” ##### 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. Weak Harms, adverse events, and risks may not outweigh beneﬁts. Abbreviations: ACP, American College of Physicians; GRADE, Grading of Recommendations Assessment, Development and Evaluation. a 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. or fractures, based on potential beneﬁts and the lack of availability of safer alternatives. After reviewing and discussing the evidence on antipsychotics to treat psychosis in patients with Parkinson disease, the panel decided to remove aripiprazole as preferred and add pimavanserin. Thus, the 2019 AGS Beers Criteria® recognize quetiapine, clozapine, and pimavanserin as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson disease (Table 3). However, none of these three excepted drugs is close to ideal in either efﬁcacy or safety, each having its own limitations and concerns. The criteria on drugs to avoid in older adults with heart failure were reorganized to add clinical nuance based on evidence, other guideline recommendations, and clinical considerations. The updated recommendations are that nondihydropyridine calcium channel blockers should be avoided in older adults who have heart failure with reduced ejection fraction; that nonsteroidal anti-inﬂammatory drug (NSAIDs), cyclooxygenase-2 inhibitors, thiazolidinediones (“glitazones”), and dronedarone should be used with caution in older adults with heart failure who are asymptomatic (ie, excellent control of heart failure signs and symptoms, with or without use of medications) and avoided in older adults who are symptomatic; and that cilostazol should continue to be avoided in older adults with heart failure of any type. Drugs To Be Used With Caution Table 4 contains drugs to be used with caution in older adults. The purpose of this table is to identify drugs for which there is some cause for concern, but for which the evidence and/or clinical context is as of yet insufﬁcient to merit inclusion in the main tables. Compared with the previous update, the following changes and additions were made: • The age threshold beyond which extra caution is advised for using aspirin for primary prevention of cardiovascular disease Avoid use as an antihypertensive Avoid in individuals with creatinine clearance 6 mg/day Imipramine Recommendation Highly anticholinergic, sedating, and cause orthostatic hypotension; safety proﬁle of low-dose doxepin (≤6 mg/day) comparable to that of placebo May induce heart failure in older adults because of potent negative inotropic action; strongly anticholinergic; other antiarrhythmic drugs preferred Worse outcomes have been reported in patients taking dronedarone who have permanent atrial ﬁbrillation or severe or recently decompensated heart failure. Use in atrial ﬁbrillation: should not be used as a ﬁrst-line agent in atrial ﬁbrillation, because there are safer and more effective alternatives for rate control supported by high-quality evidence. Use in heart failure: evidence for beneﬁts and harms of digoxin is conﬂicting and of lower quality; most but not all of the evidence concerns use in HFrEF. There is strong evidence for other agents as ﬁrst-line therapy to reduce hospitalizations and mortality in adults with HFrEF. In heart failure, higher dosages are not associated with additional beneﬁt and may increase risk of toxicity. 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. Potential for hypotension; risk of precipitating myocardial ischemia Effective for maintaining sinus rhythm but has greater toxicities than other antiarrhythmics used in atrial ﬁbrillation; may be reasonable ﬁrst-line therapy in patients with concomitant heart failure or substantial left ventricular hypertrophy if rhythm control is preferred over rate control High High Avoid as ﬁrst-line therapy for atrial ﬁbrillation unless patient has heart failure or substantial left ventricular hypertrophy Avoid High Avoid Dosage >0.125 mg/day: moderate Heart failure: low Avoid as ﬁrst-line therapy for heart failure If used for atrial ﬁbrillation or heart failure, avoid dosages >0.125 mg/day Atrial ﬁbrillation: strong Atrial ﬁbrillation: low Strong Strong Strong Dosage >0.125 mg/day: strong Heart failure: strong Strong High Strong Strong Low Low Strong Strength of Recommendation Low Quality of Evidence Avoid in individuals with permanent atrial ﬁbrillation or severe or recently decompensated heart failure Avoid this rate control agent as ﬁrstline therapy for atrial ﬁbrillation Avoid High risk of adverse CNS effects; may cause bradycardia Avoid as ﬁrst-line antihypertensive and orthostatic hypotension; not recommended as routine Avoid other CNS alpha-agonists as treatment for hypertension listed Rationale 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL Amiodarone Nifedipine, immediate release Digoxin for ﬁrst-line treatment of atrial ﬁbrillation or of heart failure Dronedarone Central alpha-agonists Clonidine for ﬁrst-line treatment of hypertension Other CNS alpha-agonists Guanabenz Guanfacine Methyldopa Reserpine (>0.1 mg/day) Disopyramide Organ System, Therapeutic Category, Drug(s) Table 2 (Contd.) 6 MONTH 2019–VOL. 00, NO. 00 JAGS Recommendation Avoid Avoid High rate of physical dependence; sedating Nonbenzodiazepine benzodiazepine receptor agonist hypnotics (ie, Z drugs) have adverse events similar to those of benzodiazepines in older adults (eg, delirium, falls, fractures); increased emergency room visits/ hospitalizations; motor vehicle crashes; minimal improvement in sleep latency and duration Lack of efﬁcacy Avoid Avoid Avoid Avoid, except in schizophrenia or bipolar disorder, or for short-term use as antiemetic during chemotherapy Older adults have increased sensitivity to benzodiazepines and decreased metabolism of longacting agents; in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults May be appropriate for seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesia Increased risk of cerebrovascular accident (stroke) and greater rate of cognitive decline and mortality in persons with dementia Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options (eg, behavioral interventions) have failed or are not possible and the older adult is threatening substantial harm to self or others High rate of physical dependence, tolerance to sleep beneﬁts, greater risk of overdose at low dosages Rationale High Moderate Moderate Moderate High Moderate Quality of Evidence 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL (Continued) Strong Strong Strong Strong Strong Strong Strength of Recommendation MONTH 2019–VOL. 00, NO. 00 Ergoloid mesylates (dehydrogenated ergot alkaloids) Isoxsuprine Barbiturates Amobarbital Butabarbital Butalbital Mephobarbital Pentobarbital Phenobarbital Secobarbital Benzodiazepines Short and intermediate acting: Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Long acting: Chlordiazepoxide (alone or in combination with amitriptyline or clidinium) Clonazepam Clorazepate Diazepam Flurazepam Quazepam Meprobamate Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (ie, “Z-drugs”) Eszopiclone Zaleplon Zolpidem Nortriptyline Paroxetine Protriptyline Trimipramine Antipsychotics, ﬁrst (conventional) and second (atypical) generation Organ System, Therapeutic Category, Drug(s) Table 2 (Contd.) JAGS 7 Proton-pump inhibitors Avoid Concerns about cardiac effects; safer alternatives available Evidence of carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women Evidence indicates that vaginal estrogens for the treatment of vaginal dryness are safe and effective; women with a history of breast cancer who do not respond to nonhormonal therapies are advised to discuss the risks and beneﬁts of low-dose vaginal estrogen (dosages of estradiol 8 weeks unless for high-risk patients (eg, oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance treatment (eg, because of failure of drug discontinuation trial or H2-receptor antagonists) Avoid, unless for gastroparesis with duration of use not to exceed 12 weeks except in rare cases Avoid Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting. Avoid insulin regimens that include only short- or rapidacting insulin dosed according to current blood glucose levels without concurrent use of basal or long-acting insulin. This recommendation does not apply to regimens that contain basal insulin or long-acting insulin. Minimal effect on weight; increases risk of thrombotic Avoid events and possibly death in older adults Chlorpropamide: prolonged half-life in older adults; can Avoid cause prolonged hypoglycemia; causes SIADH Glimepiride and glyburide: higher risk of severe prolonged hypoglycemia in older adults Vaginal cream or vaginal tablets: acceptable to use low-dose intravaginal estrogen for management of dyspareunia, recurrent lower urinary tract infections, and other vaginal symptoms Avoid, except for patients rigorously diagnosed by evidence-based criteria with growth hormone deﬁciency due to an established etiology Avoid Avoid systemic estrogen (eg, oral and topical patch) Avoid unless indicated for conﬁrmed hypogonadism with clinical symptoms Recommendation Potential for cardiac problems; contraindicated in men with prostate cancer Rationale High Moderate Moderate High Strong Strong Strong Strong Strong Strong Moderate Moderate Strong Topical vaginal cream or tablets: weak Vaginal cream or vaginal tablets: moderate High Oral and patch: strong Strong Weak Strength of Recommendation Oral and patch: high Low Moderate Quality of Evidence 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL Mineral oil, given orally Sulfonylureas, long acting Chlorpropamide Glimepiride Glyburide (also known as glibenclamide) Gastrointestinal Metoclopramide Megestrol Insulin, sliding scale (insulin regimens containing only short- or rapid-acting insulin dosed according to current blood glucose levels without concurrent use of basal or long-acting insulin) Growth hormone Estrogens with or without progestins Endocrine Androgens Methyltestosterone Testosterone Desiccated thyroid Organ System, Therapeutic Category, Drug(s) Table 2 (Contd.) 8 MONTH 2019–VOL. 00, NO. 00 JAGS Avoid for treatment of nocturia or nocturnal polyuria Strong Strong Moderate Moderate Strong Strong Strong Strength of Recommendation Moderate Moderate Moderate Quality of Evidence Abbreviations: CNS, central nervous system; HFrEF, heart failure with reduced ejection fraction; NSAID, nonsteroidal anti-inﬂammatory drug; SIADH, syndrome of inappropriate antidiuretic hormone secretion. a 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. b See also criterion on highly anticholinergic antidepressants. High risk of hyponatremia; safer alternative treatments Recommendation Avoid chronic use, unless other alternatives are not effective and patient can take gastroprotective agent (proton-pump inhibitor or misoprostol) Avoid Increased risk of gastrointestinal bleeding/peptic ulcer Avoid disease and acute kidney injury in older adults Indomethacin is more likely than other NSAIDs to have adverse CNS effects. Of all the NSAIDs, indomethacin has the most adverse effects. Avoid Most muscle relaxants poorly tolerated by older adults because some have anticholinergic adverse effects, sedation, increased risk of fractures; effectiveness at dosages tolerated by older adults questionable Oral analgesic not effective in dosages commonly used; may have higher risk of neurotoxicity, including delirium, than other opioids; safer alternatives available Increased risk of gastrointestinal bleeding or peptic ulcer disease in high-risk groups, including those >75 years or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents; use of proton-pump inhibitor or misoprostol reduces but does not eliminate risk. Upper gastrointestinal ulcers, gross bleeding, or perforation caused by NSAIDs occur in ~1% of patients treated for 3-6 months and in ~2%-4% of patients treated for 1 year; these trends continue with longer duration of use. Also can increase blood pressure and induce kidney injury. Risks are dose related. Rationale MONTH 2019–VOL. 00, NO. 00 Skeletal muscle relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine Genitourinary Desmopressin Non–cyclooxygenase-selective NSAIDs, oral: Aspirin >325 mg/day Diclofenac Diﬂunisal Etodolac Fenoprofen Ibuprofen Ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin Indomethacin Ketorolac, includes parenteral Pain medications Meperidine Organ System, Therapeutic Category, Drug(s) Table 2 (Contd.) JAGS 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL 9 Dronedarone AChEIs Thiazolidinediones (pioglitazone, rosiglitazone) Use with caution in patients with heart failure who are asymptomatic; avoid in patients with symptomatic heart failure: NSAIDs and COX-2 inhibitors Avoid in heart failure with reduced ejection fraction: Nondihydropyridine CCBs (diltiazem, verapamil) Avoid: Cilostazol Drug(s) Recommendation Dronedarone: strong Dronedarone: high Moderate All others: moderate Strong H2-receptor antagonists: Strong low Nonselective peripheral alpha-1 blockers and antipsychotics: weak Thiazolidinediones: strong Thiazolidinediones: high Nonselective peripheral alpha-1 blockers: high COX-2 inhibitors: strong COX-2 inhibitors: low AChEIs and TCAs: strong NSAIDs: strong NSAIDs: moderate AChEIs, TCAs, and antipsychotics: high Nondihydropyridine CCBs: strong Cilostazol: strong Strength of Recommendation Nondihydropyridine CCBs: moderate Cilostazol: low Quality of Evidence 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL Avoid Avoid Avoid Potential to promote ﬂuid retention As noted, avoid and/or exacerbate heart failure (NSAIDs or use with caution and COX-2 inhibitors, nondihydropyridine CCBs, thiazolidinediones); potential to increase mortality in older adults with heart failure (cilostazol and dronedarone) Rationale AChEIs cause bradycardia and should be avoided in older adults whose syncope Nonselective peripheral alpha-1 blockers may be due to bradycardia. Nonselective (ie, doxazosin, prazosin, terazosin) peripheral alpha-1 blockers cause Tertiary TCAs orthostatic blood pressure changes and should be avoided in older adults whose Antipsychotics: syncope may be due to orthostatic Chlorpromazine hypotension. Tertiary TCAs and the Thioridazine antipsychotics listed increase the risk of Olanzapine orthostatic hypotension or bradycardia. Central nervous system Avoid in older adults with or at high risk Delirium Anticholinergics (see Table 7 and full of delirium because of potential of criteria available on www. inducing or worsening delirium geriatricscareonline.org.) Antipsychoticsb Benzodiazepines Avoid antipsychotics for behavioral Corticosteroids (oral and parenteral)c problems of dementia and/or delirium H2-receptor antagonists unless nonpharmacological options (eg, Cimetidine behavioral interventions) have failed or Famotidine are not possible and the older adult is Nizatidine threatening substantial harm to self or Ranitidine others. Antipsychotics are associated Meperidine with greater risk of cerebrovascular Nonbenzodiazepine, benzodiazepine accident (stroke) and mortality in receptor agonist hypnotics: persons with dementia. eszopiclone, zaleplon, zolpidem Dementia or cognitive Anticholinergics (see Table 7 and full Avoid because of adverse CNS effects impairment criteria available on www. Avoid antipsychotics for behavioral geriatricscareonline.org) problems of dementia and/or delirium Benzodiazepines unless nonpharmacological options (eg, behavioral interventions) have failed or Nonbenzodiazepine, benzodiazepine are not possible and the older adult is receptor agonist hypnotics threatening substantial harm to self or Eszopiclone Syncope Cardiovascular Heart failure Disease or Syndrome Table 3. 2019 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 Syndromea 10 MONTH 2019–VOL. 00, NO. 00 JAGS Kidney/urinary tract Chronic kidney disease stage 4 or higher (creatinine clearance 325 mg/day Non–COX-2–selective NSAIDs All antipsychotics (except quetiapine, clozapine, pimavanserin) Antiemetics Metoclopramide Prochlorperazine Promethazine Opioids Antidepressants TCAs SSRIs SNRIs Antipsychoticsb Benzodiazepines Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics Eszopiclone Zaleplon Zolpidem Zaleplon Zolpidem Antipsychotics, chronic and as-needed useb Antiepileptics Drug(s) Moderate All others: high Opioids: moderate Quality of Evidence Moderate Avoid unless other Moderate alternatives are not effective and patient can take gastroprotective agent (ie, proton-pump inhibitor or misoprostol) Avoid Opioids: avoid except for pain management in the setting of severe acute pain (eg, recent fractures or joint replacement) Avoid unless safer alternatives are not available; avoid antiepileptics except for seizure and mood disorders Recommendation May increase risk of acute kidney Avoid injury and further decline of renal function May exacerbate existing ulcers or cause new/additional ulcers Exceptions: Pimavanserin and clozapine appear to be less likely to precipitate worsening of Parkinson disease. Quetiapine has only been studied in low-quality clinical trials with efﬁcacy comparable to that of placebo in ﬁve trials and to that of clozapine in two others. If one of the drugs must be used, consider reducing use of other CNS-active medications that increase risk of falls 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. Data for antidepressants are mixed but no compelling evidence that certain antidepressants confer less fall risk than others. Dopamine-receptor antagonists with potential to worsen parkinsonian symptoms others. Antipsychotics are associated with greater risk of cerebrovascular accident (stroke) and mortality in persons with dementia. May cause ataxia, impaired psychomotor function, syncope, additional falls; shorteracting benzodiazepines are not safer than long-acting ones. Rationale Strong Strong Strong Strong (Continued) Strength of Recommendation MONTH 2019–VOL. 00, NO. 00 Gastrointestinal History of gastric or duodenal ulcers Parkinson disease History of falls or fractures Disease or Syndrome Table 3 (Contd.) JAGS 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL 11 Lower urinary tract symptoms, benign prostatic hyperplasia Abbreviations: AChEI, acetylcholinesterase inhibitor; CCB, calcium channel blocker; CNS, central nervous system; COX, cyclooxygenase; NSAID, nonsteroidal anti-inﬂammatory drug; SNRI, serotoninnorepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. a 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. b 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. c Excludes inhaled and topical forms. Oral and parenteral corticosteroids may be required for conditions such as exacerbation of chronic obstructive pulmonary disease but should be prescribed in the lowest effective dose and for the shortest possible duration. Strong Peripheral alpha-1 blockers Doxazosin Prazosin Terazosin Strongly anticholinergic drugs, except May decrease urinary ﬂow and cause antimuscarinics for urinary incontinence urinary retention (see Table 7 and full criteria available on www.geriatricscareonline.org) Avoid in men Moderate Peripheral alpha-1 blockers: strong Peripheral alpha-1 blockers: moderate Estrogen: high Avoid in women Lack of efﬁcacy (oral estrogen) and aggravation of incontinence (alpha-1 blockers) Estrogen oral and transdermal (excludes intravaginal estrogen) Urinary incontinence (all types) in women Quality of Evidence Recommendation Rationale Drug(s) Disease or Syndrome Table 3 (Contd.) Estrogen: strong 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL Strength of Recommendation 12 MONTH 2019–VOL. 00, NO. 00 • • • • • JAGS was lowered to 70 years or older from 80 years or older. This criterion was also expanded to cover use of aspirin as primary prevention of colorectal cancer. Note that this criterion does not apply to use of aspirin for secondary prevention of either disease. In addition to the existing caution about dabigatran, the updated criteria highlight caution about use of rivaroxaban for treatment of venous thromboembolism or atrial ﬁbrillation in adults 75 years or older. Tramadol was added to the list of drugs associated with hyponatremia or syndrome of inappropriate antidiuretic hormone secretion. The chemotherapeutic agents carboplatin, cyclophosphamide, cisplatin, and vincristine were removed from this list because the panel thought the prescribing of these highly specialized drugs fell outside the scope of the criteria. Vasodilators were removed, because syncope is not unique to older adults. The combination dextromethorphan/quinidine was added to the “use with caution” table on the basis of limited efﬁcacy in patients with behavioral symptoms of dementia without pseudobulbar affect while potentially increasing the risk of falls and drug-drug interactions. The combination trimethoprim-sulfamethoxazole (TMP-SMX) should be used with caution by patients with reduced kidney function and taking an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) because of an increased risk of hyperkalemia. Drug-Drug Interactions Table 5 contains potentially clinically important drug-drug interactions to be avoided in older adults. New recommendations include avoiding use of opioids concurrently with benzodiazepines and avoiding use of opioids concurrently with gabapentinoids (except when transitioning from the former to the latter). Other additions to the table are interactions involving TMP-SMX, macrolide antibiotics, and ciproﬂoxacin. TMP-SMX in combination with phenytoin or warfarin increases the risk of phenytoin toxicity and bleeding, respectively. Macrolides, excluding azithromycin, or ciproﬂoxacin in combination with warfarin increases bleeding risk. Ciproﬂoxacin in combination with theophylline increases risk of theophylline toxicity. The concurrent use of a combination of three or more central nervous system (CNS) agents (antidepressants, antipsychotics, benzodiazepines, nonbenzodiazepine benzodiazepine receptor agonist hypnotics, antiepileptics, and opioids) and increased fall risk have been collapsed into one recommendation instead of separate recommendations for each drug class. The recommendation on avoiding concurrent use of medications that increase serum potassium has been expanded to encompass a broader range of these medications. PIMs Based on Kidney Function Table 6 contains a list of medications that should be avoided or have their dosage reduced based on kidney function. Two antibiotics have been added, ciproﬂoxacin and TMP-SMX, over concerns of increased CNS effects and tendon rupture, and worsening renal function and hyperkalemia, respectively. Dofetilide was also added because of concerns of corrected QT interval prolongation and torsade de pointes. The creatinine clearance lower limit at which to avoid edoxaban has been reduced to less than 15 mL/min. JAGS 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL MONTH 2019–VOL. 00, NO. 00 13 Table 4. 2019 American Geriatrics Society Beers Criteria® for Potentially Inappropriate Medications: Drugs To Be Used With Caution in Older Adultsa Quality of Evidence Strength of Recommendation Use with caution in adults ≥70 years Moderate Strong Use with caution for treatment of VTE or atrial ﬁbrillation in adults ≥75 years Use with caution in adults ≥75 years Moderate Strong Moderate Weak Use with caution Moderate Strong Use with caution Moderate Strong Use with caution in patients on ACEI or ARB and decreased creatinine clearance Low Strong Drug(s) Rationale Recommendation Aspirin for primary prevention of cardiovascular disease and colorectal cancer Risk of major bleeding from aspirin increases markedly in older age. Several studies suggest lack of net beneﬁt when used for primary prevention in older adult with cardiovascular risk factors, but evidence is not conclusive. Aspirin is generally indicated for secondary prevention in older adults with established cardiovascular disease. Increased risk of gastrointestinal bleeding compared with warfarin and reported rates with other direct oral anticoagulants when used for long-term treatment of VTE or atrial ﬁbrillation in adults ≥75 years. Increased risk of bleeding in older adults; beneﬁt in highest-risk older adults (eg, those with prior 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. May exacerbate or cause SIADH or hyponatremia; monitor sodium level closely when starting or changing dosages in older adults Dabigatran Rivaroxaban Prasugrel Antipsychotics Carbamazepine Diuretics Mirtazapine Oxcarbazepine SNRIs SSRIs TCAs Tramadol Dextromethorphan/ quinidine Trimethoprimsulfamethoxazole Limited efﬁcacy in patients with behavioral symptoms of dementia (does not apply to treatment of PBA). May increase risk of falls and concerns with clinically signiﬁcant drug interactions. Does not apply to treatment of pseudobulbar affect. Increased risk of hyperkalemia when used concurrently with an ACEI or ARB in presence of decreased creatinine clearance Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; PBA, pseudobulbar affect; SIADH, syndrome of inappropriate antidiuretic hormone secretion; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; VTE, venous thromboembolism. a 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 healthoutcome, quality-of-care, cost, and utilization data. DISCUSSION The 2019 AGS Beers Criteria® update contributes to the critically important evidence base and discussion of medications to avoid in older adults and the need to improve medication use in older adults. The 2019 AGS Beers Criteria® include 30 individual criteria of medications or medication classes to be avoided in older adults (Table 2) and 16 criteria speciﬁc to more than 40 medications or medication classes that should be used with caution or avoided in certain diseases or conditions (Tables 3 and 4). As in past updates, there were several changes to the 2019 AGS Beers Criteria®, including criteria that were modiﬁed or dropped, a few new criteria, and some changes in the level of evidence grading and clariﬁcations in language and rationale (Tables 8–10). The 2019 AGS Beers Criteria® is the third such update by the AGS and the ﬁfth update of the AGS Beers Criteria® since their original release.1,2,10–12 The criteria was ﬁrst published almost 30 years ago in 1991, making them the longest running criteria for PIMs in older adults. Increased risk of overdose Increased risk of severe sedation-related adverse events, including respiratory depression and death Benzodiazepines Gabapentin, pregabalin Anticholinergic Any combination of three or more of these CNS-active drugsa NSAIDs ACEIs Loop diuretics Loop diuretics Trimethoprim-sulfamethoxazole Cimetidine Ciproﬂoxacin Amiodarone Ciproﬂoxacin Macrolides (excluding azithromycin) Anticholinergic Antidepressants (TCAs, SSRIs, and SNRIs) Antipsychotics Antiepileptics Benzodiazepines and nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (ie, “Z-drugs”) Opioids Corticosteroids, oral or parenteral Lithium Lithium Peripheral α-1 blockers Phenytoin Theophylline Theophylline Warfarin Warfarin Warfarin Increased risk of bleeding Avoid when possible; if used together, monitor INR closely Avoid when possible; if used together, monitor INR closely Avoid when possible; if used together, monitor INR closely Avoid Avoid Avoid; monitor lithium concentrations Avoid; monitor lithium concentrations Avoid in older women, unless conditions warrant both drugs Avoid Avoid; if not possible, provide gastrointestinal protection Avoid routine use in those with chronic kidney disease stage 3a or higher Avoid Avoid; exceptions are when transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose, although caution should be used in all circumstances. Avoid; minimize number of anticholinergic drugs (Table 7) Avoid total of three or more CNS-active drugsa; minimize number of CNS-active drugs Recommendation Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Moderate Strong Combinations including benzodiazepines and nonbenzodiazepine, benzodiazepine receptor agonist hypnotics or opioids: high All other combinations: moderate Moderate Strong Strong Strong Strong Strong Strong Strong Strong Strong Strong Strong Strong Strong Strong Strength of Recommendation Moderate Moderate Moderate Moderate Quality of Evidence 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL Increased risk of bleeding Increased risk of urinary incontinence in older women Increased risk of phenytoin toxicity Increased risk of theophylline toxicity Increased risk of theophylline toxicity Increased risk of bleeding Increased risk of lithium toxicity Increased risk of peptic ulcer disease or gastrointestinal bleeding Increased risk of lithium toxicity Increased risk of cognitive decline Increased risk of falls (all) and of fracture (benzodiazepines and nonbenzodiazepine, benzodiazepine receptor agonist hypnotics) Increased risk of hyperkalemia Risk Rationale Another RAS inhibitor (ACEIs, ARBs, aliskiren) Interacting Drug and Class RAS inhibitor (ACEIs, ARBs, aliskiren) or potassium-sparing diuretics (amiloride, triamterene) Opioids Opioids Object Drug and Class Table 5. 2019 American Geriatrics Society Beers Criteria® for Potentially Clinically Important Drug-Drug Interactions That Should Be Avoided in Older Adults 14 MONTH 2019–VOL. 00, NO. 00 JAGS Increased risk of bleeding NSAIDs Warfarin Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CNS, central nervous system; INR, international normalized ratio; NSAID, nonsteroidal anti-inﬂammatory drug; RAS, renin-angiotensin system; SNRI, serotonin- norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant. a CNS-active drugs: antiepileptics; antipsychotics; benzodiazepines; nonbenzodiazepine, benzodiazepine receptor agonist hypnotics; TCAs; SSRIs; SNRIs; and opioids. Strong High Moderate Avoid when possible; if used together, monitor INR closely Avoid when possible; if used together, monitor closely for bleeding Increased risk of bleeding Trimethoprim-sulfamethoxazole Warfarin Quality of Evidence Recommendation Risk Rationale Interacting Drug and Class Object Drug and Class Table 5 (Contd.) Strong MONTH 2019–VOL. 00, NO. 00 Strength of Recommendation JAGS 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL 15 The 2019 update has a similar number of changes to the 2015 update but fewer changes than the 2012 update. This is likely because, with the support of the AGS and the expert panel, the criteria have been regularly updated about every 3 years since 2012. In 2019, 25 medications or medication classes to be avoided outright or in a disease condition were dropped from the AGS Beers Criteria® (Table 8). A few were also moved to a new table category or modiﬁed (Table 10). For medications to be removed from the AGS Beers Criteria®, the panel had to have new evidence or a strong rationale, for reasons such as the literature showed a change in evidence that cast new doubt on their “avoid” status. Finally, some drugs or drug-disease combinations were omitted because they are not disproportionately relevant to the older adult population; this included the criteria on drugs to avoid in adults with chronic seizures or epilepsy and in adults with insomnia. Four new medications or medication classes were added to the list of drugs to be used with caution (Table 4; additions are also summarized in Table 9). Dextromethorphan/quinidine was added because of its limited efﬁcacy, concerns for clinically signiﬁcant drug interactions, and potentially increased risk of falls in older adults. TMP-SMX was placed in the “use with caution table” because of increased risk of hyperkalemia when used concurrently with an ACEI or ARB in the presence of decreased creatinine clearance.13,14 Rivaroxaban was also added to the use with caution table for adults 75 years or older. Other important changes in the use with caution table included lowering the age threshold in the aspirin for primary prevention recommendation from 80 years or younger to 70 years or younger on the basis of emerging evidence of a major increase in the risk of bleeding at a lower age.15 The Aspirin in Reducing Events in the Elderly (ASPREE) trial, which was published outside the window of our literature search, found that low-dose aspirin used for primary prevention in older adults did not confer a reduction in mortality, disability-free survival, or cardiovascular events.16,17 In a few instances, the level of evidence was revised based on new literature and the improved modiﬁed grading method. For instance, H2-receptor antagonists were removed from the list of drugs to avoid in dementia, and the evidence level for H2-receptor antagonists was decreased to low (from moderate in 2015) for drugs to avoid in delirium.18 Again in 2019, the panel clariﬁed the language for sliding-scale insulin because this continued to be an area of confusion for clinicians. Importantly, several drugs were added to the drugdisease and drug-drug interactions tables (Tables 3 and 5). Notably, SNRIs were added to the list of antidepressant drug classes to avoid in persons with a history of falls or fractures.19,20 For this criterion, the level of evidence for opioids was changed to “moderate”; all other drugs remain at high. Two new drug-drug interactions involving opioids were added, reﬂecting evidence of substantial harms that can occur when opioids are used concurrently with benzodiazepines or gabapentinoids. Though these drug interactions involving opioids are problematic in all persons, they are growing increasingly common and may lead to greater harm in vulnerable older adults. These concerns need to be balanced with the need to treat chronic pain. A recent review of deaths from opioids concluded that the burden of opioid overdose in older adults requires special attention, noting the largest 16 2019 AGS BEERS CRITERIA® UPDATE EXPERT PANEL MONTH 2019–VOL. 00, NO. 00 JAGS Table 6. 2019 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 Medication Class and Medication Creatinine Clearance at Which Action Required, mL/min Anti-infective Ciproﬂoxacin Trimethoprimsulfamethoxazole
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