2019 AGS Beers Criteria for older adults

Abstract

Polypharmacy, often defined as the use of five or more medications, is prevalent in adults ages 65 years and older, with 40% taking 5 to 9 medications and 18% taking 10 or more.1Budnitz D.S. Lovegrove M.C. Shehab N. Emergency hospitalizations for adverse drug events in older Americans.N Engl J Med. 2011; 365: 2002-2012Crossref PubMed Scopus (1225) Google Scholar Polypharmacy can result in inappropriate prescribing of medications, causing adverse drug events (ADEs).2Steinman M.A. Landefeld C.S. Rosenthal G.E. et al.Polypharmacy and prescribing quality in older people.J Am Geriatr Soc. 2006; 54: 1516-1523Crossref PubMed Scopus (380) Google Scholar Studies have shown that ADEs in older adults can lead to increased emergency department visits and hospitalizations, resulting in increased health care utilization and cost.1Budnitz D.S. Lovegrove M.C. Shehab N. Emergency hospitalizations for adverse drug events in older Americans.N Engl J Med. 2011; 365: 2002-2012Crossref PubMed Scopus (1225) Google Scholar, 3Stockl K.M. Le L. Zhang S. et al.Clinical and economic outcomes associated with potentially inappropriate prescribing in the elderly.Am J Manag Care. 2010; 16: e1-e10PubMed Google Scholar The Beers Criteria were first developed in 1991 by Mark H. Beers, MD, to decrease inappropriate prescribing and ADEs and, in particular, to identify medications or medication classes that should be avoided in older adults in nursing homes.4Marcum Z.A. Hanlon J.T. Commentary on the new American Geriatric Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.Am J Geriatr Pharmacother. 2012; 10: 151-159Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar In 2011, after Beers’s death, the American Geriatrics Society (AGS) began to oversee the revisions and updates to the criteria. AGS has provided updates to the criteria every 3 years, starting in 2012.6American Geriatrics Society 2012 Beers Criteria Update Expert Panel American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2012; 60: 616-631Crossref PubMed Scopus (1689) Google Scholar, 7American Geriatrics Society Beers Criteria Update Expert Panel American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2015; 63: 2227-2246Crossref PubMed Scopus (1736) Google Scholar In January 2019, AGS published the latest update to the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. This update includes specific recommendations for a medication or therapeutic class that should not be considered or should be used with caution in older adults.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar The AGS Beers Criteria are widely used by health care providers, researchers, and educators but are intended primarily for practicing clinicians to manage and improve the care of adults ages 65 years and older.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar For the 2019 AGS Beers Criteria, an interdisciplinary expert panel reviewed published evidence since the last update in 2015, focusing on data from January 1, 2015, to September 30, 2017.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar During the review process, the panel determined whether new criteria should be added or if existing criteria should be removed or changed. The aim was to provide an update using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse events in older adults.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar Accreditation informationProvider: APhATarget audience: PharmacistsRelease date: November 1, 2019Expiration date: November 1, 2022Learning level: 2ACPE Universal Activity Number: 0202-0000-19-286-H04-PCPE credit: 2 hours (0.2 CEUs)Fee: There is no fee associated with this activity for APhA members. There is a $25 fee for nonmembers.APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-19-286-H04-P.Advisory board: Robert L. Page II, PharmD, MSPH, BCPS (AQ-Cards), BCGP, FCCP, FASHP, FAHA, FHFSA, professor, Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora.Disclosures: Danielle R. Fixen, Robert L. Page II, and APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see www.pharmacist.com/aphadisclosures.Development: This home-study CPE activity was developed by APhA. Learning objectivesAfter participating in this activity, pharmacists will be able to■Evaluate and make recommendations for medication regimens using the 2019 American Geriatrics Society Beers Criteria.■Identify potentially inappropriate medications and drugs to be used with caution in older adults.■Identify risks associated with clinically important drug–drug interactions in older adults.■Develop an alternative therapeutic plan for medications that have varying doses, based on renal function in older adults. Provider: APhA Target audience: Pharmacists Release date: November 1, 2019 Expiration date: November 1, 2022 Learning level: 2 ACPE Universal Activity Number: 0202-0000-19-286-H04-P CPE credit: 2 hours (0.2 CEUs) Fee: There is no fee associated with this activity for APhA members. There is a $25 fee for nonmembers. APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-19-286-H04-P. Advisory board: Robert L. Page II, PharmD, MSPH, BCPS (AQ-Cards), BCGP, FCCP, FASHP, FAHA, FHFSA, professor, Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus, Aurora. Disclosures: Danielle R. Fixen, Robert L. Page II, and APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. For complete staff disclosures, please see www.pharmacist.com/aphadisclosures. Development: This home-study CPE activity was developed by APhA. After participating in this activity, pharmacists will be able to■Evaluate and make recommendations for medication regimens using the 2019 American Geriatrics Society Beers Criteria.■Identify potentially inappropriate medications and drugs to be used with caution in older adults.■Identify risks associated with clinically important drug–drug interactions in older adults.■Develop an alternative therapeutic plan for medications that have varying doses, based on renal function in older adults. Preassessment questionsBefore participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment.1.Which medication may increase the risk of delirium?a.Pantoprazoleb.Fluticasonec.Sertralined.Ranitidine2.Which statement is correct?a.SSRIs can increase the risk of syncopal episodes and falls.b.Vaginal estrogens may be appropriate for recurrent lower urinary tract infections.c.Meloxicam is more likely than other NSAIDs to have adverse CNS effects.d.Dextromethorphan/quinidine is not recommended for adults 80 years and older with pseudobulbar affect.3.The risk of hyponatremia is increased with use of escitalopram in combination with which of the following?a.Tramadolb.TMP-SMXc.Bupropiond.Alprazolam Before participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment.1.Which medication may increase the risk of delirium?a.Pantoprazoleb.Fluticasonec.Sertralined.Ranitidine2.Which statement is correct?a.SSRIs can increase the risk of syncopal episodes and falls.b.Vaginal estrogens may be appropriate for recurrent lower urinary tract infections.c.Meloxicam is more likely than other NSAIDs to have adverse CNS effects.d.Dextromethorphan/quinidine is not recommended for adults 80 years and older with pseudobulbar affect.3.The risk of hyponatremia is increased with use of escitalopram in combination with which of the following?a.Tramadolb.TMP-SMXc.Bupropiond.Alprazolam The writing committee for the 2019 update was tasked with the following:■Incorporate new evidence on potentially inappropriate medications (PIMs) included in the 2015 AGS Beers Criteria, as well as develop new or modify existing criteria.■Grade the strength and quality of each PIMs statement based on the level of evidence and strength of recommendation (see Table 1 in this CPE article).Table 1Designations of quality of evidence and strength of recommendationsQuality of evidenceaQuality of evidence ratings for each criterion are based on synthetic assessment of two complementary approaches to evaluating the quality of evidence.ACP-based approachGRADE-based approachHigh quality“Evidence … obtained from one or more well-designed and well-executed randomized, controlled trials (RCTs) that yield consistent and directly applicable results. This also means that further research is very unlikely to change our confidence in the estimate of effect.”Consider the following five factors for the studies that comprise the best-available evidence for a given criterion:1.Risk of bias: Severity of threats to studies’ internal validity (e.g., randomized vs. observational design, potential for confounding, bias in measurement)2.Inconsistency: Do different studies provide similar or different estimates of effect size?3.Indirectness: How relevant are the studies to the clinical question at hand (e.g., nature of study of population, comparison group, type of outcome measured)4.Imprecision: Precision of estimates of effect5.Publication bias: Risk of bias due to selective publication of resultsModerate quality“Evidence … obtained from RCTs with important limitations. … In addition, evidence from well-designed controlled trials without randomization, well-designed cohort or case-control analytic studies, and multiple time series with or without intervention are in this category. Moderate-quality evidence also means that further research will probably have an important effect on our confidence in the estimate of effect and may change the estimate.”Low quality“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, lowStrength of evidencebStrength 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.StrongHarms, adverse events, and risks clearly outweigh benefitsWeakHarms, adverse events, and risks may not outweigh benefits.Source: Adapted with permission from reference 5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar.Abbreviations used: ACP, American College of Physicians; GRADE, Grading of Recommendations Assessment, Development, and Evaluation.a Quality of evidence ratings for each criterion are based on synthetic assessment of two complementary approaches to evaluating the quality of evidence.b 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. Open table in a new tab ■Convene an interdisciplinary panel of 13 experts in geriatric care and pharmacotherapy who would apply a modified Delphi method to reach consensus.■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 care settings. Abbreviations used: ACP, American College of Physicians; GRADE, Grading of Recommendations Assessment, Development, and Evaluation. The 2019 update addresses medications through the following perspectives: medications that are potentially inappropriate in older adults, medications that may exacerbate a disease or syndrome, drugs to be used with caution in older adults, those with clinically important drug interactions, and those that should be avoided or have their dose reduced due to renal function.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar Drugs with strong anticholinergic properties are one addition to the 2019 AGS Beers Criteria. As mentioned above, the intent of the AGS Beers Criteria is to improve medication selection, educate clinicians and patients, reduce ADEs, and serve as a tool for evaluating quality of care, cost, and patterns of drug use among older adults.5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar However, these criteria are not meant to be used punitively but as a guide, along with clinical judgment. There are prescribing scenarios in which medications listed in the criteria cannot be avoided or the recommendation does not apply to a specific population. Therefore, clinicians should consider patient-specific factors when determining if a medication is to be discontinued, modified, or added. The 2019 AGS Beers Criteria contain six tables: PIMs in older adults, drug–disease or drug–syndrome interactions that may exacerbate the disease or syndrome, drugs to be used with caution in older adults, drug–drug interactions that should be avoided in older adults, medications that should be avoided or have their dosage reduced with varying levels of kidney function in older adults, and drugs with strong anticholinergic properties. Table 2, Table 3, Table 4 in this CPE article are modified versions of those six tables.Table 2Incorporated changes of potentially inappropriate medications in older adultsMedication or medication classRecommendation; rationale (changes to the 2015 criteria)AnticholinergicsFirst-generation antihistaminesAvoid; clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicityAntiparkinsonian agents (benztropine, trihexyphenidyl)Avoid; not recommended for prevention of extrapyramidal symptoms with antipsychoticsAntispasmodicsAvoid; high anticholinergic and uncertain effectivenessAntithromboticsDipyridamole, oral short-actingAvoid; may cause orthostatic hypotension, and more effective alternatives available; I.V. form acceptable to use in cardiac stress testingAnti-infectiveNitrofurantoinAvoid in individuals with CrCL < 30 mL/min or long-term suppression; potential for pulmonary toxicity, hepatotoxicity, and peripheral neuropathy, especially with long-term useCardiovascularPeripheral alpha-1 blockers for treatment of hypertensionAvoid use as antihypertensive; high risk of orthostatic hypotension and associated harms, especially in older adultsCentral-alpha agonists(clonidine, guanabenz, guanfacine, methyldopa, reserpine > 0.1 mg/d)Avoid clonidine as first-line antihypertensive. Avoid other CNS alpha-agonists as listed; high risk of adverse CNS effects; may cause bradycardia and orthostatic hypotensionDisopyramideAvoid; may induce heart failure in older adults because of potent inotropic action; strongly anticholinergicDronedaroneAvoid in individuals with permanent atrial fibrillation or severe or recently decompensated heart failure; worse outcomes have been reported in patients who have permanent atrial fibrillation or severe or recently decompensated heart failureDigoxin for first-line treatment of atrial fibrillation or heart failureAvoid this rate control agent as first-line therapy for atrial fibrillation. Avoid as first-line therapy for heart failure. If used, avoid dosages > 0.125 mg/d. Atrial fibrillation: should not be used as first-line because there are safer and more effective alternatives for rate control supported by high-quality evidence. 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. 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 releaseAvoid; potential for hypotension; risk of precipitating myocardial ischemiaAmiodaroneAvoid as first-line therapy for atrial fibrillation unless patient has heart failure or substantial left ventricular hypertrophy; effective for maintaining sinus rhythm but has greater toxicities than other antiarrhythmics used in atrial fibrillationCNSAntidepressants, alone or in combination (amitriptyline, amoxapine, clomipramine, desipramine, doxepin > 6 mg/d, imipramine, nortriptyline, paroxetine, protriptyline, trimipramine)Avoid; high anticholinergic, sedating, and cause orthostatic hypotensionAntipsychotics, first (conventional) and second (atypical) generationAvoid, except in schizophrenia, bipolar disorder, or for short-term use as antiemetic during chemotherapy; increased risk of cerebrovascular accident and greater rate of cognitive decline and mortality in persons with dementia; avoid for behavioral problems of dementia or delirium unless nonpharmacological options have failure or are not possible and the older adult is threatening substantial harm to self or othersBarbituratesAvoid; high rate of physical dependence, tolerance to sleep benefits, greater risk of overdose at low dosagesBenzodiazepines (short, intermediate, and long-acting)Avoid; older adults have increased sensitivity to and decreased metabolism with long-acting agents; increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes; may be appropriate for seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesiaMeprobamateAvoid; high rate of physical dependence and sedatingNonbenzodiazepine, benzodiazepine receptor agonist hypnotics (Z drugs)Avoid; adverse events similar to those of benzodiazepines in older adults; increased emergency department visits/hospitalizations; motor vehicle crashes; minimal improvement in sleep latency and durationErgoloid mesylatesAvoid; lack of efficacyEndocrineAndrogensAvoid unless indicated for confirmed hypogonadism with clinical symptoms; potential for cardiac problems; contraindicated in men with prostate cancerDesiccated thyroidAvoid; concerns about cardiac effectsEstrogens with or without progestinsAvoid systemic estrogen (oral, topical). Vaginal cream or vaginal tablets acceptable to use low dose for management of dyspareunia, recurrent lower urinary tract infections, and other vaginal symptoms; carcinogenic potential; lack of cardio and cognitive protectionGrowth hormoneAvoid, except for patients diagnosed with growth hormone deficiency due to an established etiology; impact on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired fasting glucoseInsulin, 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)Avoid; higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care settingMegestrolAvoid; minimal effect on weight with increased risk of thrombotic events and possibly death in older adultsSulfonylureas, long-acting (chlorpropamide, glimepiride, glyburide)Avoid; chlorpropamide: long half-life and can cause prolonged hypoglycemia and SIADH; glimepiride and glyburide: higher risk of severe prolonged hypoglycemiaGIMetoclopramideAvoid, unless for gastroparesis with duration not to exceed 12 weeks except in rare cases; can cause extrapyramidal effects, including tardive dyskinesiaMineral oil, given orallyAvoid; potential for aspiration and adverse effectsPPIsAvoid scheduled use for > 8 weeks unless for high-risk patients, erosive esophagitis, Barrett’s esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance treatment; risk of Clostridium difficile infection, bone loss, and fracturesPain medicationsMeperidineAvoid; not effective in dosages commonly used and has a higher risk of neurotoxicity, including delirium, than other opioidsCOX nonselective NSAIDs, oralAvoid chronic use, unless other alternatives are not effective and patient can take gastroprotective agent; increased risk of GI bleeding or peptic ulcer disease in high-risk groups, including those > 75 years or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents; can increase blood pressure and induce kidney injuryIndomethacin,ketorolac, includes parenteralAvoid; increased risk of GI bleeding/peptic ulcer disease and acute kidney injury; indomethacin is more likely than other NSAIDs to have adverse CNS effectsSkeletal muscle relaxantsAvoid; poorly tolerated by older adults because some have anticholinergic adverse effects, sedation, and increased risk of fracturesGenitourinaryDesmopressinAvoid for treatment of nocturia or nocturnal polyuria; high risk of hyponatremiaSource: Adapted with permission from reference 5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar.Note: Recommendations are underlined; italics denote changes to 2015 criteria.Abbreviations used: CrCL, creatinine clearance; CNS, central nervous system; HFrEF, reduced ejection fraction. Open table in a new tab Table 3Incorporated changes of drug–drug, drug–disease, or drug–syndrome interactions in older adultsMedication or medication classRecommendation; rationale (changes to the 2015 criteria)CardiovascularHeart failure (cilostazol, nondihydropyridine CCBs, NSAIDs, COX-2 inhibitors, thiazolidinediones, dronedarone)Avoid: cilostazol; potential to increase mortalityAvoid in HFrEF: nondihydropyridine CCBs; may promote fluid retention and/or exacerbate heart failureUse with caution in patients with asymptomatic heart failure; avoid in patients with symptomatic heart failure: NSAIDs, COX-2 inhibitors, and thiazolidinediones (may promote fluid retention and/or exacerbate heart failure); dronedarone (potential to increase mortality)Syncope (AChEIs, nonselective peripheral alpha-1 blockers, tertiary TCAs, antipsychotics [chlorpromazine, thioridazine, olanzapine])Avoid; AChEIs cause bradycardia; nonselective peripheral alpha-1 blockers cause orthostatic blood pressure changes; tertiary TCAs and antipsychotics increase risk of orthostatic hypotension and bradycardiaCNSDelirium (anticholinergics, antipsychotics, benzodiazepines, corticosteroids, H2-receptor antagonists, meperidine, Z drugsAvoid; potential of inducing or worsening delirium; avoid antipsychotics for behavioral problems of dementia and/or delirium unless nonpharmacological options have failed or are not possible and the older adult is threatening substantial harm to self or others; antipsychotics are associated with greater risk of cerebrovascular accident and mortality in patients with dementiaDementia or cognitive impairment (anticholinergics, benzodiazepines, Z drugs, antipsychotics used chronically and “as needed”)Avoid; adverse CNS effects; avoid antipsychotics for behavioral problems of dementia and/or delirium unless nonpharmacological options have failed or are not possible and the older adults is threatening substantial harm to self or others; antipsychotics are associated with greater risk of cerebrovascular accident and mortality in patients with dementiaHistory of falls or fractures (antiepileptics, antipsychotics, benzodiazepines, Z drugs, antidepressants [TCAs, SSRIs, SNRIs], opioids)Avoid unless safer alternatives are not available; avoid antiepileptics except for seizure and mood disorders; avoid opioids except for pain management in setting of acute pain; may cause ataxia, impaired psychomotor function, syncope, additional fallsParkinson disease (antiemetics [metoclopramide, prochlorperazine, promethazine], all antipsychotics except quetiapine, clozapine, and pimavanserin)Avoid; dopamine-receptor antagonists with potential to worsen parkinsonian symptomsGIHistory of gastric or duodenal ulcers (aspirin > 325 mg/d, COX-2 nonselective NSAIDs)Avoid unless alternatives are not effective and patient can take gastroprotective agent; may exacerbate existing ulcers or cause new/additional ulcersKidney/urinary tractChronic kidney disease stage 4 or higher, CrCL < 30 mL/min (NSAIDs)Avoid; may increase risk of acute kidney injury and further decline of renal functionUrinary incontinence in women (oral and transdermal estrogen, peripheral alpha-1 blockers)Avoid in women; oral estrogen: lack of efficacyPeripheral alpha-1 blockers: aggravation of incontinenceLower urinary tract symptoms, benign prostatic hyperplasia (strongly anticholinergic drugs, except antimuscarinics for urinary incontinence)Avoid in men; may decrease urinary flow and cause urinary retentionDrug–drug interactionsRAS inhibitor or potassium-sparing diuretics and another RAS inhibitorAvoid routine use in those with chronic kidney disease stage 3a or higher;increased risk of hyperkalemiaOpioids and benzodiazepinesAvoid; increased risk of overdoseOpioids and gabapentin, pregabalinAvoid; increased risk of severe sedation-related adverse events (respiratory depression and death)Anticholinergic and anticholinergicAvoid; increased risk of cognitive declineAntidepressants (TCAs, SSRIs, and SNRIs), antipsychotics, antiepileptics, benzodiazepines, Z drugs, and opioids plus any combination of three or more of these CNS-active drugsAvoid total of three or more CNS-active drugs;All: increased risk of fallsBenzodiazepines and Z drugs: increased risk of fractureCorticosteroids (oral or parenteral) plus NSAIDsAvoid; increased risk of peptic ulcer disease or GI bleedingLithium plus ACEIs or loop diureticsAvoid; increased risk of lithium toxicityPeripheral alpha-1 blockers plus loop diureticsAvoid in older women; increased risk of urinary incontinencePhenytoin plus TMP-SMXAvoid; increased risk of phenytoin toxicityTheophylline plus cimetidine or ciprofloxacinAvoid; increased risk of theophylline toxicityWarfarin plus amiodarone or ciprofloxacin or macrolides (except azithromycin) or TMP-SMX or NSAIDsAvoid when possible; increased risk of bleedingSource: Adapted with permission from reference 5American Geriatrics Society 2019 Beers Criteria Update Expert Panel American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults.J Am Geriatr Soc. 2019; 67: 674-694PubMed Google Scholar.Note: Recommendations are underlined; italics denote changes to 2015 criteria.Abbreviations used: CCBs, calcium channel blockers; HFrEF, reduced ejection fraction; AChEIs, acetylcholinesterase inhibitors; TCAs, tricyclic antidepressants; CNS, central nervous system; CrCL, creatinine clearance; RAS, renin-angiotensin system; TMP-SMX, trimethoprim/sulfamethoxazole. Open table in a new tab Table 4Incorporated changes of medications to avoid or dose reduce with varying levels of kidney functionMedication and CrCL, mL/minRecommendation; rationale (changes to the 2015 criteria)Ciprofloxacin < 30Doses used to treat common infections typically require reduction; increased risk of CNS effects and tendon ruptureTMP-SMX < 30Reduce dose if CrCL 15–29 mL/min, and avoid if < 15 mL/min; increased risk of worsening renal fun