July CE Article

July CPE Article

2019 American Geriatrics Society Beers Criteria® Update

Authors: Mark Huffmyer, PharmD, BCGP, BCACP, CACP; Ana Vo, PharmD Candidate; Mary Sau, PharmD Candidate; Bao-Han Nguyen, MS, PharmD Candidate; Lynne Eckmann, PharmD, BCGP; Daniela C. Moga, MD, PhD The authors declare that there are no financial relationships that could be perceived as real or apparent conflicts of interest.

Universal Activity # 0143-0000-20-007-H01-P &T 1.0 Contact Hours (0.1 CEU) Expires 8/31/23

KPERF offers all CE articles to members online at www.kphanet.org

Learning Objectives: At the conclusion of this Knowledge-based article, the reader should be able to:

Define Beers Criteria® and its application.

Identify common medications to avoid or flagged with caution based on the 2019 American Geriatrics Society Beers Criteria®.

Evaluate updates from the 2015 American Geriatrics Society Beers Criteria®.

Illustrate Beers Criteria® to optimize medication regimens in older adults by evaluating risks and benefits of medications and reducing adverse drug events.

Background

From 2010 to 2050, it is projected that the older adult population (i.e., 65 years and older) will grow from 8% to 21% of the world population. With an increasingly aging population, clinical consequences arise as a result of the prevalence of comorbidities and decreased functional ability of the population. 1

Older adults are more likely to experience polypharmacy and associated inappropriate prescribing of medications. 2 Drug utilization reviews are tools that pharmacists can utilize to identify potentially inappropriate medications (PIMs) and their adverse drug reactions. Although PIMs are not a definitive contraindication for medication use in older adults, they may worsen a patient’s existing disease and require individualized evaluation of risks and benefits for decision-making. Inappropriate medications causing adverse drug reactions can have significant clinical consequences; adverse drug reactions are among the most common causes of iatrogenic harm and mortality. 3

In order to identify harmful medications and standardize prescribing guidelines for older populations over 65 years of age, Mark H. Beers, MD, developed the Beers Criteria® in 1991. 4 It has become the most widely used and longest-standing resource by clinicians in the United States of America to identify PIMs in older adults. 5, 6 As drug experts and liaisons, pharmacists and pharmacy technicians in clinical and community settings have the most important role in drug utilization review. Beers Criteria® can serve as a useful tool in helping pharmacists and pharmacy technicians be actively involved in the healthcare team to help identify medication-related problems and optimize treatment to improve outcomes. Regulatory bodies such as the Center for Medicaid and Medicare Services (CMS), Healthcare Effectiveness Data and Information Set (HEDIS), National Committee for Quality Assurance (NCQA), and Pharmacy Quality Alliance (PQA) have adapted Beers Criteria® with the same goal to improve patient outcomes. 7,8

After Beers’ death, the Beers Criteria® was adopted by the AGS, who published the first update in 2012. Since then, the AGS has updated Beers Criteria® every three years under the consideration of an interdisciplinary expert panel, including representatives from CMS, NCQA and PQA; the latest such update was published in 2019. 6 Beers Criteria® compiles a list of PIMs including (1) PIMs in older adults, (2) drug-disease or drug-syndrome interactions, (3) drugs to be used with caution in older adults, (4) drug-drug interactions that should be avoided in older adults, (5) medications that should be avoided or dose-adjusted with varying levels of kidney function in older adults, (6) drugs with harmful adverse effects, and (7) medications with strong anticholinergic properties. Rationale, recommendation, quality of evidence, and strength of recommendation are included. Quality of evidence is evaluated on an ACP- and GRADE-based approach and rated as low, moderate, or high. Strength of evidence is rated as strong or weak based on whether risk “clearly” or “may not” outweigh benefits. 6

How to Utilize the Beers Criteria®

In 2015, AGS released a set of principles to guide the application of the Beers Criteria® and optimize its implementation by clinicians. The first principle states that medications included in the Beers Criteria® should be considered potentially inappropriate, not definitely inappropriate.9 Drugs should be evaluated to ensure benefit over harm, but they are not contraindicated in the elderly population. Furthermore, to help with clinical decision-making, each criterion has a ra

tionale and recommendation that should be used to explain why and when a drug is potentially inappropriate. Because patients vary widely, understanding why a drug is included in the Beers Criteria® will help clinicians make the best decisions about which medications are inappropriate for an individual and provide safer, alternative therapies. Moreover, assessment of medication regimens should not end with Beers Criteria®. These criteria should be used as a starting point for a complete medication review, which involves evaluating each drug’s indication, adverse effects, effectiveness, and several patient factors including adherence, ability to pay, and goals of care.9 While a useful tool in the medication management of patients 65 and older, the AGS Beers Criteria® cannot be used as a universal set of rules. Clinicians should ultimately rely on their common sense and clinical judgment.9 This article will highlight some of the most frequently encountered and clinically relevant findings from the 2019 American Geriatrics Society Beers Criteria®. Recommendations are discussed for specific medication classes: drugs with strong anticholinergic properties, nonsteroidal anti-inflammatory drugs, aspirin, and proton pump inhibitors. These are followed by recommendations regarding PIM use and specific medical conditions: falls/syncope, delirium and dementia, urinary incontinence, and syndrome of inappropriate antidiuretic hormone secretion. The final two sections discuss drugdrug interactions and medications that should be avoided or have dosage reduced based on kidney function. A summary of changes to the 2015 update follows these sections.

Drugs with Strong Anticholinergic Properties

Medications with anticholinergic properties cause effects such as dry mouth, dry eyes, urinary retention, and constipation. In the older adult population with reduced renal and liver clearance capabilities and increased permeability of the blood-brain barrier, anticholinergic agents may lead to falls and cognitive impairment.6,10,11 There is increased risk of tolerance development when anticholinergics are used as hypnotics in older populations.6 Some commonly prescribed drugs with anticholinergic properties include select antidepressants, antiemetics, antihistamines, antiparkinsonian agents, antimuscarinics, and skeletal muscle relaxants. Beers Criteria® strongly recommend avoiding use of anticholinergic agents in older patients with moderate quality of evidence. One notable exception is the use of diphenhydramine for acute treatment of severe allergic reactions when the immediate benefits outweigh the potential risks.6

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Non–cyclooxygenase-selective NSAIDs such as ibuprofen, diclofenac, meloxicam, nabumetone, and others, increase risk of gastrointestinal (GI) bleeding, peptic ulcer disease, high blood pressure, and kidney injury. Risk of bleeding increases with age and patients over 75 years old are considered to be in a high risk bleeding group. Furthermore, the risk is amplified in those concurrently taking corticosteroids, anticoagulants, or antiplatelets. Risk is dose- and duration-related. Bleeding or perforation of the GI tract occurs in ~1% of patients treated for three to six months and up to 4% in those in treatment for one year. If chronic use of NSAID is indicated, consideration should be given to a gastroprotective agent such as a proton pump inhibitor (PPI) or misoprostol to reduce risk of GI bleed. The AGS presented this as a strong recommendation with moderate quality of evidence. Alternatives to oral NSAIDs include acetaminophen, nonacetylated salicylate, or SNRIs (i.e., duloxetine, venlafaxine); topical use of NSAIDs, capsaicin, or lidocaine may also be preferred.12

Aspirin for Primary Prevention

The Beers Criteria ® recommends using aspirin for primary prevention of cardiovascular disease or colorectal cancer with caution in adults aged 70 years or older. The risk of bleeding increases with age, and several studies have shown this risk outweighs the benefits in older adults. Furthermore, the ASPREE (Aspirin in Reducing Events in the Elderly) trial showed that among healthy adults who were predominantly 70 years of age or older and without an indication for aspirin, all-cause mortality was higher among patients receiving lowdose aspirin compared to placebo.13 Aspirin is still generally indicated for secondary prevention in patients with established cardiovascular disease. 6

Proton Pump Inhibitors (PPIs)

High quality of evidence supports the advisory that PPIs such as omeprazole increase risk of Clostridium difficile infection and bone loss along with fractures. The AGS strongly recommends limited duration of therapy for PPIs (less than eight weeks) unless patients have high-risk conditions such as erosive esophagitis, Barrett esophagitis, pathological hypersecretory condition, have failed other alternatives, or are under concurrent chronic NSAID or corticosteroid therapy.6 Though less potent, an H2 receptor antagonists (H2RA) may be considered as an alternative.14

Falls and Syncope

Falls are a major concern among older patients due to prevalence of concurrent bone disorders and increased risk of fractures. Broken bones, hip fractures, and head injury are among serious concerns associated with falls. Three million older adults will be treated in emergency departments, and 800,000 patients are hospitalized for fall injuries annually15. Many drugs may cause bradycardia and orthostatic hypotension, leading to risk of syncope. The AGS strongly recommends avoiding acetylcholinesterase inhibitors (AChEIs) in patients who experience syncope due to bradycardia with high quality evidence.6 Tertiary tricyclic antidepressants (TCAs) (i.e., amitriptyline, imipramine), nonselective peripheral alpha-1 blockers (i.e., doxazosin, prazosin), and some antipsychotics (i.e., olanzapine, chlorpromazine) may cause bradycardia or orthostatic hypotension. It is strongly recommended these select TCAs be avoided in older adults with syncope due to orthostatic hypotension, while nonselective peripheral alpha-1 blockers and antipsychotics are graded as weak recommendations; high quality evidence is used to make these recommendations.6

Patients with a history of falls or fractures should avoid antiepileptics, antipsychotics, benzodiazepines, ‘Z’-drugs (i.e., eszopiclone, zolpidem), antidepressants, and opioids unless safer alternatives are not an option. These drugs may cause ataxia, impaired psychomotor function, syncope, and additional falls. Consider reducing other CNS-active medications or implementing strategies to reduce falls if one of these drugs

must be used. Some antidepressants have higher risk than others, including TCAs, selective serotonin reuptake inhibitors (SSRIs), and SNRIs. The AGS conferred strong recommendations with high quality of evidence. Moderate quality of evidence suggests opioids may be considered to manage pain in acute situations but otherwise avoided.6

Fall prevention should be enforced by managing conditions such as cardiac arrhythmias, hemodynamic balance, orthostatic hypotension, and autonomic disorders. Balance exercises are also recommended if the patient is mobile.16 Alternative use for anticonvulsants for new-onset epilepsy should favor newer agents with more favorable side effect profiles (i.e., lamotrigine, levetiracetam). Neuropathic pain can be treated with SNRIs, gabapentinoids, topical capsaicin, or lidocaine patch.12 Alternatives to benzodiazepines and Z-drugs include buspirone and SNRIs for anxiety. Nonpharmacologic options should be considered prior to the use of hypnotics for sleep; these include practicing good sleep hygiene (i.e., avoiding stimulants prior to bedtime, limiting light exposure). To decrease risk of falls, SNRIs and bupropion are preferred over TCAs and SSRIs for depression.12

Delirium and Dementia

While delirium and dementia often manifest similarly with patients exhibiting confusion and cognitive impairment, the characteristics of the symptoms and etiologies are different. Delirium is often due to an acute, reversible cause and is transient. On the other hand, dementia is a chronic, progressive, and acquired impairment of executive function that is often insidious in onset.17 Drugs that may enhance these effects include anticholinergics, benzodiazepines (i.e., alprazolam, diazepam), Z-drugs, and antipsychotics. Delirium can also be induced or worsened by corticosteroids and H2RAs. Avoiding these drugs is strongly recommended due to their effects on the central nervous system (CNS). Antipsychotics should be avoided for delirium/dementia treatment unless nonpharmacologic options (i.e., behavioral interventions) have failed or are not possible and the patient threatens harm to self or others; a short course of therapy may be considered if unavoidable.6,12 Moderate quality of evidence supports these recommendations, with the exception of low-quality evidence behind claims against H2RAs.6 If nonpharmacologic options have failed, a low-dose anticholinergic agent such as risperidone or quetiapine may be used for the shortest duration possible for dementia.12

Urinary Incontinence

Urinary incontinence, especially in women, increases with age and affects quality of life. Over 200 million people are affected by incontinence globally.18 There is a lack of efficacy in the usage of oral estrogen replacement therapies. Therefore, it is strongly recommended that oral estrogen be avoided in older female patients. High quality of evidence supports this claim. Peripheral alpha-1 blockers may aggravate incontinence in women. There is a strong recommendation to avoid this class as well with moderate quality of evidence.6 Alternatives for oral estrogen may include topical or vaginal options. Escitalopram, venlafaxine, and gabapentin may also be recommended for symptoms of vasomotor instability (i.e., hot flashes).12 Lifestyle modifications should be implemented in patients presenting with urinary incontinence including losing weight in overweight patients, treating constipation, and maintaining fluid intake. Pelvic exercises that strengthen the pelvic floor muscle may be recommended. Surgical intervention may be indicated if pharmacologic options fail.19

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

A number of drug classes may exacerbate or potentiate SIADH and hyponatremia; these include antipsychotics, diuretics, SNRIs, SSRIs, and TCAs. Usage of carbamazepine, mirtazapine, oxcarbazepine, or tramadol may also be a risk. The AGS strongly cautions against use of these medications, but if they must be started, stopped, or dose-adjusted, monitoring sodium level is recommended. Moderate quality of evidence supports these recommendations.6

Drug-drug Interactions to Avoid

Several key drug-drug interactions are noted in older adults. Beers Criteria® strongly recommends avoiding concurrent use of opioids and benzodiazepines due to increased risk of overdose. Usage of opioids and gabapentin or pregabalin together is linked with increased risk of sedation, leading to respiratory depression and mortality. It is generally recommended to avoid this combination unless gabapentinoids are being used to reduce chronic opioid dose or during the period of transition from opioids to gabapentinoids for pain management.6 Any combination of three or more CNS-active drugs should be avoided due to increased risk of falls and fractures; these include TCAs, SSRIs, SNRIs, antipsychotics, antiepileptics, benzodiazepines, Z-drugs, and opioids. Moderate quality of evidence supports these recommendations.6

Medications That Should be Avoided or Have Dosage Reduction by Kidney Function

Many drugs are cleared renally. In the older population, impaired renal function is more likely; thus, it is important to take note of renally-eliminated medications and adjust the dose or avoid them altogether in these patients.6. Medications are listed below according to the creatinine clearance (CrCl) at which the dosage should be reduced or the drug should be avoided, followed by the rationale. Drugs are provided for two categories, anti-infectives and cardiovascular or hemostasis.

Anti-infectives:

Drugs that should be dose-reduced with:

CrCl <30 mL/min: ciprofloxacin due to increased risk of

CNS effects and tendon rupture.6

CrCl <30 mL/min: SMZ-TMP due to worsening renal function and hyperkalemia with SMZ-TMP.6 Drugs that should be avoided with:

CrCl <15 mL/min: SMZ-TMP due to worsening renal function and hyperkalemia with SMZ-TMP.6 Cardiovascular or hemostasis:

Drugs that should be dose-reduced with:

CrCl >30 mL/min: dabigatran in the presence of drugdrug interactions due to lack of evidence for safety and

efficacy.6

CrCl <30 mL/min: enoxaparin due to increased risk of bleeding.6

CrCl between 15 to 50 mL/min: rivaroxaban (if being used for nonvalvular atrial fibrillation) and edoxaban due to lack of evidence for safety and efficacy.6

CrCl between 20 to 59 mL/min: dofetilide due to increased risk of QTc interval prolongation and torsade de pointes.6 Drugs that should be avoided with:

CrCl <15 mL/min: rivaroxaban (if being used for nonvalvular atrial fibrillation) due to lack of evidence for safety and efficacy.6

CrCl <20 mL/min: dofetilide due to increased risk of

QTc interval prolongation and torsade de pointes.6

CrCl <25 mL/min: apixaban due to lack of evidence for safety and efficacy.6

CrCl <30 mL/min: fondaparinux due to increased risk of bleeding.6

CrCl <30 mL/min: amiloride, spironolactone, and triamterene due to increased potassium levels as well as decreased sodium levels when using triamterene.6

CrCl <30 mL/min: rivaroxaban (if being used for venous thromboembolism treatment or prophylaxis during hip or knee replacement) and dabigatran due to lack of evidence for safety and efficacy.6

CrCl <15 or >95 mL/min: edoxaban due to lack of evidence for safety and efficacy.6

Summary Changes from the 2015 AGS Beers Criteria® Update

Updating the criteria every three years allows the AGS to add new evidence-based guidelines and remove any non-pertinent information.6 From the 2015 reiteration of Beers Criteria®, the AGS removed drugs that have been discontinued from the United States market, recommendations with weak evident findings, and drugs that were no longer specific to the scope or target patient population. Of note, drug interactions with chronic seizures, epilepsy, insomnia, and vasodilator risk of syncope have been removed from recommendations due to broader recommendations that are no longer unique to elderly patients.6 Several drugs have also been added to the criteria. Glimepiride and serotonin-norepinephrine reuptake inhibitors (SNRIs) were added to the list of drugs to be avoided. Glimepiride has an increased risk of severe, prolonged hypoglycemia, and SNRIs should be specifically avoided in those with a history of falls or fractures. Additionally, ciprofloxacin and SMZ-TMP were added to the list of medications that should be avoided or have dosage reduced based on kidney function. Drug-drug interactions were also added including ciprofloxacin, macrolides (except azithromycin), and SMZTMP causing increased risk of bleeding with warfarin. Additionally, opioids should not be used concurrently with either benzodiazepines or gabapentinoids due to increased risk of

Other Resources

In addition to the Beers Criteria®, several resources are available to help in the medication review ofolder patients. GeriatricsCareOnline.org and AmericanGeriatrics.org are popular websites with additional tools, publications, and programs dedicated to the geriatric population. Additionally, AGS has an app available on Apple and Android devices called iGeriatrics. It has been updated with the latest Beers Criteria® and is a reference tool that can be kept in one’s pocket. Aside from PIMs, vaccination guidelines and fall prevention guidelines may also be useful for pharmacists.

Summary

This CE aims to highlight the most clinically relevant findings presented in the 2019 American Geriatrics Society Beers Criteria® update. Further investigation and a more thorough assessment can be done by reviewing the tables attached to the appendix directly from Beers Criteria®. The Beers Criteria® is a unique and useful tool that can help identify potentially inappropriate medication in older adults to guide drug therapy optimization including deprescribing, improve medication selection to avoid adverse drug events, and improve patient care and health-related outcomes.

References

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