What are some of the most common adverse drug events experienced by older adults?

As we age, our bodies become more susceptible to adverse drug events (ADEs).

Some of the most common ADEs experienced by older adults include increased sedation, falls, fractures, impaired or worsening cognition, increased hospitalizations, and premature death.

The Beers Criteria is a tool that can help reduce the incidence of these events by identifying potentially inappropriate medications and minimizing adverse drug reactions.

These drug-related problems include benzodiazepine withdrawal, anticholinergic effects, tardive dyskinesia, high risk of adverse CNS effects, risk of confusion, etc.

Although the list of inappropriate medications is not a perfect solution, it is useful for reducing the risk of ADEs.

What are the 2023 AGS Updated Beers Criteria®?

The Beers Criteria, first created in 1991 by Dr. Mark Beers, MD, is a set of tools that can be used to reduce the risk of adverse drug events from potentially inappropriate medications (PIMs) in the older adult population, defined as individuals over the age of 65.

The American Geriatrics Society (AGS) took over its ongoing review and updates the list every three to four years. AGS published the latest update of the Beers Criteria on May 4, 2023 in the Journal of the American Geriatrics Society (JAGS).

You can go directly to the American Geriatrics Society website to learn more about the 2023 update of the Beers Criteria here.

The expert panel responsible for its review and updating comprises a 12-member interdisciplinary panel of geriatric-trained health professionals, clinicians, and scientists in the united states, including representatives from the Centers for Medicare and Medicaid Services, the National Committee for Quality Assurance, and the Pharmacy Quality Alliance.

Any potential conflicts of interest were disclosed at the outset of the process and prior to each full panel discussion, and can be found in the disclosure section of this document.

Panel members abstained from participating in discussions where they may have had a potential conflict of interest.

The criteria focus on strong evidence of the use of potentially inappropriate medications in this population and provide guidance on avoiding or minimizing drug-related problems, including improving medication selection and medication use in the elderly.

The panel used multiple data points gleaned from observational studies, clinical trials, and systematic reviews.

The list is designed for use in any clinical setting, whether in the primary care clinic, hospital, or nursing home.

Additionally, it is used as an educational, quality, and research tool to improve older adults’ lives.

Adverse drug events are a major problem in healthcare, and they are especially problematic for older adults due to their increased vulnerability.

The Beers Criteria are important for reducing adverse drug events because they provide guidance on which medications are potentially inappropriate for the geriatric population and should be avoided.

The criteria are based on the concept that older adults have additional medical problems and medications that may not be appropriate for these patients should be avoided.

Health care providers are then able to prescribe effective alternatives instead.

There are five categories in the 2023 Beers List:

1. Medications and types of medications that are “potentially inappropriate” for older people (anticholinergic medications, benzodiazepines, sedative-hypnotics, etc)
2. Potentially inappropriate medications for older adults with certain common health problems (other chronic illnesses such as diabetes, heart failure, atrial fibrillation, frailty, etc)
3. Types of medications and medication classes that should be used with caution in older adults (certain blood pressure medications, “blood thinners” etc)
4. Combinations of drugs that may result in harmful drug-drug interactions (taking tizanidine, a common muscle relaxant with ciprofloxacin, an antibiotic, etc)
5. Medications that should be avoided or have their doses appropriately adjusted in people with poor kidney function (valium, metformin, famotidine, etc, and many, many other drugs!)

 

Examples of potentially inappropriate medications in older adults

Medication or medication class	Recommendation; rationale
Anticholinergic Agents
First-generation antihistamines (diphenhydramine, hydroxyzine, etc)	[Avoid] Clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity
Antispasmodics (Bentyl, hyoscyamine, scopolamine, etc)	[Avoid] High anticholinergic and uncertain effectiveness
Antithrombotic Agents
Nitrofurantoin	Avoid in individuals with CrCL < 30 mL/min or long-term suppression; potential for pulmonary toxicity, hepatotoxicity, and peripheral neuropathy, especially with long-term use
Cardiovascular Agents
Nifedipine, immediate release	[Avoid] Potential for hypotension; risk of precipitating myocardial ischemia (heart attack)
Amiodarone	Avoid as first-line therapy for atrial fibrillation unless patient has heart failure or
Central Nervous System Agents
Benzodiazepines (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, alcohol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesia
Endocrine Agents
Estrogens with or without progestins	Avoid 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 protection
Sulfonylureas, 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 hypoglycemia
Pain Medications
COX nonselective NSAIDs, oral	Avoid 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 injury
Skeletal muscle relaxants (Flexeril, Soma, etc)	[Avoid] Poorly tolerated by older adults because some have anticholinergic adverse effects, sedation, and increased risk of fractures

Source: The 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023 May 4. doi: 10.1111/jgs.18372. Epub ahead of print. PMID: 37139824.

Specific details of the 2023 Beers Criteria update

The 2023 update of the AGS Beers Criteria® utilized methods akin to those in the 2019 update, which involved a thorough evaluation and compilation of evidence.

These methods were influenced by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for creating clinical practice guidelines and align with the recommendations presented by the National Academy of Medicine.

How was the literature review conducted?

Literature searches were performed in PubMed spanning from June 1, 2017, to May 31, 2022.

Search terms for each criterion encompassed individual medications, drug categories, specific conditions, and combinations thereof, with an emphasis on “adverse drug events” and “adverse drug reactions,” as well as any particular focus determined by the expert panel.

The searches aimed at controlled clinical trials, observational studies, and systematic reviews and meta-analyses, applying filters for human participants, individuals aged 65 and above, and the English language.

Clinical reviews and guidelines were also incorporated to offer context.

Case reports, case series, letters to the editor, and editorials were not considered.

The searches yielded 33,965 references; 7,352 abstracts were forwarded to the panelists for evaluation, from which 1,574 references were chosen for full-text examination.

Out of these, 451 manuscripts were condensed into evidence tables, while an additional 148 were included as supplementary reports.

Drawing on evidence from the 2017-2022 literature review, outcomes from the previous AGS-led 2012, 2015, and 2019 updates, and clinical expertise, each workgroup presented their findings and recommendations for alterations (or no change) to the criteria to the full panel, followed by a discussion.

For the majority of the criteria, a consensus was reached:

• To maintain an existing criterion from the 2019 update as is.
• To amend it.
• To eliminate it completely.
• Or to introduce a new criterion.

Potential adjustments involved the selection of drug(s), the suggestion, the reasoning, the quality of evidence, and the robustness of the recommendation.

New changes to the Beers Criteria since the 2019 update

The criteria include more than 36 specific medications or medication categories that should generally be avoided for most elderly individuals.

Additionally, there are over 40 medications or medication classes that require caution or should be avoided altogether when an individual has specific health conditions or diseases.

The expert panel reclassified several medications into different categories or updated their guidance in light of new evidence.

To streamline and enhance the usability of the five lists that make up the criteria, the panel relocated several medications to a distinct list, as they exhibit low usage or are no longer accessible in the United States.

Despite these changes, the panel continues to regard these medications as potentially unsuitable for use in elderly individuals, consistent with the 2019 criteria.

Since AGS holds the copyright to the Beers Criteria, I will not list all of the medications contained in the tables.

However, here are the main highlights:

Table 1

Designations of Evidence Quality and Recommendation Strength per GRADE guidelines and American College of Physicians Grading Framework – (High, Moderate, Low quality; Strong or Weak recommendation).

 

Table 2: Organ system therapeutic category/Drugs

 

Table 2 Examples

Drug/Organ system	Rationale	Recommendation	Quality of evidence	Strength of recommendation
Nonbenzodiazepine hypnotics (zolpidem, zaleplon, etc)	Adverse effects similar to benzodiazepines (falls, delirium, fractures, car accidents, increased emergency room visits, etc)	Avoid	Moderate	Strong
Insulin, sliding scale	Higher risk of hypoglycemia	Avoid	Moderate	Strong
Megestrol	Very little effect on weight, increased risk of thrombosis and death in older adults	Avoid	Moderate	Strong

Table 3: PIMs that may worsen Drug–Disease or Drug–Syndrome Interactions

 

Table 3 Examples

Disease or Syndrome	Drug(s)	Recommendation
Heart Failure	Diltiazem, Verapamil	Avoid in heart failure with reduced ejection fraction due to potential to increase fluid retention and worsen heart failure
Syncope (Fainting)	Donepezil, Rivastigmine	Avoid in individuals who faint due to low heart rate (because these drugs lower heart rate by themselves)
Delirium	Anticholinergics, Benzodiazepines, Steroids, hypnotic sleep aids, etc	Can induce or worsen delirium
Benign Prostatic Hyperplasia (BPH), lower urinary tract symptoms	Strongly anticholinergic drugs	Avoid in men, may decrease urinary flow and cause urinary retention
Dementia or Cognitive Impairment	Antipsychotics, Benzodiazepines, Sleep hypnotics, etc	Increased stroke risk with antipsychotics, Adverse CNS effects

Table 4: Medications to be used with caution

 

Table 4 Examples

Drug(s)	Recommendations
Dabigatran for long-term treatment of nonvalvular atrial fibrillation or Venous thomboembolism (VTE)	Use caution over other DOACS (apixaban is safest) due to increased risk of GI bleeding and major bleeding
Selective serotonin reuptake inhibitors (SSRIs), mirtazapine, Tramadol, carbamazepine, etc	May cause or worsen hyponatremia or SIADH (low sodium, monitor levels closely)
SGLT2 inhibitors (Dapagliflozin, Empagliflozin, et)	Increased risk of urogenital infections, especially in women in the first month of treatment, increased risk of euglycemic (normal glucose) diabetic ketoacidosis in older adults

Table 5: Clinically important drug-drug interactions to be avoided or used with caution

 

Table 5 Examples

Drug or Class	Interacting drug or class	Recommendation
Opioids	Benzodiazepines	Avoid due to increased risk of overdose, respiratory depression
Opioids	Gabepentin, Pregabalin	Avoid due to increased risk of severe sedation, respiratory depression, death (exceptions: transitioning from opioid therapy to gabapentin or pregabalin, or when using gabapentinoids to reduce opioid dose; still use caution, though)
Warfarin	Amiodarone, Ciprofloxacin, Azithromycin, etc)	Avoid if possible; if must use together, monitor INR very closely due to increased risk of bleeding

Table 6: Drugs to avoid or reduce dosage due to varying kidney function

 

Table 6 Examples

Drug	CrCl (mL/min) at which decision is required	Recommendation
Ciprofloxacin	<30	Reduce dose due to increased risk of seizures, confusion, and tendon rupture
Nitrofurantoin	<30	Avoid, potential for pulmonary toxicity, liver toxicity, peripheral neuropathy
Spironolactone	<30	Avoid due to risk of hyperkalemia (high potassium)
Duloxetine	<30	Avoid due to increased GI adverse effects (Nausea, diarrhea)
Baclofen	eGFR <60	Avoid due to increased risk of encephalopathy requiring hospitalization in older adults. IF dosing cannot be avoided, use lowest effective dose and monitor closely

Table 7: Drugs with strong anticholinergic properties

 

Table 7 Examples

Antidepressants	Anti-nausea	Antihistamines	Urinary Incontinence	Antispasmodics	Skeletal muscle relaxants	Antipsychotics	Antiparkinson
Amitriptyline	Prochlorperazine	Chlorpheniramine	Oxybutynin	Atropine	Cyclobenzaprine	Clozapine	Benztropine
Clomipramine	Promethazine	Diphenhydramine	Tolterodine	Dicyclomine	Orphenadrine	Olanzapine	Trihexyphenidyl
Imipramine		Dimenhydrinate	Solifenacin	Hyoscyamine		Perphenazine
Paroxetine		Doxylamine	Fesoterodine	Scopolamine		Chlorpromazine

Table 8: Medications/Criteria removed since 2019 Beers Criteria Update

 

Table 8 Examples

Medication/Criterion	Reason for Removal
From Table 2
Methscopolamine	Low use
Methyldopa	Not on U.S. market
Ketoprofen	Low use
Flurazepam	Low use
From Table 3
Rosiglitazone	Not on U.S. market
Ranitidine	Removed from U.S. market
From Table 5
Warfarin + NSAIDs	Moved into Table 2
Corticosteroids + NSAIDs	Moved to Table 2
From Table 6
Apixaban in patients with CrCl < 25 mL/min (reduced kidney function)	Emergency evidence + clinical experience supporting safe use with lower kidney function
From Table 7
Loxapine	Low use

Table 9: Medications/criteria added since 2019 American Geriatrics Society Beers Criteria

 

Table 9 Examples

Medication/Criterion	Reason for addition
Table 2
Warfarin	Emerging data and changes in national recommendations/expert guidance
Table 3
Heart failure - Dextromethorphan-quinidine	Supported by package insert
Delirium - Opioids	Emerging data
History of falls or fractures - Anticholinergics	Emerging data and consistency across recommendations
Table 4
SGLT2 Inhibitors	Emerging data and clinical concern
Table 5
Warfarin + SSRIs	Supported by data
Table 6
Baclofen	Data supporting concern

Table 10: Medications/criteria modified since 2019 American Geriatrics Society Beers Criteria

 

Table 10 Examples

Medication/Criterion	Modification
Aspirin	Moved from Table 4 to Table 2 due to new evidence
Rivaroxaban	Moved from Table 4 to Table 2 on basis of accumulating evidence
Benzodiazepines	Clarified language
Sulfonylureas	Expanded to include ALL sulfonylureas due to data supporting adverse outcomes for all drugs in class.
Delirium	Updated rationale to comment on opioids and further clarify
Rivaroxaban	Clarified CrCl cutoff values to align with available evidence and package insert

 

What are some of the challenges associated with using the Beers Criteria in clinical practice?

The Beers Criteria is a set of guidelines that helps doctors decide which medications are appropriate for older adults.

However, there can be challenges associated with using the Beers Criteria in clinical practice.

The Beers Criteria are a valuable resource for healthcare providers, not a replacement for their experience and knowledge. In other words, the criteria are just that…a list of medications that provide some basic guidance to the clinician.

It is important to note that the Criteria were never meant to supersede the physician’s clinical judgment.

For example, doctors have to weigh the potential benefits of a medication against the potential risks.

Remember, just because a medication is considered ‘potentially inappropriate for older people, that doesn’t mean it should never be used. It should be considered carefully on a case-by-case basis.

Because of this, you should NEVER, EVER stop a medication on your own without consulting with your doctor simply because it appears on the Beers List!

This is why the relationship you have with your doctor is so important – your doctor knows you best – your complete medical, surgical, and social history, your medications, your response to them, your blood work and other labs, and anything else that is so important to your continued good health, quality of life, and well-being.

Nonetheless, the Beers Criteria can be a valuable tool for identifying potentially inappropriate medications that you may be taking and reducing adverse drug events.

I realize that the Beers Criteria point to some difficult-to-understand grey-area concepts.

My confident guess is that you are wondering how this applies to you…how do you begin to identify whether any medications that you are currently taking may be potentially inappropriate. Correct?

Well, to put your very valid concern into perspective, let’s apply the AGS Beers Criteria to a fictional yet realistic patient case:

John is an 85-year-old man with the following medical history:

• Osteoarthritis of the hips and knees
• Type 2 Diabetes
• Heart Failure with reduced ejection fraction
• Anxiety and Depression
• Vascular Dementia
• Insomnia

He takes the following medications:

• Apixaban 2.5 mg twice daily (Afib)
• Paroxetine 40 mg daily (Anxiety and Depression)
• Metoprolol succinate 100 mg daily (Heart Failure)
• Torsemide 20 mg daily (Heart failure)
• Glyburide 5 mg twice daily (Diabetes)
• Metformin 500 mg twice daily (Diabetes)
• Ibuprofen 600 mg three times daily (Arthritis)
• Tylenol PM Extra Strength – 2 caplets nightly (Insomnia)

 

John reports to his doctor that he has been feeling sluggish, has observed blood in his stools with every bowel movement for the past week, has had low blood sugar with symptoms almost daily, and is very concerned because he has had bad anxiety attacks.

Additionally, his mood has worsened.

As the clinical pharmacist on the team, I consult with John’s doctor and identify the following medication-related problems that may be causing John’s issues:

Problem #1: GI Bleed Assessment and Plan

John is experiencing a GI bleed most likely from the constant use of his ibuprofen, a Nonsteroidal Antiinflammatory Drug (NSAID).

Bleeding, among other problems, is a common and known adverse effect of continued NSAID use.

John is particularly at risk because he is taking apixaban, an anticoagulant he is taking to treat his afib.

While both medications are listed in the Beers Criteria, apixaban must be continued due to its life-saving need for afib.

The ibuprofen must be discontinued, as there are safer alternatives to manage John’s pain.

Problem #2: Potential Acetaminophen overdose (vigilance is key)

For example, round-the-clock acetaminophen can be used to better manage his pain.

John must be careful to ensure that he does not take more than the recommended dose, lest he risks serious liver injury.

This can be particularly troublesome because he is also taking Tylenol PM, which also contains acetaminophen.

To avoid a potentially fatal overdose, he needs to immediately stop the Tylenol PM.

Problem #3: Anticholinergic Burden Assessment and Plan

The other issue with this OTC agent is that it contains diphenhydramine, the active ingredient that is included to help him with his sleep problem.

Diphenhydramine is listed in the Beers Criteria and is known to cause sedation, falls and fractures, and worsening cognition. Additionally, emerging evidence links cumulative exposure of anticholinergic medications to an increased risk of dementia.

It has high anticholinergic properties, and those of us in the geriatric field are constantly on the lookout to remove it from our patients’ medication lists.

To better manage John’s insomnia, non-pharmacological and safer pharmacological strategies are available.

I cover these in detail in my article on insomnia.

John’s use of paroxetine, also discussed in my article on depression in the elderly, must also be stopped – not many people know this, but it also has high anticholinergic burden and in his case, the use of this agent and Tylenol PM caused a double-dose of problems for him.

There are safer alternatives in the same antidepressant drug class that John can take instead, such as sertraline or escitalopram.

Both anticholinergic medications are also worsening John’s vascular dementia due to their antagonistic effect on John’s already compromised cholinergic neurons in his brain.

Problem #4: Low Blood Sugar Assessment and Plan

John’s low blood sugar levels can be directly attributed to his use of glyburide, one of the worst offenders among the diabetic medications. Glyburide is also listed in the Beers Criteria.

In my opinion, there is absolutely no reason that any older adult should be on this medication. Unfortunately, I do see this medication being prescribed to older adults occasionally.

Again, many other safer alternatives are available for older adults with diabetes.

So, to recap, John has been experiencing multiple medication-related adverse effects, which compromised his safety above all else, in addition to his quality of life.

Through a common-sense approach of applying the clinical concepts espoused by the Beers Criteria, we have eliminated most of them and greatly improved John’s health situation.

Additionally, we have decreased John’s pill burden by 50%! John’s case is an excellent example of polypharmacy in an older adult. I cover all aspects of polypharmacy and medication safety in older adults in my article here.

What can older adults do to reduce medication-related problems?

• Know and record ALL prescription medications, herbal supplements, and over-the-counter drugs you take, and be sure to let your doctor know.
• OTC drugs, supplements, and herbals may significantly interact with your prescription drugs and harm you.
• Be specific – write down the exact names of the drugs, what dose you take, how often, and if you are experiencing any side effects from them, no matter how seemingly mild they may be.
• Ask your doctor about what side effects you can potentially experience with ALL of your medications and supplements and what you should do if you experience them.
• If in doubt about any of your medications, or you suspect that they may be on the Beers list, talk to your doctor.
• Ask them pointed questions and ask them to explain to you their rationale as to why they prescribed them to you.
• Talk to your pharmacist! Ask probing questions about every prescription and non-prescription medication, herbal, and supplement that you are taking.
• Report ALL medical and medication changes to your doctor promptly, no matter how trivial they may seem to you.
• Constantly re-assess all of your medications – are they all working? Is your changing body responding to it differently?
• Advocate, advocate, advocate for yourself! Take charge of your medications and read up on them from reputable sources (an article from the Mayo Clinic or Harvard, the American Geriatrics Society, American Heart Association, etc are more trustworthy than a random social media post written by an untrained and unqualified party purporting unproven and dangerous claims)

It is your body and your health, and you have every right to question and receive satisfactory answers from your doctor.

Summary

• The Beers Criteria are guidelines for prescribing medications to older adults to reduce the risk of adverse drug events (ADEs).
• ADEs are a major problem in older adults, leading to hospitalization, disability, and death.
• By following the Beers Criteria WHERE APPROPRIATE, we can help keep our older adults safe and healthy.