ADVANCED CLINICAL TRACK:

APPROPRIATE PRESCRIBING IN OLDER ADULTS:

A FOCUS ON THE 2015 UPDATE TO THE BEERS
CRITERIA
SATURDAY/10:15-11:15AM

ACPE UAN: 0107-9999-16-043-L01-P 0.1 CEU/1 hr

Activity Type: Knowledge-Based

Learning Objectives for Pharmacists: Upon completion of this CPE activity participants should be able to:
1. Describe physiologic changes that affect medication use in older adults
2. Discuss recent updates to the Beers Criteria and their impact on medication use in the elderly
3. Apply the Beers Criteria to a variable older adult population

Speaker: Kristen Cook, PharmD, BCPS

Kristen Cook is an Assistant Professor of Pharmacy Practice at the UNMC College of Pharmacy and a
clinical pharmacist in a PCMH Internal Medicine Clinic. She graduated from the University of Nebraska
College of Pharmacy in 2005 and completed a primary care residency in 2006 at the William Middleton VA
Hospital in Madison, Wisconsin. She has practiced in a variety of settings in internal medicine/ geriatrics
within a federally qualified community health center, ambulatory VA clinics, and an academic PCMH model.
A significant portion of Dr. Cooks time is spent teaching in the academic and clinical setting in geriatrics.
Her scholarship interests involve dementia, primary care in the older adult, and student run health clinics.
She currently is involved with a large Medicare study focusing on a model of care called the Dementia
Care Ecosystem that delivers interdisciplinary support for caregivers of patients with dementia. Dr. Cook
also serves as faculty advisor for UNMC SHARING clinics, which is an interdisciplinary student run clinic for
the uninsured. She resides in Omaha, Nebraska with her husband and two daughters, Naomi and Hattie,
who are five and four. She loves to renovate her home, travel, and watch Project Runway in her spare time.

Speaker Disclosure: Kristen Cook reports no actual or potential conflicts of interest in relation to this CPE
activity. Off-label use of medications will not be discussed during this presentation.

FEBRUARY 13, 2016 | IOWA EVENTS CENTER | DES MOINES, IOWA

Appropriate prescribing in older adults:
A focus on the 2015 update to the Beers Criteria
Kristen Cook, Pharm D. BCPS
Assistant Professor, UNMC College of Pharmacy
Primary Care Pharmacist, Nebraska Medicine

Disclosure
Kristen Cook reports no actual or potential conflicts of interest
associated with this presentation

1
 Learning Objectives
Upon successful completion of this activity, pharmacists
should be able to:

Describe physiologic changes that affect medication use in older

adults
Discuss recent updates to the Beers Criteria and their impact on
medication use in the elderly
Apply the Beers Criteria to a variable older adult population

Geriatrics: Challenges in Care

Geriatric population is fastest growing segment of US
population
Proportion of people >65y expected to increase from
12.7% in 2004 to 20.6% (82 million) by 2050

Care of older Americans will require:

An increasing proportion of health care resources
Clinicians who are alert to the specific health needs of the geriatric
population

2
 Click to edit
Click to edit Master text styles
Second level
Third level
Fourth level
Fifth level

Source: Federal Interagency Forum on Aging-Related Statistics. Older Americans 2012: Key Indicators of Well-Being. Federal Interagency
Forum on Aging-Related Statistics, Washington, DC: U.S. Government Printing Office. July 2012.

Click to edit
Click to edit Master text styles
Second level
Third level
Fourth level
Fifth level

Source:Federal Interagency Forum on Aging-Related Statistics. Older Americans 2012: Key Indicators of Well-Being. Federal Interagency
Forum on Aging-Related Statistics, Washington, DC: U.S. Government Printing Office. July 2012.

3
What is Different About the 65+ Age Group?

Age-related physiologic changes

Heterogeneous health status

Increased incidence of co-morbid illness

Atypical disease presentation

Increased incidence of iatrogenic illness

Different goals of therapy

Pharmacokinetics
Parameter Definition

Absorption The fraction of a drug dose reaching the systemic

circulation (bioavailability)
Distribution Locations in the body where a drug penetrates

Metabolism Drug conversion to alternate compounds which may be

pharmacologically active or inactive
Major metabolic organ is the liver

Excretion Drugs final route(s) of exit from the body expressed as

half-life or clearance
Major excretory organ is the kidney

4
Effects of Aging on Absorption

Passive diffusion unchanged and no change in overall

bioavailability of most drugs

Decreased active transport and decreased bioavailability

of some drugs

Decreased first pass extraction (decreased hepatic blood

flow)
Increased bioavailability for some drugs: narcotic analgesics,
propranolol, labetalol, verapamil, nifedipine, diltiazem, tricyclic
antidepressants, theophylline, methylphenidate, nitroglycerin,
Prodrugs: enalapril activation slowed or reduced

Effects of Aging of Volume of Distribution (Vd)

Aging Effect Vd Effect Examples

Body water Vd for hydrophilic Ethanol, lithium, digoxin,
drugs acebutolol, propranolol, atenolol,
plasma concentration sotalol, HCTZ, theophylline,
cimetidine, aminoglycosides,
procainamide, quinidine
Fat stores Vd for lipophilic drugs Benzodiazepines, trazodone,
terminal half-life amiodarone, haloperidol

in plasma % of unbound or free Phenytoin, warfarin, NSAIDs,

protein drug (active drug) diazepam, valproic acid,
(albumin) furosemide, propranolol,
quinidine, salicylate

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 Effects of Aging on Hepatic Metabolism

Pathway Effect Examples

Phase I: clearance and half- Diazepam, alprazolam, propranolol,
oxidation, life for some drugs CCBs, metoprolol, chlordiazepoxide,
reduction, piroxicam, diclofenac, ibuprofen,
hydroxylation, (decreased liver mass theophylline, quinidine, TCAs,
demethylation & blood flow vs. CYP- citalopram, paroxetine,
450 enzymatic activity) carbamazepine, phenytoin,
risperidone, haloperidol, omeprazole,
erythromycin
Phase II: No change Lorazepam, temazepam, oxazepam,
conjugation, warfarin, ethanol, metolprolol, prazosin,
glucuronidation, isoniazid
acetylation,
sulfation

Note: Medications undergoing only phase II metabolism are preferred in

elderly due lack of aging effect and inactive metabolites, therefore less risk of
drug accumulation and toxicity

Example: CrCl vs Age in a 55 55kg Female

Age (yr) SCr (mg/dL) CrCl (mL/min)

30 1.1 65
50 1.1 53
70 1.1 41
90 1.1 30

Rounding creatinine up in those with low values ?

6
Pharmacodynamics (PD) and Aging
Drug/Class PD Effect
Benzodiazepines Sensitivity to CNS effects: sedation, cognitive
impairment, postural sway, falls
Neuroleptics Risk of delirium, EPS, arrhythmias and postural
hypotension
Opioids Analgesic response, reduced development of tolerance
Alcohol Drowsiness and lateral sway
-blockers/- Heart rate response;
agonists
Vasodilators Reflex tachycardia
Anticholinergics/ Sensitivity to anticholinergic effects: sedation, cognitive
antimuscarinics impairment, constipation, urinary retention, dry mouth
Digoxin Cardiac sensitivity; toxicity in therapeutic range

Warfarin Response; greater inhibition of clotting factors

History- Beers Criteria

1991- Dr. Mark Beers
Nursing home setting until 1997 update
1997 and 2003 updates

2012- American Geriatrics Society

PIM (Potentially inappropriate medication)
Modified Delphi method- Institute of Medicine
Quality of evidence and strength of recommendation
3 categories
Drugs to avoid
Drugs to avoid in patients with specific conditions
Drugs to use with caution

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American
Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate
Medication Use in Older Adults. J Am Geriatr Soc 63:22272246, 2015

7
 Quality of Evidence
High
Consistent results from well-designed, well-conducted studies that directly assess
effects on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent
observational studies with no significant methodological flaws showing large effects
Moderate
Sufficient to determine effects on health outcomes, but the number, quality, size, or
consistency of included studies, generalizability , indirect nature of the evidence on
health outcomes (1 higher-quality trial with > 100 participants; 2 higher-quality trials
with some inconsistency, or 2 consistent, lower-quality trials; or multiple, consistent
observational studies with no significant methodological flaws showing at least
moderate effects) limits the strength of the evidence
Low
Insufficient to assess effects on health outcomes because of limited number or
power of studies, large and unexplained inconsistency between higher-quality
studies; important flaws in study design or conduct, gaps in the chain of evidence
Or lack of information on important health outcomes

Designations of Quality and Strength of Evidence:

ACP Guideline Grading System, GRADE
Strength of Recommendation

Strong
Benefits clearly > risks and burden OR risks and burden clearly > benefits

Weak
Benefits finely balanced with risks and burden

Insufficient
Insufficient evidence to determine net benefits or risks

8
 2015 AGS Beers Criteria
Panel selection
13 members
NCQA, Centers for Medicare/ Medicaid, Pharamacy Quality Alliance
Literature search
August 2011 to July 2014
RCTs, systematic reviews, meta-analyses, observational studies
Development process
Quality and strength ratings

2015 Beers Criteria

Avoid use Specific conditions Caution

High risks of adverse Certain May be associated with

effects OR diseases/disorders more risks than benefits
in general
Limited efficacy Drugs may exacerbate
the specified health May be the best choice
AND problems for a particular individual if
administered with caution
There are alternatives
to these medications

30+ recommendations 12+ conditions

9
 RZ is a 78 year old female who presents to your primary clinic for
medication management. She has been losing a little weight lately due to
feeling some nausea. Her husband also reports she has been getting up
confused in the middle of the night a few times per week.

Her past medical history is significant for: atrial fibrillation, ischemic stroke,
chronic kidney disease, generalized anxiety disorder, mild dementia,
COPD, chronic UTIs (2x/year) and osteoporosis.

Current medications: Vitals/ Labs:

aspirin 81mg daily Blood pressure: 135/70mmHg sitting
digoxin 0.25mg daily 124/66mmHg standing
alprazolam 0.5mg twice daily Heart rate: 48 bpm
Potassium: 3.3 mmol/L
quetiapine 25mg bedtime
Creatinine clearance: 24 ml/min
zolpidem 5mg bedtime LDL direct: 110 mg/dL
albuterol prn Hemoglobin A1c: 5.4%
omeprazole 20mg once daily Digoxin level: 1.0 ng/mL
nitrofurantoin 100mg daily
Alendronate 70mg weekly

Nitrofurantoin
Drug Rationale Recommendation Quality of Strength
evidence
Nitrofurantoin Pulmonary Avoid with creatinine Low Strong
toxicity, clearance <30
hepatotoxicity, ml/min. or for long
peripheral term prophylaxis
neuropathy with
long term use

Previous recommendation: <60 ml/min. avoid

(Geerts et al.)
eGFR Adjusted HR
50-80 0.92 (0.78-1.08)
30-49 1.06 (0.74-1.51)
10-29 1.57 (0.79-3.52)
Unknown 0.90 (0.79-1.01)
- Amount of nitrofurantoin excreted into urine is directly related to renal function
Bains A, Buna D, Hoag NA. A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment. Can Pharam J. 2009;142(5):248-252
-Geerts AF, Eppenga WL, Heerdink R, et al. Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in
primary care. Eur J Clin Pharmacol. 2013;69(9):1701-1707. .

10
UTI Treatment
Symptoms
Dark of foul smelling urine???
Catheterization
Duration of course:
7-10 days for complicated UTI

Prophylaxis
> 3 episodes per year

Treatment for Asymptomatic Bacteriuria

Positive culture (>105cfu/mL) with no symptoms
Screening
Prior to transurethral resection of prostate
Urologic procedures with mucosal bleeding
Treatment does NOT decrease:
Occurrence of symptomatic urinary infection
Improve chronic genitourinary sxs
Improve survival

Negative Outcomes w/Treatment:

Increased frequency of drug interactions
Emergence of resistant organisms
Increased cost

11
 Class 1a, 1c, III Antiarrythmics
Removed!
Evidence for rhythm control with as good or better
outcomes than only rate control

Amiodarone
Not first line unless heart failure or left ventricular hypertrophy
Dronedarone
Avoid permanent atrial fibrillation or severe heart failure
Disopyramide
Anticholinergic properties

Digoxin
Drug Rationale Recommendation Quality of Strength
evidence
Digoxin Should not be Avoid as first line Afib: Afib:
used as 1st line thearpy for afib and moderate strong
agent in afib heart failure
HF: Low HF:
Questionable If used avoid strong
effects in heart dosages
failure on >0.125mg/day
hospitalization
and possibly
higher mortality

12
 Digoxin
DIG study (digoxin vs. placebo)
Stratified by age (2092 pts 70-79) (425 pts 80+)
Ability to decrease hospitalizations regardless of age
Age was found to be significant predictor of hospitalization for
digoxin toxicity and withdrawal of therapy

Target range: 0.5-0.8 ng/mL

Renal function
Half life normal: 30-40 hours
Kidney disease: 4-6 days
CrCl 10-50 ml/min. every 36 hours or 25-75% usual dose
CrCl <10 ml/min. every 48 hours or 10-25% usual dose
Reduced volume of distribution

Antipsychotics (1st and 2nd gen.)

Drug Rationale Recommendation Quality of Strength
evidence
Antipsychotics Increased risk of stroke and Avoid Moderate Strong
greater cognitive
(1st and 2nd decline/mortality in
generation) dementia patients

Avoid for behavioral

problems of dementia
unless
nonpharmacologic
options have failed or are
not possible and the
patient is threatening
substantial harm to self
or others

13
 Antipsychotics (1st and 2nd gen.)
Risk for stroke may be more established in 2nd generation
None are FDA approved!
Possibly better for anger, aggression, paranoia.
Drug Antipsychotics Cholinesteras Antidepressan Mood
Therapy e inhibitors/ ts (SSRIs) Stabilizers
Memantine
Evidence Moderate Limited Limited Minimal

Risks Metabolic side GI upset, GI upset, Thrombocytop

effects, EPS, bradycardia hyponatremia, enia, liver
QT sleep toxicity,
prolongation, problems, QT sedation, etc.
stroke, prolongation
orthostasis
Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and
psychological symptoms of dementia. BMJ 2015;350:h369

Sleep medications
Drug Rationale Recommendation Quality of Strength
evidence
Eszopiclone, Benzodiazepine receptor Avoid Moderate Strong
agonists have adverse events
Zolpidem, similar to those of
Zaleplon benzodiazepines in older
adults (falls, delirium,
fractures), increased
hospitalizations, motor vehicle
crashes, and minimal
improvement in sleep latency
or duration.

Removed 90 day use recommendation

Berry et al.
Any benzodiazepine use prior to hip fracture
0-15 days prior: OR 1.47 (1.24-1.74)
0-30 days prior: OR 1.66 (1.45-1.90)
Alternatives: melatonin, trazodone, mirtazapine
Berry SD, Lee Y, Cai S, et al. Nonbenzodiazepine sleep medication use and hip fractures in nursing home residents.
JAMA Intern Med. 2013;173(9):754-761.

14
 Proton pump inhibitors
Drug Rationale Recommendation Quality of Strength
evidence
Proton pump Risk of clostridium Avoid schedule use High Strong
inhibitors difficile infection for > 8 weeks unless
and bone loss/ high risk patient (oral
fractures corticosteroids or
chronic NSAID use)
or other compelling
indication
C. difficile infection
Even without antibiotic use
2012 meta-anaylsis- 313,000 patients
Incident:odds ratio [OR] 1.7; 95% CI 1.5-2.9
Recurrent: odds ratio [OR] 2.5; 95% CI 1.2-5.4
FDA warning: Consider C diff in patients on PPIs with diarrhea
Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis.
Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK
Am J Gastroenterol. 2012;107(7):1011.

Proton pump inhibitors

Bone loss/ fracture
Reduced calcium absorption
Inhibition of osteoclast activity

FDA warning: Increased risk of fractures of the hip, wrist, and spine

Hospital use/ Discharge

Assess osteoporosis/ fall risk in patients on long term
H2 blockers do not appear to have the same risk

15
 Drugs to use with caution
Drug Rationale Recommendation Quality of Strength
evidence
Dabigatran Increased risk for GI Use with caution in Moderate Strong
bleed compared with those 75 years
warfarin and other
target specific
anticoagulants in
adults 75 years;
lack of data for safety
and efficacy CrCl
<30ml/min.
Antipsychotics May exacerbate Use with caution Moderate Strong
, SNRIs, or cause SIADH
SSRIs, or hyponatremia
Mirtazapine,
TCAs

Drug Interactions Table

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics
Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older
Adults. J Am Geriatr Soc 63:22272246, 2015

16
Renal dosing

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics
Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older
Adults. J Am Geriatr Soc 63:22272246, 2015

Anticholinergic Properties

American Geriatrics Society 2015 Beers Criteria Update Expert Panel.

American Geriatrics Society 2015 Updated Beers Criteria for Potentially
Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 63:2227
2246, 2015

17
Underprescribed medications- Statins

Secondary prevention
75 years: high intensity statin therapy
> 75 years: moderate intensity statin therapy
Primary prevention
Little data in those >75 years, consider additional factors
Pooled Cohort Equations: 76-79 years
http://my.americanheart.org/professional/StatementsGuidelines/Pre
ventionGuidelines/Prevention-
Guidelines_UCM_457698_SubHomePage.jsp
ASCVD vs. CHD risk calculation

Memory impairment and statins

Underprescribed medications
Metformin
Renal function
Labeling: Scr 1.4mg/dL women, 1.5mg/dL men, GFR < 60ml/min
30-45 ml/min.: Consider reducing dose to 500mg BID
<30 ml/min. stop
ACE inhibitors
Anticoagulants
Antiplatelets

18
 Anticoagulation in Older Adults
Warfarin = increased bleed risk
Elderly have increased risk of intracranial bleeding and bleeding
related to injuries from falls
Especially > 80 years
Starting doses
4mg or less
Good starting dose: 2.5mg daily

Falls Risk-----300+ times?

More quality adjusted life years with warfarin
Large number of falls- no good assessment tool
Individual specific assessment
Lower INR targets??
Other Concerns:
Transportation, adherence, polypharmacy

Anticoagulation in Older Adults

Dabigatran
RE-LY trial
Mean age 71 years
Major bleed risk increased by 20% in those 75 years and older
Beers Criteria
Renal function
Administration concerns
Costall of them
Rivaroxaban
CYP 3A4 & Renal function
Apixaban
Reduce dose if 2 of the following (afib):
Age 80 years, body weight 60kg, or serum creatinine 1.5mg/dL

19
Prescribing Cascade
Medication Adverse reaction Second medication
prescribed

Cholinesterase inhibitor Incontinence Anticholinergic

NSAIDs Hypertension Antihypertensives

Thiazide diuretics Gout Allopurinol/ colchicine

Antipsychotics EPS Levodopa,

anticholinergics

STOPP/START Criteria
STOPP (Screening Tool of Older Persons Prescriptions)/
START (Screening Tool to Alert doctors to Right
Treatment)
Europe
Organized by organ system
STOPP (n=65) and START (n=22)
Duplicate medications

20
Principles of good prescribing

Correct drug for indication

Appropriate dose
Avoid withdrawal (taper when necessary)
Cost effectiveness
Nonpharmacologic approaches
Simplify dosing schedule
Consider new symptoms related to medication

Medication Appropriateness Index

1. Is there an indication for the drug?
2. Is the medication effective for the condition?
3. Is the dosage correct?
4. Are the directions correct?
5. Are the directions practical?
6. Are there clinically significant drug-drug interactions?
7. Are there clinically significant drug-disease/condition
interactions?
8. Is there unnecessary duplication with other drugs?
9. Is the duration of therapy acceptable?
10. Is this drug the least expensive alternative compared
with others of equal usefulness?
Arch Intern Med. Vol 166, March 27, 2006

21
Summary
The new Beers Criteria provides a more evidence based
comprehensive resource for prescribers and pharmacists
to base recommendations from.

Pharmacokinetic/ pharmacodynamic changes influence

choice and monitoring of medications in older adults.

Underprescribed medications can put older patients at as

much risk as inappropriate medications on their profiles.

References
Source: Federal Interagency Forum on Aging-Related Statistics. Older Americans 2012: Key
Indicators of Well-Being. Federal Interagency Forum on Aging-Related Statistics, Washington, DC:
U.S. Government Printing Office. July 2012.
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society
2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am
Geriatr Soc 63:22272246, 2015
Bains A, Buna D, Hoag NA. A retrospective review assessing the efficacy and safety of
nitrofurantoin in renal impairment. Can Pharam J. 2009;142(5):248-252
Geerts AF, Eppenga WL, Heerdink R, et al. Ineffectiveness and adverse events of nitrofurantoin in
women with urinary tract infection and renal impairment in primary care. Eur J Clin Pharmacol.
2013;69(9):1701-1707. .
Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological
symptoms of dementia. BMJ 2015;350:h369
Berry SD, Lee Y, Cai S, et al. Nonbenzodiazepine sleep medication use and hip fractures in nursing
home residents. JAMA Intern Med. 2013;173(9):754-761.
Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis.
Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK. Am J Gastroenterol.
2012;107(7):1011.
The Digitalis Investigation Group. N Engl J Med 1997; 336:525-533

22