Updated Beers Criteria for Potentially Inappropriate

Medication Use in Older Adults

Dr. Janice Hoffman, PharmD, CGP, FASCP

Dr. Sam Shimomura, PharmD, CGP, FASHP

Western University of Health Sciences

College of Pharmacy

October 2016

Disclosure

Dr. Janice Hoffman has no conflict of interest to disclose.

Dr. Sam Shimomura has no conflict of interest to disclose.

Pharmacist Learning Objectives

• Describe the physiological changes that occur in aging and how that may affect pharmacokinetics

• State at least three principles to consider when prescribing or recommending drug therapy for older adults

• Apply Beer’s Criteria to patient cases

• Identify the key physiological changes that occur in aging.

• List three characteristics of medications that meet the Beer’s

Criteria.

• Identify from patient cases at list 3 medications that are

potentially not appropriate in the elderly according to Beer’s

Criteria.

Pharmacy Technician Learning Objectives

Physiological changes with aging

Pharmacotherapy in elderly is complicated by multi-factorial issues

◦ Age related physiologic changes

◦ Presence of multiple chronic disease states

◦ Cognitive changes

◦ Physical disabilities

◦ Patients desire vs.

ability to comply to recommended medications

Pharmacotherapy

Increased prevalence of disease

Difficulty in differentiating often subtle adverse effects from the disease

Drug-Disease Interaction or Exacerbation

◦ Anticholinergic drugs

◦ BPH

◦ Constipation

◦ Alzheimer’s Disease

◦ Confusion

◦ Benzodiazepines

◦ Depression

◦ Dementia

◦ Gait

Change in Disease States

Aging Effects on the Body2

Functional Systems Functional Changes

Sensory Losses •Reduced sense of taste, smell, sight, hearing, touch

Oral Health Status •Xerostomia - dry mouth caused by hyposalivation

•Dentures and periodontal problems

GI Function •Hypochlorhydria

•Constipation

Metabolism •Decreased glucose tolerance

•15-20% decline in resting metabolic rate

CV Function •Blood vessels become less elastic and total peripheral

resistance increases

•♂: cholesterol peak ~60 y.o.

•♀: total cholesterol & LDL continue to rise until ~70 y.o.

9

If Sally is 97 years old woman who is not eating well which of the following changes from aging may be contributing?

A. Increase in drooling or hypersalivation to accommodate dentures

B. Blood vessels become more elastic causing weakening in the legs

C. Loss in sensory functions (smell, taste and sight)

D. Increased gastric motility causing her to feel “full” faster

Question # 1

Most oral drugs are absorbed via passive diffusion

◦ No major changes in bioavailability of drug due to age-related physiologic changes

Decreased first-pass effect

(e.g. Morphine, propranolol)

results in :◦ increased bioavailability

◦ higher plasma concentrations

Changes in Absorption1

skin hydration

surface lipids

peripheral circulation

keratinization

Outcome: Possible absorption from a transdermal patch

Transdermal Absorption1

gastric emptying rate

intestinal motility

intestinal blood flow and surface area

gastric acid output - gastric pH

Outcome:

◦ No significant change in quantity absorbed

◦ Time to onset or peak may be delayed

GI Absorption1

muscle mass

peripheral circulation

connective tissue

Outcome: possible Intramuscular absorption

IM absorption1

Physiologic Changes

◦ in total body water

◦ Volume of distribution of hydrophilic drugs is

◦ in lean body mass (Scr will be )

◦ in body fat

◦ Volume of distribution of lipophilic drugs is

◦ in albumin

Distribution1

serum albumin

protein affinity binding

alpha 1- acid glycoprotein

Outcome: Increased free fraction of highly protein-bound medications

Protein Binding Changes1

We find out that Sally our 97 years old patient is not eating well due to her Depression. Which of the following physiologic complications may occur?

A. Increase in body fat will lead to larger distribution of hydrophilic drugs

B. Decrease in albumin will lead to more free drug and more adverse effects

C. Decrease stomach acid will lead to more drug being absorbed

D. Increased absorption from a transdermal patch

Question # 2

Liver is the major organ for metabolism :

Aging leads to:

◦ hepatic mass

◦ hepatic blood flow

Decreased phase-I metabolism (oxidation)

◦ clearance half life of drug Side effects

◦ (e.g.. Diazepam, theophylline, quinidine, alprazolam)

Phase II metabolism (conjugative)

◦ Less affected by age (e.g.. Lorazepam, oxazepam)

CYP 450 activity – limited changes

Metabolism2

Aging and CYP Activity2

Decreased Decreased or Unchanged

Increased

CYP 1A2CYP 2C19

CYP 2ACYP 2C9CYP 3A4

CYP 2D6

19Cusack. Am Geriatr Pharmacother 2004: 2:274: 302

Other metabolic Influences2

Factor Result

Smoking Enzyme Induction

Alcohol Enzyme Induction

Drugs Enzyme Induction/Inhibition

Diet Variable

Malnutrition Enzyme Inhibition if severe

Frailty Enzyme Inhibition

20

Physiologic Changes

◦ Renal blood flow

◦ GFR – creatinine clearance (CrCl)

◦ Tubular secretion function

◦ Stable serum creatinine due to muscle mass

Outcome:

CrCl by 50% between age 25 - 85 despite maintained SCr of 1.0 mg/dL.

Renal Excretion1

Clinical Effects:

◦ half life of renally excreted drugs

◦ concentration of renally excreted drugs

Significant for narrow therapeutic index

◦ Aminoglycosides

◦ Anticoagulants

Primary goal: prevent toxicity

Clinical Application of Renal Changes1

We also find out that our 97 year old patient smokes a pack of cigarettes daily and drinks 2 glasses of wine with dinner every night. How will these lifestyle choices affect her medications? Select the BEST answer

A. Decrease renal elimination of her medications

B. Contribute to liver enzyme Induction increasing hepatic elimination of her medications

C. Enhance topical absorption of transdermal patches increasing adverse effects

D. Decreased GI pH ( more acidic) increasing oral absorption of her medications

Question # 3

Alterations in sensitivity to drugs with age

◦ Receptor sensitivity to:

◦ benzodiazepine, warfarin, opioids

◦ side effects

◦ Receptor sensitivity to beta-blockers

◦ Baroreceptor sensitivity

◦Orthostatic hypotension with

◦ vasodilators, tricyclic antidepressants, antihypertensives

◦ Outcome: FALL risk1

Pharmacodynamics

•Receptor changes

• in number of some receptors (β receptors)

•Altered reserve capacity

•Homeostatic changes

•Increased sensitivity to drug therapeutic & adverse effects

•Increased co-morbid diseases

•Increased drug interactions from polypharmacy1

Etiology for Altered Pharmacodynamics

• Antipsychotic agents - risk of Tardive Dyskinesia and psuedoparkinsonism (receptor sensitivity)

• sensitivity to anticholinergics increased side effects

• sensitivity to warfarin risk of bleeding

• renin and aldosterone levels response to ACE-I

• NSAID, ACE-I, K+ sparing diuretics risk of hyperkalemia1

Pharmacodynamics – Outcomes

“ The genes you are born with are the genes you die with”B. Williams USC

No apparent changes during adult lifespan

◦ Possible decreased in CYP 3A4 and CYP 2A6

◦ Fast and slow metabolizers (ethnicity)

◦ N-acetyltransferase activity

◦ Slow acetylators (autosomal recessive)1

Pharmacogenomic Issues

Clinical response =

PK + PD + Individual variance ???(Brad Williams USC professor)

Applying these principles to patients ……

Dr. Mark Howard Beers with a team from Harvard, looked atprescriptions and case files for 850 residents of nursing homesaround Boston.

Researcher’s found that sedatives, antidepressants andantipsychotic drugs often caused confusion or even physicaltremors in patients.

The teams finding were published in The Journal of theAmerican Medical Association in 1988.

Beers Criteria History

This Boston study led to establish a list of drugs with knownside effects on elderly.

◦ In the year 1991,this list of drugs was published known asBeers Criteria.

◦ Consist of Potentially Inappropriate Medications (PIM) for use in older adults

Beer’s Criteria History

Incorporated new evidence on currently listed PIMs andevidence from new medications or conditions not addressed inthe 2012 update.

Incorporated 2 new areas of evidence on drug-druginteractions and dose adjustments based on kidneyfunction for select medications.

Grade the strength and quality of each PIM statement basedon level of evidence and strength of recommendation.6

2012 AGS Beers update used the following criteria:

Improve care of older adults

By reducing their exposure to Potentially InappropriateMedications (PIM).

Provide the evidence to support the PIM8

Goal of 2015 AGS Beers Criteria

Exclusion

• Age less than 65

• Hospice & Palliative care

Inclusion

• Age 65 and older

• Intended for use in ambulatory, acute, and institutionalized setting of care in the United States.

Beers Criteria

Modified Delphi method was used to systematically review and grade the evidence.

Renal Adjustment for drug

• Previously marked as “avoid”

Drug-Drug Interactions

Effects of drug-drug

interactions

Clarification of drugs from

2012 list

New ADDED changes in 2015 update

Table 2 Beer’s Potentially Inappropriate Medication(PIM) in Elderly : 2015 update

Additions to Table 2 PIM Deletions to Table 2 PIM

PPI’s for duration > 8 weeks Anti-arrhythmic drugs (Class 1a,1c, III

except amiodarone) as first-line

treatment for atrial fibrillation

Desmopressin Trimethobenazmide

*Independent of Diagnoses or Condition10

Table 3 Beer’s in Elderly : 2015 update

(Drug-drug and Drug-Disease Interactions)

37

Medication ADDED to Table 3 REMOVED

Falls and fractures- Opioids Chronic Constipation- Entire criterion

Insomnia- Armodafinil & Modafinil Lower urinary tract- Inhaled anticholinergic

drugs

Dementia or cognitive impairment-

Eszopiclone & Zaleplon

Delirium- Antipsychotics

10

Table 5: Potentially clinically important Drug-Drug Interactions

that should be avoided in older adults 10

Object

Drug and

Class

Interacting

drug and

class

Risk

Rationale

Recommendation Quality of

Evidence

Strength of

recommendation

Antidepressant

(i.e., TCAs and

SSRIs)

≥2 other

CNS-active

drugs

Increased

risk of falls

Avoid total of ≥3

CNS-active drugs Moderate Strong

Antipsychotic

≥2 other

CNS-active

drugs

Increased

risk of falls

Avoid total of ≥3

CNS-active drugs Moderate Strong

Hypnotics ≥2 other

CNS-active

drugs

Increased

risk of falls

Avoid total of ≥3

CNS-active drugs High Strong

39

Table 5: Potentially clinically important Drug-Drug Interactions that

should be avoided in older adults10

Object

Drug and

Class

Interacting

drug and

class

Risk

Rationale

Recommendation Quality of

Evidence

Strength of

recommendation

Corticosteroids

(po/iv)

NSAIDs

Increased

risk of

peptic

ulcer/GI

bleeding

Avoid; if not

possible provide

GI protection Moderate Strong

Lithium ACEIs

Increased

risk of

toxicity

Avoid, monitor

lithium conc. Moderate Strong

Warfarin Amiodarone

Increased

risk of

bleeding

Avoid when

possible;

Monitor INR

Moderate Strong

40

Table 6: Non-Anti-Infective medications to AVOID or dose REDUCE in

impaired kidney function in > 65 years10

Medication

Class/

Medication

Creatinine

Clearance

(ml/min)

Rationale Recommendation Quality

of

Evidence

Strength of

Recommendation

Cardiovascular/Hemostasis

Amiloride <30 ↑Potassium

↓ Sodium

Avoid Moderate Strong

Apixaban <25 ↑ bleeding Avoid Moderate Strong

Dabigatran <30 ↑ bleeding Avoid Moderate Strong

Edoxaban

30-50 ↑ bleeding Reduce dose

Moderate Strong<30 or

>95

Avoid

41

Table 6: Non-Anti-Infective medications to AVOID or dose REDUCE in

impaired kidney function in > 65 years 10 (cont. 2)

Medication

Class/

Medication

Creatinine

Clearance

(ml/min)

Rationale Recommendation Quality of

Evidence

Strength of

Recommendation

Cardiovascular/Hemostasis

Enoxaparin <30 ↑ bleeding Reduce dose Moderate Strong

Fondaparinux <30 ↑ bleeding Avoid Moderate Strong

Rivaroxaban 30-50 ↑ bleeding Reduce dose Moderate Strong

Spironolactone <30 ↑Potassium Avoid Moderate Strong

Triamterene <30 ↑ Potassium

↓ SodiumAvoid Moderate Strong

42

Table 6: Non-Anti-Infective medications to AVOID or dose REDUCE in impaired

kidney function in > 65 years 10 (cont. 3)

Medication Creatinine

Clearance

(ml/min)

Rationale Recommendation Quality

of

Evidence

Strength of

Recommendation

Central Nervous System and Analgesics

Duloxetine <30 GI adverse

effects

Avoid Moderate Weak

Gabapentin <60 CNS adverse

effects

dose Moderate Strong

Levetiracetam ≤80 CNS adverse

effects

dose Moderate Strong

Pregabalin <60 CNS adverse

effects

dose Moderate Strong

Tramadol <30 CNS adverse

effects

Immediate

release: dose

ER: Avoid

Low Weak

43

Which of the following medications according to the Beer’s Criteria Update 2015 should be absolutely be AVOIDED in an elderly patient with a CrCl < 30 ml/min due to risk of complications?

A. Spironolactone due to risk of decreased potassium

B. Apixaban due to increased risk of bleeding as

C. Tramadol ER due to risk of increased CNS side effects

D. Risperdone due to increased risk of Tardive Dyskinesia

Question #4

Stakeholders and Star Ratings

In 2007 star rating were created by CMS to help beneficiaries select insurance plans

◦ Plans were rated based on HEDIS scores, CMS Outcome scores and CMS data

◦ A 5-point scale - 5 = excellent and one was poor

CMS met with 15 pharmacy associations, pharmacy benefit management companies and pharmacy chains in 2013

◦ Outcomes: If health plans collaborate with community improved star ratings

45

Active Learning: Case Studies

Please work in groups of MAX 6 people

Refer to separate sheets on table

46

Case # 1

1. Metoprolol XL 50mg po daily (HTN/Afib)

2. Amlodipine 5mg po daily in AM (HTN)

3. Furosemide 20mg + KCL 10mEq daily PRN ankle swelling

4. Atorvastatin 10mg po qHS (Hyperlipidemia)

5. Levothyroxine 50mcg daily AM (Hypothyroid)

6. Omeprazole 20mg po daily (GERD)

7. Metformin 500mg po daily AM (Diabetes Type II)

8. Enoxapirin 30mg SQ daily x 14 days

8. ASA 81mg po daily (CVA prevention)

9. Calcium w/ Vit D 1000mg BID (Osteoporosis)

10. Hydrocodone/APAP 7.5/750mg 1-2 tabs q4 hrs PRN mod pain

11. Morphine 2mg po q4h PRN severe pain

12. Oxybutynin 5mg BID PRN incr urination

13. Lorazepam 0.5mg q4h PRN anxiety

14. Temazepam 7.5mg qHS PRN sleep

15. Risperidone 0.5mg HS + q4h PRN agitation (screaming at hospital)

47

A 94yo female admitted to SNF s/p ORIF R hip 3 days ago.

BP 104/68 HR 52 RR 18 Temp 98 She has no allergies and on the following medications:

Which of the following medications that is on the Beer’s Criteria can easily be discontinued?

A. Metoprolol XL

B. Omeprazole

C. Metformin

D. Risperidone PRN

Question #5

Case #1 Target #1

1. What meds could would be considered Potentially Inappropriate Medications according to the Beer’s Criteria ?

49

Case #1 Target #2

2. What labs should be monitored ?

50

Case #1 Target #3

3. What potential drug-drug interactions exist in her medication regimen?

Case #1 Target #4

4. What ADR would you be concerned about?

52

Case #1

5. How should Antipsychotics be used in SNF ? What are their risks vs. their benefits?

References

54

1. Cusack. Am Geriatr Pharmacother 2004: 2:274: 3022. O’Mahoney&Woodhouse. Pharmacol Ther 1994;61:279-2873. Resnik B, Pacala JT. 2012 Beers Criteria. J AM Geriatr Soc; 2012; 60:612-613 DOI 10.1111/j.1532-5415.2012.03921.4. Beers, MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update. Arch Intern

Med 1997; 157: 1531-15365. Fick DM, Cooper JW, Wade WE et al. Updating the Beers Criteria for Poteintally Inappropriate Medication Use in Older

Adults: Results of consensus panel of experts. Arch Intern Med 2003; 163: 2716-27246. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. AGS updates Beers Criteria for potentially

inappropriate medication use in older adults. J AM Geriatr Soc; 2012; 60: 616-631 7. Steinmen, MA, Beizer, JL, DuBeau, CE, et al. How to Use the American Geriatrics Society 2015 Beers Criteria-a Guide for

Patients, Clinicians, Health Systems, and Payors. J AM Geriatr Soc; 2015; 63: e1-e78. The 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; 2015; 63: 22227-2246 9. McCormick WC. American Geriatrics Society response to letter to the editor from Marc S. Berger “Misuse of Beers Criteria”

July 2014. J. Am Geriatr. 2014; 62(12): 2466-246710. 2015 AGS Beers Criteria and Evidence Tables. http://geriatricscareonline.org/toc/american-geriatrics-society-updated-

beers-criteria-for-potentially-inappropriate-medication-use-in-older-adults/CL001 Published 2015 Accessed 6.20.201611. Hanlon JT, et al. Alternative medications for medications in the use of high-risk medications in the elderly and potentially

harmful drug-disease interactions in the elderly quality measures. J Amer Geriatr Soc 2015;63:e8-e18

AcknowledgementsThank you to

◦ Aida Oganesyan, PharmD

◦ Brad Williams PharmD

◦ Azin Keyvani, PharmD Candidate 2017

◦ Mariam Khachatryan, PharmD

55

1. Write down the course code. Space has been provided in the daily program-at-a-glance sections of your program book.

2. To claim credit: Go to www.cshp.org/cpe before December 1, 2016.

Session Code: