The document discusses issues related to polypharmacy and adverse drug events in older adults. It notes that polypharmacy is common in seniors, putting them at higher risk for adverse drug events, hospitalizations, and costs. The document also reviews tools that can help reduce inappropriate polypharmacy and prescribing, such as Beers criteria, STOPP criteria, and comprehensive medication reviews.

1. Considerations on Polypharmacy and Adverse Drug
Events
Jonathan H. Watanabe, PharmD, PhD, BCGP
Assistant Professor
Division of Clinical Pharmacy
3rd Annual Clinical Interprofessional Geriatrics Symposium
Sunday December 4, 2016

2. Slide 2 of 16
Consequences of medical care are gaining attention
• The cost of drug-related morbidity and mortality exceeded $177.4
billion in 2000 with $121.5 billion attributed to hospitalization
costs. 1
• Adverse drug events (ADEs) lead to an estimated 99,628
hospitalizations per year2
• JAMA meta-analysis in 1998 estimated that fatal ADEs may rank
between the 4th and 6th leading cause of death in the US3
1. Ersnt FR et al. J Am Pharm Assoc. 2001; 41:192-199
2. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency Hospitalizations for Adverse Drug
Events in Older Americans. N Engl J Med 2011;365(21):2002–12.
3. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: A
meta- analysis of prospective studies. JAMA 1998;279(15):1200–5.

3. Slide 3 of 16
….and older adults are at elevated risk of
hospitalizations due to ADEs
• While people over 65 represent
14.1% of the US population,10
seniors account for more than 49% of
ADE-related hospitalizations1-3
• The risk of ADEs accelerates beyond
age 65 years old. Patients 85 and
older accounted for more than triple
the ADE-related hospitalizations in
those 65 to 69 years old4
1. Statistics on Aging [Internet]. Available from: http://www.aoa.acl.gov/Aging_Statistics/index.aspx
2. Kongkaew C, Hann M, Mandal J, et al. Risk factors for hospital admissions associated with adverse drug
events. Pharmacotherapy 2013;33(8):827–37.
3. Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. NAtional surveillance of
emergency department visits for outpatient adverse drug events. JAMA 2006;296(15):1858–66.
4. Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency Hospitalizations for Adverse Drug Events in
Older Americans. N Engl J Med 2011;365(21):2002–12

4. Slide 4 of 16
Polypharmacy associated with ADEs
• After adjusting for age, sex, and initial antihypertensive therapy in a cohort
study of 66,161 older adults, the RR was estimated at 4.3 (95% CI, 3.8–
4.8) for the polypharmacy group, when compared with the monotherapy
group.1
• Retrospective study of seniors observed that seniors with adverse drug
reactions (ADRs) were consuming more medications2
• Polypharmacy also observed to influence medication adherence, but
findings have been inconsistent3
1. Sato I et al. Drug Healthc Patient Saf. 2013; 5: 143–150.
2. Veehof LJ, et al. Adverse drug reactions and polypharmacy in the elderly in general practice. Eur J Clin
Pharmacol. 1999 Sep;55(7):533-6.
3. Watanabe JH et al. Annals of Pharmacotherapy 2013;47(10) 1253–1259
Mean number of
Medications for seniors
with an ADR
Mean number of
Medications for Seniors
without an ADR
14.7 5.5

5. Slide 5 of 16
What is Polypharmacy?
• 1st Bullet 24 Point, Color Text 1 Lighter 25%
• 2nd Level Bullet, 20 point
• 3rd Level Bullet, 18 Point, Color Accent 2
• 4th Level Bullet, 14 Point, Color Lighter 25%
Definition Source
Concurrent use of multiple medications Kroenke K. Polypharmacy: causes,
consequences, and cure. Am J Med.
1985;79:149-152.
the use of two or more medications, and
it is commonly seen in this patient
population
Munger, M.A. Drugs Aging (2010) 27:
871. doi:10.2165/11538650-000000000-
00000
Use of four or more medications wiki
increase in the number of medications or
the use of more medications than are
medically necessary
Maher R et al. Expert Opin Drug Saf.
2014 Jan; 13(1):
10.1517/14740338.2013.827660.

6. Slide 6 of 16
Polypharmacy more pronounced in seniors
• Average number of medications used by older adults
ranges from 8 to 13 studies1
• Consistent with UCSD SSPPS medication therapeutic
management sessions at assisted living facilities
• 36% of community dwelling seniors in the US used 5 or
more medications in a nationally representative survey2
• Analysis of Medicare enrollees discharged to SNFs found
an average of 14 medications3
• Average of 5.9 (±2.2) medications that could contribute to geriatric
syndromes, with falls having the most associated medications at
discharge at 5.5 (±2.2).
1. Farrell et al. Can Fam Physician. 2011 Feb; 57(2): 168–169
2. Qato DM et al. JAMA Intern Med. 2016 Apr;176(4):473-82.
3. Saraf AA et al. J Hosp Med. 2016 Oct;11(10):694-700.

7. So what can we do about reducing polypharmacy?

8. Slide 8 of 16
Medication therapeutic management (MTM) is now
a required component of LTC Pharmacy
• As of 2013, as a part of the Affordable Care Act, annual
real-time Comprehensive Medication Reviews (CMRs)
must be offered to Medicare Part D beneficiaries that meet
certain criteria

9. Slide 9 of 16
CMR Components: Direct patient interaction and
patient activation
• Targeted enrollees are
multimorbid patients ( >
2 chronic diseases)
• With Polypharmacy
(Plan CANNOT require
more than 8 drugs as
threshold for targeted
enrollment)
• With costs expected to
exceed ~$3,000 in
annual drug costs

10. Slide 10 of 16
Apply an intervention framework tied to utilization
reduction
Ramalho de Olveir et al. J Manag Care Pharm. 2010;16(3):185-95

11. Slide 11 of 16
How much time is spent talking to the patient about a newly
prescribed medication during the physician office visit?

12. Slide 12 of 16
MTM improves multiple medication related
outcomes
Outcomes
Improved medication appropriateness on medication appropriateness index 4.9 units at 12
months (P < 0.01)
Improved Odds of adherence 4.6% (95% CI, 3.211 to 5.989)
Lowered mean doses (mean difference, −2.2 doses; 95% CI, −3.738 to −0.662 )
Lowered health plan medication costs −$293 (95% CI, −501.5 to −84.5) during 6 months
Lowered hospitalization rates for diabetics (Odds Ratio 0.91 to 0.93)
Lowered hospitalization rate for heart failure patients (Hazard Ratio 0.55; 95% CI, 0.39 to
0.77
Lowered hospitalization costs (mean differences ranged from −$363.45 to −$398.98).
Lowered length of stay by 1.8 days
Viswanathan et al. JAMA Intern Med. 2015;175(1):76-87. doi:10.1001/jamainternmed.2014.5841

13. Slide 13 of 16
Tools for reducing polypharmacy
Tool Description
Medication Regimen Complexity Index (MRCI)1 65-item validated assessment that (i) dosage
formulations, (ii) dosing frequency, and (iii)
additional administration directions.
STOPP Criteria2 Designed to address limitations of Beers Criteria
for European clinicians
https://www.farmaka.be/frontend/files/publications
/files/liste-start-stopp-version.pdf
http://ageing.oxfordjournals.org/
2015 Beers Criteria3 Most recent iteration and expanded version of
Beers Criteria
Potentially Inappropriate Medication List
developed by Budnitz et al from CDC4,5
Used nationally representative data to identify
drugs most associated with ED visits
Comprehensive Medication Review form
1. Hirsch JD et al. Pharmacotherapy. 2014 Aug;34(8):826-35.
2. Ryan C et al. of STOPP and START criteria: interrater reliability among pharmacists. Ann Pharmacother.
2009 Jul;43(7):1239-44.
3. Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc.
2015 Nov;63(11):2227-46.
4.Budnitz, Daniel S., et al 365.21 (2011): 2002-2012.
5.Budnitz, Daniel S., et al. 147.11 (2007): 755-765.

14. Slide 14 of 16
Is polypharmacy always bad?
• Still must be judicious
• While polypharmacy is a signal that
medication review, reconciliation, and
MTM should be performed it is not
always an indicator of poor care
• Situations where appropriate care will
demand additional medications be
used
• Each unit increase in MRCI score was
associated with a modest but non-
significant increase in probability of
survival from readmission or ED visit
(HR 0.978; 95% CI 0.955, 1.001) in an
observational study of HF patients1
Watanabe JH et al. Ann Pharmacother. 2013 Oct;47(10):1253-9
1. Yam FK et al. Res Social Adm Pharm. 2016 Sep-Oct;12(5):713-21

15. Slide 15 of 16
Implications for polypharmacy and plan ratings
• Pharmacy Quality Alliance (PQA) perfomance measures are often
integrated into CMS Star Ratings
• Polypharmacy/Inappropriate/Unnecessary Therapy: Inappropriate
combination therapies that are potential safety concerns is now being
considered as a measure by PQA

16. Slide 16 of 16
Acknowledgements
Dr. Diane Chau
Sammi Tam, PharmD candidate
Dr. Paula Park

17. Kamal Kejriwal M.D., CMD, AGSF, FAAFP
Program Director
Geriatric Medicine Fellowship
SCPMG
Fontana
Polypharmacy and DE prescribing

18. 18
Disclosure
No relevant financial relationships with
commercial interests

19. 19
Topics Covered
• Challenges of geriatric pharmacology
Updated Beers Criteria
• Tools for De Prescribing
• Psychotropic use in Nursing Facilities

20. 20
The central question
in all of modern
American medicine…
Well, what pills
should I give her for
that?

21. 21
“It’s just because I’m OLD”
FALSE
You must understand the underlying
pathophysiology of diseases, normal
pharmacodynamics and pharmacokinetic
changes with aging, and drug-drug and
drug-disease interactions!!

22. 22
Why Geriatric Pharmacotherapy is Important
Persons aged 65 and older are prescribed the
highest proportion of medications in relation to their
percentage of the U.S. population
• Now, 13% of total population buy 33% of all
prescription drugs.
• In Elderly populations there are more deaths
due to ADE than MVA, Breast cancer or AIDS.
• By 2040, 25% of total population will buy 50% of
all prescription drugs.

23. 23
WHY GERIATRIC PHARMACOTHERAPY
IS IMPORTANT
0
10
20
30
40
50
60
70
80
90
100
Present 2040
People 65+ 65+ share of prescriptions
People <65 <65 share of presciptions
Now, people age 65+ are 13% of US population, buy 33% of prescription drugs
By 2040, will be 25% of population, will buy 50% of prescription drugs

24. 24
Why Geriatric Pharmacotherapy is
Challenging?
• FDA- approved and off-label indications
expansion
• Managed-care formularies change frequently
• Knowledge of drug-drug interactions
advances
• Drugs change from prescription to OTC
• “Nutriceuticals” (herbal preparations,
nutritional supplements) are booming

25. 25

26. 26
• Older adults rank concerns about
medication sides effects as highest on
their health priorities.
• 89% with chronic conditions willing to
attempt cessation if deemed necessary by
their providers.
• Despite the Beers criteria, inappropriate
prescriptions persists in 25% of the
community non hospitalized elderly.

27. 27
• Interventions aimed at physicians and
pharmacist such as medication reviews
and best practice alerts.
• Per EMPOWER study patients states in
33% of the cases physicians were
reluctant to change the medications.

28. 28
• Benzodiazepines one of the most
prevalent inappropriate medications
consumed: 19%
• Per Beers criteria Benzos should be
avoided in older adults due to an
excessive risk of delirium, falls, fractures
and motor vehicle accidents.
• Shown to increase the risk of amnestic
and non amnestic cognitive impairment
and may lead to incident dementia.

29. 29
Benzodiazepines
• The Number Needed to Harm is very low
compared to Number Needed To Treat
• NNT >> NNH

30. 30
• Chronic benzo users develop
psychological dependence to it.
• Makes it difficult for physicians and
consumers in implementing the tapering
protocols.
• Pt deny or minimize side effects.
• Fear of upsetting Doctor – Patient
relationship.

31. 31
What are Patients Thinking

32. 32
Empower study
What patients Think

33. 33
Patient Perspectives
• Valium is a mild tranquilizer and safe when
taken for long periods of time.
• Dose I am taking is causing no side effects
• Without Valium I would be unable to sleep
or will experience unwanted anxiety.
• Valium is best available option to treat my
symptoms.

34. 34
34
Effects of Aging on Volume of
Distribution (Vd)
•  body water  lower VD for hydrophilic drugs
•  lean body mass  lower VD for drugs that
bind to muscle
•  fat stores  higher VD for lipophilic drugs
•  plasma protein (albumin)  higher
percentage of drug that is unbound (active)

35. 35
Changes in Distribution:
Protein Binding
• Reduced protein binding with age
• Reduced protein concentrations with
disease
• Affects serum levels of drugs that bind to
proteins
• Examples: fentanyl, theophylline,
sulfonylureas, warfarin and digoxin

36. 36

37. 37
ADEs Prescribing Cascade
Source Note: Rochon PA, Gurwitz JH. Optimising drug treatment for
elderly people: the prescribing cascade. BMJ. 1997;315(7115):1097.
Reprinted with permission.
DRUG 1
DRUG 2
Adverse drug effect-
misinterpreted as a new medical condition-
Adverse drug effect-
misinterpreted as a new medical condition

38. 38
How to Avoid Getting Into Trouble with
Drugs in the Elderly
• Use proper prescribing etiquette
• Watch for drug-drug, drug-disease, and
drug-food interactions
• Don’t prescribe bad medications

39. 39
Appropriate Drug Prescribing
(proper etiquette)
• Review current prescription and non-
prescription medications, medical history, labs
• Ask about drug allergies, adverse reactions,
use of alcohol
• Start low and go slow but treat adequately
• Maximize dose before switching to another
drug
• Avoid starting two drugs at the same time

40. 40
Watch for Drug-Drug, Drug-Disease,
and Drug-Food Interactions

41. Beers list of PIMS
2015 Update
Guideline for nitrofurantoin is relaxed for
Creatinine Cl from 60 to 30
Opioids been added to list of CNS drugs to
avoid in pt with h/o falls and fractures.
Anticoagulants dose should be adjusted
based on Cr Cl.
Avoid PPI for greater than 8 weeks
Nasal Saline to use as alternative to
antihistamines
41

42. CHOOSING
WISELY
42

43. Don’t prescribe a medication without
conducting a drug regimen review.
#1 Older patients disproportionately use more
prescription and non-prescription drugs than
other populations, increasing the risk for side
effects and inappropriate prescribing.
#2Polypharmacy may lead to diminished adherence,
adverse drug reactions and increased risk of
cognitive impairment, falls and functional decline
#3 Annual review of medications is an indicator for
quality prescribing in vulnerable elderly.
43

44. Don’t use benzodiazepines or other sedative-
hypnotics in older adults as first choice for
insomnia, agitation or delirium.
#1Large scale studies consistently show that the risk of motor
vehicle accidents, falls and hip fractures leading to
hospitalization and death can more than double in older
adults taking benzodiazepines and other sedative-
hypnotics.
#2 Older patients, their caregivers and their providers should
recognize these potential harms when considering
treatment strategies for insomnia, agitation or delirium.
#3 Use of benzodiazepines should be reserved for alcohol
withdrawal symptoms/delirium tremens or severe
generalized anxiety disorder unresponsive to other
therapies
44

45. c 2007 ASCP
45
F329 - Unnecessary Meds
Regulations
• Antipsychotics - Based on a comprehensive
assessment of a resident, the facility must ensure
that:
– Residents who have not used antipsychotic drugs are
not given these drugs unless antipsychotic drug therapy
is necessary to treat a specific condition as diagnosed
and documented in the clinical record; and
– Residents who use antipsychotic drugs receive gradual
dose reductions, and behavioral interventions, unless
clinically contraindicated, in an effort to discontinue
these drugs

46. Psychotropic Use in Long Term Care
Facilities
Please do not use the above medications as
your First Line
Non Pharmacological Approaches first
Title 22 requires the consent to be taken by
the provider prior to administration of
these meds.
46

47. 47

48. Targeted Medication Classes
Anticholinergic(Antih
istamines )
LA sulfonylureas
NSAIDS
Confusion, dry mouth,
constipation and
functional decline
11% ED visits.
52% greater risk of at least
one hypogly. Episode
Increase risk of GI bleeding
/PUD
Use of misoprostol reduces
but does not eliminate.
48

49. 49
Does this sound Familiar?
Decreased use of Inappropriate meds in Elderly ( 65
yrs. and older) improves hospital safety, reduces
length of stay and rate of readmissions.
Examples of potentially inappropriate meds to avoid
in Elderly:
-Diphenhyramine, Promethazine, Hydroxyzine,
amitriptyline, imipramine, methocarbamol,
trimethobenzamide, meperidine and diazepam.

50. Innovative pill box reminders
Medminder® : $40-65 per month. Looks like
traditional pill boxes, 7 day (qid) boxes that
lock. Flashing light/audible/text
message/phone calls for reminders. Also,
caregivers can get reports via
text/emails/internet
Locked medication systems (eg e-pill): $200-
500. Dispensers that lock/alarm, like a small
omnicell/pyxis machine.
iPhone apps: Free-$3.99. Virtual pillbox. Can
set medications, dosages and times a dose is
needed. Alarms, reminders, etc.

51. https://www.youtube.com/watch?v=PXoLsW
0w1FE
51

52. Thank you!