1. Polypharmacy Jillian Hernan Fee, PharmD, BCPS Clinical Pharmacist
CarePro Home Infusion
April 25, 2014

2. Polypharmacy, what is it?
Poly (Greek) = Many
Pharmacy = Drugs/Medications
What does many drugs mean?
How many meds are too many?
Example 1 – 75 yom with CHF, CAD, DM, HTN, HLP
Example 2 – 82 yof with dementia and overactive bladder
Poly (greek) for many
Pharmacy – drugs or medications
What does many drugs mean?
Ex yom with CHF, CAD, DM, HTN, HLP
CHF: diuretic, BB, ACE-I
CAD: aspirin, BB, ACE (covered by CHF)
DM: 2 hypoglycemics, aspirin, ACE
HTN: likely covered by CAD/CHF
HLP: statin, fibrate, fish oil, niacin (maybe just 2-3 of these)
Grand total: at least 9
Ex 2- 82yof with dementia and overactive bladder
Dementia: cholinesterase inhibitor (aricept, namenda)
Overactive bladder: oxybutnin
These meds interact. What if the same prescriber isn’t writing for both?

3. CarePro Pharmacist Poll
Using multiple pharmacies, providers, and prescription drugs that may not be appropriately monitored (3)
Using multiple medications either for same condition or to treat side effects of another drug (7)
Using multiple medications that are not clinically indicated (1)
Unnecessary use of meds when fewer meds or other options may be more appropriate (1)
Using more than one pharmacy to fill rx meds (may be drug seeking behavior)
Using more than 5-7 medications (4)
Number of meds changed with RPh

4. Polypharmacy definition
This article will be referenced throughout the presentation.
They reviewed available literature, found 24 different definitions. We will review the most common on next slide, note that the first 6 are the only ones that were used more than once. Even the most common definition was only used 4 times!!
Can be positive or negative (usually negative)
Bushardt 2008

5. Polypharmacy definition
Most common in literature:
Medication does not match diagnosis (4)
Many medications, duplication of medications, drug-drug interactions (3)
Inappropriate dosing frequency (excessive duration, dose too low, dose too high), medication prescribed to treat a side effect (2)
The term “inappropriate” often occurs in definitions
Number of medications taken routinely
“Hyperpharmacotherapy”
Excessive use of drugs for treatment of disease
Not really used mainstream but I like this term
Carries a negative connotation
Medication Underutilization
Omission of an indicated and potentially beneficial medication for the treatment or prevention of disease
Most common in literature:
Medication does not match diagnosis (4)
Many medications, duplication of medications, drug-drug interactions (3)
Inappropriate dosing frequency (excessive duration, dose too low, dose too high), medication prescribed to treat a side effect (2)
The term “inappropriate” often occurs in definitions
Number of medications taken routinely
The number used varies from article to article, usually 5-9 medications
My suggestion is not to use number of meds. May miss pts and select for those who are on the right therapy
“Hyperpharmacotherapy”
Excessive use of drugs for treatment of disease
Not really used mainstream but I like this term
Carries a negative connotation
Medication Underutilization
Omission of an indicated and potentially beneficial medication for the treatment or prevention of disease
Underuse- it is a balance between limiting the number of meds and using the meds that may be beneficial
Reasons why this could happen - Speculation by Barry et al: (hasn’t really been studied)
Lack of knowledge of evidence based secondary prevention therapy
Low levels of expectation for the elderly
Desire to avoid polypharmacy
Greater focus on symptom palliation than secondary disease prevention
Ageism
Bushardt 2008, Barry 2007, Wright 2009

6. Consequences of polypharmacy
CMS estimates $50 billion annually
Adverse drug reactions
Risk increases with multiple comorbidities, use of high risk drugs (ie warfarin), and increasing numbers of meds
Adherence
ADR’s
Complex regimens
CMS estimates $50 billion annually
$50 billion is drug cost only!! Not hospitalizations, decline requiring a higher level of care, etc
Adverse drug reactions
- Risk increased with multiple co-morbidities, use of high risk meds (ie warfarin), and increasing numbers of meds
Adherence – used to be compliance.
ADR’s
Would you continue to take a med that causes an ADR??
Complex regimen- when I was a student, patient brought in bag with 19 different meds. Sat down with her and schedule and found that it was not possible for patient to take all meds correctly !!!
Bushardt 2008, Hajjar 2007

7. Consequences of polypharmacy
Inappropriate prescribing
More meds = higher risk
Beers’ list meds
Drug interactions
Is the medication list complete and correct?
Geriatric Syndromes
Increased risk of cognitive impairment
Increased risk of falls
Morbidity/Mortality
Inappropriate prescribing
More meds = higher risk
Not a causal relationship, but an associations
Beers’ list meds
Drug interactions
Same as more meds is higher risk, it’s not necessarily causal, just means there is an association
The combo’s (say 3 or more meds) may tip the point over to causing a significant interaction. Maybe would have done fine with the 2 meds
Is the med list complete a correct
Is MD working off the right list? Is it updated with every MD appt? Including other providers!!!
Geriatric syndromes:
Cognitive impairment – study in 1987 (not referenced, couldn’t find full text) – found increased risk of cognitive impairment with increasing number of meds
- Falls- Agostini study, controlled for age, cognition, vision, hearing, chronic disease states.
1-2 meds, not significant
3-4 meds – odds ratio 1.72
5 or more meds – OR 1.8
NOT CAUSAL, just means a relationship exists
Morbidity/mortality – polypharmacy increases!
Hajjar 2007, Agostini 2004

8. Who is at risk?
Men 65 and older– 12% use 10 or more drugs per day (not just rx)
Women 65 and older– same 12% use 10 or more drugs per day
Kaufman 2002

9. Who is at risk? This is rx drugs only
Men 65 and older– 19% use 5 or more rx/day
Women 65 and older– 23% use 5 or more rx/day
Kaufman 2002

10. Who is at risk? Demographic Health status Access to health care
Age, caucasian race, education
Health status
Poorer health, use of >8 medications
Diagnosis of: HTN, anemia, asthma, angina, diverticulitis, arthritis, gout, DM
Access to health care
Multiple providers, number of health care visits, supplemental insurance
Underutilization
Increased severity of comorbid conditions
Physical limitations
Caucasian race
Demographic
age, caucasian race, education
Age- 65 years and older, much higher risk the “old old” (85 years and older)
Use of all meds (not just rx) in the elderly has more than doubled since 1990 and will continue to rise. Baby Boomers!!
As of elderly were 13% of population yet used 1/3 of all rx meds
Race – cultural differences in how people perceive illness and what they do to treat
Education – may lead patients to seek care/providers
Health Status
Poorer health, use of >8 meds
Diagnosis of hypertension, anemia, asthma, angina, diverticulitis, arthritis, gout, diabetes
These are chronic conditions requiring frequent monitoring. This leads to more visits.
Access to healthcare:
Multiple providers, number of health care visits, supplemental insurance
providers don’t necessarily talk to each other, more visits = more chances to prescribe, more coverage = less barriers to starting new medication
Underuse: (risk factors for underuse)
Increased severity of co-morbid conditions
Makes sense, if you are really ill maybe MD doesn’t want to use every med in the guidelines, esp ones with long-term benefit
Physical limitations
Caucasian race
Wright study
Did not correlate with number of meds or with taking unneeded meds
Hajjar 2007, Wright 2009

11. Why elderly? Physiological changes
Decreased renal function
Decreased hepatic function
Decreased total body water and lean body mass
Decreased vision/hearing
Lack of clinical trials in elderly patients
Physiological changes: - decreased renal and hepatic function – pharmacokinetic changes
Decreased total body water and lean body mass – PKIN changes
Decreased vision and hearing
Can they understand the right way to take meds
Elderly patient’s have less reserve. They may not be able to tolerate a change that younger, healthier patients wouldn’t notice
Elderly patients are often excluded from clinical trials and are more likely to have other disease states that cause them to be excluded in other trials
We are flying by the seats of our pants!
Bushardt 2008

12. Prevalence of polypharmacy
Steinman 2006
Evaluated 196 patients taking 1,582 medications
65% of patients were taking one or more inappropriate meds
64% missing beneficial meds
42% taking inappropriate meds AND were missing beneficial meds
13% had appropriate therapy!!
Steinman study- done at the VA in Iowa City
Evaluated 196 patients taking 1582 medications
Used MAI (medication appropriateness index), Beers Criteria, and Assessment of underutilization of medication (underuse)
-65% taking one or more inappropriate meds –
62 of 91 errors were deemed severe
Risk increased with number of meds (consistent with this lecture)
64% missing beneficial meds
199 meds missing – mostly CV conditions (HTN, ASA, lipid agents)
underuse did NOT correlate with number of medications
More evidence not to use the number of meds as a trigger for evaluation
42% were taking inappropriate meds AND missing beneficial meds
13% had appropriate therapy!!
-Patients taking 7 meds or less were more likely to be missing a med (error of omission)
-Patients taking more than 7 meds were more likely to be taking an inappropriate med (error of comission)

13. Prevalence of polypharmacy
Hajjar 2005
384 frail, elderly patients’ medication regimens evaluated at hospital discharge
44% had at least one unnecessary drug
Almost 75% of these patients were on this unneeded drug prior to hospitalization
18% had 2 or more inappropriate meds
Done at 11 VA centers
- 384 frail, elderly patients’ medication regimens evaluated at hospital discharge
Used the Medication Appropriate Index to assess regimen
Patients were mostly white males, almost 50% were older than 75
- inclusion criteria included frailty (assessed with multiple scales)
- nearly 40% took 9 or more meds
- multiple comorbidities
44% had at least 1 unnecessary drug
Of the 44%:
33% were lack of indication,
20% lack of efficacy,
less than 10% were duplications
Mostly common unneeded drug classes: GI, CNS, and vitamins/minerals (H2 blockers, laxatives, antispasmodics (like oxybutynin), and TCAs)
The 25% of unneeded meds that were started in hospital were from the same classes
18% had 2 or more inappropriate meds
Risk factors from this study: multiple prescribers and 9 or more meds.
HTN was protective!! (Weird. It’s actually a risk factor)

14. Prevalence of underutilization
Wright 2009
384 frail, elderly patients’ medication regimens evaluated at hospital discharge
62% (238 patients) were missing a potentially beneficial medications
87.3% of these patients were missing this drug prior to hospitalization
25.8% (99 patients) were missing 2 or more medications
Less well studied.
Wright study: at several VA centers
Used the same cohort as the Hajjar study in the previous slide
Assessed underuse with the Assessment of Underutilization index (AOU)
Patients were mostly white males, almost 50% were older than 75
- inclusion criteria included frailty (assessed with multiple scales)
- nearly 40% took 9 or more meds
- multiple comorbidities
62% (238 pts) were missing beneficial meds
87.3% were missing this drug before hospitalization
25.8% (99 pts) were missing 2 or more meds
Most commonly undertreated conditions
CV system, endocrine/nutritional therapies, musculoskeletal system, and respiratory system.
Ex ACE-I in CHF and DM, CAD- nitrates, ASA, beta blockers
Number of meds and/or presence of polypharmacy did NOT correlate with underuse (consistent with the Steinman study)
Being discharged from medicine service (vs surgery) was protective
Perhaps surgeons are more focused on peri-operative care?
Risk factors for underutilization:
Increased comorbid disease severity (sicker patients)
Increased physcial limitations
Caucasian race (my opinion, most VA patients were white, maybe results would be different if other races were more prevalent in the cohort)

15. Assessments Beers’ List Medication Appropriateness Index STOPP
Screening Tool of Older Persons’ potentially inappropriate Prescriptions
Hyperpharmacotherapy Assessment Tool
START
Screening Tool to Alert doctors to the Right Treatment
Assessment of Underutilization Index
Geriatric Evaluation

16. Beers’ List
Originally pusblished in 1991 for residents of nursing homes
Lists of medication considered potentially inappropriate medications in elderly patients
1. Drugs to avoid in elderly
2. Drugs to avoid in elderly with certain disease states
3. Drugs to be used with caution in the elderly
Intended as a guideline only, using these meds in elderly is not automatically inappropriate
See handout
Originally published in for residents of nursing homes
Updated in 1997, 2003, and 2012 to include all geriatric practice areas
Lists of medication considered potentially inappropriate in elderly patients
Drugs to avoid
Drugs to avoid with certain disease states
Drugs to be used with caution
Intended as a guideline only. Sometimes there isn’t another medication that will work and MD must use a Beers list drug, should raise a red flag and trigger closer follow up.
Limitations:
Elderly not included in trials
Does not address meds that require changes for all patients (not just elderly) – renal dosing
Does not address the needs of patients receiving palliative and hospice care
Fick 2012

17. Beers’ List Notable 2012 changes Medications/classes to avoid
Glyburide, megestrol, sliding scale insulin
Medications/classes to avoid in certain disease states
Heart failure – thiazolidinediones (glitazones)
History of syncope – acetylcholinesterase inhibitors
Falls/fractures – SSRI’s
Medications/classes to use with caution
Prasugrel (Effient), Dabigatran (Pradaxa)
Greater risk of bleeding in the elderly
Fick 2012

18. Medication Appropriateness Index
Evaluates each medication individually based on 10 criteria for appropriateness
Limitations:
Time (10 minutes/drug)
Full scope of ADR’s not included
Assesses drug-drug or drug-disease interactions but not side effects independently
Adherence is not addressed
Validated and most often used in the literature
Each criteria scored 1, 2, or 3.
1-2= appropriate
3= inappropriate
If any item scores a 3 – drug inappropriate
Hanlon 1992

19. Indication
Effectiveness
Correct dose
Correct directions for use
Practical directions for use
Drug-drug interactions
Drug-disease interactions
Duplication
Duration of therapy
Least expensive option of EQUAL quality
Hanlon 1992

20. Summated MAI Attempted to quantify the level of inappropriateness
Grouped questions in MAI by level of importance
Group A: indication and effectiveness
Group B: dosage, correct directions, drug-drug and drug-disease interactions
Group C: practical directions, expense, duplication, and duration
Limitations – same as for MAI
Possible to score 0-18
Group A – 3 points
Group B – 2 points
Group C – 1 point
Generally speaking:
2-4 – 1 inappropriate med from group B and none from group A
5-6 – 1 item from group A and none from group B
7- above – 1 item from all groups
Limitations: same as the MAI
-Time (10 minutes/drug)
- Full scope of ADR’s not included (Assesses drug-drug or drug-disease interactions but not side effects independently)
- Adherence is not addressed
Samsa 1994

21. Gallagher 2008 (Clin Pharmacol Ther)
STOPP
Screening Tool of Older Persons’ potentially inappropriate Prescriptions
Developed in Europe
Potentially inappropriate medications are listed by organ system
Focused on meds commonly used in geriatric population in Europe
See handout
Assessment of OVERUSE
Organ systems: CV, CNS and psychotropic drugs, GI, respiratory, musculoskeletal, urogenital, endocrine, “fallers,” analgesic drugs, duplications
The authors of this article think Beers’ is too lengthy and includes meds not commonly seen in Europe
Gallagher 2008 (Clin Pharmacol Ther)

22. Hyperpharmacotherapy Assessment Tool
Suggest annual review (at minimum)
Form is set up based on various goals
I. Number of meds
II. Decrease inappropriate meds
Meeting goals, disease still present?, least expensive option, Beers List med?
III. Decrease inappropriate pharmacology
Duplications, combo meds, ADR’s, interactions
IV. Optimize dosing regimen
Is this is the lowest effective dose? Any meds taken more than BID? Adherence issues?
V. Organize sources of meds
More than one pharmacy? Mail order? Other prescribers?
VI. Patient education
See handout
The idea is to use the same form at each visit (room for up to 6 visits)
Bushardt 2008

25. Assessment of Underutilization
Developed in conjunction with MAI, works the same way.
A- no drug omitted
B- marginal omission
C- drug omitted
Could not find the original reference!!!!
Use this form along with a comprehensive list of medications and disease states to look for omissions
Jeffery 1999

26. Gallagher 2008 (Clin Pharmacol Ther)
START
Screening Tool to Alert doctors to the Right Treatment
Developed in conjunction with STOPP guidelines in Europe
Meds are screened by organ system
See handout
STOPP/START Advantages:
~1.5-3 minutes to review both scales
Gallagher 2008 (Clin Pharmacol Ther)

27. Specialized Geriatric Evaluation
Integrated team of geriatricians, social workers, nurses, and other healthcare providers evaluate medication use in both inpatient and outpatient setting
Study done at several VA centers
Assessed 834 frail, elderly veterans for adverse drug reactions and suboptimal prescribing in both outpatient clinics and as inpatients compared with usual care
Primary outcome: adverse drug reactions
Both any ADR and serious ADR’s were assessed
Results: outpatient clinics but not inpatient units reduced the risk of serious ADR’s
Specialized team trained to identify drug therapy problems in the elderly. Pharmacists consulted or attached to a team.
Patients must have been hospitalized for at least 3 days in medical or surgical ward
Outpatient period was 12 months after admission
Serious ADRs: death, hospitalization, prolonged hospitalization, permanent disability, need for intervention to prevent permanent disability
Secondary outcomes: polypharmacy (prescribing unnecessary meds), inappropriate prescribing, and underuse (omission of indicated drug therapy)
400 of the 834 patients were evaluated for suboptimal prescribing (secondary outcome)
Results:
-Most common ADRs were diarrhea and renal insufficiency in both inpatient and outpatient
-Most common SERIOUS ADRs were renal failure and hypoglycemia
Risk reduced by 35%
Inpatient units were not significant
ADR’s may not have shown up so quickly during admission
Secondary results:
Suboptimal prescribing – both inpatient and outpatient evaluation showed improvement compared with usual care
Schmader 2004

28. How well do evaluations work?
Gallagher 2011
Evaluated 382 patients randomized to usual care or evaluation with STOPP/START criteria from hospital admission to 6 months after discharge
Primary outcomes: change in MAI and AOU scores
Results
MAI – 71.1% of intervention and 35.4% of control group had improved MAI score on hospital discharge
Absolute risk reduction 35.7%
Number needed to screen: 2.8 (95%CI )
AOU – 31.6% of intervention and 10.4% of control group had a reduction in AOU score on hospital discharge
Absolute risk reduction 21.2%
Number needed to screen: 4.7 (95%CI )
The rate of potentially inappropriate prescribing increased gradually during the 6 month follow up period – authors conclude that patients should be assessed at least every 6 months
Made a total of 183 recommendations on 111 patients
92 of 101 STOPP recommendations were accepted by physician (91%)
67 of 69 START recommendations were accepted (97%)
Secondary outcomes: prevalence of falls, all cause mortality, length of hospital stay, and frequency of readmission
All non-significant but study was not powered to detect
Results:
- Number to screen = 3!!!! That is huge given that this can be done in minutes!

29. How well to evaluations work?
STOPP vs Beers’ List
Evaluated 715 admissions of elderly patients
Trained clinicians identified patients who’s admission were due to adverse effects
The number of potentially inappropriate meds identified by the 2 evaluations were compared
Results
All drugs
STOPP: found inappropriate meds in 35% of patients
Beers’ List: found inappropriate meds in 25% of patients
Admissions due to ADR’s (N=90)
STOPP: identified 91% (82 pts) of the meds as inappropriate
Beers’s List: identified 48% (43 pts) of the meds as inappropriate
Done in Europe
Rx drugs only (limitation)
STOPP vs Beers’ List
Evaluated 715 admissions of elderly patients
All medications on all patients evaluated
STOPP found inappropriate meds in 35% of patients (75% of those patients had >1PIM!!!) – 336meds
Beers’ found PIMs in 25% of patients – 226meds
Trained clinicians identified patients who’s admission were due to adverse effects
The number of potentially inappropriate meds identified by the 2 evaluations were compared
Results
All drugs
STOPP: found inappropriate meds in 35% of patients
Beers’ List: found inappropriate meds in 25% of patients
Admissions due to ADR’s (N=90)
STOPP: identified 91% (82 pts) of the meds as inappropriate
Beers’s List: identified 48% (43 pts) of the meds as inappropriate
Admissions – this is significant! Using STOPP criteria before the admission (perhaps when drug was prescribed or at FU visit) could have prevented at least some of these admissions
STOPP caught nearly twice as many problems as Beers’
Gallagher 2008 (Age and Ageing)

30. How to appropriately stop meds
Do not stop more than 1 drug at a time
Some meds require tapering off and careful monitoring during the taper period
Attempt to make changes over a longer period of time
Consider use of midlevel practioners for follow up visits and monitoring
Should not just stop 1 drug at each visit, need to carefully consider effects of stopping these meds. Both effects on the patient and effects on the other meds in their regimen
Let them MD decide which meds to stop, then PA or ARNP can do the monitoring visits
Bushardt 2008

31. Role of the dietician Grapefruit interactions
Ask patient what their meds are for
Remind patients
Take med list to every provider visit
Update the list with every visit
Tell all providers about all meds, including OTC and herbal meds

32. Agostini JV, Han L, Tinetti ME
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33. Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients
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34. Schmader KE, Hanlon JT, Pieper CF, et al
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