Geriatric Pharmacotherapy: Managing Older Adults on Multiple Medications

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Geriatric Pharmacotherapy Managing Older Adults
on Multiple Medications

• Lynne E. Kallenbach, M.D.
• Asst. Professor of Medicine
• University of Kansas Medical Center
• Landon Center on Aging
• October 5, 2007

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Overview

• What is polypharmacy?
• Relevant pharmacology
• Medication use issues with multiple Rxs
• Potentially inappropriate medications
• Approach to modifying medication profiles
• Quality prescribing

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What is polypharmacy?

• As older patients move through time, often from
  physician to physician, they are at increasing
  risk of accumulating layer upon layer of drug
  therapy, as a reef accumulates layer upon layer
  of coral.
• Jerry Avorn, MD
• From Gurwitz J. Arch Intern Med Oct 11, 2004

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Why Geriatric Pharmacotherapy Is Important

• 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

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The Burden of Injuries From Medications

• ADEs occur in 35 of community-dwelling elderly
  persons

• Incidence of ADEs 26/1000 hospital beds (2.6)

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Adverse Drug Events in Older Adults

• Serious or fatal ADEs occur in 18.5 of adults
  aged 55-64 and in 41.9 of adults aged 85 years.
• Drug related mortality is the 9th leading cause
  of death for people 65 years of age.
• It is estimated that 30 of ADEs are preventable.

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Pharmacologic Changes with Aging
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Pharmacokinetics

• Absorption
• Distribution
• Metabolism
• Excretion
• Altered by changes in body make-up
• Decreased lean mass, relatively increased fat

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Aging and Absorption

• Actual amount absorbed not changed
• Peak concentrations may be altered

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Effects of Aging on Volume of Distribution

• ? body water ? lower VD for hydrophilic drugs
• ? lean body mass, ? plasma protein (albumin) ?
  higher percentage of drug that is unbound
  (active)
• ? fat stores ? higher VD for lipophilic drugs

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Aging and Metabolism

• Metabolic clearance of a drug by the liver
• may be reduced because
• Aging decreases liver blood flow, size, and mass
• The liver is the most common site of drug
  metabolism
• Phase II pathways generally preferable for older
  patient

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The Effects of Aging on the Kidney

• ? kidney size
• ? renal blood flow
• ? number of functioning nephrons
• ? renal tubular secretion
• Result Lower glomerular filtration rate

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Serum Creatinine Does Not ReflectClearance

• ? lean body mass ? lower creatinine production
• and
• ? glomerular filtration rate (GFR)
• Result In older persons, serum creatinine stays
  in normal range, masking change in creatinine
  clearance (CrCl)

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Pharmacodynamics

• Definition Time course and intensity of the
  pharmacologic effect of a drug
• May change with aging, eg
• Benzodiazepines may cause more sedation and
  poorer psychomotor performance in older adults.
• Older patients may experience higher levels of
  morphine with longer pain relief

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Decreased homeostatic reserve

• Impacts ability to tolerate medications
• Postural hypotension
• Fluid and electrolyte problems
• Response to hypoglycemia
• Temperature regulation

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Medication Use Issues with Multiple
Prescriptions (and OTCsherbalsetc)
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General types of medication-related problems

• Unnecessary drug
• Not prescribing new needed Rx
• Contraindicated drug
• Dose too low or too high
• Adverse drug event/ drug interaction
• Nonadherence
• Prescribing cascade
• From Williams CM, Am Fam Phys Nov 15, 2002

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Prescribing Cascade

• Misinterpretation of an adverse drug reaction as
  a symptom of another condition? prescribing of
  another Rx
• Example
• Persons receiving a cholinesterase inhibitor had
  50 increase risk for subsequent anticholinergic
  drug for incontinence
• Gill et al. Arch Intern Med 2005, April 11

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Adverse Drug Events during Care Transitions

• Med changes between hosp and NH
• Mean of Rx changed
• 3.1 from nursing home to hospital
• 1.4 from hospital to nursing home
• Most were discontinuations
• ADE attributable to medication changes occurred
  in 20 usually occurred after readmission to the
  NH

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Characteristics of Older Adults with
Medication-related Problems

• 85 years and older
• 6 or more active chronic conditions
• Estimated creat clearance
• Low body weight
• Nine or more medications
• More than 12 doses of medication daily
• Previous adverse drug reaction
• From Williams CM, Am Fam Phys 2002, adapted from
  Fouts, Consult Pharm, 1997

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Risk Factors for High Risk for ADE in Older
Outpatients from an Expert Consensus Panel
From Hajjar et al. Am J Geriatr Pharmacother
2003, Dec
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Drug-Drug Interactions

• May lead to ADEs
• Likelihood ? as number of medications ?
• Most common cardiovascular and psychotropic
  drugs

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Case A

• 75 year old woman with hypertension, diabetes
  mellitus, dyslipidemia, coronary heart disease,
  congestive heart failure, osteoporosis, arthritis
  and chronic back pain, depression, and seasonal
  allergies

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Case A 15 meds
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Case B

• 85 year old woman with hypertension, dependent
  edema, dizzy spells, chronic back pain, insomnia,
  and constipation

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Case B 15 meds
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How many meds is too many?

• Med count wont distinguish cases A B
• Med count wont distinguish treatment based on
  disease-management guidelines from
  symptom-management meds
• Wont distinguish prescriber decision-making from
  patient-generated demand
• Wont distinguish appropriate from inappropriate
  medication use

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Manageable Dosing Regimens

• Manageable number of dosing times/day
• Once daily formulations if feasible
• Reduce number of medications that cant be taken
  at same time as any others
• Use of reminders, medication box set-up
• Feasible to keep track of and filled
• Affordable so patient does not skip doses to make
  the supply stretch between refills

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Potentially Inappropriate Medication Use
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Inappropriate Medications in Older Adults
Beers List

• potentially or generally inappropriate
• suboptimal prescribing
• Overall risks outweigh potential benefits
• May be ineffective and/or poorly tolerated
• May be justified in some circumstances
• Controversial
• Expert opinion by pharmacists group
• Limited evidence-base for many drugs

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Beers List Two Groups of Drugs

• Unconditionally inappropriate
• Generally best avoided regardless of
  circumstances
• Conditioned upon disease state or dose
• May only be inappropriate in specific context

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Beers List

• 1992many drugs no longer used
• 1997
• 2003
• Now the basis for consultant pharmacy review in
  nursing facilities

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Beers List Selected Highlights 1997

• Propoxyphene (but not included in Rx review
  guidelines for NH)
• Indomethcin, phenylbutazone, pentazocine
• Trimethobenzamide
• Muscle relax/antispasmodics, including ditropan
• Flurazepam
• Amitriptyline combinations doxepin
• Meprobamate
• Particular doses of other sedative hypnotics
• Chlordiazepoxide, diazepam

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Selected 1997 drugs, continued

• Disopyramide
• Digoxin above 0.125 mg except for atrial arryth
• Dipyridamole
• Methyldopa, reserpine
• Chlorpropamide
• GI antispasmodics
• Nonprescription many Rx antihistamines
• Meperidine
• Ticlopidine
• All barbiturates except phenobarbital

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Updates to Beers List in 2003 (selected
additions since 1997)
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2003 selected conditionally inappropriate by
disease state
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Potentially Inappropriate Medications for Older
Persons

• High Potential for
• Severe ADEs
• Amitriptyline
• Chlorpropamide
• Digoxin 0.125 mg/day
• Disopyramide
• GI antispasmodics
• Meperidine
• Methyldopa
• Pentazocine
• Ticlopidine

• High Potential for
• Less Severe ADEs
• Antihistamines
• Diphenhydramine
• Dipyridamole
• Ergot mesylates
• Indomethacin
• Meperidine, oral
• Muscle relaxants

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Prevalence and health consequences of
inappropriate medication use
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Findings in Kansas Medicaid Data

• Any unconditional inappropriate medication use
  during study year
• Community 21
• HCBS 48
• Nursing Facility 38
• Most common propoxyphene, antihistamines,
  amitriptyline, muscle relaxants, and oxybutynin
• Rigler et al. 2005 Ann PharmacoRx

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Inappropriate Medication in Frail Elderly
Inpatients

• 11 VAMCs
• 92 had at least one problem
• Expense (70)
• Impractical directions (55)
• Incorrect dosages (51)
• Most common drug types
• GI, CV, CNS
• Higher risk with fair/poor self-rated health

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Hospitalization and Death

• MEPS 1996, nursing home component
• Persons 65 in NH for 3 months or more
• Persons receiving inappropriate Rx
• OR 1.27 for hospitalization in following month
• OR 1.80 for hosp if Rx received for 2 months
• OR 1.28 for death
• Analyses adjusted for other key risk factors
• Lau et al. Arch Intern Med Jan 10, 2005

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Approach to the Older Patient with Multiple
Medications
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Approach to Multiple Medications

• Brown bag med review at each visit
• Including herbals and OTCs
• Determine clinical indication for each
• Motto One disease, one drug, once daily
• Avoid the prescribing cascade
• Eliminate drugs without benefit or indication
• Substitute less toxic drugs where able
• From Carlon JE, Geriatrics, 1996 5126-30

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NO TEARS Approach for Medication Review

• From Lewis T, BMJ Aug 21, 2004
• Need and indication
• Open questions
• Tests and monitoring
• Evidence and guidelines
• Adverse events
• Risk reduction or prevention
• Simplification and switches

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Interdisciplinary Medication Review

• Ambulatory older adults
• Intervention versus control groups
• Regimen changes? Function? Cost?
• Results reduced mean Rx by 1.5
• No impact on functioning
• Savings 27 per month per person
• Williams et al. JAGS Jan 2004

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Regulatory Scrutiny

• Mandated drug review already in LTC
• Medicare drug benefit
• Provider profiling increasingly common
• Pay for performance models
• Patient satisfaction monitoring
• Increasing use of electronic records
• Can expect increased scrutiny of the medication
  profiles of your patients

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The Obvious Dos and Donts

• Use effective medications to treat disease
• Use effective therapies to prevent disease
• Do not use unsafe medications
• Do not use ineffective medications

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If only it were this simple
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Quality Prescribing

• Outcomes
• Adverse Drug Events
• Drug-Drug Interactions
• Unrecognized symptoms
• Decreased quality of life
• Non-adherence
• Cost
• Adding beneficial medications

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Quality of Life Outcomes related to Beers
criteria medications

• Two phase study of 2305 older patients
• Patients reported their medications in Round 1
• Patients reported their health status in Round
  2
• Patients who were on medications on the Beers
  list in Round 1 reported significantly worse
  health status in Round 2 (P
• Fu, JAGS, 2004

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Quality Prescribing

• Preventing excess morbidity and mortality by
  reducing harmful medications
• Reduce total number of medications
• Reduce complexity of regimen
• Eliminate poorly tolerated medications
• Eliminate drugs inappropriate for older adults
• Avoid drug interactions

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And now, for the rest of the story.

• Under-utilization of effective therapies in older
  adults is widespread

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Polypharmacy A New Paradigm for Quality Drug
Therapy in the Elderly

• Under-use of beneficial Rx in older adults
• ACEI in CHF
• Anticoagulants in Afib
• Antiresorptive Rx in osteoporosis
• Disease management guidelines often favor more
  than one Rx for a condition
• Gurwitz J. Arch Intern Med 2004, Oct 11

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Average Life Expectancies

• 65 year old woman 19 years
• 75 year old woman 12 years
• 85 year old woman 6 years
• 65 year old man 16 years
• 75 year old man 10 years
• 85 year old man 5 years

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Underuse of medication

• Failure to recommend or provide a recommended
  therapy either intentionally or unintentionally
• Error of omission medical error resulting in
  increased risk of adverse event resulting from
  too little treatment e.g. subtherapeutic drug
  dosing

Hayward et al, JGIM 2005 20686-691
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Treatment benefits in older adults

• NNT may be smaller in older adults because of
  higher disease prevalence
• More bang for your buck
• Treat older adults because that is where many
  diseases are most prevalent

(Rob the bank because that is where the money is)
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Darned if you do, darned if you dont?

• Specialist heart failure care
• More appropriate pharmacotherapy for CHF by
  guidelines, but..
• Increased polypharmacy, drug interaction
  potential, drug-kidney, drug-liver interactions
• Ledwidge et al. Eur J Heart Fail March 2004
• And an ARB makes nine polypharmacy in patients
  with heart failure
• Clev Clinic J Med Aug 2004

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What is being done to address prescribing quality
for older adults?

• New initiatives
• Implications for Pay-for-Performance

Mike Steinman, MD University of California, San
Francisco
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Quality Indicators

• Assessing Care of Vulnerable Elders (ACOVE) from
  RAND Health/collaborators
• 236 if/then indicators in 4 domains
• 43 indicators re pharmacologic care

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Higashi, T. et. al. Ann Intern Med
2004140714-720
Medication Quality Indicators, Number of Eligible
Patients, and Pass Rates
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A few ACOVE indicators involving medication use

• ACE-I use in HF or proteinuria
• Beta-blocker for patient with MI
• Osteoporosis treatment
• Ca/vit D for patients on long term steroids
• Outpatient ophthalmology Rx continued when
  hospitalized
• Others

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Pass Rates from 2 managed care organizations
(Higashi et al, Ann Intern Med 2004)

• Prescribing indicated medications
• 50
• Avoiding inappropriate medications
• 97
• Education, continuity, documentation
• 81
• Medication monitoring
• 64

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Quality Improvement and Performance Measurement

• Quality improvement for medication Rx driven by
  performance measurement
• weak financial incentives to excel
• strong financial, regulatory incentives not to
  fail
• Focus on items easily measurable in large
  populations
• Substantial implications for quality measurement
  in elders

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Quality Improvement and Performance Measurement

• CMS Physician Quality Reporting Initiative
• Voluntary quality reporting program
• Bonus of up to 1.5
• 74 measures providers select relevant ones to
  report
• Disease-specific e.g., LDL
• Medication reconciliation
• Plan of care for urinary incontinence in ? age
  65

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Quality Improvement and Performance Measurement

• JCAHO
• Medication reconciliation
• Long-term care
• minimize use of antipsychotic medications

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Quality Improvement and Performance Measurement

• HEDIS measures
• Effectiveness of care measures
• 16 primarily related to medication use
• Annual monitoring for patients on persistent meds
• Drugs-to-avoid in elderly
• Potentially harmful drug-drug interactions in
  elderly

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CASES
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Case 1

• A new patient arrives in clinic for consultation.
  He is an 80 yo man with a PMH of early stage
  Alzheimers disease, HTN, osteoarthritis, BPH s/p
  TURP years ago, and hearing loss.
• Medication list includes
• Donepezil clonidine (oral)
  amlodipine
• propxyphene/ APAP lansoprazole
• naproxen oxybutynin furosemide
• meclizine

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Case 2

• An 89 yo female arrives in clinic to establish a
  new PCP. She has recently been discharged from
  the hospital after suffering a GI bleed due to
  AVMs. While hospitalized, she suffered an
  occipital lobe stroke, and it was also discovered
  that she had severe CAD for which she declined
  aggressive intervention. Her other PMH includes
  macular degeneration.
• Her major symptoms are fatigue and a sense of
  unsteadiness.

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Case 2, contd

• Medication list includes
• Stelazine 5 mg bid
• Dalmane 30 mg qhs
• ASA 81 mg QD
• Propanolol 10 mg qd
• Fish oil capsules
• Imipramine 150 mg QD
• Percocet TID prn
• Metoclopramide 10 mg qac and hs

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Recommended Reading/ References

• Williams CM. Using Medications Appropriately in
  Older Adults. American Family Physician 2002
  66(10)1917-24
• GRS Review Syllabus
• Rigler, S. SGIM Workshop on Quality
  Pharmacotherapy in Older Adults, 2007