Transcript Drug Interactions

Deprescribing Demystified
Lynsey E. Brandt, MD, PharmD
Geriatrics Consult Program
September 1, 2016
Geriatrics Consult Program
Lynsey Brandt, MD, PharmD
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Falls
Polypharmacy
Medical Complexity
Weight loss/ failure to thrive
Delirium
Depression/ Anxiety
Insomnia, Urinary
Incontinence, or Fatigue
 Need for Increased Social
Support
 Driving Concerns
 Goals of Care
 Located at Wilmington
Hospital
 Gateway Building, 5th floor
 Scheduling:
302-320-6475
Deprescribing is….
Deprescribing is….
1) A new way of thinking about medication use in
older adults
2) A systematic approach to medication debridement
3) A catchy new term that DAFP created to get
people to come to this conference
4) 1 & 2
5) 1, 2, & 3
Deprescribing is….
1) A new way of thinking about medication use in
older adults
2) A systematic approach to medication debridement
3) A catchy new term that DAFP created to get
people to come to this conference
4) 1 & 2
5) 1, 2, & 3
(August 15, 2016)
 “This is America’s other drug problem —
polypharmacy,” Maristela Garcia, director of the
inpatient geriatric unit at UCLA Medical
 “There are a lot of souvenirs from being in the
hospital: medicines they may not need,” said David
Reuben, chief of the geriatrics division at UCLA
School of Medicine.
 “There’s a tendency in medicine every time we start
a medicine to never stop it.” Ken Covinsky, UCSF
Learning Objectives
 Understand principles of safe medication use in older
adults (renal dosing, drug interactions)
 Identify medications which are high-risk in older adults
(Beers list, Anticholinergics, and selected other
examples)
 Review guidelines for deprescribing medications
 Provide deprescribing resources for providers and
patients
Case 1
 Mr. JH is an 85 yo man who resides in an assisted living
facility.
 PMH: Parkinson’s, Mild dementia (MMSE = 21), HTN,
urinary incontinence, constipation
 BP range 80/40 to 150/80
 Walks with stooped posture, unsteady gait, needs
assistance to transfer from chair to wheelchair
JH Medication List
JH (Cont)
 Pt and family asking whether all these meds
are needed…
 “Hx of falls. Assist with meds.”
 “No prior hx of HTN - on metoprolol after one elevated BP
reading. Dtr wonders if over-medicated.”
 “Dtr asking why bladder med needed since he wears a brief”
 “Family also asking why needs water pill, as ankles have not
been swollen.”
 Illustrates importance of having an advocate
 More about JH later…
The Polypharmacy Problem
 Community dwelling older adults:
 90% > 1med
 40% > 5meds
 12% > 10meds
 One third of hospitalizations in older adults are
medication-related
Gurwitz JH et al. JAMA. 2003;289(9): 1107-1116.
Scott IA et al. JAMA Internal Medicine May
2015
Consequences of Polypharmacy
 Increased healthcare costs
 Adverse drug events
 Drug interactions
 Medication Non-adherence
 Decreased functional status
 Geriatric Syndromes: Delirium, Falls, Urinary
Incontinence
Maher RL, et al. Expert Opin Drug Saf. January 2014.
How can we address
polypharmacy?
 Utilizing age-appropriate prescribing
principles
 Minimizing use of potentially inappropriate
medications
 Deprescribing when possible
Principles of Medication
Use in Older Adults
Principles of Medication Use in
Older Adults
 Renal Dosing
 Drug Interactions
 “Start Low and Go Slow”
 Beware of the Prescribing Cascade
 Potentially Inappropriate Medications
Renal Dosing
 Renal function declines with age
 Renal mass declines by 20-25% from age 30 to 80
 Glomerular Filtration Rate decreases by 10% per decade
of life after age 30
Renal Dosing
 Do not be misled by “normal” serum creatinine.
 Adjust dose when creat clearance < 60
 Calculate creatinine clearance using the Cockcroft-Gault
equation:
(140-age in years) x (Ideal body wt) x 0.85 (females)
72 (serum creatinine in mg/ dL)
Renal Dosing
What is the GFR for:
90 year old woman, who weighs 90
pounds, and has serum creatinine of 1?
Renal Dosing
 What is the GFR for: 90 year old woman, who weighs
90 pounds, and has serum creatinine of 1.0?
Drugs with renal elimination
(selected examples)
Allopurinol
Furosemide
Antibiotics
Gabapentin
- Aminoglycosides
H2 antagonists
- Fluoroquinolones
- Cimetidine
- Penicillins
- Famotidine
- Tetracyclines
- Ranitidine
- Sulfa
Lithium
- Nitrofurantoin
Metformin
Digoxin
Drug Interactions
Risk of Drug Interactions
 Increased probability of drug-drug interactions in patients
taking more medications
 Study of hospitalized older adults taking 5 or more meds
 Prevalence of cytochrome p450 interaction = 80%
 Study of community-dwelling older adults
 5 to 9 meds: 50% probability
 20 or more meds: 100%
Maher RL, et al. Expert Opin Drug Saf. January 2014
Cytochrome P450 Systems
 CYP3A
 Metabolizes >60% of prescribed drugs including:
 Calcium channel blockers, certain beta-blockers, most “statins”,
warfarin, amiodarone
 CYP2D6
 Metabolizes:
 metoprolol, propranolol, tramadol, codeine,oxycodone,TCAs,
SSRIs
Cytochrome P450 Inhibitors
 CYP3A Inhibitors
 Amiodarone, cimetidine, cyclosporin, erythromycin, itra/ketoconazole, grapefruit juice
 CYP2D6 Inhibitors
 Cimetidine, SSRIs, quinidine
My approach to Drug Interactions
 Be aware of drugs frequently implicated
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Warfarin
Amiodarone
Calcium channel blockers
Statins
SSRI
QTc-prolonging agents (atypical antipsychotics,
fluoroquinolones, citalopram)
 Take the time to review the interactions in the EMR
Strategies to check for drug
interactions
 Micromedex/ Lexicomp
 Epocrates
 The pharmacist!!
Potentially Inappropriate
Medications
The Beers List
 List of drugs which are potentially inappropriate in the
elderly
 Developed by consensus panel of geriatricians in 1991
 Used by regulators to evaluate nursing home medication
lists
 Utilized by third party payors to evaluate medication lists
The Beers List (selected examples)
Drug
Reason
Alternative
Antihistamines- 1st
generation
(diphenhydramine)
Anticholinergic
effects
Nonsedating
antihistamines
(loratadine)
Long-acting
benzodiazepines
(diazepam)
Sedation
Short-acting
benzodiazepines
(lorazepam)
Narcotics (meperidine) Active metabolite
Morphine
Hypoglycemic agents
(chlorpropamide)
Shorter-acting
agents (glipizide)
Long half-life,
renally excreted,
risk of
hypoglycemia
Other high-risk medications
 Study of 177,504 ER visits for adverse drug events
 33% of the visits were due to:
 Digoxin
 Warfarin
 Insulin
(“DWI”)
 Drugs on the Beers list accounted for only 3.6% of visits
Budnitz et al. Annals of Internal Medicine. December 4, 2007 vol. 147 no. 11 755-765
Drugs with Anticholinergic Properties
Elavil (amitriptyline)
Flexeril (cyclobenzaprine)
Cogentin (benztropine)
Atarax/Vistaril(hydroxyzine)
Bentyl (dicyclomine)
Levsin (hyoscyamine)
Ditropan (oxybutynin)
Antivert (meclizine)
Detrol (tolterodine)
Ipratropium (atrovent)
Benadryl (diphenhydramine)
Phenergan (promethazine)
Prescribing Cascade
Could this apply to pt JH?
Deprescribing
Case 2: LG
 90 yr old woman
 PMH
 Hypertrophic cardiomyopathy
 Osteoporosis
 Memory loss
 Reason for consultation: Weakness
 Medications : Furosemide 20 mg 3x/wk, Calcium, Vit D,
Alprazolam 0.25 mg daily at bedtime
LG (cont.)
 Pt reports that she has been taking alprazolam daily at
bedtime since her husband passed away in 2007
 She has a history of 2 prior falls, which she attributes to
tripping
 You want to address the long-term benzodiazepine use,
but have discussed this with her previously & she was
not interested in stopping the medication.
 How to proceed?
 What resources exist to help address this problem?
Deprescribing
Definition:
The systematic process of identifying and
discontinuing drugs in instances in which
existing or potential harms outweigh existing
or potential benefits within the context of an
individual patient’s care goals, current level of
functioning, life expectancy, values, and
preferences.
Scott IA et al. JAMA Internal Medicine May 2015
Definition (cont)
 Patient-centered
 Involves inherent uncertainties
 Requires:
 Shared decision-making
 Informed consent
 Close monitoring of effects
Scott IA et al. JAMA Internal Medicine May 2015
When to consider deprescribing?
 Patient presents with new symptoms which could be
adverse drug effect (i.e. falls, confusion, fatigue)
 End-stage disease/ terminal illness
 Receiving high-risk drugs/ combinations
 Receiving preventive drugs in scenarios where drug can
be safely discontinued (i.e. d/c bisphosphonate after 5
years with no increase in osteoporotic fracture risk over
the ensuing 5 years)
Scott IA et al. JAMA Internal Medicine May 2015
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Priority Drugs for Deprescribing
 Aim to ID and prioritize med classes where evidencebased deprescribing guidelines would be of benefit
 Survey of 65 Canadian geriatrics experts (36
pharmacists, 19 physicians, 10 CRNP)
 Modified Delphi approach
 5 priorities: benzodiazepines, atypical antipsychotics,
statins, tricyclic antidepressants, and proton pump
inhibitors.
Farrell B, et al. Plos ONE. Jan 1 2015. Vol 10 Issue 4. re
Deprescribing Protocol
5 Steps of Deprescribing*
1.) Ascertain all drugs the patient is currently taking and
reasons for each one
2.) Consider overall risk of drug-induced harm in individual
patients to determine the appropriate intensity of
deprescribing intervention
3.) Assess each drug in regard to its current or future
benefit potential compared with current or future harm /
burden potential
Scott IA et al. JAMA Internal Medicine May 2015
5 Steps (cont).*
4.) Prioritize drugs for discontinuation that have the lowest
benefit-harm ratio and lowest likelihood of adverse
withdrawal reactions or disease rebound syndromes
5.) Implement a discontinuation regimen and monitor
patients closely for improvement in outcomes or onset of
adverse effects.
*These steps can be applied to a patient of any age who
takes multiple long-term medications
Scott IA et al. JAMA Internal Medicine May 2015
Deprescribing Protocol (cont.)
 Current indications
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Why/ when started?
Was diagnosis substantiated?
Prescribing cascade
Is there continued benefit?
Are other nonpharmacologic therapies available?
Deprescribing Protocol (cont.)
 Is patient actually taking the drug?
 Does drug fit with patient’s life circumstances?
 Advanced dementia
 Metastatic cancer
 Does likely benefit of drug outweigh potential for harm?
 Consider “high-risk” drug classes: opioids, benzos,
psychotropic drugs, NSAIDs, Anticoagulants, digoxin, cardiac
drugs, hypoglycemic agents, anticholinergic drugs.
Deprescribing Protocol (cont.)
Group drugs into 2 categories:
1.) Disease/ symptom control
2.) Preventive
Deprescribing:
Evidence of Efficacy
 Drug withdrawal trials
 Multifaceted interventions aimed at reducing
inappropriate prescribing across multiple drug classes
and settings
Scott IA et al. JAMA Internal Medicine May 2015
Drug Withdrawal Trials
 Systematic review of 31 withdrawal trials (15 RCT, 16
observational)
 Pts 65 and over
 Multiple drug categories: Antihypertensives, psychotropics,
benzodiazepines
 Dc’d without harm in 20 to 100% of patients
 *Reduction in falls and improvement in cognitive and
psychomotor function (Psychotropics, Benzos)
 Also replicated in another review (van der Cammen)
Iyer at al. Drugs Aging, 2008:25(12)1021-1032.
Drug withdrawal trials (cont.)
 Review of 9 randomized-trials
 Demonstrated safety of withdrawing antipsychotic agents
 Used for behavioral and psychologic symptoms of
dementia
 80% of participants with dementia were able to safely
stop antipsychotics
Declercq T et al. Cochrane Database Syst Rev. 2013.
Drug withdrawal trials (cont.)
 Australian National Blood Pressure study
 Not designed as deprescribing trial
 Found that 37% of participants remained normotensive 1 yr
after drug withdrawal
Neson MR, et al. BMJ. 2002.
Empower Study
(Eliminating Medications Through Patient Ownership of End Results)
 Test whether the direct-to-consumer educational
brochure is effective at reducing benzos, compared to
usual care
 Cluster randomized trial :
 The cluster is the community pharmacy from which patients
are recruited
 Randomized to brochure immediately or after a 6-month
waiting period
 Inclusion criteria = benzo use for 3 months+, age 65+
Tannenbaum et al. JAMA Internal Medicine 2014.
EMPOWER = “Eliminating medications
through patient ownership of end results.”
ownership of end results”
EMPOWER Study Results
 86% of participants completed 6-month follow-up
 62% or recipients in intervention group initiated conversation
about benzodiazepine therapy cessation
 At 6 months, 27% of the intervention group had discontinued
benzodiazepine vs 5% of control group (Risk difference of
23%, 95% CI 14-32%. )
EMPOWER Study Conclusions
 Direct-to-consumer education effectively elicits
shared decision-making related to overuse of
medications that increase the risk of harm in older
adults.
 How can we apply these results in practice?
 Deprescribing.org
Summary:
Strategies for successful deprescribing
 Empowered patients
 Query pts about adverse effects
 Practical guidance on how to safely wean particular
classes of drugs
Barriers to Deprescribing
 Clinical complexity
 Time constraints
 Multiple prescribers
 Incomplete information
 Ambiguous / changing goals of care
 Uncertainty about benefits/ harms or continuing or
stopping certain meds
 “More is better” philosophy
JH Medication List
Case 1 (JH) follow-up
 BP 100/60- reduced lasix to 3x/ wk
 Reduced oxybutynin to 5 mg daily – no apparent chg in
sx
Case 1 (JH) follow-up
 Follow-up visit:
 BP- follow-up -now on lasix 3x/ wk. States had SBP 150 this
AM.
 BP on my exam 80/40
 DC’d lasix
 Metoprolol may also be dc’d
 No change in urinary symptoms on lower dose oxybutynin
Case 2 (LG) Follow-up
 At time of last visit, LG was contemplating a change in
her alprazolam usage
 Plan to implement Deprescribing.org resources…
Geriatrics Consult Program
Lynsey Brandt, MD, PharmD







Falls
Polypharmacy
Medical Complexity
Weight loss/ failure to thrive
Delirium
Depression/ Anxiety
Insomnia, Urinary
Incontinence, or Fatigue
 Need for Increased Social
Support
 Driving Concerns
 Goals of Care
 Located at Wilmington
Hospital
 Gateway Building, 5th floor
 Scheduling:
302-320-6475
Questions?