Polypharmacy and the Management of Mul4ple Chronic Condi4ons Cara Tannenbaum MD, MSc Paula Rochon MD, MPH, FRCPC Barbara Farrell BScPhm, PharmD, FCSHP
Panel Cara Tannenbaum MD, MSc Prac4cing geriatrician, Associate Professor of Medicine and Pharmacy Michel Saucier Endowed Chair on Geriatric Pharmacology Health and Aging, Université de Montréal.
Paula Rochon MD, MPH, FRCPC Vice President and Senior Scien4st, Women’s College Research Ins4tute, Women’s College Hospital Professor, Department of Medicine, University of Toronto.
Barbara Farrell BScPhm, PharmD, FCSHP Pharmacist, Bruyère Geriatric Day Hospital and Scien4st, Bruyère Research Ins4tute – OOawa. Assistant Professor, Department of Family Medicine, University of OOawa and Adjunct Assistant Professor, School of Pharmacy, University of Waterloo.
Disclosures n Cara has previously consulted for Pfizer, Allergen, Watson
and Ferring Pharmaceu4cals but reports no conflicts of interest for this presenta4on.
n Paula has no conflicts of interest for this presenta4on. n Barbara has no conflicts of interest for this presenta4on.
Polypharmacy n Polypharmacy is a risk factor for: n Drug-‐drug interac4ons n Prescribing cascades n Difficulty managing the complex pa4ent n Resul4ng in: n Falls and cogni4ve impairment n Emergency room visits and hospitaliza4ons
Objec4ves n Par4cipants will be able to: 1. Recognize “inappropriate” prescribing 2. Use interprofessional interven4ons to reduce inappropriate prescribing 3. Recognize prescribing cascades 4. Iden4fy poten4al drug-‐drug and drug-‐disease interac4ons in clinical prac4ce guidelines 5. Have an approach to tapering or stopping medica4ons
Outline n “Inappropriate” prescribing n Case presenta4on #1 n Group discussion of Beers and STOPP/START n Prescribing Cascades n Case presenta4on #2 n Group/Panel discussion on prescribing cascades n Avoiding drug interac4ons in clinical prac4ce
guidelines n n
Case presenta4on #3 Group/Panel discussion on drug interac4ons
n Take home 4ps
“Inappropriate” Prescribing Case 1 Mrs. A } Widow living alone } 84 years old } Severe knee pain limi4ng } } } } }
mobility Ocen confused, unable to get out of bed 3 falls in the last year Doesn’t want to go out anymore Not always taking meds Children think she should no longer be living alone
} } } } } } } } } } } } } } } } }
ASA 81mg daily ibuprofen 400mg bid* dimenhydrinate 50mg qhs lorazepam 1mg qhs* warfarin as directed* metoprolol 50mg bid* amlodipine 10mg daily* ramipril 5mg daily* Lakota capsules qid furosemide 40mg bid* atorvasta4n 40mg daily* dextromethorphan syrup lansoprazole 30mg daily* oxybutynin XL 10mg daily* vit. B12 1200mcg daily* Potassium daily* calcium/vit D bid*
Medica4ons What do we mean by “Medications”? • Prescription Drugs • Over the Counter Products • Herbal Therapies
Group Discussion
Using Beers and STOPP/START GROUP 1
GROUP 2
n Read the case
n Read the case
n Apply the Beers
n Apply the STOPP/
criteria to iden4fy medica4on problems
START criteria to iden4fy medica4on problems
9
Screening tool impressions n Were the criteria effec4ve in iden4fying drug therapy
problems? n Were there other problems not picked up by these screening tools? n What are the limita4ons of these screening tools?
Mrs. A’s history • Atrial fibrillation – metoprolol and warfarin • Husband died - lorazepam 10 years ago
3-5 years ago
2 years ago
• • • • •
Knee pain - ibuprofen Hypertension – ramipril Cough – dextromethorphan Hypertension – amlodipine Daughter told her to take ASA for hypertension
• • • • • • • •
Ankle swelling; furosemide Potassium low; potassium Nausea; dimenhydrinate Nausea (and taking ibuprofen): lansoprazole B12 levels low; B12 supplement Knee pain: Lakota Nocturia; oxybutynin Osteopenia: calcium/vitamin D 11
A prescribing ‘web’
ramipril
ASA dextromethorphan
amlodipine
furosemide
potassium
Ibuprofen
dimenhydrinate
oxybutynin lorazepam lansoprazole vitamin B12
Mrs. A’s medica4on changes
• Stop ASA and Lakota • Decrease dimenhydrinate
Week 2 • Switch ibuprofen to acetaminophen • Physio and exercise • Stop B12
Week 1
• Document BP target • Begin amlodipine taper • Begin lansoprazole taper
Week 3 13
Mrs. A’s medica4on changes • Stop amlodipine • Increase acetaminophen dose • Start lorazepam taper • Provide sleep hygiene education
Week 4
Week 5 • Switch acetaminophen to small dose hydromorphone • Taper ramipril • Start furosemide taper • Add lactulose
• Stop ramipril • Stop furosemide • Stop potassium • Taper oxybutynin
Week 6 14
Mrs. A’s medica4on changes • Stop dextromethorphan and dimenhydrinate • Review and advise re: salt and calcium intake • Start HCTZ • Continue lorazepam taper
Week 7
Week 8 • Stop oxybutynin • Stop lorazepam • Change lansoprazole to prn • Provide heartburn education
• Change metoprolol to bisoprolol • Combine calcium and vitamin D • Stop lansoprazole
Week 9 15
Acer a 10 week Day Hospital stay Mrs. A’s medica4ons
Mrs. A’s life:
§ Hydromorphone 0.5mg q12h
§ Knee pain much improved
§ Hydrochlorothiazide 12.5mg
§ Geong out of the house now
daily § Bisoprolol 2.5mg daily § Warfarin as directed § Caltrate Select with Vitamin D twice daily § Lactulose 15ml daily
§ Urgency and nocturia beOer (up
1-‐2x/night) § Sleep improved (to bed 10pm, up about 7am) § Meal 4mes normal (8, noon, 6) § Bruising and gum bleeding gone § No heartburn, nausea, cough or swollen ankles 16
Examples of team contribu4ons to managing polypharmacy n Physiotherapist – helping to manage pain, assis4ng with exercise n n n n
n n
programs Social Worker – helping to deal with anxiety, depression, isola4on affec4ng sleep and depression Occupa4onal therapist – helping with mobility aids to manage pain Die4cian – helping to use dietary approaches instead of supplementa4on Nurse – monitoring impact of medica4on changes, providing educa4on re: nonpharmacologic approaches (sleep hygiene, GERD management) Recrea4on therapist – helping to deal with isola4on, access to programs Pharmacist – helping to iden4fy drug-‐related problems, develop plans for medica4on changes and monitoring
Prescribing Cascades Case 2: Mrs. B n Mrs. B was diagnosed with
vascular demen4a acer a stroke, MMSE 16
n Her son read on the internet that
donepezil improve symptoms of vascular demen4a
n She is prescribed donepezil to
improve her memory
Prescribing Cascades Case 2: Mrs. B n On subsequent visit, dose of
donepezil is increased
n 2 months later, returns for visit
and describes problem with incon4nence
n Referral sent to urology to assess
incon4nence
Urologist prescribes oxybu4nin to treat incon4nence
Is this a problem?
Urologist prescribes oxybu4nin to treat incon4nence n Oxybu4nin acts by blocking cholinergic receptors and
preven4ng s4mula4on by acetylcholine.
n Opposing cholinergic mechanisms n Two small studies found no clinical deteriora4ons in the
MMSE score in pa4ents taking both cholinesterase inhibitors and bladder an4cholinergic agents.
Sakadkibara et al. J Am Geriatr Soc 2009 Isik et al. J Nutr Health Aging 2008
An4cholinergics and cholinesterase inhibitors An4cholinergic toxidromes “Mad as a ha'er, dry as a bone, the bowel and bladder lose their tone.” An4cholinergics can cause confusion and urinary reten4on
Cognitive Decline Improved Memory Urinary Retention Incontinence
http://en.wikipedia.org/wiki/Toxidrome
What is a Prescribing Cascade? Initial Drug Therapy
New Medical Condition
New Drug Treatment
Further Medical Condition Rochon PA, Gurwitz JH. BMJ 1997
What prescribing cascades have you seen?
Common examples n Ibuprofen → hypertension → an4hypertensive n Metoclopramide → parkinsonism → Sinemet n Risperidone → parkinsonism → an4parkinson meds n Amlodipine → edema → furosemide n Lithium → tremor → propanolol
Common Examples n Amitriptyline → cogni4on → donepezil n Furosemide → hypokalemia → potassium n Omeprazole → low B12 → B12 supplement
Over the counter: n Narco4c → cons4pa4on → laxa4ves n Lorazepam → morning drowsiness → caffeine n Enalapril → cough → dextromethorphan
Mrs B’s Prescribing Cascade Cholinesterase Inhibitors
Urinary Incontinence
Anticholinergic Drug
Cognitive Decline and Delirium Gill SS, Rochon PA et al. Arch Intern Med 2005
What the data shows n 44884 older adults in Ontario with demen4a n Average age more than 80 n Almost 65% were women
Gill SS, Mamdani MM, Rochon PA et al Arch Intern Med 2005
Combined use of ChI with overac4ve bladder medica4ons may worsen func4on Change in activity of daily living score in fairly independent nursing home residents (top quartile) ChI Alone
ChI + OAB med
0
Daily living score (units)
In high-functioning nursing home residents, dual use of -0.2 cholinesterase inhibitors and overactive bladder medications -0.4 may result in greater rates of functional decline. -0.6 -0.8
ChI Alone ChI + OAB med
-1 -1.2
-1.08
-1.4 -1.6 -1.8
Sink KM, et al. J Am Geriatr Soc. 2008; 56: 847-853.
-1.62
Taking pa4ent preference into account n What would you do for Mrs. B? n A) con4nue to prescribe both donepezil and oxybutyn n B) discon4nue donepezil n C) discon4nue oxybutyn n D) discon4nue both
Panel Discussion
Is there always a right or wrong?
Avoiding Drug Interactions in Clinical Practice Guidelines n Clinical guidelines typically focus on a single disease at a 4me n The reality is that people ocen have mul4ple coexis4ng medical
condi4ons
n In Canada:
1-‐in-‐4 seniors has > 3 condi4ons n Seniors with 1-‐2 chronic condi4ons take 3-‐4 prescrip4on medica4ons n Seniors with 3 or more condi4ons take 6 different medica4ons on average n
Canadian Institute for Health Information. Seniors and the Health Care System: What is the Impact of Multiple Chronic Conditions. Ottawa, Ontario, 2011.
Avoiding Drug Interactions in Clinical Practice Guidelines
Case 3: Mr. S 9 medical condi4ons n Cardiovascular disease – STEMI
82 years old
n n n n n n n n
10 & 2 years ago, admiOed last year for heart failure, EF 30% Hypertension x 20 years Diabetes Type 2 x 15 years Hypercholesterolemia x 15 years Osteoporosis x 10 years Hypothyroidism x 8 years Post-‐prostatectomy for prostate cancer x 5 years Urinary incon4nence x 1 year Depression x 6 months
Mr. S. 16 medica4ons n Amiodarone 200 mg bid, Furosemide 40 mg n n n n
82 years old
n n n n
bid, ASA 80 mg daily Monopril 10 mg daily, Nifedipine XL 30 mg daily Atorvasta4n 10 mg po daily Mewormin 500 bid, Glyburide 5 mg bid, Rosiglitazone 2 mg bid Alendronate 70 mg/wk, Calcium carbonate 1000 mg/day, Vitamin D 800 IU/day Pantoprozole 40 mg daily Levothyroxine 0.125 mg daily Oxazepam 15 mg po qhs Started on paroxe4ne 40 mg daily 6 months ago
Great job following the guidelines! Chronic heart failure
(2012 Canadian Cardiovascular Society guidelines)
ACE inhibitor and diuretics
Hypertension target 130/80
ACE inhibitor and CCB
(2011 Canadian Hypertension Educa4on Program recommenda4ons for pa4ents with diabetes)
Diabetes target HbA1C < 7%
Oral hypoglycemic agents
(2008 Canadian Diabetes Associa4on clinical prac4ce guidelines)
Dyslipidemia target LDL-C < 2.0 mmol/L
Statin
(2008 Canadian Diabetes Associa4on clinical prac4ce guidelines for high risk diabe4c pa4ents)
Osteoporosis
Bisphosphonate, Calcium, Vitamin D
(2010 Canadian Osteoporosis Society guidelines)
Use of ASA in elderly
Proton Pump Inhibitor to reduce GI bleeding
ssocia4on of Gastroenterology (2009 Canadian A C onsensus Group o n long-‐term NSAID therapy and gastroprotec4on)
Urinary incontinence
Consulta4on o n Incon4nence) (2012 Interna4onal
Kegel exercises!
Read the case again, list any drug interac4ons n Drug-‐food interac4ons
n Drug-‐disease interac4ons Night-time diuretics Venous insufficiency
n Drug-‐drug interac4ons n n
Pharmacokine4cs : what the body does to the drug Pharmacodynamics : what the drug does to the body
Interaction 1: Calcium inhibits levothyroxine absorption Ca2++ Synthroid
X Drug-food or drug-drug interaction Singh et al. JAMA 2000;283:2822-2825
Interaction 2: Glitazone oral hypoglycemics increase risk of heart failure n Health Canada warning 2001 on Avandia®
(rosiglitazone maleate): n Thiazolidinedione (TZD) class of oral
hypoglycemic agents can cause fluid reten4on, which can exacerbate or lead to heart failure
Increases preload
n 2012 Canadian Cardiovascular Society
guidelines recommend against the use of glitazone hypoglycemic agents in pa4ents with chronic heart failure
Blood backs up, causing heart failure Weakened heart muscle can’t squeeze as well
Drug disease interaction http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/medeff/avandia_hpc-cps-eng.pdf
Interaction 3: ACE inhibitors , calcium channel blockers, loop diuretics contribute to urinary incontinence
Drug disease interaction
Tannenbaum C. BJUI online 2011
Interaction 4: Proton pump inhibitors reduce antifracture efficacy of bisphosphonates Lower Risk
Higher Risk
No PPI 2 years PPI Any PPI 0
0.50
1.00
1.50
PPI’s increase gastric pH : diminished absorption of Ca2+ vitamin B12?
2.00
Risk of Hip Fracture with Alendronate in Adults > 70 years old Drug disease / drug-drug interaction Abrahamsen et al. Arch Int Med 2011;171:998-1004 *17% of the population studied was male
Cytochrome interac4ons 5,6,7,8,9,10…. Many drugs are ac4vated or inac4vated by different hepa4c cytochrome (CYP) enzymes. n When two or more drugs share the same metabolic pathway, there may
be compe44on for drug metabolism leading to changes in serum levels of certain drugs. CYP3A4
CYP2B6 CYP2C19 CYP1A2
CYP2D6 CYP2C8
CYP2C9
What happens when each cytochrome gets overloaded by too many drugs?
Altered biotransformation → Drug levels too high → Side effects OR → Drug levels too low → Therapeutic failure
Each medica4on binds differently to its cytochrome
Inhibitor
Strong binding
Weak binding
Moderate binding
Facilitator
Most frequent interac4ons are with cytochromes CYP3A4 and CYP2D6 Among 100 patients age 65+ with 5+ medications Cytochrome
Proportion of interactions (%)
3A4
70.1
2D6
22.7
2C9
3.4
2C19
2.1
1A2
1.7
2B6
0
Zakrzewski-Jakubiak et al. Am J Ger Pharmacother 2011
Food and herbals also bind to different cytochromes
3A4 Inhibitor
2D6, 2C9, 3A4 Inhibitor
3A4 Inducer, 2C9 Inhibitor
CYP 2C9
Cytochrome-‐mediated interac4ons can increase toxicity or reduce efficacy Medication
CYP 1A2
CYP 2B6
CYP 2C8
CYP 2C9
CYP 2C19
CYP 2D6
CYP 3A4
Amiodarone Furosemide
No cytochrome metabolism
Alendronate
No cytochrome metabolism
Paroxetine Nifedipine Levothyroxine
No cytochrome metabolism
Oxazepam
No cytochrome metabolism
ws-ddi.intermed-rx.ca
Atorvastatin Monopril
No cytochrome metabolism
Glucophage
No cytochrome metabolism
Glyburide Rosiglitazone Pantoprazole Inhibitor
Strong affinity substrate
Moderate-weak affinity substrate
275 pa4ents aged 65+ admiLed to an acute care hospital 80% had cytochrome drug-‐drug interac4ons drug-drug interactions The number of cytochrome increases as a function of the number of drugs consumed
Mr. S
Doan et al. Ann Pharmacotherapy 2013
Can we reduce the risk of drug-‐drug interac4ons for Mr. S?
Mr. S’s history
>10 years ago
2-10 years ago
>1 year ago
• • • • •
Hypertension– nifedipine XL Diabetes – metformin, glyburide, rosiglitazone High cholesterol - atorvastatin First myocardial infarction – ASA Isolated episode of atrial fibrillation in CCU - amiodarone
• Osteoporosis screening – alendronate, calcium, Vit D • Hypothyroidism – synthroid • Second myocardial infarction, congestive heart failure – lasix, monopril • Insomnia during hospitalization – discharged with oxazepam • Gastroprotection – pantoprazole • Radical prostatectomy for prostate cancer • Urinary incontinence – Kegel’s • Depression due to incontinence - paroxetine 49
Other inappropriate/unnecessary prescrip4ons n Amiodarone : Beers list, prescribing cascade causing
hypothyroidism, no recurrence of A. fib, cytochrome inhibi4on
n ASA: Canadian Cardiovascular Society recommends to avoid
in pa4ents with reduced ejec4on frac4on heart failure
n Lasix 40 mg bid: Canadian Cardiovascular Society
recommends dose reduc4on in stable pa4ents
n Alendronate: 5-‐10 years increases the risk of atypical
fractures, is it being absorbed?
n Paroxe4ne: can we treat the cause of Mr. S.’s depression?
What to do first? n Decide what should be tapered or stopped n Stop the easy ones (no longer needed, have long half-‐
lives, don’t cause adverse drug withdrawal events) n n n
Amiodarone Alendronate ASA
n Stop the drugs causing side effects n Drugs that can cause adverse drug withdrawal events
need to be tapered e.g. beta-‐blockers, benzodiazepines, SSRIs, PPIs, diure4cs, narco4cs, an4convulsants, an4psycho4cs
From UpToDate
PA Rochon. http://www.uptodate.com/contents/drug-prescribing-for-older-adults
Mr. S’s medica4on changes
• Stop ASA • Stop rosiglitazone • Stop amiodarone • Monitor glucose
Week 1
Month 2 • Provide sleep hygiene education • Teach heart failure self-management • Start glyburide taper 2.5 mg bid
• Begin twenty week oxazepam taper • Begin nifedipine XL taper 20 mg once daily • Stop alendronate
Month 4 53
Mr. S’s medica4on changes
• Stop nifedipine • Start bisoprolol 2.5 mg bid (not metabolized by CYP 450) • Switch atorvastatin to rosuvastatin (CYP2C9)
Month 6
Month 8 • Start elastic stockings • Start furosemide taper 20 mg bid • Discontinue glyburide • Increase dose of metformin 500 tid
• Start pantoprazole taper 20 mg daily • Increase dose of bisoprolol 5 mg bid • Discontinue oxazepam • Continue furosemide taper 20 mg daily
Month 10 54
At 1 year follow-‐up Mr. S’s medica4ons
Mr. S’s life:
§ Bisoprolol 5 mg bid
§ Less fluid reten4on
§ Monopril 10 mg daily
§ Less fa4gued
§ Lasix 20 mg at 5 pm
§ Urinary urgency and urge
§ Mewormin 750 mg 4d § Rosuvasta4n 10 mg daily § Synthroid 0.125 mg – repeat
TSH yearly § Calcium and Vitamin D (no longer given at same 4me as synthroid) § Schedule repeat bone density in 6 months
incon4nence improved § No more weakness/ unsteady gait § Lower risk of falls § Lower risk of hypoglycemia § Less depressed: taper and discon4nue paroxe4ne over the next 2 months 55
Take home 4ps n Use screening criteria to iden4fy ‘poten4ally n n n n n n n
inappropriate medica4ons’ For every sign or symptom, always ask ‘can this be caused by a drug’? Review the chronology of all prescrip4ons Review indica4ons Subs4tute with drugs not metabolized by the same cytochrome Change the 4me of administra4on of the drug Use non-‐pharmacologic approaches Work as a team: pharmacist, nurse, physio etc.
Resources and References n Beers:
hOp://www.americangeriatrics.org/ health_care_professionals/clinical_prac4ce/ clinical_guidelines_recommenda4ons/2012 n STOPP/START: hOp://www.biomedcentral.com/imedia/ 3973756062468072/supp1.doc n InterMED-‐Rx: ws-‐ddi.intermed-‐rx.ca n Drug discon4nua4on algorithm: hOp://www.uptodate.com/contents/drug-‐prescribing-‐for-‐ older-‐adults
