Adjusting and Withdrawing Medications in the Elderly

Adjusting and Withdrawing Medications in the Elderly Louise Mallet, B.Sc.Pharm., Pharm.D., CGP Professor in Clinical Pharmacy, Faculty of Pharmacy, University of Montreal Clinical Pharmacist in Geriatrics, Geriatric pharmacy consult, MUHC 2015-11-24 1

Disclosure of Commercial Support No conflict of interest 2015-11-24 2

Objectives At the end of the presentation, the participants will be able to: 1. Describe the consequences of polypharmacy in the elderly; 2. Adjust and stop medications safely in the elderly; 3. Deprescribe drugs safely in elderly patients using a systematic approach. 2015-11-24 3

Mrs. TT Mrs. TT., 90 year old woman, who lives with her son. He is responsible to administer her medications Amlodipine 2.5 mg po daily Candesartan 16 mg po daily Indapamide 2.5 mg po daily Omeprazole 20 mg po daily Alendronate 70 mg po q week Cal + Vi D 500/400 po bid Domperidone 10 mg po bid Atorvastatin 20 mg po daily Saxagliptine 5 mg po daily Metformin 850 mg po tid Acetaminophen 500 mg po tid 2015-11-24 4

Mrs. TT Medical history: Hypertension, Diabetes, Osteoarthritis, Osteoporosis Cal Cr Cl = 15 ml/min Weight: 40 kg B.P. range between 140-160 Glucose: Between 9-12 mmol/l 2015-11-24 5

Definition of polypharmacy 1. More than 4 medications 2. More than 5 medications 3. More than 10 medications 4. All of the above 5. None of the above 2015-11-24 6

Definition of polypharmacy Often define by the total number of medications More than 4 or 5 or 9 or 10 Problematic to apply a cutoff number May result in underprescribing Indication for medication changes over time: o Functional status of patient, goals of care, life expectancy Pa#erson SM et al. Cochrane Database Syst Rev 2012;5:CD008165 2015-11-24 7

Risk factors for polypharmacy Demographic factors: Increased age, white race, education Health factors: Depression, hypertension, depression, anemia, asthma, angina, diverticulosis, osteoarthritis, gout, diabetes mellitus, and use of more than 9 medications Access to health care: Number of health care visits, supplemental insurance, multiple providers Hajjar ER et al. Polypharmacy in the elderly. Am J Geriatr Pharm 2007;5345-51 2015-11-24 8

Consequences of polypharmacy Increased risk of: Receiving an inappropriate medication Presenting an adverse drug reaction Presenting a geriatric syndrome Presenting a medication cascade Having drugs interactions Receiving medications with an anticholinergic load Not taking their medications Increasing morbidity and mortality Hajjar ER et al. Polypharmacy in the elderly. Am J Geriatr Pharm 2007;5345-51 2015-11-24 9

New word: 2003 Medline: 2011 Deprescribing Help guide medication review Critical review to stop medications : o with no clear indication o no clear efficacy for the patient o not appropriate for the goals of care o non adherence Frank C. CMAJ 2014;186:407-8 2015-11-24 10

What is Deprescribing? Process of stopping, tapering, discontinuing or withdrawing drugs supervised by a clinician Goal: managing polypharmacy and improving outcomes 2015-11-24 11

Evaluation For each medication: Indication, goal of therapy, effectiveness, safety, compliance Dose adjustment (for weight of the patient and decreased renal function Association between medications and geriatric syndromes Medication cascade Beers criteria STOPP/START criteria Anticholinergic Load Drug interactions 2015-11-24 12

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Goals of therapy Glycemic targets BP target Inform the patient of the goals of therapy Inform the other health prof of the goals of therapy Fit Vulnerable Frail 2015-11-24 14

Appropriate prescribing: The Pyramid Model Holmes, Arch Int Med, 2006 2015-11-24 15

Weight for your patient Cross-sectional study for patients admitted to 2 wards at Royal North Hospital in Sydney Patients admitted to orthopaedic ward: 22/78 (28%) were weighed Patients admitted to medical ward: 27/124 (22%) were weighed More haemorrhagic complications for patients that were not weighed: for anticoagulation Hilmer SN et al. Failure to weigh patients in hospital: a medication safety risk. Internal Med J 2007;37:647-50. 2015-11-24 16

Which formula 85 year-old woman admitted for Gen. Det. Weight: 38 kg Serum creatinine: 45 μmol/l Which formula do you use in this patient to estimate her Cr Cl? http://www.globalrph.com/multiple_crcl.htm 2015-11-24 17

What to do now? 85 year-old woman admitted for Gen. Det. Weight: 38 kg Serum creatinine: 45 μmol/l Six months later, you see this patient and she has a serum creatinine of 90 μmol/l. Look at the Trend and not only one value Use your clinical judgment 2015-11-24 18

Geriatric syndromes Falls Delirium Anorexia Urinary incontinence Dizziness Immobility Drugs > 4 drugs, antipsychotics, antidepressants, benzodiazepines, etc Drugs with anticholinergic properties Digoxine, metronidazole, angiotensin converting enzyme inhibitors (ACEI), lithium Diuretics, sedative-hypnotics, inhibitors of acetylcholinesterase, ACEI A lot of drugs Side effects from antipsychotics, etc 2015-11-24 Orthostatic hypotension Cardiovascular agents, antipsychotics, benzodiazepines, etc etc 19

Prescription cascade Drug n 0 1 Side effect interpreted as a new disease Addition of drug n 0 2 Side effet interpreted as a new disease. Rochon et coll. BMJ 1997 2015-11-24 20

Find the cascade 81 year-old woman admitted to the ER from LTC facility. She has the following medications. o Amlodipine 5 mg po daily o Irbesartan 150 mg po daily o Betahistine 16 mg po bid o Acetaminophen 500 mg po tid prn o Aggrenox 1 capsule po bid o Vitamin D 10,000 units every Sunday o Calcium 500 mg po daily Blood pressure on admission: 130/80 lying position and 100/50 sitting position 2015-11-24 21

Mrs. HTN 94 year-old woman admitted to the hospital for pain Blood pressure in ER: 190/90 Medications at home: o Amlodipine 2.5 mg po daily o Diclofenac 75 mg po bid : 2 wks ago o Pantoprazole 40 mg po daily: 2 wks ago o Vitamin D 10,000 u q week o Calcium 500 mg po bid In ER, dose of Amlodipine increased to 5 mg po daily. Admitted to geriatric unit 2015-11-24 22

Mrs. HTN Medication cascade: Diclofenac Hypertension Dose of amlodipine increased to 5 mg in ER Admitted to geriatric stop diclofenac Decreased blood pressure Same dose of amlodipine 5mg Still on Pantoprazole decreased Magnesium Magnesium replacement 2015-11-24 23

Target the most common o o o o o o o o o Furosemide Urinary incontinence Oxybutynin Gabapentin/pregabalin Peripheral edema Furosemide Risperidone Rigidity Sinemet Ciprofloxacin Hallucinations Risperidone Lithium Tremors Propranolol Alendronate GI side effects Pantoprazole Amlodipine Peripheral edema Furosemide Antihypertensive Dizziness Betahistine Donepezil Urinary incontinence Oxybutynin or tolterodine 2015-11-24 24

Consequence of a cascade Delirium Fall Hip Fracture Confusion Urinary frequency Hospitalization 2015-11-24 25

Beers list: Inappropriate medications CLINICAL INVESTIGATIONS American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel The 2015 American Geriatrics Society (AGS) Beers Criteria are presented. Like the 2012 AGS Beers Criteria, they include lists of potentially inappropriate medications to be avoided in older adults. New to the criteria are lists of select drugs that should be avoided or have their dose adjusted based on the individual s kidney function and select drug drug interactions documented to be associated with harms in older adults. The specific aim was to have a 13-member interdisciplinary panel of experts in geriatric care and pharmacotherapy update the 2012 AGS Beers Criteria using a modified Delphi method to systematically review and grade the evidence and reach a consensus on each existing and new criterion. The process followed an evidence-based approach using Institute of Medicine standards. The 2015 AGS Beers Criteria are applicable to all older adults with the exclusion of those in palliative and hospice care. Careful application of the criteria by health professionals, consumers, payors, and health systems should lead to closer monitoring of drug use in older adults. J Am Geriatr Soc 2015. Key words: Beers List; medications; Beers Criteria; drugs; older adults; polypharmacy older adults is one strategy to decrease the risk of adverse events. Interventions using explicit criteria have been found to be an important component of strategies for reducing inappropriate medication usage. 3 5 The AGS Beers Criteria for PIM Use in Older Adults are one of the most frequently consulted sources about the safety of prescribing medications for older adults. The AGS Beers Criteria are used widely in geriatric clinical care, education, and research and in development of quality indicators. In 2011, the AGS assumed the responsibility of updating and maintaining the Beers Criteria and, in 2012, released the first update of the criteria since 2003. The AGS has made a commitment to update the criteria regularly. The changes in the 2015 update are not as extensive as those of the previous update, but in addition to updating existing criteria, two major components have been added: 1) drugs for which dose adjustment is required based on kidney function and 2) drug drug interactions. Neither of these new additions is intended to be comprehensive, because such lists would be too extensive. An interdisciplinary expert panel focused on those drugs and drug drug interactions for which there is evidence in older adults that they are at risk of serious harm if the dose is not adjusted or the drug interaction is overlooked. JAGS Oct 2015 he American Geriatrics Society (AGS) Beers Criteria Tfor Potentially Inappropriate Medication (PIM) Use in Older Adults is an explicit list of PIMs best avoided in older adults in general and in those with certain diseases or syndromes, prescribed at reduced dosage or with caution or carefully monitored. Beers Criteria PIMs have been found to be associated with poor health outcomes, including confusion, falls, and mortality. 1,2 Avoiding PIMs in From the Special Projects & Governance, American Geriatrics Society, New York, New York. Address correspondence to Mary Jordan Samuel, Manager, Special Projects & Governance, American Geriatrics Society, 40 Fulton Street, 18th Floor, New York, NY 10038. E-mail: msamuel@americangeriatrics.org DOI: 10.1111/jgs.13702 OBJECTIVES The specific aim was to update the 2012 AGS Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse drug events in older adults. The strategies to achieve this aim were to: Incorporate new evidence on currently listed PIMs and evidence from new medications or conditions not addressed in the 2012 update. Incorporate two new areas of evidence on drug drug interactions and dose adjustments based on kidney function for select medications. Grade the strength and quality of each PIM statement based on the level of evidence and strength of recommendation. Convene an interdisciplinary panel of 13 experts in geriatric care and pharmacotherapy who would apply a modified Delphi method to the systematic review and JAGS 2015 2015, Copyright the Authors Journal compilation 2015, The American Geriatrics Society 0002-8614/15/$15.00 2015-11-24 26

Beers List: Worst of the Worst Drug Diphenhydramine, dimenhydramine Digoxin at dose >0.125mg/ day Metoclopramide (Maxeran, Reglan) Short-acting and long-acting benzodiazepines Amitriptyline (Elavil) Nitrofurantoin Glyburide Problem Anticholinergic: confuses and sedates Toxic due to decreased renal clearance Extrapyramidal side effects Sedation, falls, fractures Anticholinergic: confuses and sedates Potential for pulmonary toxicity; lack of efficacy in patients with Cr Cl < 30 ml/min avoid long term use Risk of hypoglycemia; active metabolite JAGS 2015: 0ct 2015-11-24 27

Inappropriate drugs: what to do? Avoid prescribing drugs which are on the avoid prescribing Beers s list drugs whichappear Discontinue on the or taper Beers list inappropriate drugs Consider safer medications 2015-11-24 28

Age and Ageing 2014; 0: 1 6 STOPP doi: 10.1093/ageing/afu145 and START criteria STOPP/START criteria for potentially inappropriate prescribing in older people: version 2 DENIS O MAHONY 1,2,DAVID O SULLIVAN 3,STEPHEN BYRNE 3,MARIE NOELLE O CONNOR 2,CRISTIN RYAN 4, PAUL GALLAGHER 2 Age and Ageing Advance Access published October 16, 2014 The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 1 Geriatric Medicine, University College Cork, Cork, Munster, Ireland 2 Geriatric Medicine, Cork University Hospital, Cork, Munster, Ireland 3 School of Pharmacy, University College Cork, Cork, Munster, Ireland 4 School of Pharmacy, Queen s University, Belfast, Northern Ireland, UK Address correspondence to: D. O Mahony. Tel: (+353) 214922396; Fax: (+353) 214922829. Email: denis.omahony@ucc.ie Abstract Purpose: screening tool of older people s prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts. Keywords: inappropriate prescribing, older people, STOPP/START criteria Downloaded from http://ageing.oxfordjournals.org/ at Universite de Montreal on November 27, 2014 Introduction Adverse drug reactions (ADRs) in older people currently represent a serious and growing public health problem [1]. Polypharmacy and inappropriate prescribing (IP) are wellknown risk factors for ADRs, which commonly cause adverse clinical outcomes in older people [2, 3]. IP encompasses potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) [4]. STOPP/START criteria for potential IP in older people recognise the dual nature of IP by including a list of PIMs (STOPP criteria) and PPOs (START criteria). Since the first iteration of STOPP/ START criteria in 2008 [5], our research group has shown a number of important properties of STOPP/START criteria, namely: STOPP criteria medications are significantly associated with adverse drug events (ADEs), unlike Beers 2003 criteria medications [6]. STOPP/START criteria as an intervention applied at a single time point during hospitalisation for acute illness in older people significantly improve medication appropriateness [7], an effect that is maintained 6 months postintervention. STOPP/START criteria as an intervention applied within 72 h of admission significantly reduce ADRs (with an 1 2015-11-24 29

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Methods Drugs with anticholinergic properties Effet on cognitive function, delirium and physical function and mortality 47 studies 60 044 participants 2015-11-24 31

Summary 2015-11-24

JAGS 2015 Beers Criteria 2015-11-24

Lecouteur D et al. Deprescribing. Australian Prescriber 2011;34:182-5 2015-11-24 34

Evidence base available for the drug in question in terms of: indication, dose, patient, demographics, potential benefits versus risks NO/NOT SURE STOP DRUG Is there an indication for this specific patient? NO YES Is the drug effective for this specific patient? NO YES Has the patient experienced adverse effects from the drug in question or is there an increased risk of adverse events? NO Is there another drug which may be superior to the drug in question (in terms of safety and/or efficacy)? NO Can the does be reduced with no significant risk? YES YES Change to an another agent Garfinkel et al, 2007, 2010 CONTINUE DOSE NO YES REDUCE DOSE 2015-11-24 35

Mrs. TT Mrs. TT., 90 year old woman, lives with her son. He is responsible to administer her medications Amlodipine 2.5 mg po daily Candesartan 16 mg po daily Indapamide 2.5 mg po daily Omeprazole 20 mg po daily Alendronate 70 mg po q week Cal + Vi D 500/400 po bid Domperidone 10 mg po bid Atorvastatin 20 mg po daily Saxagliptine 5 mg po daily Metformine 850 mg po tid Acetaminophen 500 mg po tid Question to ask: What medications does she take? Weight Cal Cr Cl = 15 ml/min Goals of therapy Dosage adjustment Medication cascade Beers Criteria Anticholinergic load 2015-11-24 36

Mrs Dry Mouth Medication history : o Metoprolol 75 mg po bid o Coumadin 4 mg po daily o Celecoxib 200 mg po daily prm o Gabapentine 400 mg am et 300 mg at bedtime o Venlafaxine XR 300 mg po daily o Levothyroxine 0.075 mg po daily o Atorvastatin 40 mg po daily o Fesoterodine 4 mg LA 4 mg po daily o Pantoprazple 40 mg po daily o Latanoprost 0.005% 1 gtte 1x/at bedtime in both eyes o Naproxen 500 mg bid x 3 days 2015-11-24 37

Mrs Dry Mouth Medications delivered in dispill She takes her medications, knows her medications. Takes her Celebrex daily Intolerance : Aspirine Medical history: A. fib., urinary incontinence, pain, hypothyroidism, «tremors» 2015-11-24 38

Mrs Dry Mouth Medication history : o Metoprolol 75 mg po bid o Coumadin 4 mg po daily o Celecoxib 200 mg po daily prm o Gabapentine 400 mg am et 300 mg at bedtime o Venlafaxine XR 300 mg po daily o Levothyroxine 0.075 mg po daily o Atorvastatin 40 mg po daily o Fesoterodine 4 mg LA 4 mg po daily o Pantoprazple 40 mg po daily o Latanoprost 0.005% 1 gtte 1x/at bedtime in both eyes o Naproxen 500 mg bid x 3 days 2015-11-24 39

79 year-old woman admitted to ER for Gen Det Medications at home: Pregabaline 75 mg po 2x/d Venlafaxine XR 75 mg po daily Domperidone 10 mg po qid Metoclopramide 10 mg po bid Clonazepam 0.5 mg po qid Risperidone 0.5 mg po daily Dimenhydrinate 50 mg po q 4 hrs prn (180/month) Coumadin 5 mg po daily Janumet 1000 + 50 mg (metformine + sitagliptine) bid Glyburide 5 mg po bid Rosuvastatin 20 mg po daily Ramipril 5 mg po daily Bisoprolol 5 mg po daily Amlodipine 10 mg po daily Pantoprazole 40 mg po daily Levothyroxine 0.075 mg po daily Colace 100 mg po bid 2015-11-24 40

79 year-old woman admitted to ER for Gen Det Medications at home: Pregabaline 75 mg po 2x/d Venlafaxine XR 75 mg po daily: was on Citalopram 40 mg po daily d/c april 8 2015 Domperidone 10 mg po qid Metoclopramide 10 mg po bid: EPS Clonazepam 0.5 mg po qid: Risperidone 0.5 mg po daily anticholinergic Coumadin 5 mg po daily Janumet 1000 + 500 mg (metformine + sitagliptine) bid Glyburide 5 mg po bid: Rosuvastatin 20 mg po daily (leg pain then pregabalin) Ramipril 5 mg po daily Bisoprolol 5 mg po daily Amlodipine 10 mg po daily Pantoprazole 40 mg po daily Levothyroxine 0.075 mg po daily Colace 100 mg po bid QTc 2015-11-24 41

Need to stop thinking in SILO 2015-11-24

For safer prescribing press here 2015-11-24 43

Conclusion louise.mallet @umontreal.ca 2015-11-24 44