polypharmacy and inappropriate medication use in patients with … · 2018-07-16 · polypharmacy...

Polypharmacy and Inappropriate Medication Use in Patients with

Cognitive Impairment

Yeoh Ting Ting Ting Ting Yeoh (Ms)

BSc (Pharmacy), Hons, MSc (Oncology), BCGP, BCOP, BCACP Oncology Specialist Pharmacist

30 June 2018

2

Faculty Disclosure

✓ No, nothing to disclose Yes, please specify:

I, Ting Ting Yeoh, have no financial relationship or affiliation to disclose.

3

When?

What & How?

Why?

Outline

4

The Relationship between Medication-use & Cognitive Impairment in Older cancer patients

5

Cancer

Age

Mul-pleComorbidity

&Polypharm

Cogni-veimpairment

(CI)

Riskfactorforcancer

www.cancer.gov/about-cancer/causes-preven2on/risk/ageHolmesHMetal(2008).JAmGeriatrSoc56:1306-1311LangeM.etal(2014).CancerTreatmentReviews40:810-817

AssociatedwithCI

Associatedwith↑comorbidity&polypharmacy

6

Cancer

Age

Mul-pleComorbidity

&Polypharm

Cogni-veimpairment

(CI)

Chemotherapy-relatedCogni-veImpairment(CRCI)/

‘Chemobrain’

CIaffectssurvival&adherence

Riskfactor

LibertYetal(2016).PLoSONE11(8):e0159734LohKPetal(2016)JGeriatrOnc7:270-180VitaliMetal(2017).CritRevinOncHematol118:7-14

Associa-on

Associa-on

7

Cancer

Age

Mul-pleComorbidity

&Polypharm

Cogni-veimpairment

(CI)

Chemotherapy-relatedCogni-veImpairment(CRCI)/

‘Chemobrain’

CIaffectssurvival&adherence

Ass’dwithpoorercogni-vecapability

Riskfactorforcancer

RiskfactorforCI

EllioWRAetal(2015).CurrClinPharmacol.10:213-221RawlesMJetal(2018):JAmGeriatrSoc.DOI:10.1111/jgs.15317

Pronetonon-adherence

What is polypharmacy?

9

Definition of Polypharmacy (Poll)

A.  Utilisation of 5 or more medications B.  Utilisation of 7 or more medications C.  Utilisation of 11 or more medications

D.  Utilisation of 2 or more medications for more than 240 days

E.  Taking multiple unnecessary medications

Masnoonetal(2017).BMCGeriatrics17:230

138 definitions of Polypharmacy & associated

terms (e.g. minor polypharmacy) have been

identified!

11

What can we, as Healthcare Professionals, do?

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Supporting elderly patients

Review appropriateness

Deprescribing Ensure adherence

13

Potentially Inappropriate Medications (PIM)

14

Examples of tools to identify PIMs in Older Adults

•  Beers Criteria for PIM use in Older Adults •  STOPP/ START Criteria for Potentially

inappropriate prescribing in older people •  Medication Appropriateness Index (MAI) •  Others: HEDIS DAE, IPET, Zhan, ACOVE-3

WhitmanA.M.etal(2016)TheOncologist21:723-730

IPET=ImprovingPrescribingintheElderlyToolACOVE-3=AssessingCareofVulnerableElders-3

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Important PIMs in Dementia/ Cognitive Impairment

•  Anticholinergics (e.g. certain antidepressants, antiparkinsonians, skeletal muscle relaxants, antipsychotics, antimuscarinics, antispasmodics, antiemetics)

•  H2- receptor antagonists (e.g. famotidine, ranitidine)

•  Benzodiazepines •  Benzodiazepine- receptor agonist hypnotics

(e.g. Zolpidem)

•  Antipsychotics for behavioural problems of dementia & delirium (unless non- pharmacological options have failed and the older adult is threatening to harm to self/ others)

Please refer to Holmes HM et al (2008), J Am Geriatr Soc 56: 1306-1311 for a list of PIMs in Advanced Dementia

AmericanGeriatricsSociety(2015)JAmGeriatrSoc.DOI:10.1111/jgs.13702

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De-prescribing

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What is prescribing?

ü diagnose a problem ü make a therapeutic decision ü alter the natural history

ü consider the risk associated with individual drugs

ü consider the cumulative risk from multiple drugs due to pharmacokinetic and pharmacodynamics interactions

ScoWIA.JAMAInternMed2015Mar

18

What is prescribing?

ü a positive, patient- centred intervention ü with inherent uncertainties ü requires shared decision making

ü informed patient consent ü and close monitoring of effects


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What is deprescribing?

ü Diagnose a problem ü Make a therapeutic decision ü Alter the natural history

ü Consider the risk associated with individual drugs

ü Consider the cumulative risk from multiple drugs due to pharmacokinetic and pharmacodynamics interactions


20

What is deprescribing?

ü A positive, patient- centred intervention ü with inherent uncertainties ü requires shared decision making

ü informed patient consent ü and close monitoring of effects


21

What is De- prescribing?

De- prescribing is defined as 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.


22

Published De-prescribing Tools

De-prescribing in general populations: •  5- step de-prescribing tools by Scott et al. De-prescribing in cancer/ end-of-life care: •  OncPal de-prescribing tools by Lindsay et al.

ScoWIAetal(2015).JAMAInternMed175(5):827-34LindsayJetal(2015).JSupportCareCancer.23:71-78

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5-Step Deprescribing Process

Performacomprehensivemedica-on-indica-on

reconcilia-on

Consideroverallriskofdrug-induced

harm

Assesseachmedica-onforeligibility

tobediscon-nued

Priori-semedica-onsfordiscon-nua-on

Implementdrugdiscon-nua-on

planandmonitoradverse

withdrawaleffects

Step1 Step2 Step3 Step4 Step5

ScoWIAetal(2015).JAMAInternMed175(5):827-34

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Steps 3 & 4:

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Step 5: Implement drug discontinuation plan and monitor adverse withdrawal effects

•  Monitor for adverse withdrawal reactions or return of symptoms

•  Counsel patient/caregiver on steps to take

•  Implement non-pharmacological measures

•  Document process and outcome, communicate to other healthcare providers



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Barriers to de-prescribing

•  High- levels of clinical complexity •  Limited consultation time •  Fragmented care among multiple prescribers •  Incomplete information (on past rationales for, and

patient tolerance of, drugs) •  Ambiguous or changing care goals •  Uncertainty about the benefits & harms of

continuing & discontinuing specific drugs •  Community & professional attitudes toward more

rather then less use of drugs •  Fear of adverse effects


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De-prescribing in end-of-life: Continuum of Palliative Cancer Care

FerrisFD(2009)JClinicalOncology.27:3052-58

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2009

2013

2014

2015 2018

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StevensonJ(2004).BMJ.329:999-1012

Table: Factors influencing the likelihood of continuing treatment for medical comorbidities in patients with life- limiting illness

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OncPal De-prescribing Guideline in end- of- life care Medica-on

ClassMedica-on Considera-onsforlimited

benefitExplana-on

Blood Aspirin For1opreven2on Longtermbenefitsatpopula2onlevel.LiWleshortorintermediatetermriskofstopping.Drugsforprimarypreven2onhave,ingeneral,noplaceinthetreatmentofend-of-lifepa2entssince2me-to-benefitusuallyexceedslifeexpectancy

Cardiovascularsystem

Dyslipidaemia-sta2ns,fibrate,eze2mibe

Allindica2ons Long-termbenefitsatpopula2onlevel.LiWleshort/intermediatetermriskofstopping

An-hypertensives

Ifsoleuseistoreducemild-moderatehypertensionfor2opreven2onofCVevents/asmanagementofstableCAD

Long-termbenefitsatpopula2onlevel.Ongoingtherapyunnecessaryinmostshortenedlifeexpectancy

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LindsayJetal(2015).JSupportCareCancer.23:71-78

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OncPal De-prescribing Guideline: It’s Role

•  Assist in identifying potentially inappropriate medications (PIMs)

•  Aid in rationalization of medications

LindsayJetal(2015).JSupportCareCancer.23:71-78

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Challenges for deprescribing in end- of- life

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ToddA(2015).IntJClinPharmdoi:10.1007/s11096-015-0148-6KutnerJS(2015).JAMAInternMeddoi:10.1001/jamainternmed.2015.0289StevensonJ(2004).BMJ;329:999-1012

Guidelines applicable to general elderly populations are not directly transferrable

Predicting the time of ‘shift’

General practitioner? Oncologist? Other specialist?

How do you explain end of life to patients?

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Recommendations to support De-prescribing

1.  Shared decision- making in prescribing & deprescribing medications

2.  Not prescribing a medication should be presented as a reasonable alternative for patients late in life, when appropriate

3.  De- prescribing is a part of prescribing 4.  Prescribers have to embrace uncertainty 5.  Difficult discussions now will simplify difficult

decisions in the future

ToddA(2015).IntJClinPharmdoi:10.1007/s11096-015-0148-6

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Improving Adherence

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Improving adherence

•  Simplifyregimen(reduceno.ofdrugs/frequency)

•  Educatepa2ent(importanceofmeds,awarenessofgoals)

•  Integratedinterven2ons(regularmedreviews,systemiccoopera2onbetweenphysicians&pharmacists)

•  Dataontheuseofaidsiscontroversial

EllioWRAetal(2015).CurrClinPharmacol.10:213-221CostaEetal(2015)PaAentPreferenceandAdherence9:1303–1314Mis2aenPetal(2006)BMCHealthServiceRes.7:47CampbellNLetal(2012)AmJGeriartPharmacother10:165-177

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When?

What & How?

Why?

Regular, ongoing

Decision Tools/ Algorithms + Shared- decision making

Complex interaction among age, cancer, comorbidities & cognitive status calling for individualised

therapies

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References Cancer therapy and Cognitive impairment •  Vitali M. et al. (2017) Cognitive impairment and chemotherapy: a brief overview. Current Reviews in

Oncology/ Hematology 118: 7-14 •  Given C.W. et al. (2016) Care of the Elderly Patient on Oral Oncolytics for Advanced Disease. Current

Geriatrics Report 5:233- 239 •  Libert Y et al. (2016) Vulnerabilities in Older Patients when Cancer Treatment is Initiated: Does a

Cognitive Impairment impact the 2-year survival? PLoS ONE 11(8):e0159734 doi:10.1371/journal/pone.0159734

•  Karuturi M. et al. (2016) Understanding cognition in older patients with cancer. Journal of Geriatric Oncology 7: 258-269

•  Lange M. et al. Cognitive dysfunctions in elderly cancer patients: A new challenge for oncologists. Cancer Treatment Review 40: 810-817

•  Libert Y et al (2016). Vulnerabilities in Older Patients when Cancer Treatment is initiated: Does a cognitive impairment impact the two-year survival? PLoS ONE 11(8): e0159734

•  Loh KP et a (2016). Chemotherapy- related cognitive impairment in older patients with cancer. J Geriatr Onc 7: 270-280

Polypharmacy and Cognitive Impairment •  Oyarzun-Gonzalez XA et al (2015). Cognitive Decline and Polypharmacy in an elderly population. J Am.

Geriartr Soc 63(2): 397-99 •  Rawle MJ e al (2018). Associations between polypharmacy and Cognitive and Physical Capability: A

British Birth Cohort Study. J Am Geriatr Soc DOI: 10.1111/jgs.15317 •  Elliott RA et al (2015) Ability of Older person with dementia or cognitive impairment to manage

medicine regiments: A Narrative Review Curr Clin Pharmacol 10:213-221 Polypharmacy/ Potentially inappropriate Medications among Cancer Patients •  Goh I, et al. (2018) Prevalence and Risk of Polypharmacy among elderly cancer patients receiving

chemotherapy in ambulatory oncology setting. Current Oncology Report 20:38 •  Whitman, A.M. et al (2016) A Comprehensive Look at Polypharmacy and Medication Screening Tools

for older cancer patients. The Oncologist 21: 723-730

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References (continued)

Polypharmacy/ Potentially inappropriate Medications among Older Persons •  Rawle M.J. (2018) Association between polypharmacy and cognitive and physical

capability: A British Birth Cohort Study. Journal of American Geriatrics Society doi:10.11111/jgs.15317

De-prescribing •  Scott I.A. et al. (2015) Reducing Inappropriate Polypharmacy- The process of

Deprescribing. JAMA Intern Med. 175(5): 827-834 •  Akinbolade O. et al. (2016) Deprescribing in Advanced Illness. Progress in Palliative Care

24(5): 268-271 •  Kutner J.S. et al. (2015) Safety and Benefit of discontinuing statin therapy in the setting of

advanced, life- limiting illness. 175(5): 691- 700 •  Lindsay J. et al. (2014) The development and evaluation of an oncological palliative care

deprescribing guidelines: the “OncPal deprescribing guideline’. Support Care Cancer doi: 10.1007/s00520-014-2322-0

•  Stevenson J. et al. (2004) Managing comorbidities in patients at the end of life. BMJ 329: 909-12

•  Reeve E. et al. (2016) The Ethics of deprescribing in older adults. Bioethical Inquiry 13: 581-590

Others •  Masnoon et al (2017) What is polypharmacy?A systematic review of definitions. BMC

Geriatrics 17:230 •  Costa E et al (2015Interventional tools to improve medication adherence: review of

literature Patient Preference and Adherence 9: 1303–1314 •  Mistiaen P et al (2006). Interventions aimed at reducing problems in adult patients

discharged from hospital to home: a systematic meta-reviewBMC Health Service Res. 7:47

•  Campbell NL et al (2012) Medication Adherence in Older Adults With Cognitive Impairment: A Systematic Evidence-Based Review. Am J Geriart Pharmacother 10:165-177

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Thank you

40

About NCCS

40

41

Comprehensive Cancer Care

Joint Tumour Board

Counseling Support

Oncologic Nursing

Palliative Care

Surgical Oncology

Medical Oncology

Radiation Oncology

Oncologic Imaging

Research

42

Manpower

CATEGORY ApproxNumber(31Mar2014)

Clinicians 141 Nursing 136

AlliedHealth 173 Research 194

Administra-on/Ancillary

257

Total 901

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Instances when de-prescribing can be considered

ü  presenting with a new symptom or clinical syndrome suggestive of ADE;

ü manifesting advanced or end-stage disease, terminal illness, dementia, extreme frailty, or full dependence on others for all care;

ü  receiving high-risk drugs or combinations;

ü  receiving preventive drugs for scenarios associated with no increased disease risk despite drug cessation

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De- prescribing in End- of- Life

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Case Vignette

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A 68 year old woman with extensive small cell lung cancer & rapid weight loss also has long term mild hypertension with no evidence of end organ damage. What would you do about her antihypertensive treatment? a)  Stop drug treatment because she has a terminal illness b)  Continue the drugs because you would not want her blood

pressure to get worse (and the conversation about stopping them may be difficult because last year you told her she would be taking these drugs for the rest of her life)

c)  Wait until she develops postural hypotension and then consider reducing her drugs

d)  Reduce her drugs and watch carefully

StevensonJ.BMJ2004;329:999-1012

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OncPal Deprescribing Guideline (cont’d)

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Medica-onClass

Medica-on Considera-onsforlimitedbenefit

Explana-on

MusculoskeletalSystem

OsteoporosisMedica-ons-bisphosphonates,raloxifene,stron2um,denosumab

Exceptifusedforthetreatmentofhypercalcaemiasecondarytobonemetastases

Longtermbenefitsatpopula2onlevel.LiWleshortorintermediatetermriskofstopping.

Alimentarytractandmetabolism

Pep-culcerprophylaxis-Protonpumpinhibitors,H2antagonists

Lackofanymedicalhistoryofgastrointes2nalbleeding,pep2culcer,gastri2s,GORD/GERD,ortheconcomitantuseofan2-inflammatoryagentsincludingNSAIDsandsteroids

Ongoingtherapyunnecessaryinmostshortenedlifeexpectancy

LindsayJ.JSupportCareCancer2015;23:71-78

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OncPal Deprescribing Guideline (cont’d)

Medica-on Considera-onsforlimitedbenefit Explana-on

OralHypoglycaemics Ifsoleuseistoreducemildhyperglycaemiaforsecondarypreven2onofdiabe2cassociatedevents

Poten2alshort-termcomplica2onsoutweighbenefits

Vitamins,Minerals,Complementary-alterna2vemedicines

Ifnotindicatedtotreatalowbloodplasmaconcentra2on

Noevidenceforeffec2veness

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LindsayJ.JSupportCareCancer2015;23:71-78

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Conceptual Frameworks

Consider factors such as: ü  Remaining life- expectancy ü  Goals of care

ü  Time to benefit (of meds)

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ToddA.IntJClinPharm(2015)doi:10.1007/s11096-015-0148-6HolmesHMetal.ArchInternMed2006;166(6):605-9CurrowDCetal.ArchInternMed2006;166(21):2404GarfinkelDetal.ArchInternMed2010;170(18):1648-54

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Can Artificial Intelligence (AI) solve problems with Polypharmacy/ PIM?

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Potential utilities of AI in De-prescribing

•  Risk prediction tools •  Clinical decision support tools •  Machine/ Deep Learning algorithms •  ‘Dr De- prescriber’?

o  Ethicalissueso  Whathappentoshared-decision

making?

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Research/ Practice Gaps

Future research questions

•  Quantitative data on health outcomes from active deprescribing programs in elderly cancer patients

•  Quality of life outcomes from active deprescribing programs in elderly cancer patients

•  Pharmacoeconomic data on the benefits of active deprescribing programs in elderly cancer patients

•  Effectiveness of collaboration between Medical Oncologists, Palliative Care Specialist, Geriatrician, Family Physicians and Pharmacists

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Step 1: Perform a comprehensive medication-indication reconciliation

•  Include prescription and non-prescription drugs

•  Document indication for each drug •  Identify ADRs and non-compliance



•  Drug factors o  Number of drugs

o  History of toxicity/ADRs

o  Use tools e.g. BEERS list, STOPP criteria

•  Patient factors

o  Age (>80y)

o  Cognitive impairment o  Multiple comorbidities o  Multiple prescribers



Step 2: Consider overall risk of drug-induced harm

Step 3: Assess each medication for eligibility to be discontinued

•  Jointly consider life expectancy and treatment goals

•  Identify medications used for o  Unconfirmed diagnosis

o  Confirmed diagnosis but no evidence for choice of treatment

o  Counteracting ADR of other medications



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Step 4: Prioritise medications for discontinuation •  Discontinue medication with greatest harm and least

benefit first

•  Taper dose of medications that cause withdrawal symptoms

•  Ensure patient/caregiver is comfortable with decision

•  Discontinue one at a time



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To stop or not to stop?

ü Pharmacokinetics/ dynamics of drugs ü Prognosis ü Pathophysiology of death

ü Measure of benefit ü Aims of intervention ü Psychological concerns

StevensonJ(2004).BMJ.329:999-1012

58

OncPal De-prescribing Guideline: Limitations

•  Steps to de- prescribe including planning the medication withdrawal (tapering, if required), monitoring and follow up after cessation not included

•  Risks associated with withdrawal of medications, including potential stress to patients & carers, and potential adverse drug withdrawal reactions not addressed

58

LindsayJetal(2015).JSupportCareCancer.23:71-78ReeveE(2014).JSupportCareCancer;doi:10.1007/s00520-014-2445-3

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Ethical Issues in de-prescribing: Principlism Approach

Beneficence

Non-maleficence

Autonomy

Jus2ce

Reeve,E.etal(2016).BioethicalInquiry13:581-590

polypharmacy and inappropriate medication use in patients with … · 2018-07-16 · polypharmacy...

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