“Its easier to start than to stop”

Managing medicines risk in the elderly

patient with polypharmacy and chronic

disease

Setting the scene

May 2016

The impact of chronic disease in

the NZ aging population is the

most challenging issue

facing the health sector

How are we to manage this

challenge?

Mrs T, 79 yrs

• IHD

• CHF

• Atrial fibrillation

• Systolic hypertension

• Type II Diabetes

• Glaucoma

• Osteoarthritis

• Gout

• Chronic renal failure

• Falls risk

2

Medications (13)

Frusemide 20 mg mane

Candesartan 16mg mane

Metoprolol CR 95 mg nocte

Doxazocin 8 mg mane

GTN spray PRN.

Diltiazem CR 120 mg mane.

Codalgin prn

Aspirin 100 mg mane

Simvastatin 10 mg nocte

Allopurinol 300 mg daily

Zopiclone 7.5 mg nocte

Xalatan (Latanoprost) eye drops

Cosopt (Dorsolamide + Timolol) eye drops.

What is Mrs T’s

cumulative medicines

risk?

+

Age and co-morbidities,

Psycho-social & environmental risk factors

Multiple clinical interventions

(multiple prescribers)

How do we manage cumulative medicines risks in patients with chronic disease and

complex medicines regimens?

1. Shift the focus of multi-disciplinary chronic disease management from the hospitals to the community.

(Brand C et al. Int Med J 2007,37: 653. Scott I. Int Med J2008,38:427)

2. Focus on prescribing apropriateness

3. Medication Management Planning (MMP)

‘OPTIMED’ - Goal

Design and implement a sustainable service to

optimise complex drug treatment

Target

Patients taking 6 or > daily medicines

Sth Wairarapa: 680

Masterton area: >2000

Referral criteria

• 6 or more daily medications (Steinman M et al JAGS 2006, 54: 1516).

• Living at home.

• Managing own medicines.

• No age limit.

Optimed service model

• “A patient focused, documented, shared

decision-making process, to identify and

manage treatment risks in the context of

aging and coexistent morbidity – future

proofing against cumulative medicines

risk”.

OPTIMED service components

• Patient consent.

• Medicines reconciliation (community pharmacy).

• Specialist assessment + practice-based MDT

• Risk management recommendations (RMRs).

• GP/Patient shared decision-making

• Medicines management plan (MMP)

• Communication - OPTIMED electronic template)

• Synchronised dispensing (community pharmacy).

• OPTIMED education programme (GPs and practice

staff).

Medicines risk variables – scored electronic template

• Comorbidities

• ADR/allergy

• Medication complexity

• Drug intolerance

• Medication adherence

• Pt’s understanding of

treatment

• Drug + drug

• Drug + disease

interactions

• High risk drugs

• High risk life-style

factors

High Risk Medicines

Insulin, Sotalol, Opiates, Warfarin, Clozapine,

Statins, Digoxin, Antihistamines,

Antipsychotics, Anticholinergics,

Antidepressants, Alpha blockers, Diltiazem,

Nitrates, Tramadol, BDZs, NSAIDs, K sparing

diuretics, Cyclosporin, Methotrexate,

Azathioprine, Phenytoin, Carbamazepine,

Colchicine, Steroids, Azole antifungals,

Glibenclamide, HIV Protease Is, Lithium,

Perhexiline, ACE-Is, ARBs, Timoptol eye

drops, Clopidogrel, Amiodarone, LMW Heparin,

High risk life style factors

• 6 or more medications

• Age >70

• Living alone

• Unsteadiness – (walking aids)

• Deafness

• Vertigo

• Visual impairment

• Orthostatic symptoms

• Incontinence

• Constipation

• Complex social circs.

• Ethanol excess

• Falls (3 months)

Audit

62 patients, taking 6 or more medicines daily,

– 3 Wairarapa Medical Centres,

– 3 non-attenders

– 59 (25 M, 24 F).

– Mean age 65 yrs

• Retrospective audit of risk management

recommendations

– baseline (OPTIMED review), 6 months (uptake of

RMRs), 2 years (% sustainabilty of RMRs)

Audit end points

1. Uptake (6months) and sustainability (mean 25

months) of Risk Management Recommendations

(RMRs), post OPTIMED review.

2. Change in medication complexity.

3. Non-OPTIMED dispensing during the audit period.

4. Frequency of clinical interventions pre and post

OPTIMED review.

Cumulative medicines risk -

component scores.

Mean (SD)

Medicines History 1.8 (1.4) (tolerability, allergies/ADRs, adherence, awareness)

High risk medicines 4.2 (1.5)

Drug/drug interaction 1.0 (1.1)

Drug/disease interaction 0.6 (0,9)

High risk life style factors 6.9 (2.4)

Medicines complexity 13.9 (4.4)

(Mean, SD)

Baseline Endpoint

Medications (n) 10.0

(3.1)

10

(3.2)

Doses 13.1

(4.9)

13.8

(5.5)

Frequency 4.7

(2.1)

5.2

(2.5)

Complexity

score

14.7

(4.3)

15.2

(4.9)

Medicines complexity

Daily medications range 6 - 23

Medication Baseline Endpoint

ACE-I / ARB 50 45

Statin 40 38

Insulin 15 15

Alpha blocker 16 9*

Nitrates 11 11

BDZs 12 13

Warfarin 10 9

Diltiazem 12 5*

Other 72 65

TOTAL 251 224 (P <0.05)

Change in high-risk medications prescribed

during the audit period

0

10

20

30

40

50

60

0 10 20 30 40 50 60 70

Risk score

Patients

Baseline

Endpoint

Mean score = 29

Total cumulative medicines risk scores

RMRs implemented for whole audit period

RMR

categories

Specialist

RMRs

Mean

RMRs per

patient

Implementation

at 6 months

(%)

Implementation

at 2 yrs

(%)

Stop 79 1.2 59.6 58.4

Modify 67 1.1 52.2 49.3

New Medicine 46 0.6 52.1 50 .8

Total 192 2.8 (range 0 –7)

P > 0.05

Paired t tests

Non-

OPTIMED

changes

Mean

New 183 3.0

Stopped 184 3.0

Modified 98 1.6

Non-OPTIMED medication changes

during audit period

Total medication changes 657

OPTIMED RMRs 192

(n = 62)

Pre-assmt.

weekly drug

costs

($)

Change in

weekly cost post

assmt.

3 months

($)

Change in weekly

cost post assmt.

6 months

($)

% cost

reduction

6 months

Mean (range)

18.34 - 5.4

(+17.5 - 37.4)

- 6.97

(+12.3 - 35.9)

- 38%

NOTE: The change in weekly cost = OPTIMED changes + all other

medicines changes

Impact of RMRs on weekly

medicines costs (NZ$)

Conclusion

The OPTIMED service can provide safe and

sustainable medication management for high risk

patients, in the community:

– 38% weekly medicines cost reduction within 6 months

– 54% OPTIMED RMRs actioned within 6 months

– > 90% OPTIMED RMR sustainability over 2 years.

The challenge is to promote DHB

commitment to sustain such services in the

longer term.

Acknowledgements

Practice Staff at the Carterton, Martinborough,

Featherston & Greytown Medical Centres.

Dr A Lincoln Dr L Cherry

Dr I McArthur Dr M Berry

Dr C Cherry Dr Pathmanathan

Dr D Heard Dr S Phillips

James Mitchell (OUW summer student)

Prof M Weatherall (OUW)

David Holt & David Mitchell (Community Pharmacy Partners)

OPTIMED learning points

1. Medication management plan

Four parts:

1. Clinical and therapeutic assessment - risk management recommendations.

2. Medication management plan – shared decision-making

3. Community Pharmacy assessment and support - Pharmacy LTC service

4. Implementation of risk management recommendations

Optimed learning points –

2. medicines review

1. Identify medical conditions, diagnostic certainty, life

expectancy.

2. Identify therapeutic objectives & priorities, including preventive treatment targets.

3. Medicines reconciliation

4. Review medicines appropriateness, in clinical context.

5. Identify patient specific risk factors: ADRs/allergies, medicines complexity, high risk medicines content and life-style factors.

6. Determine medicines to be started, discontinued or doses altered

7. Document and communicate

OPTIMED learning points –

3. Ongoing safe medicines management

• Regular medicines review

• Safe medication withdrawal.

• Strategies for high risk medicines management in the community.

• Managing ‘uncertainty’ - prioritisation of long term complex therapeutic objectives.

• Targeted education of practice staff.

• Patient education

OPTIMED – learning points

4. Spin-off for chronic disease management:

• Sustained improvement in prescribing

appropriateness.

• Specialist out-reach clinics for high risk

patients.

• Improved GP/community pharmacy

communication.

Five key issues in the

management of polypharmacy?

Drug-drug interactions

• Diltiazem/ Verapamil + Statins (+ CRF)

• Alpha blockers + Nitrates (+ age)

• ACE-I + K-sparing diuretics

• Combinations of CNS depressants (opiates,

BDZs, TCADs, SSRIs)

• NSAID + ACE-I

• Clopidogrel + Omeprazole

• Tramadol + Warfarin

Patient - GP consultations per year

during the audit period

Definitions!

Treatment Burden

Cumulative Medicines Risk

Treatment Burden - components

• Multiple co-morbidities.

• Cumulative medicines risk

• Multiple clinics for different conditions.

• Hospital admissions (acute problem focused).

• Lab tests, Drs visits, medicines to collect and

manage.

• Patient’s personal social and environmental risk

factors (insomnia, visual impairment, falls risk)

• The work of communication and information

management.

Cumulative medicines risk components

• Chronic disease risk: - cumulative actual risk of chronic disease (increases with age and co-morbidities).

• Treatment Risk: [chronic disease risk - medication benefit] + medication risk.

• Cumulative Medicines Risk: total treatment risk over time (increases with number of medicines and the number of co-morbidities).

• Work of Treatment

Types of Adverse Reactions

• Type 1: ADR as a result of the intended drug effect: eg Clonidine and dry mouth.

– Predictable (dose dependent)

– Individually variable.

• Type 2: Unexpected, rarer & may not have been reported before: eg Phenytoin and gum hypertrophy.

– Unpredictable

– Idiosyncratic (includes allergies and foetal malformations)

Drug “Side Effects”

“Side effects” are often minimised and patients are poorly informed“

– Frequently occur with the therapeutic effect - generally dose dependent ,

– e.g: nausea, drowsiness, abd discomfort, tireness, dry mouth etc.

• Always ask - think in terms of tolerability

• Beware of new symptoms!

Patient risk factors for ADRs (Onder et al. Arch Int Med. 2010;170:1142-1148)

Variable Weighting

≥4 co-morbid conditions 1

Heart failure 1

Liver disease 1

e-GFR < 60 mls/min 1

Medications:

≤ 5 0

5 - 7 1

≥ 8 4

Prev. ADR 2

Benefit vs Risk –

how much to tell the patient?

• Always inform the patient of the risks

– Type 1 effects – always (most common ones)

– Type 2 effects - “what is reasonable” (HDC).

• Avoid information overload - beware the ‘internet patient’.

• Read the Data Sheet, but drug companies don’t tell all of the story.

Benefit vs Risk

• Difficult !

– singular benefit – but multiple risks, with

variable weighting.

– new drugs – limited knowledge of ADRs.

• Prescriber’s perception of ADR risk

– influenced by personal experience, severity

and frequency.

• Patient’s expectations ?

• Shared decision-making

Medicines treatment ‘complexity’

Daily medicines (DM) 9.5 (2.9)

Daily doses (DD) 13.1 (5.4)

DD/DM 1.37

Medicines complexity 13.9 (4.4)

(mean+/- SD, n= 59))

Advice consensus of 3 C&C specialist physicians)

• Reduce Lipex dose immediately

• Switch Metoprolol to low dose conventional formulation

27.5 mg BD and titrate to control ventricular rate.

• Stop Diltiazem (+ renal impairment = Lipex toxicity)

• Stop Doxazocin (+ GTN + hypotension and falls)

• Stop Paradex (ineffective paracetamol dose + addictive)

• Stop Codalgin (ineffective codeine dose)

• Regular Paracetamol; consider opiate

• Reduce Allopurinol dose (renal impairment)

• Stop Timolol eye drops; non-betablocker alternative.

• Stop Frusemide; trial of Bendrofluazide

• Dont stop Zopiclone

Language!

1. “Treatment burden” - cumulative

potential risk of complex medication

regimens in chronic disease (TB).

– imposed on the patient as result of:

fractured care, multiple co-morbidities,

specific disease Guidelines, etc.

• “Chronic disease burden” - cumulative

actual risk of chronic disease (CDB)

– increases with age and co-morbidities

Treatment burden

(Chronic Disease risk - medication risk/benefit) +

medication risk = treated risk

Treated risk + number of meds = treatment burden

• Medication risk increases with number of medicines.

• Chronic disease risk increases with the number of co-

morbidities.

• Since the benefits and risks of multiple medications

cannot be readily quantified, the sum of the

comorbidities + medicines may be used as a surrogate

for Treatment burden.

Treatment Burden

• Multiple co-morbidities.

• Medicines risk factors

+

• Multiple clinics for different conditions.

• Hospital admissions (acute problem focused).

• Lab tests, Drs visits, medicines to collect and

manage.

• Patient’s personal social and environmental risk

factors (insomnia, visual impairment, falls risk)

The work of communication and information

management.

Why stop the medicine?

• Patient intolerance.

• Risk of adverse drug event doubles for >5 meds.

• Treatment burden - unacceptable cumulative medicines risk.

• Functional incapacity - increasing falls risk.

• Changing disease status – depression, cognitive impairment.

• Non-adherence with medication.

• Medical error.

Patient’s perspective

• Stopping / changing “essential” treatment

– a threat to wellbeing.

– psychological dependence

• Rational process for starting treatment

– “So why stop it” !

• Constant reinforcement to adhere to treatment

– “So why stop it - when nothing has changed”?

Challenge to the Dr / patient relationship

Prescriber’s perspective

• Multiple co-morbidities + multiple medical interventions = multiple treatments:

– Who has control?

• Mixed messages from multiple specialists

– What are the right choices?

• Guidelines for specific diseases

– multiple co-morbidities are not acknowledged as management problems

• Communication breakdown of specialist / GP interface

– role of the Community pharmacy?

Community Pharmacist’s

perspective

• Patient support for stopping /changing treatment

– Part of the treatment team

– Pharmacist has the actual dispensing data

– Medicines Use Review complements process of change in treatment

Communication between Patient’s GP

and Pharmacist is crucial – how can you facilitate this?

Stopping / changing meds - process

• Patient consent - involved and supported

– Pharmacist should be informed

• When stopping think of withdrawal syndromes

– advise and support accordingly

• One step at a time - but

– Stopping one medicine may require revision of multiple medicines

• Communicate the changes to all involved

– Dont forget relatives

Drug withdrawal syndromes

Withdrawal syndromes - principles

• Most withdrawal syndromes are self inflicted.

• The test of a withdrawal effect is it’s alleviation when treatment is restarted.

• Mechanisms are complex – reflecting multiple homeostatic processes activated during chronic drug treatment.

• Drugs causing rebound effects on the cardiovascular system are most dangerous when the system is already compromised.

• High index of suspicion when new symptoms develop during chronic treatment.

Withdrawal syndromes

1) TCADs / SSRIs

• Likely after only 6 weeks of treatment

• Shorter half life drugs.

• Onset within days of stopping

• Insomnia, flu-like symptoms, nausea, imbalance, hyper-arousal and sensory disturbance.

• Gradual tapering over at least a month

• Discontinuation syndromes occur in approx 20% of patients on ‘stable’ chronic treatment.

Withdrawal syndromes

2) Benzodiazepines

• Onset within days.

• More common with shorter half life BDZs.

• Increased risk of convulsions in elderly.

• Adrenergic symptoms, insomnia, weight

loss, anxiety, agitation, cognitive

impairment.

• Gradual tapering may require switch to

Diazepam.

• Psychological dependence is very strong

and develops early in treatment

Withdrawal syndromes

3) Beta blockers

• Hyper-adrenergic symptoms and signs within 1-2 days, maximal in 4-8 days.

• Duration 10-14 days.

• Risk increased with pre-existing IHD.

• Most risky with symptomatic IHD in ambulatory patients and in those with Felodipine / Nifedipine co-treatment.

• Withdraw gradually over 2-3 weeks but avoid high risk scenarios.

Other withdrawal syndromes

• Calcium channel blockers – Rebound angina

• Statins – Ischaemic stroke

• Proton pump inhibitors – Rebound hyperacidity

• Diuretics – Oedema, bloating - often cyclical

• Steroids – Mood swings, mostly in children

• Nitrates – Rebound angina

• Clonidine & methyldopa – Adrenergic crisis

OPTIMED Team

• GP (lead carer)

• Visiting specialist

• Practice nurse

• Community pharmacist

• (PHO clinical pharmacist)

• (Nurse practitioner)

Reflection !

• Was this prescribing justifiable?

• Why should it be changed?

• Why do prescribers differ in their choice of

medicine?

• It is possible to stop or change medication,

but it is much simpler to start it !

‘We Need Minimally Disruptive Medicine’ (May et al. BMJ, 2009, 339:485-7)

“Clinicians lack the tools to detect patients

overwhelmed by the burdens of treatment,

and they lack strategies to lift these

burdens”.

How might we manage Mrs T’s

long term treatment risk ?

‘Shift the focus for Chronic Disease

Management from the specialist

hospital setting to multi-disciplinary

management in the community’.

(Brand C et al. Int Med J 2007,37: 653.

Scott I. Int Med J2008,38:427)

Challenge: manage Mrs T’s

medicines risk ?

‘Shift the focus for Chronic Disease management

from the specialist hospital setting to multi-disciplinary management in the community’.

(Brand C et al. Int Med J 2007,37: 653. Scott I. Int Med J2008,38:427)

OPTIMED

A community based service innovation to manage

cumulative medicines risk in patients with chronic disease

and complex medicines regimens.

“Medication Management Plans’

Individual cumulative medicines

risk scores

0

10

20

30

40

50

60

0 10 20 30 40 50 60 70

patients

score

Mean 28.6, SD 7.6.

Community Pharmacy / GP

communication

• Patient prescription tracker:

– Patient owned, web based,

– Confidential communication between patient, GP and community pharmacy,

– Automatic medicines reconciliation,

– Graphical presentation of changes in prescribing,

– Linked to structured pharmacy care programme

Prescribing in the elderly: key steps

• Prioritise therapeutic objectives – Determine efficacy for elderly

– Determine life expectancy

– Determine preventative targets

• Take a medicines Hx – Identify critical social and environmental risk factors

– Hx of allergy & ADRs

– Drug tolerability

– Adherence

• Complete a medicines reconciliation

• Discuss harm:benefit issues (patient’s/Dr’s expectations)

• Determine starting dose (start low – go slow)

• Monitor function and QOL (as well as primary disease outcomes)

Prescribing in the Elderly:

Principles

Check renal function (e-GFR<60 ml/min)

“Start low – go slow”

Simplest possible regimen

Regular medication review

“Its easier to start than to stop”

Therapeutic Traps in the Elderly

• Higher risk of drug/drug interactions.

• Higher risk of drug/disease interactions.

• Higher risk of ADRs & ADEs

• Higher risk of non-adherence with drug treatment

• Multiple co-morbidities blur the therapeutic

objective.

• Increased sensitivity to drug effect.

• Decreased organ functional reserve

Inappropriate prescribing

- “the selected drug is not clinically effective, or the benefit is outweighed by the risk; or the dose, route, or frequency of dosing are inappropriate”.

- Diltiazem + high dose Simvastatin

- ACE-Is as monotherapy (when a thiazide diuretic should be

added)

- Alpha blockers + Metoprolol

- Amiodarone without a monitoring strategy

- BDZs in sleep apnoeoa

- Verapamil or Diltiazem in heart failure

- Opiates in renal failure

- Hypoglycaemic agents in alcoholics or elderly malnutrition

- Dypyridamole as monotherapy

High risk in the Elderly with

Renal Impairment

• Morphine

• Diazepam

• Digoxin

• Aminoglycosides

• Lithium

• Metformin

• Tramadol

• ACE I

NSAIDs in the Elderly –

beware !

• Check renal function.

• CNS effects are prominent (confusion,

unsteadiness).

• GI bleeding risk increased.

• Multiple drug interactions: ACE-Is,

Diuretics, Lithium, Digoxin, Warfarin.

• Watch for fluid retention in Heart Failure.

• Regular review of need - avoid long term if

possible.

Chronic Pain Management

in the Elderly

• Options (as of July 2010)

– Paracetamol (regular use, NOT ‘prn’)

– Codeine

– DHC Continus ?

– Tramadol (& SR) ?

– Oxycodone (& SR) ?

– Morphine (& SR)

– NSAIDs (Voltaren) / Cox 2 inhibitors

(Celecoxib)

Codeine (3-methyl morphine)

• Analgesic effect due to CYP 2D6 metabolism to morphine. Limited benefit in 10% population.

• Dose 60 mg 4h - avoid compound OTC formulations (inadequate amounts for any effect)

• Effective for ~ 4h.

• Constipation ++

• “ A very inefficient way of giving morphine”

Tramadol

• Same analgesic level as paracetamol.

• Dose-dependent respiratory depression.

• Nausea, agitation, confusion, sweating,

seizures – espec. elderly.

• Halve dose in renal impairment.

• TCADs, SSRIs, neuroleptics increase the

risk of seizures and serotonergic

syndrome.

• Not subsidised – very expensive.

Medicines risk management

categories

1. Modify (drug dose/route/frequency).

2. Stop (stat. or gradual withdrawal)

3. New medicine (new indication, or

substitute for same indication)

4. GP review (GP decision after OPTIMED

review)

5. Potential drug/drug interaction

6. Potential drug/disease interaction

7. Adherence review (community pharmacy)

8. Patient understanding

Other High Risk Medicines

in the Elderly

• Alpha blockers (Terazosin, Doxazosin)

• Anticholinergics TCAD, antihistamines,

Benztropine)

• Warfarin (increased sensitivity)

• Digoxin (increased falls risk)

• Colchicine (poisoning in renal impairment)

• Opiates (increased sensitivity & decreased

renal elimination)

What is your role, as the patient’s Nurse,

in managing this patient’s medication to

optimise their health gain?

• Patient’s understanding

• Communication of issues to medical staff

• Detection & reporting of ADRs/ADEs

• Supporting and facilitating the shared-

decision prescribing/treatment process.

GP prescription changes 6 months after

OPTIMED review

RMR

Total

prescription

changes

GP compliance

at 6 months (%)

Stop 79 59.6

Modify 67 52.2

(GP review) 54 28.1

New Medicine 46 52.1

Total 192* 53.6%

*Total prescription changes exclude 54 ‘GP review’ decisions

made after the OPTIMED review – to stop, modify, or add a new drug.

Mrs T’s cumulative medicines risk

• Medicines complexity (number, frequency, etc.

• Medicines reactions/interactions,

• ‘High risk’ medicines content (CardizemDiltiazem, Doxazosin, BDZs, etc).

+

• Age and co-morbidities,

• Life style & environmental risk factors

• Multiple clinical interventions (multiple prescribers)

“Treatment burden”

0

5

10

15

20

25

30-39 40-49 50-59 60-69 70-79 80-89 90-99

No. of patients

Age

Osteoarthritis Hypertension Diabetes Heart disease Kidney disease Gout Glaucoma

Diet

Exercise

Smoking

Alcohol

Age

+

1 - 2

3 - 4

1 - 3

1 - 2 NZ dep.

index

+

9 – 17 daily medications

1 - 3

Polypharmacy in the elderly is

inevitable !

1

1 - 2