Marije HamakerDepartment of geriatric medicine

Diakonessenhuis

Utrecht, the Netherlands

Polypharmacy

Treviso, Italy 2017

Disclosure

Nothing to disclose

Outline

• Definition and prevalence of polypharmacy

• Age related changes in relation to

pharmacokinetics and pharmacodynamics

• Adverse drug reactions

Definition of polypharmacy

Polypharmacy is generally defined as the regular use

of 5 or more prescription medications on a regular

basis.

Guthrie B et al. BMJ 2012;345:bmj.e6341

Guthrie B et al. BMJ 2012;345:bmj.e6341

Number of chronic disorders

by age-group

The Lancet 2012;380:37-43

Comorbidity of 10 common conditions

Guthrie B et al. BMJ 2012;345:bmj.e6341

Over the counter medication

• 71% of elderly use one

or more over the

counter medications

• 50% uses homeopathic

medicines, herbal or

nutritional supplements

• Multiple physicians and pharmacies

• No regular medication review

• Treating ADRs with other drugs

• Reluctance to discontinue medication

Drugs & Aging 2003; 20(11): 817-832

Healthcare providers

Medication discrepancies

• When asking patients, general practitioner and

pharmacy what medication a patient is taking:

– In 87% patients there is one or more discrepancies

between what each of them think is the proper list of

medications

– In >25% of patients, symptoms were caused by medication

use inaccurately described in referral letter

American Journal of Geriatric Pharmacotherapy 2009;7:93-104

Medication management by age

Consequences of polypharmacy

• Prescribing errors

• Cost

• Undertreatment

• In Western countries, adverse drug reations:

• cause 3–5% of all hospital admissions

• are responsible for 5–10% of in-hospital costs

• cause a substantial increment in morbidity and

mortality

Curr Pharm Des. 2014;20(19):3256-63.

Polypharmacy in elderly cancer patients

• In patients with metastatic cancer:

– 81% is taking one or more medications predefined

as a long-term treatment of comorbodity

– 52% of patients had side effects attributed to

these medications

Supportive Care in Cancer 2010:18;651-5

Limited life expectancy and polypharmacy

Holmes, Clin Pharmacol Ther 2009

Age-related changes and

polypharmacy

Physiologic ageing

Anesthesiol Clin North America 2000;18:74

Consequences for pharmacokinetics and

pharmacodynamics I

Age related change Effect

Increased gastric pH

Slightly decreased

absorption

Delayed gastric emptying

Reduced splanchnic blood flow

Decreased absorption surface

Decreased gastrointestinal motility

Current Medicinal Chemistry 2010;17:571-84

Age-related change Effect

Increased body fat mass Increased volume of distribution

and half-life of lipophilic drugsReduced lean body mass

Reduced total body water Increased plasma concentrations

of water-soluble drugs

Consequences for pharmacokinetics andpharmacodynamics II

Current Medicinal Chemistry 2010;17:571-84

Age-related change Effect

Increased body fat mass Increased volume of distribution

and half-life of lipophilic drugsReduced lean body mass

Reduced total body water Increased plasma concentrations

of water-soluble drugs

Reduced serum albumin Increased free-fraction of highly

protein bound acidic drugs

Consequences for pharmacokinetics andpharmacodynamics II

Current Medicinal Chemistry 2010;17:571-84

Age-related change Effect

Reduced hepatic blood flow and

overall liver mass

Less effective first-pass

metabolism and phase I

metabolism

Reduced renal blood flowImpaired renal elimination of

water-soluble drugsReduced glomerular filtration

rate

Consequences for pharmacokinetics andpharmacodynamics III

Current Medicinal Chemistry 2010;17:571-84

Adverse drug reactions

The Beer’s Criteria

• List of medications frequently used to identify

inappropriate prescribing in older people (65 years and

older)

• Limitations:

• Several drugs no longer available or rarely used

• Recommend avoidance regardless of medical disease

• Recommend avoidance based on presence of

medical disease

• Does not address underutilization

J Am Geriatr Soc 2012 Apr; 60 (4): 616-31

Rates of emergency hospitalizations

for ADR in older U.S. adults

Budnitz et al. NEJM 2011

Most ADR are not related

to inappropriate drugs

1

10

100

0 2 4 6 8 10 12 14 16 18 20

number of drugs taken

percen

t o

f p

ati

en

ts w

ith

AD

R

ADRs in relation to polypharmacy

Be aware: trials vs. reality

©Erna Beers 2013

As a result….

Dumbreck et al BMJ 2015

Medication review

Medical history

MedicationCurrent complaints

Six questions

• What is missing?

• What is really being taken?

• What is unnecessary or not/no longer required?

• Are there any side-effects?

• What relevant interactions are to be expected?

• Does the dosage or dosing frequency need to be

adjusted?

Underprescribing

Patients with polypharmacy have a significantly

higher chance of being undertreated

• 43% in patients with 5+ drugs vs. 14% in

patients ≤ 4 drugs

British Journal of Clinical Pharmacology 2007;65:130-3

Potential interactions between

anticancer drugs and non-anticancer drugs

Lancet Oncol 2011; 12: 1249–57

ADR and represcription

• Of drugs stopped during hospitalisation due to

ADRs

– 49% was not mentioned in the discharge letter

– 27% was represcribed within 6 months

• For serious ADRs, represcription was 22%

Archives Internal Medicine 2006;

CGA and appropriate medication use

Onder et al. Curr Drug Metabolism 2011

What is a prescribing cascade?

Common prescribing cascades

Take home messages

• Regular medication review in the elderly is needed to:

– Reduce adverse events (e.g. falls, hospitalizations)

– Reduce pill burden and costs

– Increase adherence with remaining medications

– Improve quality of life

• Setting appropriate treatment goals is highly relevant

• Trial populations from studies on which (most)

treatment guidelines are not representative of the

elderly or the frail