There’s A Pill For That

(But should my patient be on it?)A Review of Tools for the Evaluation of Optimal Prescribing in Geriatric Patients

Marilyn N. Bulloch, PharmD, BCPSAssistant Clinical ProfessorHarrison School of Pharmacy, Auburn University and

Adjunct Assistant Professor, University of Alabama-Tuscaloosa School of Medicine

mjn0004@auburn.edu

Objectives Describe pharmacokinetic and

pharmacodynamic changes in the geriatric patient that impact medication use

Define suboptimal prescribing Evaluate clinical tools for assessing

appropriate use of medications in the elderly patient

Geriatric Medication Discourse Heterogenous patient population Variation in physiological status Co-morbidities Lack of evidence-based medicine Communication Compliance Self-medication

Variables Impacting Medication Effects

Figure 1. Klotz U. Drug Met Rev 2009;41:58

Age-Related Physiologic Changes

Dosing regimenPlasma

Concentration in plasma

Concentration at site of action Effect

Pharmacokinetics

Pharmacodynamics

Adapted from: Nolin TD et al. Figure 6-1, 2009

Pharmacokinetic Changes

Absorption

↑ Gastric pH

↓ GI motility

↑ Gastric emptying

↓ GI blood flow

↓ Absorption surface

Distribution

↓ Lean muscle mass

↑ Body fat

↓ Body water

↓ Albumin

↓ Cardiac output

Metabolism

↓ Enzyme activity

↓ Liver mass

↓ Liver blood flow

Elimination

↓ GFR

↓ Kidney blood flow

↓ Renal tubular

function

Klotz U. Drug Met Rev 2009;41:67-76Corsonello et al. Cur Med Chem 2010;17:571-84

Pharmacodynamic Changes Changes at receptor site

↓ number of receptors Altered effects at receptor or post-receptor levels

causing changes in end-organ response ↓ sensitivity at receptor site Diminished or exaggerated pharmacologic response

Altered reflex response Altered neurotransmitters Hormonal changes Changes in mental status

Corsonello et al. Cur Med Chem 2010;17:571-84Chaurasia et al. J Indian Aca Geri 2005;2:82-88

What is “Suboptimal Prescribing” Overuse - polypharmacy Inappropriate prescribing

Medications where risk > benefit Disagrees with accepted medical standards

Underutilization Omitted but necessary

Hanlon et al. J Am Geriatr Soc 2001;49:200-209

Implicit versus Explicit ToolsImplicit Criteria

Use published literature and patient information

Influenced by clinical knowledge, experience, and judgment

May be time consuming Patient focus

Explicit Criteria

Developed from: Published literature Expert opinion Consensus techniques

Require little/no clinical judgment

High reliability and reproducibility

Medication or disease focus

Shelton et al. Drugs Aging 2000;16:437-450

The Beers List Beers Criteria for Potentially Inappropriate

Medication Use in Older Adults Explicit list of medications, doses, and durations

that should be avoided in geriatric patients Developed from expert consensus through

extensive literature review For all patients ≥ 65 years old Adopted by CMS in 1999 for nursing home

patients

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630 Beers et al. Arch Intern Med 1991;151:1825-1832

Beers Criteria 2012 Updates Partnership with American Geriatrics Society Three Categories – 53 medications or classes

Medications to avoid in any patient ≥ 65 years Medications to avoid in patients ≥ 65 years with

certain diseased or syndromes Medications to be used with caution in patients ≥ 65

years ***NEW*** Formally potentially inappropriate medications Sufficient # plausible reasons for use in certain individuals Potential for misuse or harm substantial: extra caution in use

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630

Beers Criteria 2012 Updates Organization

Major therapeutic class or organ system Rationale Recommendation Quality of Evidence Strength of Recommendation

19 medications or classes removed Examples: Ferrous sulfate, stimulant-laxatives

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630

Beers Criteria New medications to avoid in any older adult Glyburide Megestrol Sliding scale insulin Anitiparkinson agents:

benztropine, trihexypehidyl

Scopolamine (except palliative care)

Alpha1 blockers: prazosin, terazosin

Metoclopramide

Antiarrhythmic drugs (1a, 1c, III) – as 1st line

Dronedarone Spironolactone >25mg/day Phenobarbital Nonbenzodiazepine

hypnotics All non-COX selective

NSAIDs Aspirin > 325 mg/day

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630

Beers Criteria New medications to avoid in certain diseases Heart failure: thiazolidineones, cilostazol, dronedarone,

non-dihydropyridine calcium channel blockers, NSAIDs Syncope: acetylcholinesterace inhibitors, alpha1 blockers, olanzapine Seizures/epilepsy: olanzapine, tramadol Delirium: TCAs, anticholinergics, benzodiazepines, corticosteroids,

H2-receptor antagonists, meperidine

Dementia/cognitive impairment: H2-receptor antagonists, zolpidem Falls/fracture history: SSRIs, antipsychotics Parkinson disease: all antipsychotics (except quetiapine and

clozapine), promethazine, prochlorperazine CKD stage IV-V: triamterene Urinary incontinence: estrogen BPH: inhaled anticholinergics

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630

Beers Criteria Medications to Be Used With Caution

Aspirin for primary prevention of cardiac events in patients ≥ 80 years

Dabigatran in patients ≥ 75 years or CrCl <30 mL/min Prasugrel in patients ≥ 75 years Vasodilators in patients with syncope SIADH/hyponatremia

Agents- antipsychotics, carbamazepine, carboplatin, cisplatin, mirtazapine, SNRIs, SSRIs, TCAs, vincristine

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. J Am Geriatr Soc 2012;60:616-630

McLeod Criteria Developed by Canadian consensus expert panel 38 practices involving medications grouped as cardiovascular,

psychotropic, analgesics, and miscellaneous 3 categories of inappropriate prescribing in geriatrics

Drugs contraindicated due to unacceptable risk-benefit ratio Drugs causing drug-drug interactions Drugs causing drug-disease interactions

Inclusion Criteria Clinically significant ↑ risk of serious ADEs More/equally effective & less risky alternatives available Prescribing practice occurs often enough that prescribing change could

↓ morbidity in geriatrics Rating of clinical importance:1 (not significant) to 4 (highly significant) Provides alternative therapy recommendations

McLeod et al. Can Med Assoc J 1997;156:385-391

IPET Improving Prescribing in the Elderly Tool: “Canadian Criteria” Developed for inpatients utilizing McLeod Criteria List of 14 most common prescribing errors in

routine clinical practice that should be avoided. Not based on physiological symptoms Does not address omission Weighted towards cardiovascular, psychotropic, and

NSAID use Errors

Avoidance of beta blockers in heart failure Avoidance of benzodiazepines with long half-lives under any

circumstance

Naugler et al. Can J Clin Pharmacol 2000;7:103-107

STOPP & START Developed by expert consensus panel for Ireland and

United Kingdom Criteria arranged according to relevant physiological systems

Cardiovascular Central Nervous System Gastrointestinal Respiratory Musculoskelatal Urogenital (STOPP only) Endocrine

Specific criteria: analgesics, drugs that affect geriatrics who fall, duplicate drug class therapy

Gallagher et al. Clin Pharm Ther 2011;89:845-854Gallagher et al. Int J Clin Pharm Ther 2008;45:72-83Rynn et al. Ann Pharmacother 2009;43M157e1-3

STOPP & STARTSTOPP

Screening Tool of Older Person’s Prescriptions

Addresses potentially inappropriate medications

65 rules or criteria Each criteria given concise

explanation Most criteria related to drug-drug or

drug-disease interactions Sets maximum doses for digoxin

(125 mcg) and aspirin (150 mg) Other criteria address: indication,

place in therapy, duration of use, Defines renal failure as GFR 20-50

mL/min

START Screening Tool to Alert

doctors to the Right Treatment

Addresses potential errors of omission or underutilization

22 rules or criteria Lists medication therapy that

should be utilized in patients with specific medical conditions

Gallagher et al. Clin Pharm Ther 2011;89:845-854Gallagher et al. Int J Clin Pharm Ther 2008;45:72-83Rynn et al. Ann Pharmacother 2009;43M157e1-3

Prescribing Indicators Tool Developed using 50 most frequently prescribed medications and

medical conditions in Australia Incorporates risk vs. benefit, co-morbidities, life expectancy, quality of

life, and patient preferences. 48 indicators

18 address avoidance of medications in specific disease states/conditions 19 concern use of recommended treatment 4 involve medication monitoring 4 concern drug interactions [ 3 specific interactions; 1 addresses any

interactions] 1 involves changes in medication within 90 days 1 concerns smoking 1 addresses vaccination

Not rated by severity

Basger et al. Drugs Aging 2008;25:777-793

ACOVE Quality Indicators Assessing Care of Vulnerable Elders Applied to community-dwelling geriatrics Developed by expert panel via literature review Quality indicators [QI] that measure quality of

care in vulnerable elderly patients across the continuum of care

Shrank et al. JAGS 2007;55:S373-S382Knight et al. Ann Intern Med 2001;135:703-710

Hospital care and surgery Operative care Screening and prevention Undernutrition

Disease states Care coordination End-of-life Hearing loss Medication use

ACOVE Quality Indicators Medication Use QI - 20

Address medication reconciliation, drug regimen reviews, education, drug avoidance, monitoring, and risk reduction

4 additional QIs regarding NSAIDs and aspirin 75 additional QI regarding medication initiation,

adjustments, and discontinuations 4 addition medication-related QI

Shrank et al. JAGS 2007;55:S373-S382Knight et al. Ann Intern Med 2001;135:703-710

HEDIS Health Plan Employer Data & Information Set Use of high-risk medications in the elderly

Originally created by expert panel in 2003 for the National Committee on Quality Assurance

Classified Beers List into 3 categories : Always avoid Rarely Appropriate Some Indications

“Always Avoid” and “Rarely Appropriate” included

Pugh et al. J Manag Care Pharm 2006;12:537-545Gray et al. J Manag Care Pharm 2009;15:568-571

Medication Appropriateness Index

Hanlon et al. J Clin Epidemiol 1992;45:1045-1051Samsa et al. J Clin Epidemiol 1994;47:891-896Holmes HM et al. Arch Int Med 2006;166:605-609O’Mahony D, et al. Age Ageing 2008;37:138-41

Evaluator Rating• Appropriate (Weight x 0)• Marginally appropriate (Weight x 0.5)• Inappropriate (Weight x 1)

Domain Weight

1. Is there an indication for the drug? 3

2. Is the medication effective for the condition 3

3. Is the dosage correct? 2

4. Are the directions correct? 2

5. Are the directions practical? 1

6. Are there clinically significant drug-drug interactions? 2

7. Are there clinically significant drug-disease interactions? 2

8. Is there unnecessary duplication with other drugs? 1

9. Is the duration of therapy acceptable? 1

10. Is this drug the least expensive alternative compared with others of equal utility? 1

Min = 0 = Completely appropriateMax = 18 = Completely inappropriate

Time Until Benefit Model

Figure 3. Holmes et al. Arch Intern Med 2006;166:605-608

Good Palliative-Geriatric Practice Algorithm

Garfinkel et al. Arch Intern Med 2010;170:1648-1654

The ARMOR ToolA Assess Total # of medications & certain

medicine groups with potential for adverse outcomes

Beers Criteria Analgesics Beta Blockers Antidepressants Antipsychotics PsychotropicsVitamins Supplements

R Review Potential for Interactions: drug, disease, pharmacodynamic Functional status impactSubclinical ADRsDrug benefit vs. primary body function

M Minimize Nonessential medications Lack evidence for useRisk outweigh benefitHigh potential for negative impact on function

O Optimize Address Duplication & redundancyRenal and hepatic dosingGradual dose ↓ for antidepressantsAdjust drugs : oral hypoglycemics (HbA1c), beta blockers (heart rate, pacemakers), warfarin (INR), phenytoin (free phenytoin level)

R Reassess Heart rate, blood pressure, and O2 saturationFunctional, cognitive, and clinical statusMedication compliance

Haque R. Ann Long-Term Care 2009;17:26-30

Drug Burden Index Measures total exposure to medications with

anticholinergic and/or sedative properties If both: classified as anticholinergic

Higher DBI associated with impaired physical function Each additional unit of drug burden is equivalent to 3

additional physical comorbidities Does not adequately address risk versus benefit Does not incorporate PK/PD changes Assumes a linear dose relationship

Castelino et al. Drugs Aging 2010;27:135-148

Drug Burden Index

D – daily dose of medication δ – minimum efficacious daily dose approved

by Food & Drug Administration Total drug burden – sum of the drug burden of

all anticholinergic or sedative medications the patient is exposed to

Castelino et al. Drugs Aging 2010;27:135-148

There’s A Pill For That Should my patient be on it?

Many tools were developed by small panels Most tools have only been evaluated in

limited clinical studies Tools do not replace clinical judgment

Questions?