Patricia M. Curtin, MD, FACP, CMD Section Chief, Geriatric Medicine Member, Pharmacy and Therapeutics Committee Clinical Assistant Professor, Jefferson.

Prescribing Medications for the Elderly

APN Pharmacology Update ConferenceMarch 28, 2014

Patricia M. Curtin, MD, FACP, CMD Section Chief, Geriatric Medicine Member, Pharmacy and Therapeutics CommitteeClinical Assistant Professor, Jefferson Medical College

OBJECTIVES

Know and understand:

•The pathophysiology of aging related to processing medications in older adults

•Strategies for prescribing medications in older adults in order to avoid adverse drug events

•Medications that should be avoided in older adults and why

TOPICS COVERED

• Challenges in geriatric pharmacotherapy

• Key issues in geriatric pharmacology

• Principles of prescribing for older patients

• Risk factors for adverse drug events for older patients/mitigate

• AGS 2012 Updated Beers Criteria for Potentially Inappropriate Medication (PIM) Use

• AGS “Choosing Wisely” Campaign: What physicians/patients should question (related to medications)

• Hot off the press: JNC 8, ADA, FDA, CCHS Wish Lists

Sources and Resources

• CCHS Pharmacy ADR reports• Medication Safety Committee Wish List• AGS Beers Criteria (article, pocket card-$1) • ABIM Choosing Wisely Campaign—AGS List• Geriatric Dosage Handbook (Semla)• CCHS Formulary (Lexicomp)-Geriatric Considerations• CCHS Nurse-Pharmacist Referral (Powerchart) • WISH Website (References>Staff references>WISH)• Epocrates www.epocrates.com• iGeri app (iPhone, iPad)-($2.99)

WHY GERIATRIC PHARMACOTHERAPY IS IMPORTANT

Now, people age 65+ are 13% of US population, buy 33% of prescription drugsBy 2040, will be 25% of population, will buy 50% of prescription drugs

Geriatrics Review Syllabus 8th Edition, 2013, Chapter 11, Pharmacotherapy, Semla, PharmD

WHY GERIATRIC PHARMACOTHERAPY IS CHALLENGING

• More drugs are available each year

• FDA and off-label indications are expanding

• Formularies change frequently; substitutions made

• Drugs change from prescription to OTC-easier access

• “Nutraceuticals” (herbal preparations, nutritional supplements)

• Multiple Providers and Prescribers - 20% of Medicare beneficiaries have 5 or more chronic

conditions and 50% receive 5 or more medications

- Guideline based therapy• Data on medication efficacy and dosing come from clinical trials:

• Older adults are excluded from many randomized controlled trials• Studies that include older adults often are not representative

– Exclude multiple chronic illnesses

• We don’t know what we don’t know

What we do know: Age Related Changes in Physiology

• Increased Body fat• Decreased lean body mass• Decreased total body water• Decreased serum albumin (protein)• Decreased hepatic cell mass• Decreased liver blood flow• Decreased metabolism• Decreased renal mass• Decreased renal blood flow

PHARMACOKINETICS

• Absorption

• Distribution

• Metabolism

• Elimination

FACTORS THAT AFFECTDRUG ABSORPTION

• Absorption (bioavailability) is not changed much by aging

• Route of administration

• What is taken with the drug (meds/tube feeds)

• Gastric pH may increase or decrease absorption of some drugs

• GI motility and enzymes

• Peak serum concentrations may be lower OR higher-variable

• Co-morbid illnesses

GRS 8; Pharmacotherapy

EFFECTS OF AGING ONVOLUME OF DISTRIBUTION (VD)

• Age-associated changes in body composition can alter drug distribution (where a drug penetrates and time to do so)

• body water lower VD for hydrophilic (likes water) drugs

• lean body mass lower VD for drugs that bind to muscle (digoxin- lean body mass, increase concentrations of dig)

• plasma protein (albumin) higher percentage of drug that is unbound (active) (phenytoin)

• fat stores higher VD for lipophilic (likes fat) drugs (benzos, phenytoin, valproic acid, lidocaine)

GRS 8; Pharmacotherapy

AGING AND METABOLISM

• The liver is the most common site of drug metabolism

• Aging decreases liver blood flow, size and mass• Metabolic clearance of a drug by the liver may be reduced

GRS 8; Pharmacotherapy

KEY CONCEPTS ABOUTDRUG ELIMINATION

• Half-life: Time for serum concentration of drug to decline by 50%

• Clearance: Volume of serum from which the drug is removed per unit of time (eg, L/hour or mL/minute)

GRS 8; Pharmacotherapy

KIDNEY FUNCTION IS CRITICAL FOR DRUG ELIMINATION

• Most drugs exit the body via the kidney

• Reduced elimination drug accumulation and toxicity

• Aging and common geriatric disorders can impair kidney function

GRS 8; Pharmacotherapy

THE EFFECTS OF AGING ON THE KIDNEY

kidney size

renal blood flow

number of functioning nephrons

renal tubular secretion

Result: Lower glomerular filtration rate (GFR)

GRS 8; Pharmacotherapy

SERUM CREATININE DOES NOT REFLECT CREATININE CLEARANCE

lean body mass lower creatinine production

and

glomerular filtration rate (GFR)

Result: In older people, serum creatinine may stay in normal range, masking change in creatinine clearance (CrCl)Normal Creatinine Clearance: >60ml/min (age dependent)

GRS 8; Pharmacotherapy

TWO WAYS TO DETERMINE CREATININE CLEARANCE

Measure• Requires 24-hour urine collection• Time-consuming

Estimate • Usually done with the Cockroft-Gault equation* (*one of the most important equations to know)

(140 – age)(Ideal weight in kg) x (0.85 if female)=ml/min 72 X Creatinine (mg/dL)

Which of these meds need to be renally dosed for reduced Creatinine clearance?

• Ultram (Tramadol)• Zantac (Ranitidine)• Neurontin (Gabapentin)• Claritin (Loratadine)• Levaquin (Levofloxacin)• Tenormin (Atenolol)• Zyloprim (Allopurinol) • Bactrim (Trimethoprim-Sulfa)

PHARMACODYNAMICS

• Definition: Physiologic effects of the drug

• May change with aging, for example:

Benzodiazepines may cause more sedation and poorer psychomotor performance in older adults (likely cause: reduced clearance of the drug and resultant higher plasma levels)

Older patients may experience longer pain relief with morphine

SUCCESSFUL PHARMACOTHERAPY

• Uses the correct drug

• Prescribes the correct dosage

• Targets the correct condition

• Is appropriate for the patient

Failure in any one of thesecan result in adverse drug events (ADEs)

(75% of ADEs are dose related)

Geriatric Pharmacotherapy Principle: Start low, Go slow, but Go and

Avoid starting 2 drugs at same time (if possible)

Adverse Drug Effects (ADEs)

ADEs occur in 35% of community-dwelling

older adults

Incidence of ADEs in hospitals: 26/1000 beds

(2.6%)

ADEs are responsible for 5% to 28% of acute geriatric hospital admissions

MEDICATIONS MOSTCOMMONLY INVOLVED IN ADEs

• Cardiovascular drugs, diuretics, NSAIDs, hypoglycemics, antipsychotics, and anticoagulants

• Medications with a narrow margin of safety (synthroid, phenytoin, lithium, valproic acid, aminoglycosides, anticoagulants, digoxin, hypoglycemic agents, etc)

• CCHS….same, except add opioids/benzodiazepines

Geriatrics Review Syllabus, Pharmacotherapy, Semla et al

Adverse Drug Events After Hospital Discharge in Older Adults: Types, Severity, and Involvement of Beers Criteria Medications J Am Geriatr Soc. 2013; 61: 1894-1899

RISK FACTORS FOR ADEs

• Age 85 or older

• Female

• Low body weight or low BMI

• Estimated CrCl < 50 mL/min

• 5-9 or more medications

• 12 or more doses of drugs/day• 6 or more concurrent chronic conditions

• Prior adverse drug event

ADE PRESCRIBING CASCADE

Drug 1

Drug 2

Adverse drug effect— misinterpreted as a new medical condition

-

Adverse drug effect—misinterpreted as a new medical condition

OPTIMIZING PRESCRIBING

• Achieve balance between over and under prescribing of beneficial therapies

• >20% of ambulatory older adults receive at least one potentially inappropriate medication

• Nearly 4% of office visits and 10% of hospital admissions result in prescription of medications classified as never or rarely appropriate

AGS UPDATED 2012 BEERS CRITERIA FOR POTENTIALLY INAPPROPRIATE MEDICATION USE IN OLDER ADULTS

Mark H Beers, MD 1954-2009

MD, Univ of Vermont First med student to do a

geriatrics elective at Harvard‘s new Division on Aging

Geriatric Fellowship, Harvard Faculty, UCLA/RAND Co-editor, Merck Manual of

Geriatrics Editor in Chief, Merck Manuals“A ballet-dancing opera

critic who hiked the Alps and took up rowing after

diabetes cost him his legs”

BEERS CRITERIA

• Originally developed in 1991, 1997, 2003 and updated in 2012 by the American Geriatrics Society (by 11 member panel)

• Intend to improve drug selection and reduce exposure to potentially inappropriate medications (PIM) in older adults

• Recommendations are evidence-based and in 3 categories: Drugs to avoid Drugs to avoid in patients with specific diseases or syndromes Drugs to use with caution

• Available at AGS web site: www.americangeriatrics.org

American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.

BEERS CRITERIA

Potentially inappropriate medications include medications that:

Have limited effectiveness in older adultsAre associated with poor outcomes

DeliriumGI bleedingFalls

Have safer alternatives availableAmerican Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2012;60:616–631.

Table 1: Designations of Quality and Strength of Evidence:

ACP Guideline Grading System, GRADEQuality of Evidence High

• Consistent results from well-designed, well-conducted studies that directly assess effects on health outcomes (2 consistent, higher-quality RCTs or multiple, consistent observational studies with no significant methodological flaws showing large effects)

Moderate • Sufficient to determine effects on health outcomes, but the number, quality, size, or

consistency of included studies, generalizability , indirect nature of the evidence on health outcomes (1 higher-quality trial with > 100 participants; 2 higher-quality trials with some inconsistency, or 2 consistent, lower-quality trials; or multiple, consistent observational studies with no significant methodological flaws showing at least moderate effects) limits the strength of the evidence

Low • Insufficient to assess effects on health outcomes because of limited number or power of

studies, large and unexplained inconsistency between higher-quality studies; important flaws in study design or conduct, gaps in the chain of evidence

• Or lack of information on important health outcomes

Table 1: Designations of Quality and Strength of Evidence:

ACP Guideline Grading System, GRADEStrength of Recommendation

StrongBenefits clearly > risks and burden OR risks and burden

clearly > benefits

WeakBenefits finely balanced with risks and burden

InsufficientInsufficient evidence to determine net benefits or risks

What can Prescribers and other interdisciplinary team members do?

Collaborate with other team members/disciplines using AGS POCKETCARDS

Tables (*pocket card limited to first 3 tables)

Table 2 – PIMs (organ system/therapeutic category) Table 3 – PIMs due to Drug – Disease/Syndrome

Interaction Table 4 – Medications to be used with caution Table 5 – Medications moved or modified Table 6 – Medications removed Table 7 – Medications added Table 8 – Antipsychotics Table 9 – Drugs with strong anticholinergic

properties (Tables 2,3,4 in article=Tables 1,2,3 in pocket card)

Table 9: Drugs with strong “anticholinergic” properties? What’s the problem?

May reduce acetylcholine levels in patients who already have reduced levels: those who are elderly, have dementia and/or delirium Increased risk of anticholinergic side effects=confusion/delirium, constipation, urine retention, orthostasis, paradoxical excitement, tachycardia, visual disturbances, dry mouth

Over 600 drugs with Anticholinergic Activity

• Furosemide (Lasix)• Triamterene/HCTZ• Digoxin• Dipyridamole (Persantine)• Theophylline anhydrous• Warfarin (Coumadin)• Prednisolone• Nifedipine (Procardia)• Isosorbide Dinitrate• Codeine• Diphenhydramine• Olanzapine• Paroxetine• Promethazine

• Tune, L.E. , Egell, S. Dementia. Geriatric Cognitive Disorders 1999. Courtesy of Susan Scanland, MSN, APRN, GNP

• AGS Beers Criteria, 2012

• Captopril• Imipramine/Desipramine• Amitriptyline (Elavil)• Cimetidine (Tagamet)• Ranitidine (Zantac)• Tobra/clinda/gentamycin• Ampicillin• Hydralazine• Diazepam (Valium)

• Oxybutynin (Ditropan)

Table 2 (Table 1 in pocket guide): Drugs to AvoidOrgan System/ TC/Drug

Rationale Recommend. Quality of Evidence

Strength of Recommend.

Anticholinergics:First generation antihistamines/antispasmodics

Antiparkinson

Highly anticholinergic; clearance reduced with age; may use in severe allergic rxn

Not rec for EPS

Avoid

Avoid

High/Moderate

Moderate

Strong

Strong

Nitrofurantoin Pulmonary toxAlternativesLack of efficacy <60 mL/min

Avoid long term use; avoid if CrCl <60 mL/min

Moderate Strong

Alpha blockers High Risk of orthostasis

Avoid use as BP med

Moderate Strong

Digoxin >0.125mg/d

High doses-no benefit/toxicityin HF

Avoid Moderate Strong

DIGOXIN

Digoxin itself or Digoxin toxicity can cause: Confusion nausea loss of appetite lethargy bradycardia heart block

DIGOXIN

0.125 mg. dose effective; rarely use 0.25 mg

Half-life is 30-40 hours; up to 70 hrs in elderly

May be able to dose 2-3x/week Therapeutic “range”-.7-2.0. Patients don’t need to always be “in

the range”. Lower levels may be better (.5-.8)

(DIG trial, elderly CHF patients)

Table 2: Drugs to Avoid Organ System/ TC/Drug: CNS

Rationale Recommend. Quality of Evidence

Strength of Recommend.

Tertiary TCAs Highly anticholinergic, sedating, orthostasis

Avoid High Strong

Antipsychotics, conventional and atypicals

Increase CVA and mortality in dementia pts

Avoid unless danger to self/others Nonpharm fail

Moderate Strong

Non BenzodiazepineHypnotics (“z”)

Ineffective at tolerated doses, antichol SE, falls

Avoid Moderate Strong

BenzodiazepineShort, intermediate, and long acting

Risk cognitive effects and injury (fall/MVA/fx); rare use appropriate: seizures, etoh/ benzo WD/ELOC

Avoid for treatment of insomnia, agitation, or delirium

High Strong

Sedatives/HypnoticsWhat Benzodiazepines should we use in elderly?• NONE - but if necessary (pre-med, COPD, etc): • Ativan (Lorazepam)-(0.25mg. - 0.5 mg. q 8 hr. PRN (po/IM/IV) (half-life 10-16 hrs); (maximum daily dose 2 mg) Peaks at 1 hr. OR• Serax (Oxazepam) 10 mg. q 8-12 hr. po prn (half-life 5-20 hrs); (max dose 30mg/d)

• For Sleep—refer to CCHS Sleep Protocol, WISH Website

Organ System/ TC /Drug: Misc

Rationale Recommend. Quality of Evidence

Strength of Recommend.

Megestrol Minimal effect on weight; risk of thrombosis/death

Avoid Moderate Strong

Chlorpropamide Glyburide

SIADH; both withHypoglycemia risk

Avoid High Strong

Insulin, sliding scale

Hypoglycemia risk w/o benefit

Avoid Moderate Strong

Metoclopramide EPS and Tardive Dyskinesia

Avoid, unless gastroparesis

Moderate Strong

Non-COX NSAIDs/ IndomethacinKetorolac

GI bleeding; Protection w/ PPIs or misoprostol

Avoid chronic use

Moderate

High

Strong

Skeletal muscle relaxants

Anticholinergic, sedation, fall/fracture; effectiveness at tolerated doses-?

Avoid Moderate Strong

Table 3: PIMs to Avoid due to Drug-Disease or Drug-Syndrome Interactions

Disease/Syndrome Drug Recommend/Rationale/QOE/SR

Heart Failure NSAIDS Avoid, Moderate, Strong CCBS (fluid retention)

Delirium All TCAs, Antichol Avoid, Moderate, Strong Benzos, hypnotics (adverse CNS effects) H2 Antagonists

Dementia Antichol, Benzos Avoid, High, Strong H2Antagonists (adverse CNS effects) Zolpidem, Antipsychotics (increased risk of CVA/mortality)

Falls Anticonvulsants, Avoid, High, Strong Antipsychotics, (ataxia, impaired psychomotor fcn, Benzos, Hypnotics syncope) TCAs, SSRIs

Take homes: AGS 2012 Beers Criteria

Don’t let the perfect be the enemy of the good Beers PIMs are only part of appropriate prescribing Target initiatives to high prevalence/high severity

meds (based on local data, where possible) Stopping meds should be done with same

consideration as starting Not meant to supersede clinical judgment or

individual patient values or needs

AGS Beers Criteria Website

Criteria Full Article Editorial Perspective

Beers Criteria Pocket CardBeers Criteria App

Public Education Resources for Patients & Caregivers AGS Beers Criteria Summary 10 Medications Older Adults Should Avoid Avoiding Overmedication and Harmful Drug Reactions What to Do and What to Ask Your Healthcare Provider if a Medication You Take is

Listed in the Beers Criteria My Medication Diary - Printable Download Eldercare at Home: Using Medicines Safely - Illustrated PowerPoint Presentation

Available at:Americangeriatrics.org

ABIM: CHOOSING WISELY CAMPAIGNAGS: Top Ten Things Physicians and Patients Should Question

Medications (2013)

1. Don’t recommend percutaneous feeding tubes in patients with advanced dementia; instead offer oral assisted feeding

2. Don’t use antipsychotics as first choice to treat behavioral and psychological symptoms of dementia

3. Avoid using medications to achieve Hgb A1C <7.5% in most adults age 65 and older: moderate control is better

4. Don’t use benzodiazepines or other sedative-hypnotics in older adults as first choice for insomnia, agitation, delirium

5. Don’t use antimicrobials to treat bacteriuria in older patients unless specific urinary tract symptoms are present

• www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society

ABIM: CHOOSING WISELY CAMPAIGNAGS: Top Ten Things Physicians and Patients Should Question

Medications (2014)6. Don’t prescribe cholinesterase inhibitors for dementia

without periodic assessment for perceived cognitive benefits and adverse GI effects

7. Don’t recommend screening for breast or colorectal cancer, nor prostate cancer (w PSA test) without considering life expectancy and the risks of testing, overdiagnosis and over treatment

8. Avoid using prescription appetite stimulants or high-calorie supplements for treatment of anorexia or cachexia in older adults; instead, optimize social supports, provide feeding assistance and clarify patient goals and expectations.

9. Don’t prescribe a medication without conducting a drug regimen review.

10. Avoid physical restraints to manage behavioral symptoms of hospitalized older adults with delirium

CCHS Pharmacists’ “Choosing Wisely” WISH LIST

• Hold parameters for antihypertensives• Add STOP dates to Antibiotic orders• Appropriate use of PPIs (pantoprazole, etc)• Add senna/docusate when starting opioids• Avoid antipsychotic use for acute delirium• Try to avoid concomitant use-opioids/benzos• Anticoagulants-new, bridging, reversals

Speaker’s “Choosing Wisely” Wish List• Reconcile and validate list/how pt takes meds• Provide an indication for each medication• Calculate Creatinine Clearance on every pt.• DO NOT start dementia medications as an inpatient (donepezil, memantine, etc)-no benefit in hospital, risk of ADEs• Watch acetaminophen dosing 3000-4000mg• Consider new JNC8 goal of >60yo, BP<150/90

CASE (1 of 4)

• A 77-year-old man comes to the office because he has had increased difficulty with urination, including straining to void and occasional urinary incontinence.

• History includes benign prostatic hyperplasia, depression, seasonal allergies, type 2 diabetes mellitus, and peripheral neuropathy.

• Medications include tamsulosin 0.4 mg at bedtime, metformin 1,000 mg q12h, fluticasone inhaler 2 sprays in each nostril daily, diphenhydramine 25 mg q12h as needed, and aspirin 81 mg/day.

CASE (2 of 4)

• His peripheral neuropathy improved with initiation 3 weeks ago of duloxetine 60 mg/day; he had experienced intolerable adverse effects with gabapentin and pregabalin.

• His allergies have been worse over the past month, and he has been taking a dose of diphenhydramine at bedtime with excellent symptom control.

• On physical examination, the prostate is not enlarged. Urinary analysis is normal.

CASE (3 of 4)

Which of the following is the most appropriate management for this patient?

A.Discontinue diphenhydramine.

B.Discontinue duloxetine.

C.Begin extended-release tolterodine.

D.Obtain postvoid residual urine level.

CASE (4 of 4)

Which of the following is the most appropriate management for this patient?

A.Discontinue diphenhydramine.

B.Discontinue duloxetine.

C.Begin extended-release tolterodine.

D.Obtain postvoid residual urine level.

Prescribing Principles for Older Adults

Reconcile/validate how pt really takes medsTry nonpharmacological interventions firstBalance risk vs. benefitStart low and go slowAvoid inappropriate medicationsDiscontinue unnecessary medicationsMonitor for side effects; avoid prescribing cascadeConsider patient’s goals of care

Zwicker D. Nursing Standard of Practice Protocol: Reducing Adverse Drug Events. Available at: http://consultgerirn.org/topics/medication/want_to_know_more