When to Spare Some Pharmaceutical Care

Jovino Hernandez PharmDClinical Manager

Winter Haven Hospital Pharmacy Services

Goals

Recognize the incidence of polypharmacyIdentify The Risk Associated with

PolypharmacyClassify Agents that Pose the Most Risk

to the Elderly PopulationDevelop Strategies to Decrease

Polypharmacy

Introduction

All drugs can be considered “poisons”The more we ingest, the more apt we are

to have issues Clinical guidelines often call for multiple

medicationsAppropriate medication use beneficial to

patientsChallenge is not to tip the scale toward

adverse events

What is Polypharmacy?

Usually described numerically as five or more prescribed medications at any time

European Project AgeD in Home Care (ADHOC) uses 9 or more medications

orAdministration of more medications than

clinically indicated

Our Aging Population

Chronic Diseases are on the riseMultiple Medications are often used to

treat chronic illnessSharp rise in aging population300% Rise in elderly disabled in North

America by 2050Average North American over the age of

60 years has 2.2 chronic diseases

Our Aging Population

Statistics

Statistics

Statistics

Average elderly patient in community consumes 4 medications daily

Average elderly patient in a nursing home consumes 7 medications on average

Risk Factors

Advanced Age 13% of US population Account for 33% of prescription and 40% on nonprescription use

Female 57% of women greater than 65 years take at least 5 medications 12% take at least 10

Low Education Level Multiple Morbidities

Average adult over 60 years has 2.2 chronic conditions Often based off of evidence based medicine Core Measures

Depression Multiple Prescribers Frailty

Risk Factors (Prescriber)

Practice EnvironmentLow number of listed patientsHigh WorkloadLow rate of admission to hospitalHigh practice prescribing rateHigh average number of prescribed

medicationsLower prevalence in female prescribersNo association with age or duration of practice

Risk Factors (Prescriber)

Medical GuidelinesIntended to support physicians in their drug

choiceUsually focus on one disease stateTend generate more drug therapy especially

when compoundedExamples: CHF, AMI, COPD

Risk Factors (Prescriber)

Prescribing HabitsDominate perception that diseases should be

treated with drugsA visit to a provider should end with a

prescriptionCan lead to a medical cascade of prescribing

Risk Factors (Prescriber)

Physician BehaviorFailure to make a proper medical reviewPoor communication amongst prescribersMistrust of guidelines that decrease

medications use (Antibiotics)

Risk Factors (Patient to Prescriber)

Good interaction essentialReviews of entire medication list with

provider is essentialPersonnel continuity

Multiple providers and pharmacies increase the risk of polypharmacy

Risk

Polypharmacy Associated WithPoor AdherenceInappropriate PrescribingAdverse Drug ReactionsDrug InteractionsGeriatric SyndromesMorbidity/Mortality

Poor Adherence

Nonfulfillment Prescribed but never filled

NonpersistencePatients decides to stop taking without being

advised be health professionalNonconforming

Incorrect DosingSkipping DosesIncorrect times

Inappropriate Prescribing

The use of medications that introduce a greater risk of adverse drug-related events where a safer, as-effective, alternative therapy is available to treat the same condition.

Includes Use of medicines at a higher frequency Longer then clinically necessaryDrug-Drug InteractionsUnderuse of clinically relevant medications

Adverse Reactions

An unfavorable medical event related to medication misuse or

Noxious or unintended response t medication despite appropriate drug dosage or prophylaxis, diagnosis or therapy of medical conditions

Adverse Reactions

4.3 million ADR related health care visits in 2005

Occur in up to 35% of elderly patients in outpatient setting

Account for 10% of ER visits

Adverse Reactions

Higher amount of meds, higher rate of ADRS2 Meds 13%5 Meds 58%7 or more Meds 82%

Adverse Reactions

Most Common ClassesCardiovascularDiureticsAnticoagulantsNSAIDsAntibioticsHypoglycemic

Drug Interactions

Elderly at risk ComorbiditiesNutritional Status

Number of drug interactions increase as number of morbidities and medications increase

Often more medications are added to treat these issues that further complicate problems

Geriatric Syndromes

Cognitive ImpairmentsMedications implicated in up to 39% of casesFour or more medications added the day before

a delirium episode is a risk factorFinnish Study on Cognitive Impairment

No Polypharmacy – 22% riskPolypharmacy – 33% RiskExcessive Polypharmacy – 54% Risk

Geriatric Syndromes

Cognitive Impairments (cont)Delerium

OpiodsBenzodiazepinesAnticholinergics

DementiaBenzodiazepineAnticonvulsantsAnticholinergicsTricyclic Antidepressants

Geriatric Syndromes

FallsIncrease morbidity and mortalityCardiovascular, Psychotropic

Urinary IncontinenceDiureticsPsychotropics OpioidsSedatives

Geriatric Syndromes

NutritionAssociated with poorer nutritional statusDecreased intake of soluble and nonsoluble

fiber, fat soluble vitamins, B vitamins and minerals

Increased intake of cholesterol, glucose and sodium

Medications (Beers)

Updated in 2012Goal

The goal of the 2012 AGS Beers Criteria is to improve care of older adults by reducing their exposure to potentially inappropriate medications (PIMs)Improving selection of drugsEvaluating patterns of drug use within populationEducating on proper drug useEvaluating health-outcome, quality care, cost, and use

data

Medications (Beers)

Three CategoriesPotentially inappropriate medications and

classes to avoid in older patientspotentially inappropriate medications and

classes to avoid in older adults with certain diseases and syndromes

medications to be used with caution inolder adults

Beers Criteria for Potentially Inappropriate Use in Older Adults

Medication/Class Rationale

Anticholinergics(diphenhydramine, hydroxyzine, promethazine Clearance reduced, confusion, dry mouth, constipation. Diphenhydramine ok for acute allergic reaction

Alpha1 blockers (doxazosin, prazosin, terazosin) High risk of orthostatichypotension, alternative agents have superior risk/benefit

profile

Antiarrhythmic drugs (Class Ia, Ic,III) (amiodarone, dronaderone, sotalol)

Rate control yields better balance of benefits than rhythm for most older pts

Tricyclic Antidepressants (TCAs) (amitriptyline, doxepin >6mg/d, imipramine

Sedation, orthostatic hypotension

Antipsychotics, first (conventional)and second (atypical) generation (haloperidol, aripiprazole, olanzapine, risperidone, ziprasidone)

Increased risk of cerebrovascularaccident (stroke) and mortality inpersons with dementia

Benzodiazepines (alprazolam, lorazepam, temazepam, clorazepate, chlordiazepoxide, diazepam, zolpidem (not quite a benzodiazepine)

Increased sensitivity, delirium, cognitive impairment, falls. May still be appropriate for some in

Beers Criteria for Potentially Inappropriate Use in Older Adults

Medication/Class Rationale

Insulin, Sliding Scale Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting

Megestrol Minimal effect on weight; increases risk of thrombotic events and possibly death in older adults

Glyburide Greater risk of hypoglycemia in older patients

Metoclopramide Avoid, unless for gastroparesis

Meperidine Not an effective oral analgesic in dosages commonly used; may cause neurotoxicity; safer alternatives available

Indomethacin, Ketorolac Increase risk of GI bleeding and PUD

Carisoprodol, Cyclobenzaprine Poorly tolerated, sedation, questionable efficacy

Potentially Inappropriate Due to Drug–Disease or Drug–Syndrome Interactions That May Exacerbate the Disease or Syndrome

Disease or Syndrome Drug Rationale

Heart Failure NSAIDs, COX-2 Inhibitors, Diltiazam, Verapramil, Pioglitazone, Rosiglitazone, Dronedarone

Potential to promote fluid retention and exacerbate heartfailure

Syncope Doxazosin, Prazosin, Terazosin Increases risk oforthostatic hypotension

Chronic seizuresor epilepsy

Bupropion, Olanzapine, Tramadol Lowers seizure threshold

Delirium TCAs, Anticholinergics, Benzodiazepines, corticosteroids, meperidine,

Avoid in patients with or at high risk for delirium

Dementia andcognitiveimpairment

Anticholinergis, Benzodiazipines, Zolpidem, Antipsychotics

CNS effects. Anitpsychotics -Increase in stroke and mortality in persons with dementia

History of falls orfractures

Anticonvulsants,AntipsychoticsBenzodiazepines, Zolpidem,TCAs and SSRIs

Ability to produce ataxia, impaired psychomotor function,syncope, and additional falls;

Potentially Inappropriate Due to Drug–Disease or Drug–Syndrome Interactions That May Exacerbate the Disease or Syndrome

Disease or Syndrome

Drug Rationale

Parkinson’sdisease

All antipsychotics except for Quetiapine and Clozapine)Antiemetics-MetoclopramideProchlorperazine, Promethazine

Dopamine receptor antagonists with potential to worsenparkinsonian symptoms.

History of gastricor duodenal ulcers

Aspirin (>325 mg/d) Non–COX-2 selective NSAIDs May exacerbate existing

May exacerbate existing ulcers or cause new or additional ulcers

Urinary incontinence(all types) in women

Estrogen oral and transdermal(excludes intravaginal estrogen)

Aggravation of incontinence

Lower urinarytract symptoms,benign prostatichyperplasia

Ipratropium, Tiotropium, Anticholinergics (except antimuscarinics for urinary incontinence)

May decrease urinaryflow and causeurinary retention

Stress or mixedurinary incontinence

Doxazosin, Prazosin, Terazosin

Potentially Inappropriate Due to Drug–Disease or Drug–Syndrome Interactions That May Exacerbate the Disease or Syndrome

Drug Rationale Recommendation

Dabigatran Greater risk of bleeding than with warfarin in adults 75 or greater; lack o evidence for efficacy and safety inindividuals with CrCl < 30 mL/min

Use with caution in adultsaged _75 or if CrCl < 30 mL/min

Antipsychotics, Carbamazepine, Mirtazapine, SSRIs, TCAs

May exacerbate or cause syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; need to monitor sodium level closely when starting or changing dosages in older adults due to increased risk

Use with caution

Preventions

BarriersClinician uncomfortable with changing or

discontinuingParticularly medication prescribed by another

clinician

Little evidence based support on discontinuing medications

Patients psychologically or physical dependant on medication

Discontinuing medication perceived as inadequate care

Prevention

Barriers (cont)Potential harms such as adverse drug

withdrawal events (ADWEs)Clinically significant symptoms or signs likely caused

by medication cessationCardiovascular and CNS classes most common

Prevention

ConsiderationsDuration of each medicationIs there still an indication for each medicationAre indications consistent with current

guidelinesAdherence

If patient well without taking, pointless to continue prescribing

Prevention

Prescribing cascadeDiscontinuing medication may reveal adverse

effects of other therapies

Very little evidence to guide withdrawal process for polypharmacyA gradual tapering is often recommended

Prevention

Clinical Controlled TrialsMedication Reviews by pharmacistPrescriber Education ProgramsAcademic detailingComprehensive geriatric assessmentsMultidisciplinary interventions engaging

prescribers and pharmacists

Prevention

Nurses RoleInformationInstructionOrganization

Prevention

Information –Discuss with patientsKeep an accurate list of medicationsKeep complete list of medical providers and

contact informationPost the name and telephone number of local

pharmacy

Prevention

Instruction: Teach patients aboutEach medication, including name, appearance,

purpose and effectsPotential adverse effects and interactions of

each medicationImportance of contacting healthcare provider

with concerns and questionsPotential drug –related problems that warrant

emergency care

Prevention

Instructions (continued)Importance of taking medications exactly as

directedImportance of using only one pharmacy to

obtain drugs

Prevention

Organization: To help manage drugsAvoid sharing medicationsStore medication in secure dry area away from

sunlightRefrigerate if necessaryDispose of old medications properly

Prevention

No single approach extensively studiedPrescribing and impact on outcomes

inconsitent throughout studiesBest approach is probable a combined

approachPatient needs to be involved in the

process

Where Are We Now?

No charges over C. diff outbreak

No-one is to face charges in

connection with an outbreak of

Clostridium difficile which left 90

people dead.

C. difficile Outbreak Causes

Concern At Local Hospital

Tuesday June 3, 2008

CityNews.Ca Staff

Quebec 2004

March 2003 a rise of severe CDAD in Montreal and regions in Quebec1

12 Hospitals studied over 6 months in 2004

1719 cases reviewed

Logo LG, Porier L, Miller Ma, et al, A predominantly clonal multi-institutional outbreak of Clostridium difficile-associate diarrhea with high morbidity and mortality, N Engl J Med 2005;353:2442-9

Quebec 2004Age

Age (yrs)Age (yrs) CasesCases No of Cases No of Cases per 1000 per 1000 admissionsadmissions

% Attributable % Attributable 30-Day 30-Day Mortality RateMortality Rate

<40<40 7676 3.53.5 2.62.6

41-5041-50 8585 11.211.2 1.21.2

51-6051-60 181181 20.020.0 3.23.2

61-7061-70 272272 24.424.4 5.15.1

71-8071-80 523523 38.338.3 6.26.2

81-9081-90 458458 54.454.4 10.210.2

>90>90 114114 74.474.4 14.014.0Logo LG, Porier L, Miller Ma, et al, A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality, N Engl J Med 2005;353:2442-9

Quebec 2004Antibiotics

AntibioticAntibiotic Odds RatioOdds RatioAny CephalosporinAny Cephalosporin 3.83.8

11stst Generation Generation 2.42.4

22ndnd Generation Generation 6.06.0

33rdrd Generation Generation 3.03.0

Any FluoroquinoloneAny Fluoroquinolone 3.93.9

CiprofloxacinCiprofloxacin 3.13.1

Gatifloxacin/MoxifloxacinGatifloxacin/Moxifloxacin 3.43.4

LevofloxacinLevofloxacin 0.60.6

ClindamycinClindamycin 1.61.6

MacrolidesMacrolides 1.31.3

Penicillin w/Penicillin w/ββ-Lactamase Inh-Lactamase Inh 1.21.2

CarbapenemsCarbapenems 1.41.4

Logo LG, Porier L, Miller Ma, et al, A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality, N Engl J Med 2005;353:2442-9

Quebec 2004

Attributed Mortality 6.9%A previous Canadian study 6 years prior had 1.5%

mortality rate1

All hospitals had the similar dominant strain (129 of 157 isolates or 82%)

Among the 38 patients who acquired CDAD in the community, 37% had NAP1/027

Isolates of dominant strain resistant to all quinolones but susceptible to clindamycin

Logo LG, Porier L, Miller Ma, et al, A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality, N Engl J Med 2005;353:2442-9

NAP1/027 Strain

Linked to several outbreaks in Canada, Britain, US, and Netherlands.

Has been around since 1984 Has become fluoroquinolone resistant since then

Can produce 16 times more toxin A and 23 times more toxin B than standard strain

Produces an extreme amount of sporesHigher mortality and colectomies Has in many area become the dominate strain

Possibly due to severe diarrheaAntibiotic trends

Florida

1998-20031

Codes as C. diff on discharge34/100,000 to 70.2/100,000

• Biggest change from 2000-2001 (35.0 to 46.9)

Death among patients coded with C. Diff94.8/1000 to 106.7/1000

• More than 80% of deaths were 75 or older

Authors felt the NAP1/027 was a contributing factor

Sanderson, R A, Bendixsen O, Increasing Clostridium difficile morbidity and mortality, Florida hospitals, 1998-2003, Abstract 2006 Conference on Antimicrobial Resistance

Community-Acquired

Definition controversialMany have been in a health care facility recentlyLocal study showed that 79% of CDAD patients in

hospital acquired if considering 30 day readmission criteria

Young patients without a history of antibiotic use becoming more commonMany have close contact with diarrheal CDAD1

NAP1/027 is out in the community

1Centers for Disease Control and Prevention. Severe Clostridium difficile-associated disease in populations previously at low risk—Four States, 2005. MMWR Morb Mortal Wkly Rep 2005;54:1201-5

Risk Factors(Hospitalized Patients)Increasing Age (excluding infancy)

Younger population is becoming more at riskSeverity of Underlying DiseaseNon-surgical gastrointestinal proceduresPresence of nasograstric tubesAnti-ulcer medicationsICU StayLength of Hospital StayAntibiotics

Length of therapyMultiple Antibiotics

Antibiotics

FluoroquinolonesOriginally considered a low riskReadily available, particularly ciprofloxacinEliminates gram negative and anaerobicFull resistance to the newer NAP1/027 strain

Appropriate use

Use narrower spectrum where possible

Minimize usage of “double coverage” Streamline antibiotics as soon as possible

Minimize the use of agents that are largely excreted in the gut to minimize the selection of resistant gram negatives and destroy gut flora

Minimize use of agents that have significant antianaerobic activity-spare gut anaerobes

Shorten the length of therapy