When to Spare Some Pharmaceutical Care

1
When to Spare Some Pharmaceutical Care

• Jovino Hernandez PharmD
• Clinical Manager
• Winter Haven Hospital Pharmacy Services

2
Goals

• Recognize the incidence of polypharmacy
• Identify The Risk Associated with Polypharmacy
• Classify Agents that Pose the Most Risk to the
  Elderly Population
• Develop Strategies to Decrease Polypharmacy

3
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
  medications
• Appropriate medication use beneficial to patients
• Challenge is not to tip the scale toward adverse
  events

4
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
• or
• Administration of more medications than
  clinically indicated

5
Our Aging Population

• Chronic Diseases are on the rise
• Multiple Medications are often used to treat
  chronic illness
• Sharp rise in aging population
• 300 Rise in elderly disabled in North America by
  2050
• Average North American over the age of 60 years
  has 2.2 chronic diseases

6
Our Aging Population
7
Statistics
8
Statistics
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Statistics

• Average elderly patient in community consumes 4
  medications daily
• Average elderly patient in a nursing home
  consumes 7 medications on average

10
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

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Risk Factors (Prescriber)

• Practice Environment
• Low number of listed patients
• High Workload
• Low rate of admission to hospital
• High practice prescribing rate
• High average number of prescribed medications
• Lower prevalence in female prescribers
• No association with age or duration of practice

12
Risk Factors (Prescriber)

• Medical Guidelines
• Intended to support physicians in their drug
  choice
• Usually focus on one disease state
• Tend generate more drug therapy especially when
  compounded
• Examples CHF, AMI, COPD

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Risk Factors (Prescriber)

• Prescribing Habits
• Dominate perception that diseases should be
  treated with drugs
• A visit to a provider should end with a
  prescription
• Can lead to a medical cascade of prescribing

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Risk Factors (Prescriber)

• Physician Behavior
• Failure to make a proper medical review
• Poor communication amongst prescribers
• Mistrust of guidelines that decrease medications
  use (Antibiotics)

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Risk Factors (Patient to Prescriber)

• Good interaction essential
• Reviews of entire medication list with provider
  is essential
• Personnel continuity
• Multiple providers and pharmacies increase the
  risk of polypharmacy

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Risk

• Polypharmacy Associated With
• Poor Adherence
• Inappropriate Prescribing
• Adverse Drug Reactions
• Drug Interactions
• Geriatric Syndromes
• Morbidity/Mortality

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Poor Adherence

• Nonfulfillment
• Prescribed but never filled
• Nonpersistence
• Patients decides to stop taking without being
  advised be health professional
• Nonconforming
• Incorrect Dosing
• Skipping Doses
• Incorrect times

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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 necessary
• Drug-Drug Interactions
• Underuse of clinically relevant medications

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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

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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

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Adverse Reactions

• Higher amount of meds, higher rate of ADRS
• 2 Meds 13
• 5 Meds 58
• 7 or more Meds 82

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Adverse Reactions

• Most Common Classes
• Cardiovascular
• Diuretics
• Anticoagulants
• NSAIDs
• Antibiotics
• Hypoglycemic

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Drug Interactions

• Elderly at risk
• Comorbidities
• Nutritional 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

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Geriatric Syndromes

• Cognitive Impairments
• Medications implicated in up to 39 of cases
• Four or more medications added the day before a
  delirium episode is a risk factor
• Finnish Study on Cognitive Impairment
• No Polypharmacy 22 risk
• Polypharmacy 33 Risk
• Excessive Polypharmacy 54 Risk

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Geriatric Syndromes

• Cognitive Impairments (cont)
• Delerium
• Opiods
• Benzodiazepines
• Anticholinergics
• Dementia
• Benzodiazepine
• Anticonvulsants
• Anticholinergics
• Tricyclic Antidepressants

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Geriatric Syndromes

• Falls
• Increase morbidity and mortality
• Cardiovascular, Psychotropic
• Urinary Incontinence
• Diuretics
• Psychotropics
• Opioids
• Sedatives

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Geriatric Syndromes

• Nutrition
• Associated with poorer nutritional status
• Decreased intake of soluble and nonsoluble fiber,
  fat soluble vitamins, B vitamins and minerals
• Increased intake of cholesterol, glucose and
  sodium

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Medications (Beers)

• Updated in 2012
• Goal
• 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 drugs
• Evaluating patterns of drug use within population
• Educating on proper drug use
• Evaluating health-outcome, quality care, cost,
  and use data

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Medications (Beers)

• Three Categories
• Potentially inappropriate medications and classes
  to avoid in older patients
• potentially inappropriate medications and classes
  to avoid in older adults with certain diseases
  and syndromes
• medications to be used with caution in
• older adults

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Beers Criteria for Potentially Inappropriate Use in Older 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 orthostatic hypotension, 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 gt6mg/d, imipramine Sedation, orthostatic hypotension
Antipsychotics, first (conventional)and second (atypical) generation (haloperidol, aripiprazole, olanzapine, risperidone, ziprasidone) Increased risk of cerebrovascular accident (stroke) and mortality in persons 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
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Beers Criteria for Potentially Inappropriate Use in Older Adults 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
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Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome 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 heart failure
Syncope Doxazosin, Prazosin, Terazosin Increases risk of orthostatic hypotension
Chronic seizures or epilepsy Bupropion, Olanzapine, Tramadol Lowers seizure threshold
Delirium TCAs, Anticholinergics, Benzodiazepines, corticosteroids, meperidine, Avoid in patients with or at high risk for delirium
Dementia and cognitive impairment Anticholinergis, Benzodiazipines, Zolpidem, Antipsychotics CNS effects. Anitpsychotics -Increase in stroke and mortality in persons with dementia
History of falls or fractures Anticonvulsants,Antipsychotics Benzodiazepines, Zolpidem, TCAs and SSRIs Ability to produce ataxia, impaired psychomotor function, syncope, and additional falls
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Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome
Disease or Syndrome Drug Rationale
Parkinsons disease All antipsychotics except for Quetiapine and Clozapine) Antiemetics-Metoclopramide Prochlorperazine, Promethazine Dopamine receptor antagonists with potential to worsen parkinsonian symptoms.
History of gastric or duodenal ulcers Aspirin (gt325 mg/d) NonCOX-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 urinary tract symptoms, benign prostatic hyperplasia Ipratropium, Tiotropium, Anticholinergics (except antimuscarinics for urinary incontinence) May decrease urinary flow and cause urinary retention
Stress or mixed urinary incontinence Doxazosin, Prazosin, Terazosin
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Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome Interactions That May Exacerbate the Disease or Syndrome Potentially Inappropriate Due to DrugDisease or DrugSyndrome 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 in individuals with CrCl lt 30 mL/min Use with caution in adults aged _75 or if CrCl lt 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
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Preventions

• Barriers
• Clinician uncomfortable with changing or
  discontinuing
• Particularly 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

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Prevention

• Barriers (cont)
• Potential harms such as adverse drug withdrawal
  events (ADWEs)
• Clinically significant symptoms or signs likely
  caused by medication cessation
• Cardiovascular and CNS classes most common

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Prevention

• Considerations
• Duration of each medication
• Is there still an indication for each medication
• Are indications consistent with current
  guidelines
• Adherence
• If patient well without taking, pointless to
  continue prescribing

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Prevention

• Prescribing cascade
• Discontinuing medication may reveal adverse
  effects of other therapies
• Very little evidence to guide withdrawal process
  for polypharmacy
• A gradual tapering is often recommended

39
Prevention

• Clinical Controlled Trials
• Medication Reviews by pharmacist
• Prescriber Education Programs
• Academic detailing
• Comprehensive geriatric assessments
• Multidisciplinary interventions engaging
  prescribers and pharmacists

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Prevention

• Nurses Role
• Information
• Instruction
• Organization

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Prevention

• Information Discuss with patients
• Keep an accurate list of medications
• Keep complete list of medical providers and
  contact information
• Post the name and telephone number of local
  pharmacy

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Prevention

• Instruction Teach patients about
• Each medication, including name, appearance,
  purpose and effects
• Potential adverse effects and interactions of
  each medication
• Importance of contacting healthcare provider
  with concerns and questions
• Potential drug related problems that warrant
  emergency care

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Prevention

• Instructions (continued)
• Importance of taking medications exactly as
  directed
• Importance of using only one pharmacy to obtain
  drugs

44
Prevention

• Organization To help manage drugs
• Avoid sharing medications
• Store medication in secure dry area away from
  sunlight
• Refrigerate if necessary
• Dispose of old medications properly

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Prevention

• No single approach extensively studied
• Prescribing and impact on outcomes inconsitent
  throughout studies
• Best approach is probable a combined approach
• Patient needs to be involved in the process

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Where Are We Now?
C. difficile Outbreak Causes Concern At Local
Hospital Tuesday June 3, 2008 CityNews.Ca Staff
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.
48
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
  20053532442-9

49
Quebec 2004Age
Age (yrs) Cases No of Cases per 1000 admissions Attributable 30-Day Mortality Rate
lt40 76 3.5 2.6
41-50 85 11.2 1.2
51-60 181 20.0 3.2
61-70 272 24.4 5.1
71-80 523 38.3 6.2
81-90 458 54.4 10.2
gt90 114 74.4 14.0
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
20053532442-9
50
Quebec 2004Antibiotics
Antibiotic Odds Ratio
Any Cephalosporin 3.8
1st Generation 2.4
2nd Generation 6.0
3rd Generation 3.0
Any Fluoroquinolone 3.9
Ciprofloxacin 3.1
Gatifloxacin/Moxifloxacin 3.4
Levofloxacin 0.6
Clindamycin 1.6
Macrolides 1.3
Penicillin w/ß-Lactamase Inh 1.2
Carbapenems 1.4
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
20053532442-9
51
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
20053532442-9
52
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 spores
• Higher mortality and colectomies
• Has in many area become the dominate strain
• Possibly due to severe diarrhea
• Antibiotic trends

53
Florida

• 1998-20031
• Codes as C. diff on discharge
• 34/100,000 to 70.2/100,000
• Biggest change from 2000-2001 (35.0 to 46.9)
• Death among patients coded with C. Diff
• 94.8/1000 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
54
Community-Acquired

• Definition controversial
• Many have been in a health care facility recently
• Local 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 common
• Many 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 riskFour
  States, 2005. MMWR Morb Mortal Wkly Rep
  2005541201-5

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Risk Factors(Hospitalized Patients)

• Increasing Age (excluding infancy)
• Younger population is becoming more at risk
• Severity of Underlying Disease
• Non-surgical gastrointestinal procedures
• Presence of nasograstric tubes
• Anti-ulcer medications
• ICU Stay
• Length of Hospital Stay
• Antibiotics
• Length of therapy
• Multiple Antibiotics

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Antibiotics

• Fluoroquinolones
• Originally considered a low risk
• Readily available, particularly ciprofloxacin
• Eliminates gram negative and anaerobic
• Full resistance to the newer NAP1/027 strain

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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