Adverse Drug Events in the Older Adult Population · Adverse Drug Events in the Older Adult Population Alan Lukazewski, RPh, CDE, CGP Oakwood Lutheran Senior Ministries 1. This educational

Adverse Drug Events in the Older Adult Population

Alan Lukazewski, RPh, CDE, CGPOakwood Lutheran Senior Ministries

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This educational session is possible through the generous 

support of the Helen Bader Foundation

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Safe Communities

Objectives1) Assess the impact of adverse drug events on the older

adult population2) Recite the most common adverse drug events leading to

ER visits and hospitalizations3) Recognize drug-induced geriatric syndromes4) List the most commonly involved drugs associated with

adverse drug events5) Describe the key risk factors associated with adverse

drug events6) Identify the most common causes of adverse drug

events in older adults7) Select the tools that can be used to reduce adverse drug

event risk

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Adverse Drug Event (ADE)

Definition: An unintended effect from a drug that produces symptoms sufficient to cause a person to seek medical attention

ORO Produces symptoms sufficient to

affect function or quality of life

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Impact  of ADEs• Older adults are 4 to 7 times more likely

to experience an ADE

• 13 to 30% of hospital admissions due to ADEs versus 3-6% of the population

• 2/3rd of hospital discharges associated with adverse medical events are ADEs

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Impact  of ADEs

• ADEs now 4th or 5th leading cause of death by disease

• Rate of increase in reported ADE fatalities to FDA from 2000 to 2010 was 451%

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Cost of ADEs

O Ambulatory care- $1300

O Hospital- $7000-$10,000• Increased length of hospital stay

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Most Common ADEsADEs most commonly leading to ER visit or hospitalization:

• Gastrointestinal bleeding• Electrolyte imbalance• Hypoglycemia• Internal bleeding• Falls• Delirium• Drug toxicity• Renal failure

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Commonly Associated DrugsDrugs most commonly implicated in ER visits and hospitalization:

• Warfarin (Anti-coagulants)• Insulin• Oral anti-diabetic agents• Anti-platelets• ACEIs/ARBs• Diuretics• NSAIDs• Opiates

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Commonly Associated Drugs

Drugs most commonly implicated in ER visits and hospitalization:

• Antibiotics• Antineoplastics

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Drug‐Induced Geriatric Syndromes

The “Soft ADEs”O FallsO Memory lossO DeliriumO Urinary IncontinenceO PainO DepressionO Insomnia

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Geriatric Syndromes

Functional Decline SyndromeO Loss of one or more ADLs

O Increased morbidityO Increased mortality

O Any ADR reduces function

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What don’t’ we know?

“You see only what you look for and recognize only what you

know”-Dr. M. Chisner

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Real butUnrecognized ADEs

• Hypomagnesemia from PPIs• Memory loss from statins• Renal failure from PPIs • Neuropathy from statins• Pain from bisphosphonates• Urinary incontinence from cholinesterase

inhibitors

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Risk Factors

Number of drugs• 30% used >= 5 drugs = 4% risk of

serious drug-drug interactions• 2-4 drugs = baseline comparator

• 4-fold increase 5-7 drugs• 8-fold increase 8-10 drugs• 13- fold increase 11-13 drugs

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Risk Factors

• Number of co-morbid conditions• Care Transitions

• Age• Renal impairment• Gender• Use of PIMs• Use of “narrow therapeutic index” drugs

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ADE Causation

• Lack of monitoring 40-60%• Drug-drug interactions 13-26%• Adverse drug reaction from new

drug• Increased drug burden causing

delirium or falls• Changes in adherence patterns

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Lack of Monitoring

• Electrolytes• Blood glucose• Drug levels• Vital signs (BP and orthostatics)• INR• Patient symptoms

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Drug‐Drug Interactions• 13-26% of all ADEs

• Pharmacist must screen and alert prescriber and nurse

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Drug‐Drug Interactions: Attempts to Classify Relevance

• 2005: consensus panel developed list of 25 serious DDI’s in older adults• “Which one’s matter?” –J. Hanlon

• Frequently narrow therapeutic index drugs

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Top drug‐drug interactions: 20 years ago

O Procainamide – AmiodaroneO Procainamide – CimetidineO Procainamide – TrimethoprimO Cimetidine – QuinidineO Cimetidine - TheophylineO Cimetidine – DisopyramideO Cimetidine - QuinidineO Carbamazepine – DiltiazemO Phenytoin – CimetidineO Phenytoin – FluoxetineO Phenytoin - WarfarinO Phenytoin – TheophyllineO Phenytoin – AmiodaroneO Digoxin – Amiodarone

O Digoxin – QuinidineO Digoxin – VerapamilO Lithium – ACE InhibitorsO Lithium – NSAIDsO Lithium - DiureticsO Theophylline – ErythromycinO Warfarin – AmiodaroneO Warfarin – SulfamethoxazoleO Warfarin – QuinolonesO Warfarin – MacrolildesO Quinidine – Fluvoxamine

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Top drug‐drug interactions: 20 years ago

O Procainamide – AmiodaroneO Procainamide – CimetidineO Procainamide – TrimethoprimO Cimetidine – QuinidineO Cimetidine - TheophylineO Cimetidine – DisopyramideO Cimetidine - QuinidineO Carbamazepine – DiltiazemO Phenytoin – CimetidineO Phenytoin – FluoxetineO Phenytoin - WarfarinO Phenytoin – TheophyllineO Phenytoin – AmiodaroneO Digoxin – Amiodarone

O Digoxin – QuinidineO Digoxin – VerapamilO Lithium – ACE InhibitorsO Lithium – NSAIDsO Lithium - DiureticsO Theophylline – ErythromycinO Warfarin – AmiodaroneO Warfarin – SulfamethoxazoleO Warfarin – QuinolonesO Warfarin – MacrolildesO Quinidine – Fluvoxamine

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Top drug‐drug interactions

O ACEIs – potassium-sparing diuretics

O ACEI’s - potassium supplements

O Anti-hypertensives – NSAIDsO NSAIDs - corticosteroidsO Diuretics – NSAIDs O Verapamil – Beta-blockersO Digoxin – MacrolidesO Warfarin – AspirinO Warfarin – AntiplateletsO Warfarin – NSAIDs

O ARBs potassium-sparing diuretics

O ARBs – potassium supplements

O SSRIs- OpiatesO SSRIs – NSAIDsO SSRIs - AspirinO Sulfonylureas –

SulfamethoxazoleO Trimethoprim – ACEIsO Trimethoprim - ARBs

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Observational Studies: Where the data are strongest

• Population-based studies

• Nested case control• Nested case crossover

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Drug Interactions that Matter Most

• ACEIs + K+-sparing diuretic• Risk for hospitalization for

hyperkalemia OR = 20.3• After receiving a K+ sparing

diuretic within previous7 days

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Drug Interactions that Matter Most

• Overall risk for hip fracture from benzodiazepine (BZD) use OR 1.2

• BZDs + interacting drugs• Risk for hospital admission d/t hip

fracture OR 1.5 – 2.1

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Drug Interactions that Matter Most

• Calcium channel blockers (CCBs) + macrolides (erythromycin, clarithromycin)• Risk for hospital admission d/t

hypotension/shock = OR 3.7–5.8• After addition of macrolide within 7

days• Does NOT include azithromycin

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Drug Interactions that Matter Most

• Digoxin + macrolides• Risk for hospital admission d/t

digoxin toxicity = OR 11.7• Clarithromycin 14.83, azithromycin

3.71, erythromycin 3.69• After addition of macrolide within 7

days

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Drug Interactions that Matter Most

• Glyburide + SMX/TMP• Risk for hospital admission d/t

hypoglycemia = OR 6.6• After addition of SMX/TMP within 7

days

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Drug Interactions that Matter Most

• Warfarin + SMX/TMP (sulfa)• Risk of hospitalization d/t GI

bleeding = OR 2.04 – 3.84• After addition of SMX/TMP within

14 days• Many antibiotics showed increased

ORs; SMX/TMP most pronounced

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Drug Interactions that Matter Most

• Warfarin + NSAIDs• Risk of hospitalization d/t GI

bleeding = OR 3.58• For those with NSAID use in prior

90 days• NSAIDs = ibuprofen, naproxen,

meloxicam, nabumetone, celecoxib

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Observational Studies: Where the data are strongest

• Warfarin + aspirin• Warfarin + aspirin are overused

with little evidence benefit in 800,000

• Estimates suggest 800-1200 unnecessary deaths each year

• Reserve for high-risk groups

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SSRIs plus NSAIDs or Aspirin

• Increased risk for GI bleeding• Adjusted risk for SSRI use alone = 2.6 (CI

1.7-3.8)• Adjusted risk for NSAIDs alone = 3.7 (CI

3.2-4.4)• Adjusted risk for SSRIs + NSAIDs = 15.6

(CI 6.6-36.6)• Adjusted risk for SSRIs + aspirin = 7.2 (CI

3.1-17.1)34

Drug Interaction Intervention Strategies

• Discontinue precipitant drug• Change precipitant drug• Alter dose of either drug• Initiate target monitoring

• Patient education of key symptoms to monitor

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ADE DetectionO Temporal association

O Any new symptom should be considered an ADE

“Assume the drug is responsible until proven otherwise”

O Surrogate markers eg. Serum K+

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Temporal Association

Association of time with the onset of a known adverse effect after starting a drug or increasing the doseO Discontinuation of drug and abatement of

symptoms supports suspected ADEO Re-challenge further increases likelihood

drug was responsible

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Naranjo ScaleO Are there previous conclusive reports of this

reaction?O Was the reaction more severe when the dose was

increased or less severe when the dose was decreased?

O Did the patient have a similar reaction to the same or similar drugs in any previous exposure?

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Self‐ReportingSelf-reporting of ADEsO Reliable O 0.70 sensitivity, 0.85 specificityO 1/3rd not reported to MDO 1/3rd of those reported not acted

upon by MDO No action led to increased severity

of ADEs39

Prescribing Cascades

Definition: The addition of a drug that is

used to treat a side-effect from an existing drug assuming the side-effect is a new medical condition

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Prescribing CascadesO NSAIDs HTN Anti-HTN

O HCTZ Gout Allopurinol

O Amlodipine Edema Diuretic

O BisPO4 Pain Analgesic

O Aricept Incontinence Detrol

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Prescribing Cascades

O Statin Neuropathy Gabapentin

O Statin Memory loss Aricept

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ADE Prevention26-95% preventable

50-55% in most referencesO Increase monitoringO Avoid serious drug-drug interactionsO Adjust drug doses based on renal

functionO Managing care transitionsO Medication minimization

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Screening Tools(explicit criteria)

O Beer’s AGS updated Beer’s criteria

2012O STOPPO ARS and Drug Burden Index

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ADE Prevention in Care Transitions

Care transitions associated with high risk for ADEs

50% of ADEs will have occurred by 14th day post-discharge

O New medicationsO Lack of monitoringO Changes in adherence patternsO Poor patient education

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ADE Prevention in Care Transitions

Create a Medication Action PlanO Pharmacists: Use screening tools to

identify risk and create MAP for nursing to follow up

O Nursing: Use MAP to incorporate monitoring for ADEs and learn! Build your working knowledge-base

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Medication MinimizationDoron Garfinkel, MDO Community-based older adults average age 82 y/oO Protocol for medication discontinuation O 58% of drugs recommended for discontinuation

O 88% acceptance rate (4.2 drugs per patient)O 2% restarted due to re-emergence of condition

O 81% overall success rateO No adverse medical events or deaths

O 88% reported global improvement in healthO 56 out of 64 had measured improvement in cognition

O MMSE scores went from 14 to 24; 14 to 23; 14 to 30

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Medication MinimizationDoron Garfinkel, MDO LTC residents (N=119)

O Average age approx. 82 y/oO Discontinued 2.8 drugs per resident

O 18% failure rateO 1-year mortality in control group = 45%

O 21% in study groupO Hospitalization rate in control group = 30%

O 11.8% in study group

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Summary

• ADEs are more common in older adults• ADEs can cause serious harm or death• ADEs can lead to decline in function and

quality of life• Many ADEs can be prevented through:

• Improving monitoring• Avoiding serious drug-drug interactions• Provider and patient education

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Summary

• Self-reporting of ADEs is a valid tool in their detection and our ability to mitigate their effects

• Medication minimization may improve function and quality of life

• Medication minimization may reduce the incidence of ADEs

• United Way of Dane County: 608-246-4350

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Abbreviations•ACEI = ACE inhibitor- enalapril, lisinopril, captopril, fosinopril•ARB = angiotenson receptor blocker•SMX/TMP = Bactrim DS, Septra DS (sulfa drug or sulfonamide)•Sulfonylurea = glyburide, glipizide, glimepiride (OHA or oral htypoglycemiaagent)•NSAID = non-steroidal anti-inflammatory drug (ibuprofen, naproxen, nabumetone, or Motrin, Aleve, Celebrex)•CCB = calcium channel blocker (verapamil, amlodipine, diltiazem, nifedipine)•OR = odds ratio: Any OR over 1.0 is significant, but >2.0 is most significant. The higher the OR, the greater the chance of an ADE.•CI = confidence interval: Statistical measure when narrow means data are more reliable. •ARS = anti-cholinergic risk scale•DBI = drug burden index

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References

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