determining medication risk vs....
TRANSCRIPT
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DETERMININGMEDICATION RISK VS.
BENEFIT
ELLEN FULP, PHARMD, CGPCCEOL 39TH ANNUAL HOSPICE & PALLIATIVE CARE
CONFERENCECOLUMBIA, SOUTH CAROLINA
SEPTEMBER 29, 2015
Examine medication appropriateness
Review rational prescribing
Analyze common nonessential medications in thehospice setting
Evaluate medication risk and benefit at end of life
Discuss interdisciplinary team (IDT) determinations
Complete several case examples
OBJECTIVES
Few guidelines exist for determining how and whento discontinue medications
Medication appropriateness provides a means toevaluate medication need
But what is medication appropriateness?
Medication appropriateness refers to whether amedication is useful in an individual clinical situation
based on both the attributes of the medication andthose of its recipient.
MEDICATION APPROPRIATENESS
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Important factors for determining medicationappropriateness:
Remaining life expectancy of patient
Time until therapeutic benefit of medication
Goals of care
Treatment target
MEDICATION APPROPRIATENESS
1. Is there an indication for the drug?
2. Is the medication effective for the condition?
3. Is the dosage correct?
4. Are the directions correct?
5. Are the directions practical?
6. Are there clinically significant drug-drug interactions?
7. Are there clinically significant drug-disease/conditioninteractions?
8. Is there unnecessary duplication with other drugs?
9. Is the duration of therapy acceptable?
10. Is this drug the least expensive alternative compared withothers of equal utility?
MEDICATION APPROPRIATENESS INDEX
PRESCRIBING MODEL
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Diminished benefit
Clinical improvement
Stabilization
Increased risk
Medication-related adverse effects
Drug interactions
Unsafe use
High-risk drugs in older adults
INDICATIONS FOR DISCONTINUATION
Recognizing an indication for discontinuing amedication
Identifying and prioritizing the medication to betargeted for discontinuation
Documentation and approval of discontinuationrecommendation
Discontinuing the medication along with propercoordination with the patient, caregivers and otherhealthcare providers
Monitoring the patient for beneficial or harmfuleffects
STEPS FOR DISCONTINUING
ADVERSE DRUGWITHDRAWAL EVENTS
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Significant set of signsor symptoms caused bythe removal of a drug
Often abbreviatedADWE to distinguishfrom adverse drugevents (ADE)
Common medications
β-blockers
Centrally actingsympatholytics
Sedative hypnotics
Opiates
Tricyclicantidepressants
Antipsychotics
Stimulants
Corticosteroids
ADVERSE DRUG WITHDRAWAL EVENTS
True physiological withdrawal reactions
Reappearance or increase in the condition for whichthe drug was prescribed
Ex. hypertension after stopping clonidine
New set of symptoms
Ex. weakness and nausea after stoppingcorticosteroids for COPD
Exacerbation of the underlying disease
Ex. worsening angina after discontinuation of nitrates
TYPES OFADVERSE DRUG WITHDRAWAL EVENTS
TYPES OF DISCONTINUATION
• Most agents may be discontinued without ADE or ADWE• Low likelihood of dependence or withdrawal• Ex. Antihistamines, corticosteroids (< 2 weeks)
Abrupt
• High likelihood of dependence or withdrawal• Ex. Cardiovascular agents, benzodiazepines,
corticosteroids (> 2 weeks)Taper
• Other agents can be stopped with monitoring• Ex. Gastric, respiratory tract, musculoskeletal agents
Stopand
Monitor
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Patient
Frequency and severity of disease stateexacerbations
Comorbidities
Drug interactions
Type of medication
Most problematic are cardiovascular and CNS agents
Carefully monitor patients after medicationdiscontinuation
ADVERSE DRUG WITHDRAWAL EVENTS
COMMONNONESSENTIAL
MEDICATIONS
HMG-CoA reductaseinhibitor
Inhibits HMG-CoAreductase (rate limitingstep in cholesterolsynthesis)
Increase in LDLreceptors and LDLcatabolism
Lescol® (fluvastatin)
Pravachol® (pravastatin)
Mevacor® (lovastatin)
Zocor® (simvastatin)
Lipitor® (atorvastatin)
Livalo® (pitavastatin)
Crestor® (rosuvastatin)
STATINS
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MECHANISM OF ACTION
•HMG-CoAreductaseinhibited (ratelimiting step incholesterolsynthesis)
InhibitionInhibition
•Reduction in theproduction ofmevalonic acid(early precursorof cholesterol)
ReductionReduction •Upregulation ofLDL receptorexpression onhepatocytes
CompensationCompensation
•Accelerated LDLuptake
•Decreased TC,LDL, VLDL, TGlevels
CatabolismCatabolism
Indications
Primary prevention
Secondary prevention
Primary hyperlipidemia
Mixed hyperlipidemia
Other lipidemias asappropriate
Adverse Effects
GI upset (N/V, pain)Muscle injury
(myalgias, myopathyand rhabdomyolysis)
Hepatic and renaldysfunction
Incident risk ofimpaired glucosemetabolism anddiabetes
Drug interactions Cognitive impairment
STATINS
A recent 2014 multisite study randomized 381patients with life-limiting illness to discontinue orcontinue their statins (1:1).Rate of death within 60 days was not statistically
significant between the continue and discontinuegroups. The discontinue group had longer median time to
death. Total QOL was better among the discontinue group.
The investigators concluded that it is unlikely thatharm will accrue when statins being used for primaryprevention are discontinued in the setting of end oflife.
CLINICAL EVIDENCE
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Antiplatelet agent(P2Y12 antagonist)
Inhibits ADP-mediatedplatelet aggregation
Platelets blocked byclopidogrel are affectedfor the remainder oftheir lifespan (~7 to 10days)
Plavix® (clopidogrel)
Similar drugs in thisclass include:
Brilinta® (ticagrelor)
Effient® (prasugrel)
Aspirin (antiplateletwith differing MOA)
CLOPIDOGREL
Indications
Recent MI, stroke orestablished peripheralarterial disease (PAD)
Acute coronarysyndrome (ACS)
PCI (stent placement)for ACS and non-ACSindications
Adverse Effects
Increases risk ofbleeding
Epistaxis
Hemorrhage
Purpura
Skin rash, pruritus
Drug interactions
CLOPIDOGREL
MECHANISM OF ACTION
Irreversible inhibition of the P2Y12receptors on platelets
Inhibition of activation of the plateletglycoprotein complex
Inhibition of platelet aggregation for thelife of the platelet (typically 7 to 10 days)
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The CAPRIE trial found clopidogrel to only bemodestly more effective than aspirin in reducingCV events in patients with atherosclerosis, buttreatment periods ranged from 1 to 3 years,exceeding life expectancy for most hospicepatients.
Clopidogrel seems beneficial when added to ASAbefore and after PCI and acute coronary events.
There is no evidence to suggest that any patientshould use clopidogrel for more than one yearafter an MI or PCI.
CLINICAL EVIDENCE
Loop Diuretic
Inhibits reabsorption ofsodium and chloride
Increases excretion ofwater, sodium, andother electrolytes
Lasix® (furosemide)
Similar drugs in thisclass include:
Bumex® (bumetanide)
Demadex® (torsemide)
FUROSEMIDE
Indications
Edema, heart failure
Acute pulmonaryedema
Hypertension
Adverse Effects
Dizziness,lightheadedness,blurred vision,hyperglycemia
Dehydration
Muscle cramps,tiredness, fainting
Polyuria, nocturia
Hypotension
FUROSEMIDE
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MECHANISM OF ACTION
Decreasedfluid equatesto decreased
bloodvolume and
bloodpressure
Action
Increasedexcretion of
water,sodium,chloride,
magnesiumand calcium
Excretion
Inhibition ofsodium and
chloridereabsorption
in theascending
loop of Henleand distal
renal tubule
Inhibition
At least one study has suggested that only certainsubpopulations of congestive heart failure patientsactually benefit from diuretics.
JNC-8 guidelines do not recommend loop diuretics(i.e. furosemide) for the initial treatment ofhypertension.
A study of ADEs that required an ER visit found that86.1% of ADEs were associated with a single drug.Diuretics and anti-diabetic agents comprised 29% ofthese hospital visits related to electrolyteimbalances and AMS in the elderly.
CLINICAL EVIDENCE
Bisphosphonates
Inhibit bone resorption,leading to an indirectincrease in bonemineral density
Fosamax® (alendronate)
Actonel® (risedronate)
Boniva® (ibandronate)
BISPHOSPHONATES
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MECHANISM OF ACTION
Binds tohydroxyapatite sites
in bone
Inhibits osteoclastmediated bone
resorption
Reduced boneturnover, increasedbone mass, indirect
increase in bonemineral density
Indications
Osteoporosis inpostmenopausalfemales
Osteoporosis in males
Osteoporosis secondaryto glucocorticoid use
Paget’s disease
Adverse Effects
GI effects (reflux,esophagitis, ulcers)
Flu-like symptoms
Hypocalcemia
Musculoskeletal pain
Osteonecrosis of thejaw
Atypical femurfractures
BISPHOSPHONATES
Bisphosphonates have not been shown to appreciablyreduce fractures among postmenopausal women whohave not had a previous fracture, as well as thosewith relatively normal bone density.
Long-term studies of bisphosphonates suggest thattheir benefit does not extend beyond three years ofinitial treatment.
Bisphosphonate elimination half-life exceeds 10years.
CLINICAL EVIDENCE
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Acetylcholinesteraseinhibitor
Inhibits centrally-activeacetylcholinesteraseincreasingacetylcholine availablefor synaptictransmission in the CNS
Aricept® (donepezil)
DONEPEZIL
MECHANISM OF ACTION
Inhibition
Reversibly andnoncompetitivelyinhibitsacetylcholinesterase(enzyme responsiblefor the breakdown ofacetylcholine)
Increase
Increasedconcentrations ofacetylcholineavailable for synaptictransmission in theCNS
Improvement
Modestimprovements incognitive deficits
Indications
Alzheimer’s disease
Mild to moderate
Moderate to severe
Adverse Effects
N/V/D
More common in lowweight patients (<55kg)
Insomnia
Headache, pain
Anorexia and weight loss
Hypertension
Syncope
DONEPEZIL
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Courtney et al., investigated whether donepezilactually produced clinical benefit in 565 Alzheimer’spatients.
MMSE cognition scores improved by 0.8 points
Functionality BADLS scores improved by 1.0 point
No significant benefits were seen between donepeziland placebo in behavioral or psychologicalsymptoms, psychopathology, formal care costs,unpaid caregiver time, adverse events or deaths.
CLINICAL EVIDENCE
Stimulates insulinrelease from thepancreatic beta cells,reduces glucose outputfrom the liver,increases insulinsensitivity at peripheralsites
Glucotrol® (glipizide)
Diabeta® (glyburide)
Micronase® (glyburide)
Glynase® (glyburide)
Amaryl® (glimepiride)
SULFONYLUREAS
MECHANISM OF ACTION
Action
•Stimulation of insulin from the pancreatic beta cells•Decreased glucagon production in the liver
Utilization
•Release of insulin moves glucose from the bloodinto cells
Reduction•Reduction in blood glucose levels
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Indications
Diabetes (Type 2)
Adverse Effects
Hypoglycemia
Nausea
Skin reactions
Abnormal LFTs
SULFONYLUREAS
Gerstein et al., studied 10,251 diabetic patients todetermine whether intensive glucose control wouldreduce CV events in these patients (who had CVD oradditional CV risk factors).
Intensive therapy actually increased mortality and didnot significantly reduce major CV events.
Hypoglycemia is a significant risk factor fordizziness, weakness and altered mental status whichcan lead to devastating falls.
Long-acting sulfonylureas (ex. glyburide) meet theBeers Criteria and are not recommended in theelderly.
CLINICAL EVIDENCE
Vitaminsupplementation
Examples
Multivitamins
Calcium
Vitamins A, D, E, K (fatsoluble)
Vitamins B, C (watersoluble)
Saw palmetto
Ginger
Glucosamine
VITAMINS AND SUPPLEMENTS
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Indications
Indicated as asupplement to diet in:
Alcoholism
Malabsorption orgastric bypass
Prenatal women
Hemodialysis orparenteral nutritionpatients
Adverse Effects
GI upset (N/V/D) Fat soluble vitamins (A, D,
E, and K) can accumulateand cause toxicity
Vitamin A (osteopenia andbirth defects)
Iron (constipation) Vitamin D (hypercalcemia) Beta-carotene (increased
risk of lung cancer in highrisk adults)
Vitamin C (nephrolithiasis)
VITAMINS AND SUPPLEMENTS
Randomized trials that have examined the role ofantioxidant supplements in reducing CV disease havenot found positive effects.
MVI supplementation is not recommended forprimary prevention of chronic diseases due to lack ofefficacy.
Vitamin E and beta-carotene have been associatedwith adverse outcomes in lung cancer and all-causemortality.
It is suggested that supplementing the diet of wellnourished adults has no clear benefit in theprevention, nor the treatment of chronic disease.
CLINICAL EVIDENCE
Evaluate patient specific antihypertensive goals, aswell as diuretic use when they elect hospice
Contrast patients with symptoms (ex. angina) versuspatients with no symptoms (ex. primary prevention)
Don’t treat “numbers”
Overtreatment can lead to orthostatic hypotension
Increases fall risk
Decreases quality of life
Recognize agents that commonly cause orthostasis
ANTIHYPERTENSIVES
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MECHANISM OF ACTION
Selected Indications
Treatment ofhypertension
Management of anginaand heart failure
Acute MI treatment
Diabetic nephropathy
Secondary preventionin post-MI
Adverse Effects
Hypotension
Dizziness
Fatigue
Cough
Hypersensitivityreactions
Angioedema
ANTIHYPERTENSIVES
JNC-8 recommends a blood pressure goal of<150/90mmHg in patients 60 years of age or olderwithout diabetes or chronic kidney disease.
The ACCORD trial of 4,733 diabetic patients at high riskfor CV events found that intensive blood pressure control(i.e. targeting SBP<120mmHg versus SBP<140mmHg)did not reduce rate of fatal and nonfatal major CV events.
In the JATOS trial of 4,418 elderly (65-85 years)hypertensive patients, no differences were foundbetween the strict-treatment group (SBP<140 mm Hg)and the mild-treatment group (SBP≥140 mm Hg and<160 mm Hg) in the incidence of CVD and renal failurefor two years of treatment.
CLINICAL EVIDENCE
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Medications that affect the central nervous systemare commonly used in hospice patients
However, most meet Beers Criteria as potentiallyinappropriate in the elderly
Adverse effects range from mild sedation to cardiacarrhythmias and death
So how do we evaluate the use of CNS agents
in the hospice population?
CENTRAL NERVOUS SYSTEM AGENTS
CNS agents have a place in hospice care when usedappropriately
Always consider all sources for changes in cognition,mood and behavior before initiating CNS agents
Screen for underlying etiology
Triggers
Environmental changes
Iatrogenic
Redirect the patient if no source found
CENTRAL NERVOUS SYSTEM AGENTS
Triggers
• Infection• Constipation• Urinary retention• Pain (untreated
or uncontrolled)• Hunger
Environment
• Strong lights• Noise• Unfamiliar (i.e.
moving fromhome to longterm care)
Iatrogenic
• Use ofprecipitatingmedications
• Anticholinergics• Benzodiazepines
CENTRAL NERVOUS SYSTEM AGENTS
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•SSRI, SNRI, Atypical, Tricyclics•Serotonin Modulators
Antidepressants
•Typical, AtypicalAntipsychotics
•Benzodiazepines•Miscellaneous
AntianxietyAgents
•Anticonvulsants•Antimanics
MoodStabilizers
MECHANISM OF ACTION
Indications
Depression
Anxiety
Insomnia
Seizure control
Behavioral issues
Psychoses
Adverse Effects
Sedation
Cognitive impairment
Dizziness
Hypotension
QT prolongation
Anticholinergic effects
Extrapyramidalsymptoms (EPS)
CENTRAL NERVOUS SYSTEM AGENTS
For appropriate use of CNS agents, consider thefollowing:
1. Start with PRN dosing.
2. Choose agents with lowest adverse effects.
3. When titrating, use lowest dose and largest dosinginterval.
4. Monitor for clinical improvement, adverse effectsand need for additional or alternate therapy.
5. Use frequent medication reviews (or stop dates) toreduce risk of unnecessary use.
CENTRAL NERVOUS SYSTEM AGENTRECOMMENDATIONS
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INTERDISCIPLINARYTEAM DETERMINATIONS
Information about discontinuing nonessentialmedications should be used as recommendationsonly
Each patient and their medications must beevaluated individually by the IDT team, medicaldirector, attending physician, and care managers
Medications should not be discontinued without IDTapproval
Continued medications should be deemed includedor excluded from the hospice benefit by the IDT team
IDT DETERMINATIONS
PATIENT CASES
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AG is 68 year old male with end stage COPD on hospiceservice. His medications include oxygen 2L per nasal cannula,Duoneb®, simvastatin, vitamin C, Advair® 500/50, andtemazepam.
Which medications might be considered for discontinuation inthis patient?A. SimvastatinB. TemazepamC. Vitamin CD. AdvairE. A and C
PATIENT CASE
BE is a 92 year old female with end stage dementia (FAST 7c)on hospice service. Her medications include donepezil,morphine concentrate, lorazepam, APAP, calcium carbonate,MVI and Senna-S.
Which medications might be considered for discontinuation inthis patient?A. APAPB. Calcium carbonateC. DonepezilD. MVIE. B, C, and D
PATIENT CASE
ES is a 72 year old male admitted to hospice service formetastatic pancreatic cancer. His medications includefurosemide, Oxycontin®, MVI, atorvastatin, and Senna-S.
Which medications might be considered for discontinuation inthis patient?A. FurosemideB. MVIC. AtorvastatinD. Senna-SE. B and C
PATIENT CASE
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Call your AvaCare pharmacist withquestions or concerns aboutdiscontinuing nonessential
medications.
Phone:866-794-1044
Fax:866-794-5661
QUESTIONS?
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