Side Effect Burden in the Elderly Population Joshana K. Goga Pharm.D. BCPP Sheppard Pratt Health System University of Maryland School of Pharmacy September 2013 Objectives • Recognize high risk medications in the elderly population • Evaluate medications on Beer’s criteria • Evaluate medications with anticholinergic load • Evaluate STOPP approach Aging Population Based on online data from the U.S. Census Bureau’s 1 Physiological Changes in Elderly • • • • • • • • • • • Cardiac output decreases Blood pressure increases and arteriosclerosis develops Lungs show impaired gas exchange, a decrease in vital capacity and slower expiratory flow rates Creatinine clearance decreases with age although the serum creatinine level remains relatively constant due to a proportionate age-related decrease in creatinine production Slowing of gastrointestinal system with trophic gastritis and altered hepatic drug metabolism Progressive elevation of blood glucose occurs with age on a multifactorial basis Osteoporosis is frequently seen due 'to a linear decline in bone mass after the fourth decade Epidermis of the skin atrophies with age and due to changes in collagen and elastin the skin loses its tone and elasticity Lean body mass declines with age and this is primarily due to loss and atrophy of muscle cells Degenerative changes occur in many joints and this, combined with the loss of muscle mass, inhibits elderly patients locomotion Liver function decline-patient variability Prescription use in Elderly • • • • • • • Elderly patients take about three times as many medications as younger patients do1 According to the Medicare, the average number of prescriptions per year, including refills, is currently 28.5 per senior (up from 19.6 in 1992) Greatest consumers of prescribed and non-prescribed medications2 Average cost per prescription has also jumped from $28.50 in 1992 to $42.30 in 2000, an increase of 48% In 2012, prescription drug prices rose 3.6%, twice the 1.7% inflation rate, Bureau of Economic Analysis data Since the elderly have less participation in drug trials, there is insufficient information on the side effects and adverse reactions of drugs on the elderly As a result, older patients have to rely on general guidelines with information extrapolated from other age groups to make decisions regarding prescription drug use 1 1.Shaughnessy, F., Allen, Anderson, J., Robert, 1995. "Drug Prescribing for the Elderly." Family Practice Recertification VOL 17, No. 11: 62-69. 2. United States Pharmacopeia, 2000. "Guiding Principles for Enhancing the Likelihood of Positive Medication Use Outcomes in Geriatric Patients." The United States Pharmacopeial Convention. Prescription Use in the Elderly • Social circumstances such as living alone, difficulty in visiting their primary physician • Confusion resulting from the use of multiple medications, memory problems and failing vision leading to impaired functioning • Failure to comply with the complicated drug treatment plan and poor understanding of the drug treatment Elderly : Risk of Adverse Drug Events • over 700,000 emergency department visits each year • Nearly 120,000 pts each year need hospitalization for further treatment after ER • Older adults (65 years or older) are twice as likely as others to come to emergency departments for adverse drug events • over 177,000 emergency visits each year and nearly seven times more likely to be hospitalized after an emergency visit CDC 2013 National Action Plan • The National Action Plan for Adverse Drug Event Prevention has two key objectives: identify common, clinically significant, preventable, and measurable adverse drug events (ADEs); and align the efforts of federal health agencies to reduce patient harm from these specific ADEs nationally. National Action Plan • Based on national ADE data from inpatient and outpatient settings, three types of ADEs were considered to be common, clinically significant, preventable, and measureable, and therefore selected as the high-priority targets of this Action Plan. • The three initial targets of the Action Plan are: • 1) Anticoagulants (primary ADE of concern: bleeding) • 2) Diabetes agents (primary ADE of concern: hypoglycemia) • 3) Opioids (primary ADE of concern: accidental overdoses/oversedation /respiratory depression) National Action Plan The Plan suggests a four–pronged approach to reduce patient harms from these three ADEs: Surveillance, Prevention, Incentives and Oversight, and Research Tool: Beer’s Criteria History • First introduced 1997, updated 2003, 2012 • Expert panel consisting of geriatrician, geriatric psychiatrist, and pharmacist • Identify “potentially inappropriate medications” (PIMs) to avoid in the over 65 population • Associated with poor patient outcomes - limited efficacy in older adults Fick DM Updating the Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults. Archives of Internal Medicine. 2003;163:2716-2724 Tool: Beer’s Criteria • Current update partnership with American Geriatric Society • PIMs categorized into two broad groups: – Medications to avoid in older adults regardless of diseases or conditions – Medications considered potentially inappropriate when used in older adults with certain diseases or syndromes • Third group added: medications that should be used with caution Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults Drug Rationale Recc Aspirin for primary prevention of cardiac events Lack of evidence of benefit vs. risk in pts age >80 Use with caution in adults >80 Dabigatran (Pradaxa) Greater risk of bleeding than with warfarin in adults aged >75; lack of evidence for efficacy and safety in pts CrCl < 30 mL/min Use with caution in adults aged >75 or if CrCL < 30 mL/min Prasugrel (Effient) Greater risk of bleeding in older Use with caution adults; risk may be offset by benefit in adults age > in highest-risk older adults (e.g. with 75 prior MI or DM) Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults Drug Rationale Recc Antispychotics Carbamazepine Carboplatin Cisplatin Mirtazapine SNRIs SSRIs TCAs Vincristine May exacerbate or cause syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; need to monitor sodium level closely when starting or changing dosages in older adults due to increased risk Use with caution vasodilators May exacerbate episodes of syncope in individuals with history of syncope Use with caution Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults Drug Indication Beers recc Alternatives Nitrofurantoin Anti-infective, often used for UTI Gram(+)cocci, incl. Staph, enterococci; Gram(-) bacilli but variable activity (need sensitivity testing) vs Klebsiella, Enterobacter, Proteus Fluoroquinolones (best penetration into prostate gland) -Levofloxacin*, ciprofloxacin Bactrim (women only) Beta-lactams -Carbenicillin indanyl -3rd/4th gen cephalosporins -Ceftibuten -Cefixime Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl < 60 mL/min due to inadequate drug concentration in the urine. Moderate quality evidence, strong recommendation to avoid for long-term suppression; avoid in patients with CrCl < 60 mL/min Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults Drug Indication Beers recc Alternatives Clonidine Hypertension Thiazide diuretics ACE inhibitors Angiotensin receptor blockers Calcium channel blockers Beta blockers High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension Low quality evidence but strong recommendation to avoid as 1st line hypertensive Beer’s Criteria for Potentially Inappropriate Medication Use in Older Adults Drug Indication Beers recc Long-acting sulfonulureas -Chlorpropamide Glyburide Type 2 diabetes Alternatives Chlorpropamide: prolonged Glipizide half-life in older adults; can cause prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycemia in older adults. High quality evidence, strong recommendation to avoid altogether Anticholinergic Load • Cumulative effect of several medications with anticholinergic properties • Risks =Dry eyes, dry mouth, urinary retention, constipation, tachycardia, delirium Tool: Anticholinergic Load Rudolph JL. The Anticholinergic Risk Scale and Anticholinergic Adverse Effects in Older Person s. Archives of Internal Medicine. 2008;168(5):508-513 Tool: STOPP • newer criteria to identify potentially inappropriate medications in elderly • including drug–drug and drug–disease interactions, drugs which increase risk of falls and drugs which duplicate therapy • They were developed by a panel of 18 experts in geriatric pharmacotherapy including physicians, pharmacologists, pharmacists and a psychiatrist. • Unlike the Beers criteria, STOPP criteria have been significantly associated with avoidable adverse drug events in older people that cause or contribute to hospitalization1 Tool: STOPP VS Beers • STOPP criteria are organized according to physiological systems, whereas Beers criteria are not • STOPP criteria deal with drugs that are currently in widespread use; Beers criteria include several drugs that are no longer available in • STOPP criteria place special emphasis on potential adverse drug-drug interactions and duplicate drug class prescription, whereas Beers criteria do not • STOPP criteria contain several common instances of potentially inappropriate prescribing that are not mentioned in Beers criteria Tool: STOPP • • • • • • • • • • • • • • Cardiovascular System Digoxin > 0.125mg with impaired renal function (Clcr < 50ml/min) Loop diuretic -for edema only,first line monotherapy for hypertension Beta blocker with COPD with verapamil Diltiazem or verapamil with NYHA Class III or IV heart failure Calcium channel blockers with constipation Aspirin and warfarin without H2 receptor antagonist or PPI Dipyridamole as monotherapy for CV secondary prevention Aspirin With history of PUD,Doses > 150mg/day,With no history of coronary, cerebral or peripheral vascular disease,To treat dizziness not due to cerebrovascular disease Warfarin – > 6 mo. for first uncomplicated DVT >12 mo. for first uncomplicated PE Aspirin, clopidogrel, dipyridamole or warfarin with concurrent bleeding disorder Tool: STOPP Central Nervous System and Psychotropics • TCA’s (Tricyclic Antidepressants) • With dementia • With glaucoma • With cardiac conduction abnormalities • With constipation • With opiate or calcium channel blocker • With prostatism or urinary retention • Long term benzodiazepines (> 1 month) • Long term neuroleptics • With parkinson’s (> 1 month) • As long term hypnotics • Phenothiazines with epilepsy • Anticholinergics to treat extra-pyramidal symptoms of neuroleptics • SSRI’s with hyponatremia • > 1 week use first generation antihistamines (diphenhydramine, chlorpheniramine, promethazine, cyclizine) Tool: STOPP • • • • • • • • Gastrointestinal Respiratory Musculoskeletal Urogenital Endocrine Drugs that adversely affect those prone to falls (≥ 1 fall/3mo Analgesics Duplicate Drug class Beers VS. STOPP • STOPP criteria and Beers criteria have several areas of overlap • Both sets of criteria emphasize the higher risk of adverse drug reactions and events in older people with use of long-acting benzodiazepines, tricyclic antidepressants, anticholinergic drugs, and non– cyclooxygenase 2–selective nonsteroidal antiinflammatory drugs. Both sets of criteria also focus on several common potential adverse drugdisease interactions in older people Beers VS. STOPP • OBJECTIVES: The purpose of this study was to utilize STOPP and Beers Criteria to identify PIMs in geriatric patients at an inpatient psychiatric facility, with the goal of implementing a formal process for assessing medication regimens. This process would be expected to decrease adverse outcomes • METHODS: Both criteria were used by the pharmacist to identify PIMs and recommendations were made to address the PIMs. A retrospective chart review evaluated whether utilization of the two criteria led to a significant change in number of PIMs and associated adverse outcomes • The primary outcome was the change in number of PIMs for the Beers Criteria versus the STOPP Criteria. Secondary outcomes included the change in number of PIMs, falls, required referrals/transfers, and medication-specific ADEs for each set of criteria assessed separately M.Snyder etal. Application of STOPP Criteria and Beers Criteria in an Inpatient Psychiatric Facility and Impact on Utilization of Potentially Inappropriate Medications and Adverse Outcomes, Poster presentation CPNP Annual Meeting 2012 Beers VS. STOPP • RESULTS: Twenty-nine patients met inclusion criteria, and 76 treatment recommendations were made. More PIMs per patient were identified at baseline utilizing STOPP (mean±SD,3.9±2.3)versus Beers Criteria (mean±SD, 2.2±1.3) (p<0.001) • The number of PIMs decreased using STOPP (from 112 to 66; mean decrease per patient -1.6±1.5, p<0.0001) and Beers Criteria (from 63 to 23; mean decrease per patient -1.4±1.1, p<0.0001), although the change was not significant for STOPP vs. Beers (p=0.375). All secondary outcomes decreased using both criteria • CONCLUSIONS: Utilization of each set of criteria by the pharmacist led to a significant decrease in PIMs and adverse outcomes decreased at follow-up using both criteria. Implementation of a process for assessing medication regimens of geriatric patients utilizing the Beers and/or STOPP Criteria would likely be beneficial to this institution Case Side Effect Burden • RS is an 83 year old white, widowed male presenting to SPH with agitation, grabbing staff by the throat, and being delusional. He was transferred from Meritus Medical Center ER. Case Side Effect Burden • Pt behaviors are changed from baseline x 4 weeksbecoming increasingly agitated and threatening –such as grabbing a nurse by the throat at his AL facility. Also, he has been raising his fist to the staff and peers. Patient is delusional thinking that the nurses station is his home. He is impulsive and difficult to redirect. • Pt dementia has progressed rapidly, as he was on his own until this past thanksgiving when he had a heart attack. • Pt claims to have been in A-fib for a long time and was on blood thinners at one point. Denies palpitations, diaphoresis, chest pain, and dizziness Case Side Effect Burden • Past Medical History – Bilateral Aortic Aneurysms – Eczema – Chronic A-fib – CHF – GERD s/p cholestectomy – HTN – Hx of MI, CABG – DM – Renal insufficiency Allergies: “morphine” and “oxycodon Case Side Effect Burden • Social History: RS is a high school graduate. Worked on a railroad, owned a bar and bounced for it. Served in the Navy during WWII. Wife died 15 years ago. Sister describes patient has highly intelligent, motivated, and having a good sense of humor prior to illness. Currently resides in assisted living facility • Family History: father was a railroader and farmer. Mother was a homemaker. There were 10 siblings-2 others still living. 1 brother was an alcoholic Outpatient Medication Aspirin 81mg Inpatient Medication Aspirin 81 mg Indication CAD/DM Lorazepam 1 mg q6h prn Anxiety Ambien 5 mg qhs Insomnia Furosemide 80 mg qam, 40 mg qpm Furosemide 80 mg qam, 40 mg qpm CHF glyburide 5 mg qd Glyburide 5 mg qam DM Imdur 30 mg qd Isosorbide mononitrate 30 mg qam CAD K-Dur 20 mEq tid Potassium Chloride 20 mEq tid Supplement Vitamin D 1000 U qd Supplement Metoprolol 40 mg qhs Metoprolol 25 mg bid HTN Donepezil 5 mg qd Donepezil 5 mg qam Dementia Seroquel 25 mg bid Clonidine 0.1 mg PRN Agitation Aspirin 81 mg qam CAD/cardioprotection Chlordiazepoxide 50 mg q6 prn Alcohol Withdrawal Enoxaparin 40 mg qd DVT prophylaxis Hydrocortisone 2.5% topical bid Eczema Sliding scale insulin DM Case Side Effect Burden Physical Exam • HEENT normal • Lungs- bilateral diminished bases • Heart: irregular rate • Abdominal- normal • Extremities 2+ bilateral ankle edema • Skin: thick flaking patches to skin on hands and arms. Some open and abraised areas. Skin thin and bruised on forearms. Abrasion to right lower shin, scabbed, no erythema. • Muscular: normal • Neurological/motor exam: normal Case Side Effect Burden • • • • • • • Weight=79.3 kg Height=70 inches Temp =98.3 RR= 18 HR=92 Sitting BP= 90-130’s/50-80’s Standing BP= 112/70 Case Side Effect Burden • Atrial Fibrillation with Rapid Ventricular Response • 120 bpm • No acute ST segment changes Labs Lab Result Lab Result Glucose 100 mg/cL CrCl 38.5 mL/min Na 145 mEq/L HgA1c 6.7% K 4.1 mEq/L Cholesterol 129 mg/dL Cl 106 mEq/L Anion Gap 7.0 TG 74 mg/dL Osmolality 305 mOSM/Kg HDL 33.3 mg/dL Ca 9.0 mg/dL LDL 94 mg/dL GFR 44 mL/min/1.73m^2 TSH 2.73 ulU/mL B12 583.8 pg/mL BUN 29 mg/dL Cr 1.5 mg/dL Case Side Effect Burden Assessment for: falls : Daily [minimum for score>17] 1. Age : Over 70 2. History of Falls : Fallen 1 to 2 times 3. Medication and Treatment : Antihypertensive, Antipsychotic 4. Cognition : Altered awareness of one's immediate Physcial environment, Impulsiveness, Impaired Cognition 5. Physical Status : Fatigue and weakness 6. Orthostasis : Not Applicable 7. Gait and Balance - Get-up-and-go Test. : Pushes up, successful in one attempt, Balance problems walking, decreased muscle coordination Jerking or instability when walking Gait pattern changes when walking 8. Elimination : Unremarkable Fall Risk Score Total : 21 Institute Fall Risk Precautions Level of Interventions : Assessment Score 18 - 26 CATEGORY 2 Identified Fall Risk Interventions : Problem identified on MTP Routine observation checks and document on rounds sheet Bed in low position Instruct pt to get up slowly Keep hallway clear of excess furniture, equipment, supplies Adequate lighting\prompt cleanup spills\wet floors RN/MD review pt's medications for fall related issues RN/MD review use of PRNs RN/MD review observation level Instruct pt to notify staff of dizziness Encourage fluids, monitor standing BP once per day Notify MD of falls Get PT Consult order if fall occurs/for gait/balance problem • Case Side Effect Burden • Brainstorming • Rate Control – Are you concerned with a HR of 120? – Aortic aneurysms? • Rhythm Control? • Do we anti-coagulate this patient? – Fall risk? – Dabigatran vs. Warfarin vs. clopidogrel plus aspirin • Do we worry about this patient’s dementia? • What concerns you about these medications?