Inappropriate Drug Use in the Elderly-Revised Beer's Criteria ...

Inappropriate Drug Use in the Elderly-Revised Beer's Criteria ...

Inappropriate Drug Use in the Elderly-Revised Beers Criteria for 2012-Patient Safety Initiative James W. Cooper, RPh, PhD, BCPS, CGP, FASCP, FASHP, Emeritus Professor of Pharmacy Care and Consultant Pharmacist, College of Pharmacy, University of Georgia, formerly Clinical Assistant Professor,Department of Family Medicine, Medical College of Georgia and President, Consultant Press at Session Objectives

1. List drugs considered inappropriate for use in the elderly and discuss rationale 2. State safer alternatives for inappropriate drugs 3. Discuss evidence that inappropriate drug use results in adverse drug outcomes 4. Delineate an action plan for intervention when inappropriate drug use is detected in ones practice Latest Research

Liu GG and Christensen DB, JAPhA 2002;42:847-57 reviewed 11 studies and found that up to 40% of nursing home and 21% of community-dwelling elderly were receiving inappropriate drugs-predominantly propoxyphene, amitriptyline and LABZsRisk factors were: polyRx, poor health status and female sex Psychoactive Load and Hospitalization RiskCooper JW, Burfield AH et al. Psychotropic and Psychoactive Drugs and Hospitalization Rates in Nursing Facility Residents. Pharmacy Practice 2007;5(3):140-4 A monthly repeated-measures assessment method that incorporated all conditions,diseases and medication changes was done on each resident to determine patient demographics, medication usage, and hospitalizations.Results: The rates of hospitalization ranged from 0.04

to 0.07 per patient/month for any psychoactive usage in those with and without dementia as a diagnosis. The rate of hospitalization during the study period for those with no current psychotropic nor regular psychoactive usage was 0.02 and 0.03/pt./month for those respectively with and without the diagnosis of dementia, yet 86% of this sample had used psychotropics orother psychoactive drugs before the period of observation. Conclusion: Preliminary evidence is offered that suggests psychotropics and psychoactive drugs and the total "load" of these drugs may be associated with an increase in the rate and risk of all hospitalizations within a single skilled nursing facility Beers Studies to date Beers MH et al Explicit criteria for determining inappropriate medication use for nursing home

residents, Arch Intern Med 1991;151:825-32. Beers MH. Explicit criteria for determining potentially inappropriate medication use by the elderly. An update ibid 1997; 157:1531-6. Fick DM, Cooper JW, Wade WE, Beers MH et al. Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults Arch Int Med 2003;163:2716-24. Adverse Outcomes Associated with Inappropriate Drug Use in Nursing Homes Ann Pharm 2005:39 Matthew Perri III, Ajit M Menon, Aparna D Deshpande, Shashank B Shinde, Rong Jiang, James W Cooper et al

METHODS: A cohort design was used to review 1117 patient medical records in 15 Georgia nursing homes with a high risk of polypharmacy. Prevalence of inappropriate medication use among elderly patients, as defined by the Beers criteria, was estimated. The adverse health outcomes of hospitalizations, emergency department visits, or deaths were identified from Medicaid claims data. RESULTS: A total of 519 (46.5%) patients received at least one inappropriate medication and 143 (12.8%) patients experienced at least one adverse health outcome. Logistic regression revealed that the total number of medications taken (OR 1.139, 95% CI 1.105 to 1.173) significantly increased the likelihood of receiving an inappropriate drug, while having a diagnosis of dementia (OR 0.748, 95% CI 0.565 to 0.991) decreased the likelihood. Inappropriate medication use increased the likelihood of experiencing at least one adverse health outcome more than twofold (OR 2.34, 95% CI 1.61 to 3.40). Propoxyphene use alone was significantly associated with the occurrence of an adverse health outcome (OR 2.39, 95% CI 1.54 to 3.71). CONCLUSIONS: Inappropriate drug use was common in our study cohort. Inappropriate use of medication in the elderly, particularly propoxyphene, is associated with a higher risk of adverse health outcomes .

Categories of Inappropriate Use in 2003 Study Fick et al. Criteria for potentially inappropriate medication use in older adults: 1. Considering diagnoses or conditions 2. Independent of diagnoses or conditions Drugs and why?

Propoxyphene (Darvon) and combination products (Darvon Cpd, Darvocet N, Wygesic )-ARE NOW OFF THE MARKET and Offered few analgesic advantages over acetaminophen, yet has the side effects of other narcotic drugs-to include 20-36 hrs. half life of norpropoxyphene metabolite and increased risk of delirium, confusion, falls, TdP due to QTc prolongation (Cooper JW Cons Pharm 1997)-Alternative-TOPICAL NSAIDs, start with 40% methylsalicylate topically to localized pain, then 1% diclofenac (Voltaren) cream, then 5% ketoprofen gel WITH with 500-650mg APAP up to3g/day. If opioid is needed consider tramadol 37.5/325mg APAP as Ultracet up to 3 tabs/day or hydrocodone 2.5-5mg QID with APAP (codeine has many drug interactions preventing conversion to morphine)-Also Propoxyphene increased adverse health outcomes( ER visits, deaths and hospitalization costs) 240% compared with APAP for pain in NH residents . Perri M, Cooper JW et al Ann Pharm 2005. (see prior slide)

Pain Intervention Cases and Costs MG a 77 yowf, 56 220 lbs. GDS=2 , VAS=5-7, Given propoxyphene/APAP (DVN) QID for OA. Over 2 weeks became progressively more disoriented to time, place and person (GDS 2->6). Thioridazine and flurazepam added and admitted to NF 3 X for 3 to 4 months/admission over next yearCost?- $60,000+ MG Case Intervention

Taper DVN weekly QID->TID->BID->QHS then d/c, replacing each DVN dose decrease with 650mg APAP Taper thioridazine then flurazepam 25% of dose q 2 weeks . VAS then 6-7, GDS=12 ;After DVN and psychotropic tapered and pt. Taking 500mg of APAP QID VAS=5-7, changed to celecoxib 400mg/day but HBP/CHF , then back to APAP 500mg QID +Ultracet tab BID X one week then one tab BID. Added 70% sorbitol 30->60ml HS. MG Case Outcome

Over next three years, MG lived with daughter on this regimen at $7,200/yr MG kept GDS of 1-2 and VAS scores of 2-3 on this regimen MG resumed knitting and making pralines 1st-2nd year: $60,000Cost savings? 7,200= $52,000 saved Analgesics and Antiinflammatrories-contd

Indomethacin (Indocin, Indocin SR)Of all available nonsteroidal, anti-inflammatory drugs, this drug produces the most central nervous system side effects and has high likelihood of causing gastritis, anemia and GI bleeds.Alternatives- APAP 3g/day, low-dose ibuprofen (up to 800mg/day), or naproxen 220mg BID or COX-2 selectives Celebrex or Mobic for up to two weeks, but no more, due to risk of Dementia, HBP, MI, CVA and/ OR CHF, AND NEVER With hx OF HBP,MI, CVA OR CHF (Cooper JW and Burfield AH JAPhA 2009 and AGS Pain Guidelines 2009) Pain Meds- contd Pentazocine (Talwin)-is a narcotic analgesic that

causes more central nervous system side effects, including confusion and hallucinations, more commonly than other narcotic drugs. Additionally, it is a mixed agonist and antagonist Alternative-other opioid, preferably tramadol, hydrocodone, oxycodone, fentanyl or morphine if moderate to severe chronic pain is present (malignant or non-malignant) AFTER FULL DOSE APAP (3g/day) FIRST STEP with TOPICAL NSAIDs for localized pain! Pain Meds- contd Meperidine- (Demerol or Demonal) May not be an effective analgesic and may have many disadvantages to other narcotic drugs- esp.

normeperidine metabolite with t1/2 of 17-35 hrs and amphetamine-like side effects of CNS excitation to seizures (Omnicare GLs and AHFS 2012). REMEMBER- meperidine was orginally a substitute for atropine! Alternatives- tramadol up to 100mg/day, lowdose hydrocodone AFTER FULL-DOSE APAP AND TOPICAL NSAIDs FIRST STEP! Case Intervention RT an 81 yoaam with RA/OA, NHL, given meperidine 25mg PO q 6 h over first week went from GDS 2-3 to 6-7 and had haloperidol 1-3mg TID added. 3 ER visits for fall evaluations and Fx left hip and right arm and 27 episodes of agitation/harmful

behavior over the next month Unnecessary Costs- $800+/fall and $25 per agitation episode + hospitalization $12,000=$15,000 RT Case Intervention Intervention- Stop meperidine, taper haloperidol weekly by 25% dose and start celecoxib 200mg QD, then morphine CR 15>30mgBID stimulant laxative-Outcome- GDS improved to 3-4, VAS was 2-3 with Celebrex 200mg/day &morphine up to 60 mg BID and no ER visits nor falls after haloperidol taper for last 6 months of life-Pain Tx Costs after intervention-$1,500- BUT Celecoxib raised BP and 17lbs fluid wt- so stopped and changed to APAP 500mg q4h ATC!

Inappropriate Pain Medscontd Ketorolac (Toradol)-Acute and long-term usage should be avoided in older persons as a significant number have asymptomatic gastrointestinal pathology. Up to of the elderly have GERD and may have PUD Hx. Alternatives- APAP up to 3g/day, Celebrex or Mobic up to two weeks IF NO BP or WEIGHT GAIN SEEN and/or topical methylsalicyalte 40%, then Voltaren then ketoprofen gel 515% to affected areas BID-TID. Case Intervention An 81 yo male fell and broke rt. Hip- the orthopod did not consider Hx of PUD and ordered Toradol

post-op. Pt. c/o epigastric distress after 1st dose and dark stools were noted next AM. H/H dropped from 12/36 ->11/33. PCP/RPh intervention to stop after 3 doses- orthopod started rofecoxib 25mg led to BP 180/105 and edema-changed to celecoxib 200mg/day with lansoprazole 15mg AM X 30 days with BP increase and 2+ edema, changed to tramadol/APAP tab up to QID X 7days, then APAP 500mg q4h ATC. Inappropriate NSAIDs Long-term (>2weeks) usage of full dosage longer half-life non- Cox selective NSAID agents (diclofenac, naproxen, oxaprozin, piroxicam) Potential to produce GI bleeding, acute renal failure, high blood pressure,

heart failure, acute myocardial infarctiongastroprotection will not prevent GI problemsAlternatives- APAP, shorter-acting ibuprofen(not with ASA) or naproxen in low dose, OR COX-2 selectives for up to two weeks- watch concurrent ASA, oral alendronate, risedronate, ibandronate even monthlyprefer topical diclofenac then ketoprofen 2-5% to affected areas (Cooper JW SMJ 1999, JAGS, 1996, Cons Phar, 1997 and 2005 and Cooper and Burfield JAPhA 2009) Case Intervention MD was a 77 yowf with OA who was given full-dose LA NSAIDs that resulted in 5 hospitalizations for NSAID gastropathy over a 3-year period. Cost >$71,000 (Cooper JW, Wade WE JGDT 1998;12(1):95-6) Intervention- Change attending clinician!

place on APAP 650/hydrocodone 2.5 mg QID, 70% sorbitol 30ml hs. VAS went from 5-6 to 1-2. Cost=$650/yr Inappropriate PolyRx The concomitant use of daily multiple gastropathic agents ( NSAIDs, ASA, bisphosphonates, corticosteroids) without gastroprotective agents proton pump inhibitor or misoprostol ONLY NOT H-2 blockers! Greatly increased risk of exacerbation of GERD, gastritis and PUD Alternatives- APAP for NSAIDs, weekly to biweekly/monthly bisphosphonates weekly alendronate, risedronate if NO GERD/PUD or yearly bisphosphonates (Zometa/Reclast),

Micaclcin NS or PTH fragement self-injection (Forteo) for 3 to 6 months, H pylori eradication for safe ASA, corticosteroids to inhalation if COPD after tiotropium baseline. (AMDA 2009 COPD Alendronate and Naproxen are Synergistic in Causing Gastric Ulcers (Arch Int Med 2001;161:107-110) Since both NSAIDs and bisphosphonates can cause gastric ulcers-be careful how they are used together! A 10-day study of 18 women and 8 men age >30 yrs given 10mg/day of alendronate, 500mg naproxen sodium BID or both found with 1-4 week washout between crossovers

found that 2 alendronate (8%), 3 naproxen (12%) and ten (38%) receiving both developed endoscopic evidence of ulcers! Hx GERD/PUD Nonsteroidal anti-inflammatory drugs, aspirin (>325mg) (Coxibs excluded ?)-GERD in 75% and Gastric or duodenal ulcers Hx in over 50%-ALL NSAIDs May exacerbate existing ulcers or produce new/additional ulcers esp. with low-dose ASA or clopidogrel (Plavix), or prasugrel(Effience) Alternatives- APAP for pain, H. pylori eradication for safe ASA use with clarithromycin+ PPI for 5-7 days followed by daily PPI, NO LONG-TERM FULL DOSE NSAIDs (AGS Pain GLs 2009)!!!!!

Pharmacoeconomic outcomes of NSAID intervention acceptance and rejection ny Nursing/Pharmacy Team NSAID recommendation 90% acceptance has been shown to save over $100,000 per 100 bed facility per year when accepted and decrease hospitalizations by 92%-NSAID recommendation 10% rejection has been shown to cost more than $40,000 per year in same facility and triple hospitalization rate and $2,000/ month costs with 20% not returning! Cooper JW, Cons Pharm1997 and 2005 Patients at risk for GI Bleeding Still receive NSAIDs

Nearly three-fourths (73%) of older patients who have been hospitalized for GI bleeds still receive NSAIDs at some point after their discharge (Rotterdam study). 51% low-dose ASA;4% NSAID with oral anticoagulant (OA) but no antiulcer drug; 35% received NSAID with an antiulcer drug; 8% received NSAID with OA and an antiulcer drug . Visser LE et a;. Br J Clin Pharmacol 2002; 53:183-8 Warfarin, Pradaxa, Xarelto LMWH or heparin Interactions

Aspirin >325mg/day, any NSAIDs, with Dipyridamole (DP) (Persantine), but ER-DP/ASA (Aggrenox) OK BY ITSELF, NO Ticlopidine (Ticlid) and clopidrogrel (Plavix) Blood-clotting disorders receiving oral or IM anticoagulant therapy- May prolong clotting time and elevate INR values, or inhibit platelet aggregation, resulting in an increased potential for bleeding. AHFS, Omnicare , AGS, AMDA 2012 GLs Case An 81 year-old minister with CHF and DVT was taking ASA 81mg/day. On admission to

hospital for acute CHF secondary to rofecoxib, the ASA dose was increased to 325mg/day, warfarin 10mg/day started and enoxaparin 50mg q12 hrs started. Pt. c/o acute stomach pain on 3rd hospital day and despite 8 units of packed rbcs died that night. Intervention- a lawsuit for wrongful death ! Platelet Inhibitors- Ticlopidine-Has been shown to be no better than aspirin in preventing clotting and may be considerable more toxic to the bone marrow and requires periodic CBCAlternative-clopidogrel (Plavix) note may be used with low-dose ASA for CABG and post angioplasty for high-risk pts. Prasugrel (Effience) may

be better than clopidogrel. CAREFUL WITH COUMADIN, PRADAXA or XARELTO. But need gastroprotection with PPI (Aciphex or Prevacid) and probably H. pylori eradication before long-term PPI and PPI may make either clopidogrel or prasugrel less effective. Inappropriate Psychotropics/Psychoactiv es Amphetamines, pseudoephedrine and anorexic agents-due to concerns about potential for agitation,delirium, dependence, hypertension, angina, myocardial infarction, TIAs and CVAs.

Alternatives-NS nasal spray and PAT (push-away table) Inappropriate Antiemetic Trimethobenzamide (Tigan)Is one of the least effective antiemetic drugs, yet it can cause extrapyramidal side effect (EPS) Alternatives- all other antiemetics, but some are also considered inappropriate? Inappropriate Antihistamines

Single and combination preparations containing chlorpheniramine (Chlor-Trimeton), diphenhydramine (Benadryl), hydroxyzine (Vistaril, Atarax), cyproheptadine (Periactin), promethazine (Phenergan), tripelennamine, and dexchlorpheniramine (Polaramine)All nonprescription and many prescription antihistamines may have potent anticholinergic properties-Diphenhydramine (Benadryl) Should not be used as a hypnotic and when used to treat allergic reactions it should be used in the smallest possible dose. May cause confusion and sedation and falls and worsen BPH in men. Alternatives- Loratidine (Claritin) NOW OTC, Clarinex, Allergra, other phenothiazines and haloperidol as antiemtics, but NOT cetirizine (Zyrtec) also OTC as its active metabolite of hydroxyzine NOR its levo-isomer, levocetirizine (Xyzal)

Insomnia and meds Decongestants, Theophylline (Theodur), pentoxyphylline (Trental) Methylphenidate (Ritalin), MAOIs are likely to worsen insomnia due to CNS stimulant effects Fluoxetine (Prozac) DAILY Insomnia due to CNS stimulant effects and 10-14 day half-life- OK weekly IF NO sleep nor agitation problems- Inappropriate in Parkinsonism

Metoclopramide (Reglan)-NOW BLACK BOX WARNING 5/09 BUT not more than >10-15mg/day, conventional AND atypical antipsychotics, Tacrine (Cognex), donepezil (Aricept), galantamine (Razadyne), but rivasitgmine (Exelon) PATCH has been approved for Parkinsons dementia- Due to their antidopaminergic cholinergic effects. Cognex is Inappropriate for dementia, with other three agents and Namenda preferred. Alternatives for harmful behavior-buspirone 30mg/day, acetaminophen 3g/day, 70% sorbitol or PEG (Miralax) daily Inappropriate in Cognitive Impairment or Depression

Barbiturates, Anticholinergics, Antispasmodics, Muscle Relaxants in cognitively impaired, due to CNS altering effectsCNS stimulants in Cognitive impairment-Due to CNS-altering effects CNS stimulants, thyroid preparations and in hyperthyroidism may produce or worsen hyperthyroid states Long-term benzodiazepine use in depression may produce or exacerbate depression Sympatholytic agents in depression may produce or exacerbate depression (eg

methyldopa, 5K MCG Study Spruill et al.) Inappropriate meds in Anorexia and malnutrition CNS stimulants, due to appetite suppressing effects-DAILY Fluoxetine (Prozac) and methylphenidate produces anorexia and malnutrition-due to appetite suppressing effects Amphetamines-Due to CNS stimulant side effects , remember that oral seligelene (Eldepryl) and topical (EMSAM) patch have two amphetamine metabolites Alternatives-weekly fluoxetine, other SSRIs that

may cause wt. gain e.g. citalopram/escitalopram, mirtazapine and dose seligilene AM only Inappropriate Muscle Relaxants and Antispasmodics Methocarbamol (Robaxin), Carisoprodol (Soma), Oxybutynin (Ditropan), Orphenadrine (Norflex) Chlorzoxazone (Paraflex), Metaxalone (Skelaxin), Cyclobenzaprine (Flexeril). Most muscle relaxants and antispasmodic drugs are poorly tolerated by the elderly, leading to anticholinergic side effects, sedation, and weakness. Additionally, their effectiveness at doses tolerated by the elderly is questionableAlternatives- tolterodine (DetrolLA), fesoterodine (Toviaz) or oxbutinin patch (Oxytrol) or gel (Gelnique) for urge incontinence.

Inappropriate BZs Flurazepam (Dalmane), diazepam (Valium), chlorazepate (Tranxene), and other longeracting benzodiazepines-Benzodiazepines with an extremely long half-life in the elderly (5-7 days), producing prolonged sedation and increasing the incidence of falls and fracture. Alternatives-SSRIs, buspirone or short-acting benzodiazepines (BZs) e.g. oxazepam are preferable (Cooper JW Cons Pharm 2005, Cooper and Burfield Geriatrics and Aging, 2008 and JAPhA 2009) Inappropriate BZs

Doses greater than lorazepam (Ativan), 3mg; oxazepam (Serax), 60mg; alprazolam (Xanax), 2mg; temazepam (Restoril), 15mg; zolpidem (Ambien), 5mg; triazolam (Halcion), 0.25mg-Because of increased sensitivity to benzodiazepines in the elderly, smaller doses may be effective as well as safer. Total daily doses should rarely exceed the HCFA suggested maximums Alternatives- SSRIs for 30 days before BZ taper if pt. wants to d/c BZ or lessen use (e.g. paroxetine 10-20mg, sertraline 2550mg, citalopram 20-40mg or escitalopram 10-20mg/day continuously and increasing to max dose to d/c BZs) Inappropriate BZ Combos

Chlordiazepoxide (Librium), chlordiazepoxideamitriptyline (Limbitrol) clidiniumchlordiazepoxide (Librax), and diazepam (Valium)Chlordiazepoxide and diazepam have a long half-life in the elderly (often several days), producing prolonged sedation and increasing the risk of falls and fractures. Alternative-Short- and intermediate-acting benzodiazepines are preferred if a benzodiazepine is required, but again an SSRI may be preferable Inappropriate Antidepressants Daily Fluoxetine-Long half-life of drug and risk of producing excessive CNS stimulation, sleep disturbances and

increasing agitation, as well as the need for anxiolytics, hypnotics, or antipsychotics Alternatives- weekly fluoxetine 2080mg or other SSRIs previously mentioned Inappropriate Antidepressants Amitriptyline (Elavil), Chlordiazepoxideamitriptyline (Limbitol), Perphenazineamitriptyline (Triavil)-Because of its strong anticholinergic and sedating properties, amitriptyline is rarely the antidepressant of choice for the elderlyDoxepin (Sinequan)Because of its strong anticholinergic and sedating properties,

doxepin is rarely the antidepressant of choice for the elderly Alternatives-SSRIs previously mentioned and may be use also for neuropathic pain (e.g. PHN) Inappropriate Antipsychotics-1 Thioridazine (Mellaril)-CNS, QTc and EPS side effects and Mesoridazine (Serentil)-CNS, QTc and EPS side effects. Taken off the market in the UK! Ray W et al. Arch Gen Psych 2001; 58:1161-7. Examined Tenn. Medicaid pts. 1988-1993 and found that those with severe CV disease who received moderate doses of older conventional antipsychotics had 3.5-fold increase of sudden cardiac death (TDP?) compared with similar

pts.not receiving these drugs.All PRN antipsychotics without orders for routine dosing No data of efficacy; much data on toxicity and see CATIE trials as well as Inappropriate Antipsychotics-2 Olanazapine (Zyprexa)-Obese patients may stimulate appetite and increase weight gain as well as cause new type 2 DM and much higher fall rate than other APs and prevent cholinesterase inhibitor efficacy. (Cooper JW in prep [falls] and Meyer JM. J Clin Psychiatry 2002 May;63(5):425-33 for DM risk relative to risperidone.-Alternatives- risperidone (Risperdal), paliperidone (Invega), quetiapine (Seroquel), aripriprazole (Abilify) may be safer in terms of CV and wt. gain risk. Latuda, Saphris and Ziprasidone (Geodon) may be safer in terms of wt. Gain and diabetes but NOT CV risk BUT ALL SHOULD BE

STOPPED WITHIN 30 DAYS if used for dementia-see new warning on all as of August 2008! Inappropriate Anxiolytics Meprobamate (Miltown, Equanil)-is a highly addictive and sedating anxiolytic. Those using meprobamate for prolonged periods may be addicted and may need to be withdrawn slowly-use an SSRI or buproprion for 2-4 weeks before trying taperSoma(carisprodal) is meprobamate prodrug! All barbiturates (except phenobarbital)* Except when used to control seizures.- Inappropriate Antidiabetic Agent

Chlorpropamide (Diabinese)It may have a prolonged half-life in the elderly and could cause prolonged hypoglycemia. Additionally, it may be the only oral hypoglycemic agent that causes SIADH. Alternatives- insulin-sensitizing agents first if Cpeptide >1ng/ml indicating pt. still making insuline.g. metformin, glitazones (except in CHF), alphaglucosidase inhibitors acarbose/miglitol (Precose/Glyset, then sulfonylureas or glitinides (Starlix or Prandin) UNSURE- about role of Antidiabetic Alternatives Two new classes of agents are available as incretin mimetics: the glucagon-like peptide 1

(GLP-1) agonists, which facilitate incretion-like effect by facilitating insulin release at mealtimes in a glucose-dependent manner. They also enhance gastric emptying, suppress glucogon secretion and produce weight loss. Exanetide (Byetta) is a GLP-1 agonist which can not be recommended at this time as an insulin-sparing agent due to cost and lack of adequate studies in the older adult with type 2 DM (see ). Byetta may be used with metformin, a TZD (Actos, Avandia), or a sulfonylurea, but not insulins in younger patients. It comes as a fixed dose 60-dose pen which is injected twice a day. The second type of drug in this class of insulin-sparing agents is the dipeptidase-4 (DDP-4) inhibitors such as sitigliptin (Januvia) which produces a GLP-1 effect by decreasing the metabolism of this hormone and thereby increase insulin release in a glucose-dependent manner. The DDP-4 inhibitors may be used as monotherapy or in combination with metformin or a thiazolidinedione (TZD, eg Actos or Avandia). Janumet is a combination of metformin and sitigliptin. (see AVOID ACTOS AND AVANDIA due to numerous risks of CHF, kidney cancer! Inappropriate GI Meds

The following gastrointestinal antispasmodic drugs- Dicyclomine (Bentyl), hyoscyamine (Levsin, Levsinex), propantheline (Pro-Banthine), belladonna alkaloids (Donnatal and others), and clidinium-chlordiazepoxide (Librax) should be avoided (especially for long-term use)Gastrointestinal antispasmodic drugs may be highly anticholinergic and generally produce substantial toxic effects in the elderly to include confusion, disorientation, delirium, falls and interference with cholinesterase inhibitors for dementia (Aricept, Exelon and Razadyne) (Cooper JW, Burfield AH, Annals LTC,2003:4[11]: 50) Inappropriate GI drugs

Mineral Oil (Haleys MO)-Potential for aspiration and adverse-effects. Safer alternatives available- 70% sorbitol 30120ml/day Cimetidine (Tagamet) Central nervous system side-effects including confusionprefer ranitidine or famotidine or PPI Long term use of stimulant laxatives, except in the presence of chronic pain requiring opiate analgesics, but try 70% sorbitol or PEG (Miralax) and MOM first if not in CRF Inappropriate Thyroid Dessicated Thyroid Due to concerns

about cardiac effects (T3 storms). Safer alternatives available-Thyroxine Be sure that sensitive TSH is done q 36 months in all pts. on any thyroid or antithyroid med (N=2-6ng/ml)- high means not enough thyroid, low means too much and need to cut dose Inappropriate Antihypertensive Agents Methyldopa (Aldomet); methyldopa/hydrochlorothiazide (Aldoril)May cause bradycardia and exacerbate depression in the elderly

Reserpine at doses > 2.5mg-May induce depression, impotence, sedation, and orthostatic hypotension Alternatives- diuretics, ACEI/ARBs, calcium channel blockers, some beta blockers Inappropriate Antihypertensive and Vasodilating Agents Guanethidine (Ismelin)-May cause orthostatic hypotension due to 5-7 day

half-life. Safer alternatives exist (ACEI/ARBs). Guanadrel (Hylorel) May cause orthostatic hypotension Cyclandelate (Cyclospasmol) Lack of efficacy. Safer alternatives available. Isoxsuprine (Vasodilan) Safer alternatives available Inappropriate Antihypertensives Short acting Nifedipine (Procardia, Adalat)-Potential for angina Clonidine (Catapres) Potential for orthostatic hypotension and CNS

adverse effects Inappropriate BP/BPH Meds Doxazosin (Cardura), prazosin and terazosin (Hytrin)Potential for toxicity pedal edema to CHF, cardiac, dry mouth, and urinary problems and worsened CHF from ALLHAT trial-tamsulosin (Flomax), silodosin (Rapaflo) and alfuzosin (Uroxaltra) NOT linked with low BP/CHF problems Clonidine (Catapres)-Potential for orthostatic hypotension and CNS adverse effects Alternatives- Diuretics, ACEI, ARBs, Calcium Channel and some selective beta blockers

Inappropriate in Stress incontinence Alpha-blockers (Doxazosin, Prazosin, Terazosin), Anticholinergics, Tricyclic antidepressants, long-acting benzodiazepines (BZ)-May produce polyuria and worsening of incontinence Alternatives- Kegel if coherent, more Chux pads if not! Inappropriate CV Drugs

Disopyramide (Norpace, Norpace CR) Of all antiarrhythmic drugs, this may be the most potent negative inotrope and therefore may induce heart failure in the elderly. It is also strongly anticholinergic. When appropriate, other antiarrhythmic drugs should be use Digoxin (Lanoxin).- in doses >0.125mg/day Except when treating atrial arrhythmias. Inappropriate CV Drugs Short-acting Dipyridamole (Persantine) ALONE or with ASA-consider the longacting Dipyridamole below (which has different properties in older adults)Extended-release dipyridamole/ASA (Aggrenox) is fine in TIA and

ischemic/thrombotic CVA prevention, but do NOT add extra aspirin! Inappropriate CV Meds Amiodarone (Cordarone)-Due to association with QT interval problems, risk of provoking torsades de pointes, hypothyroidism, pulmonary fibrosis, catarracts and lack of efficacy in older adults- BUT CAST study is extrapolated. Dronedarone (Multaq) is ALSO not to be used in chronic afib due to in creased death risk! May still see used in Hx of sudden CV standstill- do ECG, TFTs, PFTs and eye exams q 6-12 months. Dronedarone (Multaq) is newer BUT LESS SAFE derivative .

Inappropriate in Heart failure Disopyramide (Norpace), high sodium content drugs (sodium, sodium salts including alginate, bicarbonate, biphosphate, citrate, phosphate, salicylate, & sulfate), glitazones (Actos and Avandia), oral HRT and all fulldose NSAIDs, perhaps pregabalin (Lyrica) Due to negative inotropic effect or potential to promote fluid retention and exacerbation of heart failure NSAIDs and CHF in Elderly Pts. A matched case-control study of the

relationship of NSAIDs and CHF hospitalization found: Use of full-dose NSAIDs week before admission doubled risk of admission Longer-half life NSAIDs were more likely than shorter-half life agents to cause exacerbation One in 5 of CHF admissions were associated with NSAID usage (Page J, Henry D Arch Int Med 2000;160:777-784) NSAID Use increases risk of CHF relapse

Rotterdam study of 7,277 noninstitutionalized ~70yo, 62% female pop. Found that use of any NSAID (not low dose ASA) after Dx of CHF increased RR of relapse by 9.9 (little OTC NSAID use in netherlands) Feenstra J et al. Arch Int Med 2002;163:265-70 Fluid Retention and NSAIDs A 5-year study of NSAIDs and wt. Gain before COX-2s selectives were introduced found 4 suspected cases with traditional NSAIDs. A five-year subsequent study since COX-2s were introduced in the same long-term

care facility found 34 suspected cases with almost exclusive use of COX-2 inhibitors and the same prevalence of OA between both periods , with rofecoxib more likely than celecoxib or valdecoxib to lead to BP, edema or CHF admission[ rofecoxib halflife 18-20hrs vs. 8-10 hrs for cele-or valdecoxib. Risk doubled when used with a glitazone, eg rosi-or pioglitazone (Cooper JW, in prep data) Inappropriate Antinfective Macrodantin, Macrobid-due to functional renal impairment in elderly (Cooper JW J Pharmacoepi 1991) ave. Creatinine clearance 40 mlmin or LESS of 80 yo and higher risk of peripheral neuropathy, pneumonitis and hemolytic anemia. Safer alternatives available (TMP if not on ACEI/ ARB or K-sparing diuretic, eg triamterene)

Inappropriate Dose and Indications Iron supplements >325mg daily Total absorption may not occur with higher doses. May increase constipation risk. Iron also does not get Hgb>10 in anemia of chronic diseaseReverse situation- refusal to use iron when erythrocyte-stimulating proteins [ESPs] (Procrit/Epogen or Aranesp) is in use- one case used $15,000 before Fe started! Hgb 6-7---->10 in 30 days-NEW BLACK BOX warning FOR ESPs in CRF or, chemo-associated anemiano Hgb>11-11.5! Inappropriate in Syncope or

Falls Short to intermediate- to longer-acting benzodiazepines, Tricyclic antidepressants, most antipsychotics (APs), propoxyphene-May produce ataxia, impaired psychomotor function, syncope, and additional fallsAlternatives- Buspirone, MAYBE SABZ (oxazepam), PREFER->SSRI, dose reduction of APs -risperidone may be safer short-term and PREFER APAP 500mgq4h ATC for agitation! Conventional Psychotropic tapering, Buspirone Conversion,Agitation,Falls, ER/Hospitalization and Deaths

In studies of NF residents with AD who were agitated and treated with psychotropics ,tapering and buspirone conversion decreased the number of agitation AND fall episodes by 75% and improved cognition over a 6-month study period. Failure to stop psychotropics doubles ER/ Hosp and death risk! (Cooper JW, Cobb HH , Burfield AH , Cons Pharm, 2001;16:358-363; Cooper JW, Cons Pharm & JAMA 1997, and Cooper JW, and Burfield AH Pharm Pract 2007 and Consult Pharm 2007 , Geriatric and Aging 2008 and JAPhA 2009) Other Fall Risk Interventions That Work

Gait , Balance, Exercise and Strength Assessment and training Environmental changes-removal of throw rugs, change slippery shoes & floors, add assist devices Home Assessment Anticipate and Address transfer issues Impact of Interventions on Geriatric Prescribing Impact of consultation on

geriatric patient prescribing (Lipton HL, et al., Med Care 1992;30-646-58). 236 Hospitalized patients 65 yo or older with 3 or more meds, 88% had at least one--> Clinically-significant Rx problem and 22% had serious to lifethreatening ADR problem due to meds; pharmacist consult intervention in-hosp., discharge &1 & 2 months afterward decreased problems vs.

control group In-hospital ADRs and Costs In hospital ADRs rank between 4th and 6th as leading causes of death in the USA- Lazarou J, et al. JAMA 1998;279:12005) 2.2 million hospitalized pts. Had serious ADRs and 106,000 died in 1994 via meta-analysis of 39 studies Two studies document high costs of ADRs within the

hospital: Classen DC, et al. JAMA 1997;277:301-6 & Bates DW, et al. Ibid:307-11. In 1st, a 4-year study, ADRs occurred in 2.43/100 admissions AND--> ADR costs contd In 1st study, each ADR added 2+ days to LOS, >$2,200 in costs and doubling of death rate 2nd study (Bates)

over 6 months, 247 ADRs were identified from 4,108 admssions Almost one-third of ADRs were deemed preventable. For preventable ADRs there was a 4.6 days increase in LOS & cost of $5,857; for all ADRs 2.2 days and $3244 increase in cost/ADR

Intervention Cost-Savings by Prevalence of Problems 1. NSAID Gastropathy hospital admissionsleading ADR: 5-year study routine H/Hs with NSAIDs-check lower eyelid/nailbeds colorreduced from 39 in 4 years (JAGS) to 3 in 5 years in recommendation acceptance group Even with 90% recommendation acceptance, the 10%

rejection group had 9 hospitalizations; saving/year $115,489 for acceptance, but lost $40,166 with rejection. Aver. Cost per admission=$14,419 (Cooper JW, Consult Pharm 1997;792-6) Cost-Savings: Falls and fractures Pyschoactive load 2. Second most common ADR

admission: each fall costs $858. Drugs most commonly associated- BZs, antipsychotics, TCAs, narcotic analgesics, antihistamines;hospiti alization=$12,000+ reduction and buspirone conversion reduced falls from 0.4 to 0.06/pt/month for savings of $58,812/ yr for acceptance and lost $99,211 with rejection of rec.s(Cooper Consult Pharm

1997; 12: 1294-1309 & JAMA 1997:278:1742-3.) Intervention in Diabetics and hospitalizations 3. With monthly assessment, both fewer episodes of hypo-/ hyperglycemia & DM-related hospitalizations were seen with accepted (3/26) vs. rejected (9/31) rec. groups (Cooper JW, Consult Pharm 1995;10:40-5)

DM consultation is current area of reimbursement mandate by states Question remainshow did patients get less than adequate medication assessment? An Approach to Inappropriate Drugs in the Elderly

1st rule in health care-Do no harm 2nd rule- If its not broken do not try to fix it 3rd rule-if its broken offer several alternatives to fix it Regulators may want to use the inappropriate

drug list as a hammer and anvil for all HCPs Be sure you have a clinical problem before rec. change! Summary and Conclusions In the year elderly become progressively to severely disabled a large proportion are hospitalized for a small number of diagnoses, most of which relate to drug

use. (Ferruci L, et al JAMA 1997;277:728-34) ADRs are only 1/3 of drug-related admissions; other 2/3 are related to nonadherence to prescribed Tx (Cooper JW, et al. AJHP 1977; 34:738-42) How can health care practitioners improve drug use among older adults?

Consumer Responsibilities And Rights Concerning Medications Patients should be able to give the name of each drug, how to use the drug and what to expect from the drug in order to best use the drug in their overall treatment schemePatients should expect reasonable medication outcomes! You may want to present these slides-at or email me at [email protected] for free copy. Dr. Jack Finchams superb book Taking Your Medicine is highly recommended for the caregiver and layperson who wants to better understand their medications and may be ordered via e-mail to [email protected] .Thank you!

Additional Resources Geriatric Medication Management30 hr CME/CPE/CNE course providors yet to be determined. 15 hrs on Lab Tests and Physical Assessment of the Older Adult at click or For other CGP prep or other CE resources, see, and or Potential Conflicts of

Interest Dr. Cooper has served on PAST advisory boards, speakers bureaus and/or received grant support from: Abbott, Aventis, Bayer, BMS, Boehringer-Ingleheim, Ciba-Geigy, Forest labs, Glaxo-SKB, J&J,Janssen,Orthobiotech, P&G, Pfizer-Roerig, PurduePharma, Astra Zeneca, Lilly-Dista, Merck, Organon, Watson labs and Novartis. Currently only B-I, Forest and Pfizer. CPE/CME/CNE Questions

1. Which analgesic is inappropriate? A. APAP B. meperidine C. tramadol D. hydrocodone 2. T or F-Inappropriate drugs are a cause of increased morbidity, mortality and health care costs in the elderly Questions, contd 3. Drugs may be inappropriate with

which of the following diagnoses? A. CHF B. HBP C. Gastric or duodenal ulcers D. Seizure history E. any or all of the above Questions and Key 4. The 3rd rule in health care is-A.Do no harm

B.If its not broken do not try to fix it C.if its broken offer several alternatives to fix it D. none of the above Key1.b, 2-T, 3-E, 4-C

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