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Medication-related problems are common, costly and often preventable in older adults and lead to poor outcomes. Estimates in past studies in ambulatory and long-term care settings found that 27% of adverse drug events (ADE’s) in primary care and 42% of ADE’s in longterm care were preventable, with most problems occurring at the ordering and monitoring stages of care. In a study of the 2000/2001 Medical Expenditure Panel Survey, the total estimated healthcare expenditures related to the use of PIM’s was $7.2 billion. Explicit criteria can identify high-risk drugs using a list of PIM’s that have been identified through expert panel review as having an unfavorable balance of risks and benefits by themselves and considering the alternatives available. A list of PIM’s was developed and published by Beers and colleagues for nursing home residents in 1991 and subsequently expanded and revised in 1997 and 2003 to include all settings of geriatric care. The 2012 update continues to categorize the PIM’s in three categories: Medications to avoid regardless of diseases or conditions, medications considered potentially inappropriate when used in certain diseases or syndromes and medications that should be used with caution. ANTICHOLINERGICS (excludes TCA’S) Rationale Brompheniramine Highly anticholinergic; clearance Carbinoxamine reduced with advanced age and Chlorpheniramine tolerance develops when used as Clemastine hypnotic; greater risk of confusion, Cyproheptadine dry mouth, constipation and other Dexbrompheniramine anticholinergic effects and toxicity. Dexchlorpheniramine Use of diphenhydramine in special Diphenhydramine (oral) situations such as acute treatment Doxylamine of severe allergic reaction may be Hydroxyzine appropriate. Promethazine Triprolidine ANTIPARKINSON AGENTS Rationale Benztropine (oral) Not recommended for prevention Trihexyphenidyl of extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. ANTISPASMODICS Rationale Belladonna alkaloids Highly anticholinergic, uncertain Clidinium-chlordiazepoxide effectiveness. Dicyclomine Hyocyamine Propantheline Scopolamine ANTITHROMBOTICS Rationale Dipyridamole, oral short acting* May cause orthostatic (does not apply to extended hypotension; more effective Release combination with aspirin) alternatives available; intravenous form acceptable for use in cardiac stress testing. Ticlopidine* Safer effective alternatives available. ANTI-INFECTIVES Rationale Nitrofurantoin Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl under 60ml/min due to inadequate drug concentration in the urine. CARDIOVASCULAR Rationale ALPHA-1 BLOCKERS: High risk of orthostatic Doxazosin hypotension; not recommended as Prazosin routine treatment for hypertension; Terazosin alternative agents have superior risk benefit profile. ALPHA AGONISTS, CENTRAL High risk of adverse CNS effects; Clonidine may cause bradycardia and Guanabenz* orthostatic hypotension; not Guanfacine* recommended as routine Methyldopa* treatment for hypertension. Reserpine (under 0.1 mg/d)* CARDIOVASCULAR continued Rationale Antiarrythmic drugs (Class Ia, IC, Data suggests that rate control III) yields better balance of benefits Amiodarone and harms than rhythm control for Dofetilide most older adults. Dronedarone Amiodarone is associated with Flecainide multiple toxicities, including Ibutilide thyroid disease, pulmonary Procainamide disorders and QT interval Propafenone prolongation. Quinidine Sotalol CARDIOVASCULAR, continued Rationale Disopyramide* Disopyramide is a potent negative inotrope and therefore may induce heart failure in older adults; strongly anticholinergic; other antiarrhythmic drugs preferred. Dronedarone Worse outcomes have been reported in patients taking dronedarone with permanent atrial fibrillation or heart failure. In general, rate control is preferred over rhythm control for atrial fibrillation. CARDIOVASCULAR, continued Rationale Digoxin, above 0.125 mg/d In heart failure, higher doses associated with no additional benefit and may increase risk of toxicity; slow renal clearance may lead to risk of toxic effects. Nifedipine, immediate release* Potential for hypotension; risk of precipitating myocardial ischemia. Spironolactone, above 25mg/d In heart failure, the risk of hyperkalemia is higher in older adults especially if taking above 25mg/d or taking concomitant NSAID, angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or potassium supplement. CENTRAL NERVOUS SYSTEM Rationale Tertiary TCA’s, alone or in Highly anticholinergic, sedating combination: and cause orthostatic hypotension; Amitriptyline safety profile of low dose doxepin Chlordiazapoxide-amitriptyline (below 6mg/d) is comparable with Clomipramine that of placebo. Doxepin, above 6mg/d Imipramine Perhenazine-amitriptyline Trimipramine CENTRA NERVOUS SYSTEM , continued Rationale Antipsychotics, first generation (conventional): Increased risk of cerebrovascular Chlorpromazine accident (stroke) and mortality in Fluphenazine persons with dementia. Haloperidol Loxapine Molindone Perphenazine Pimozide Promazine Thioridazine Thiothixene Trifluoperazine Triflupromazine CENTRAL NERVOUS SYSTEM, continued Rationale Antipsychotics, second generation (atypical) Same as first generation. Aripiprazole Asenapine Clozapine Iloperidone Lurasidone Olanzapine Paliperidone Quetiapine Risperidone Ziprasidone CENTRAL NERVOUS SYSTEM, continued Rationale Thioridazine Highly anticholinergic and risk of Mesoridazine QT interval prolongation. Barbiturates: High rate of physical dependence; Amobarbital* tolerance to sleep benefits; risk of Butabarbital* overdose at low dosages. Butalbital Mephobarbital* Pentobarbital* Phenobarbital Secobarbital* CENTRAL NERVOUS SYSTEM, continued Rationale Benzodiazepines Older adults have increased Short and intermediate acting: sensitivity to benzodiazepines and Alprazolam slower metabolism of long acting Estazolam agents. In general, all Lorazepam benzodiazepines increase risk of Oxazepam cognitive impairment, delirium, Temazepam falls, fractures and motor vehicle Triazolam accidents in older adults. Long acting: May be appropriate for seizure Clorazepate disorders, rapid eye movement Chlordiazepoxide sleep disorders, benzodiazepine Chlordiazepoxide-amitriptyline withdrawal, ethanol withdrawal, Clidinium-chlordiazepoxide severe generalized anxiety Clonazepam disorder, periprocedural Diazepam anesthesia, end of life care. Flurazepam Quazepam Chloral hydrate* Tolerance occurs within 10 days, and risks outweigh benefits in light of overdose with doses only 3 times the recommended dose. Meprobamate High rate of physical dependence; very sedating. Nonbenzodiazepine hypnotics Benzodiazepine receptor agonists Eszopiclone that have adverse effects similar to Zolpidem those of benzodiazepines in older Zaleplon adults (e.g., delirium, falls, fractures); minimal improvement in sleep latency and duration. Ergot mesylates* - Isoxsuprine Lack of efficacy. ENDOCRINE: Androgens Potential for cardiac problems and Methyltestosterone* contraindicated in men with Testosterone prostate cancer. Desiccated thyroid Concerns about cardiac effects; safer alternatives available. ENDOCRINE RATIONALE Estrogens with or without Evidence of carcinogenic potential progestins (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women. Evidence that vaginal estrogens for treatment of vaginal dryness is safe and effective in women with breast cancer, especially at doses of estradiol below 25 ug twice weekly. Growth hormone Effect on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, impaired fasting glucose. ENDOCRINE 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. Sulfonylureas, long duration Chlorpropamide: prolonged Chlorpropamide half-life in older adults; can cause Glyburide prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycemia in older adults. GASTROINTESTINAL RATIONALE Metoclopramide Can cause extrapyramidal effects including tardive dyskinesia; risk may be even greater in frail older adults. Mineral oil, oral Potential for aspiration and adverse effects; safer alternatives available. Trimethobenzamide One of the least effective antiemetic drugs; can cause extrapyramidal adverse effects. PAIN Meperidine Not an effective oral analgesic in doses commonly used; may cause neurotoxicity; safer alternatives available. PAIN RATIONALE Non-COX selective NSAID’s, oral Increase risk of GI bleeding and Aspirin (above 325 mg/d) peptic ulcer disease in high risk Diclofenac groups, including those Diflunisal aged above 75 or taking oral or Etodolac parental corticosteroids, Fenoprofen anticoagulants or antiplatelet Ibuprofen agents. Use of proton pump Ketoprofen inhibitor or misoprostol reduces Meclofenamate but does not eliminate risk. Upper Mefenamic acid GI ulcers, gross bleeding or Meloxicam perforation caused by NSAID’s Nabumetone occur in approximately 1% of Naproxen patients treated for 3-6 months Oxaprozin and in approximately 2-4% of Piroxicam patients treated for 1 year. These Sulindac trends continue with longer Tolmetin duration of use. GASTROINTESTINAL Rationale Indomethacin Increases risk of GI bleeding and Ketrolac, includes parental peptic ulcer disease in high risk groups. (See above Non-COX selective NSAID’s). Of all the NSAID’s, indomethacin has most adverse effects. Pentazocine* Opiod analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs; is also a mixed agonist and antagonist; safer alternatives available. PAIN Rationale Skeletal muscle relaxants: Most muscle relaxants are poorly Carisoprodol tolerated by older adults because Chlorzoxazone of anticholinergic adverse effects Cyclobenzaprine sedation, risk of fracture, Metaxalone effectiveness at dosages tolerated Methocarbamol by older adults is questionable. Orphenadrine DISEASE OR SYNDROME DRUG RATIONALE NSAID’s and COX-2 inhibitors Potential to promote fluid retention and Nondihydropyridine CCB’s (avoid - exacerbate heart failure. CARDIOVASCULAR: Heart Failure only for for systolic heart failure): Diltiazem Verapamil Pioglitazone, rosiglitazone Cilostazol Dronedarone DISEASE OR SYNDROME DRUG RATIONALE Syncope AChEls Increase risk of Peripheral alpha blockers: orthostatic Doxazosin hypotension Prazosin or bradycardia. Terazosin Tertiary TCA’s Chlorpromazine,olanzapine, thioridazine Chronic seizures Bupropion Lowers seizure or epilepsy Chlorpromazine threshold; may Clozapine be acceptable Maprotiline in patients with Olanzapine well controlled Thioridazine seizures in whom Thiothixene alternatives are Tramadol not effective. DISEASE OR SYNDROME DRUG RATIONALE Delirium All TCA’s Avoid in older adults Anticholinergics with or at high risk of delirium because of Benzodiazepines inducing or worsening Chlorpromazine delirium in older adults; Corticosteroids if discontinuing drugs H2-receptor antagonist used chronically, taper to avoid withdrawal symptoms. Meperidine Sedative Hypnotics Thioridazine DISEASE OR SYNDROME DRUG RATIONALE Dementia and Anticholinergics Avoid because of cognitive Benzodiazepines adverse CNS effects. impairment H2-receptor antagonists Avoid antipsychotics for behavioral Zolpidem problems of Antipsychotics, chronic dementia unless and as-needed use nonpharmacological options have failed and patient is a threat to themselves or others Antipsychotics are associated with an increased risk of cerebrovascular accident (stroke) and DISEASE OR SYNDROME DRUG RATIONALE History of Anticonvulsants Ability to produce falls or Antipsychotics ataxia, impaired Fractures Benzodiazepines psychomotor function, Nonbenzodiazepine hypnotics syncope, and additional Eszopiclone falls; shorter-acting Zaleplon benzodiazepines are Zolpidem not safer than long- TCA’s and selective serotonin reuptake inhibitors acting ones. DISEASE OR SYNDROME DRUG RATIONALE Insomnia Oral decongestants: CNS stimulant effects Pseudoephedrine Phenylephrine Stimulants: Amphetamine Methylphenidate Pemoline Theobromines: Theophylline Caffiene DISEASE OR SYNDROME DRUG RATIONALE Parkinson’s All antipsychotics Dopamine receptor disease Antiemetics: antagonists with Metochlopramide potential to worsen Prochlorperzaine parkinsonion symptoms. Promethazine Quetiapine and clozapine appear to be less likely to precipitate worsening of Parkinson’s disease. DISEASE OR SYNDROME DRUG RATIONALE Chronic Antimuscarinics for Can worsen Constipation urinary incontinence constipation; agents Darfenacin urinary incontinence: Fesoterodine antimuscarinics overall Oxybutynin (oral) differ in incidence of Solifenacin constipation; response Tolterodine variable; consider Trospium alternative agent if Nondihydropyridine CCB: Diltiazem Verapamil constipation develops. DISEASE OR SYNDROME DRUG Chronic constipation, First-generation antihistamines as continued single agent or part of combination products: Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbropheniramine Dexchlorpheniramine Diphenhydramine Doxylamine Hydroxyzine Promethazine Triprolidine RATIONALE DISEASE OR SYNDROME DRUG Chronic constipation, Anticholinergics and continued Antispasmotics: Antipsychotics Belladonna alkaloids Clidiniumchlordiazepoxide Dicyclomine Hyoscyamine Propantheline Scopolamine Tertiary TCA’s: Amitriptyline Clomipramine Doxepin Imipramine Trimipramine RATIONALE DISEASE OR SYNDROME DRUG Chronic constipation, Anticholinergics and continued Antispasmotics: Antipsychotics Belladonna alkaloids Clidiniumchlordiazepoxide Dicylcomine Hyoscyamine Propantheline Scopolamine Tertiary TCA’s: Amitriptyline, Clomipramine, Doxepin, Imipramine, Trimipramine RATIONALE DISEASE OR SYNDROME DRUG RATIONALE History of gastric Aspirin (above 325 mg) May exacerbate or duodenal ulcers Non-COX2 selective NSAID’s existing ulcers or cause new or additional ulcers. Chronic kidney NSAID’s May increase risk of disease, Stages IV or V Triamterene (alone or kidney injury. in combination) Urinary Estrogen oral and Aggravation of Incontinence transdermal (excludes incontinence. (all types) intravaginal estrogen) in women Aspirin Lack of evidence of Use with caution in for primary prevention benefit versus risk in adults over 80. of cardiac events individuals over 80 Dabigatran Greater risk of Use with caution in bleeding than with adults aged above 75 warfarin in adults aged or if CrCl below above 75; lack of 30mL/min. evidence for efficacy and safety in individuals with CrCl Below 30 mL/min Pasugrel Greater risk of Use with caution in bleeding in older adults above 75. adults; risk may be offset by benefit in highest risk older adults (e.g., with prior myocardial infarction or diabetes mellitus DIEASE OR SYNDROME DRUG RATIONALE Lower urinary tract symptoms, Inhaled anicholinergic agents May decrease urinary flow and cause benign prostatic hyperplasia Strongly anitcholinergic drugs urinary retention. except antimusscarinics for urinary incontinence Stress or mixed urinary incontinence Alpha blockers: Doxazosin Prazosin Terazosin Aggravation of incontinence. DRUG RATIONALE RECOMMENDATION Aspirin, for primary prevention Lack of evidence of benefit versus risk in Use with caution in adults over age 80. of cardiac events individuals over age 80 Dabigatran Greater risk of Use with caution in bleeding than with adults over age 75 or warfarin in adults aged If CrCl less than 30mL above 75; lack of /min. evidence for efficacy and safety in individuals with CrCl less than 30mL/min Prasugrel Greater risk of Use with caution in bleeding (may benefit adults above age 75. higher risk adults with prior myocardial injury or diabetes mellitus DRUG RATIONALE RECOMMENDATION Antipsychotics May exacerbate or Use with caution. Carbamazepine cause syndrome of Carboplatin inappropriate Cisplatin antidiuretic hormone Mirtazapine secretion or Serotoninnorepinephrine hyponatremia; need to reuptake inhibitor monitor sodium level Selective serotonin closely when starting reuptake inhibitor or changing dosages Tricyclic antidepressants in older adults due to increased risk Vincristine Vasodilators May exacerbate episodes of syncope in individuals with history of syncope Use with caution. Previously, as many as 40% of older adults received one or more of the medications on this list, depending on the care setting. These criteria have some limitations: Older adults are often underrepresented in drug trials, The criteria does not address other types of PIM’s that are not unique to aging and Hospice and palliative care patients needs (symptom control being paramount) are not completely addressed. Finally, these criteria are not meant to supersede clinical judgment or an individual’s values and needs. Prescribing and managing disease conditions should be individualized and involve shared decision making. The American Geriatric Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS 2012:1-16. Victor J. Sobolewski, III, D.O. Visiting Physicians West Allis, WI 262-949-1893