Inappropriate Medication Use in the Elderly

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1 Inappropriate Medication Use in the Elderly Amanda Ilenin, Pharm.D. OhioHealth Dublin Methodist Hospital & OhioHealth Grady Memorial Hospital Kristian Navickas, Pharm.D. OhioHealth McConnell Heart Health Center Erica Wibberley, Pharm.D. OhioHealth Marion General Hospital

2 Disclosures The presenters have no actual or potential conflict of interest in relation to this presentation

3 Objectives At the end of this program, the learner will be able to: 1. Explain physiologic changes related to medication use that occur in older adults 2. Identify potentially inappropriate medications (PIM) for older adults 3. Understand risks of using specific PIM in older adults 4. Recommend non-pharmacological and pharmacological alternatives for older adults

4 Statistics Global population >65 years expected to be 22% in 2050 (up from 11% in 2010) 35% of ED visits for adverse drug events (ADEs) 7 times more likely to be hospitalized due to ADE 27% ADEs could be prevented in primary care 42% in long-term care PIM = $7.2 billion in healthcare expenditures JAMA. 2016;316(20): Scientifica. 2012; 2012: J Am Geriatr Soc. 2012; Apr;60(4):

5 Why So Many ADEs in Older Adults? Age-related physiologic changes Comorbidities Poly pharmacy PIM Lack of trials Drug Saf. 2012;35 Suppl. 1:29-45.

6 Potentially Inappropriate Medications Linked strongly with poor patient outcomes ADEs, hospitalizations, death Some have limited effectiveness in older adults Some associated with serious problems Delirium, falls, fractures, etc. Clinical judgment on individual basis J Am Geriatr Soc Apr;60(4):

7 Age-Related Physiologic Changes

8 Age-Related Pharmacokinetic Changes Absorption Reduced gastric acid secretion Decreased bioavailability Ex: calcium, iron Reduced GI motility and blood flow Reduced hepatic blood flow ( first past extraction) Increased bioavailability Ex: morphine Br J Clin Pharmacol. 2004;57(1):6-14.

9 Age-Related Pharmacokinetic Changes Distribution Less lean body mass Less total body water Increased body fat Hydrophilic medications» concentrations Ex: digoxin Lipophilic mediations» Vd, concentrations, delayed onset, t1/2 Ex: diazepam Br J Clin Pharmacol. 2004;57(1):6-14.

10 Age-Related Pharmacokinetic Changes Metabolism Reduced liver blood flow Effects depend on each drug Phase I metabolism = increased bioavailability No change in Phase 2 metabolism Prodrugs = reduced/slowed bioavailability Elimination Kidney reduced function GFR creatinine clearance (CrCl) Cockroft and Gault equation Br J Clin Pharmacol. 2004;57(1):6-14.

11 Estimating Renal Function Cockroft and Gault equation CrCl = (140 age) (IBW) 72 x Scr X 0.85 (if female)

12 Pharmacodynamics - Considerations What the drug does to the body DRUG PD EFFECT CAUSE Diazepam sedation Phase 1 hepatic metabolism Morphine analgesia hepatic metabolism Scopolamine cognitive function cholinergic system function Warfarin anticoagulation inhibition of factors II, VII, IX, X Br J Clin Pharmacol. 2004;57(1):6-14.

13 Case Question CC is a 69 year old male kg (IBW = 84.5) Which physiologic change(s) have likely occurred? a. Increased gastric acid secretion b. Reduced body fat c. Reduced liver blood flow d. Reduced elimination (CrCl) e. C & D

14 Case Question CC is a 69 year old male kg (IBW = 84.5) Which physiologic change(s) have likely occurred? a. Increased gastric acid secretion b. Reduced body fat c. Reduced liver blood flow d. Reduced elimination (CrCl) e. C & D

15 Tools to Evaluate PIM Use

16 Various Tools to Prevent PIM Over 46 tools identified 20 referred to previously published tools 36 targeted geriatric population 14 focused on over-prescribing Most not clinically validated Eur J Clin Pharmacol. 2014;70:1-11.

17 Various Tools to Prevent PIM Beers Criteria Significant correlation with negative clinical outcomes Less-studied tools Kaiser Permanente Model Lipton Criteria STOPP Criteria NCQA Criteria Eur J Clin Pharmacol. 2014;70:1-11.

patients Reduce ADRs Use common sense & clinical

18 Using Tools to Evaluate PIMs Intentions: Improve medication selection Educate clinicians and patients Reduce ADRs Use common sense & clinical judgement J Am Geriatr Soc. 2015;63(12):e1-e7. Clipartkid.com

19 Key Considerations Potentially inappropriate meds, not definitely Evaluate patient-specific factors Understand rationale for inclusion of meds Caveats exist for most meds Recommend safer non-pharmacological and pharmacological options Includes lifestyle changes J Am Geriatr Soc. 2015;63(12):e1-e7. J Am Geriatr Soc. 2015;63(12):e8-e18 = alternative = new in 2015

20 Beers Criteria Goal: To improve the care of older adults by reducing their exposure to PIM Started in 1991 Intended to: Improve medication selection Educate clinicians and patients Reduce ADEs Evaluate quality of care in older adults J Am Geriatr Soc Apr;60(4): J Am Geriatr Soc Nov;63(11):

21 Beers Criteria 2015 Updates PIMs and older adults Nitrofurantoin Antiarrhythmics Sedative-hypnotics PPI use over 8 weeks Desmopressin for nocturnal polyuria Drug-disease PIMs Sedative-hypnotics in dementia/cognitive impairment Opioids in fall or fracture risk J Am Geriatr Soc Nov;63(11):

22 Beers Criteria Tables Avoid in most older adults Avoid with specific diseases / symptoms Use with caution Potentially inappropriate drug-drug interactions *excludes antimicrobials Avoid or reduce dose for renal function *excludes antimicrobials J Am Geriatr Soc Nov;63(11):

23 Medications to Avoid in Most Older Adults High Quality of Evidence Strong Recommendation to Avoid

24 Certain Antiarrhythmics Removed recommendation to avoid class Ia, Ic, III antiarrhythmics Rate vs rhythm control: Similar rates of mortality and morbidity Rate control may be preferred in older adults Reduced risk of toxicities Lower cost Simplification J Am Geriatr Soc Apr;60(4): J Am Geriatr Soc Nov;63(11):

25 Potentially Inappropriate Antiarrhythmics Amiodarone Dronedarone Toxicities include thyroid disease, pulmonary disorders, QT-interval prolongation Avoid as first-line A.fib, unless CHF or LVH Poor outcomes in A.fib and heart failure Digoxin Avoid doses > mg for any indication Avoid as first line in A.fib Disopyramide Highly anticholinergic May induce CHF J Am Geriatr Soc Nov;63(11):

26 Antidepressants Tricyclic Antidepressants Amitriptyline, clomipramine, doxepin (doses >6 g/d), imipramine, nortriptyline, desipramine Highly anticholinergic Dry mouth, constipation, urinary retention, confusion Sedating Orthostatic hypotension SSRIs Paroxetine: Highly anticholinergic Citalopram at doses >20mg/day J Am Geriatr Soc Nov;63(11):

27 Sulfonylureas, Long-Duration Glyburide Risk of prolonged hypoglycemia Chlorpropamide Risk of prolonged hypoglycemia Risk of SIADH (syndrome of inappropriate antidiuretic hormone secretion) Alternatives Glimepiride, glipizide (avoid XL formulation) J Am Geriatr Soc Nov;63(11): Pharmacist s Letter J Am Geriatr Soc Dec;63(12):e8-e18.

28 Proton Pump Inhibitors Omeprazole, pantoprazole, lansoprazole, etc Associated with C. diff infection, bone loss, and cognitive impairment Avoid scheduled use for >8 weeks, unless: High-risk patients (oral corticosteroid use, chronic NSAIDS) Erosive or Barret s esophagitis Failure of alternative agents Alternatives: H2RAs, as needed calcium carbonate, lifestyle modifications J Am Geriatr Soc Nov;63(11):

29 Case Question RH is a 68 YOM who struggles with controlling his diabetes and often has issues with hypoglycemia. Which of RH s diabetes medications has an increased risk of prolonged hypoglycemia? a) exanatide b) glyburide c) metformin d) sitagliptin

30 Case Question RH is a 68 YOM who struggles with controlling his diabetes and often has issues with hypoglycemia. Which of RH s diabetes medications has an increased risk of prolonged hypoglycemia? a) exanatide b) glyburide c) metformin d) sitagliptin

31 Medications to Avoid in Most Older Adults Moderate Quality of Evidence Strong Recommendation to Avoid

32 First-Generation Antihistamines Hydroxyzine Promethazine Meclizine Diphenhydramine (oral) Chlorpheniramine Nasal saline spray Loratadine, cetirizine Intranasal corticosteroid Highly anticholinergic Confusion Dry mouth Constipation Urinary retention Reduced clearance with older age Tolerance develops when used as hypnotic *diphenhydramine - may be appropriate for acute severe allergic reactions in certain situations* J Am Geriatr Soc Nov;63(11): J Am Geriatr Soc Dec;63(12):e8-e18.

33 Benzodiazepines Increased sensitivity, slower metabolism Risk of delirium, falls, fractures, cognitive impairment AVOID for treatment of insomnia, agitation, delirium May be appropriate for some situations Preferred in the elderly: Lorazepam, oxazepam, temazepam L O T Anxiety buspirone, SNRI Sleep non-pharmacological strategies J Am Geriatr Soc Nov;63(11): J Am Geriatr Soc Dec;63(12):e8-e18.

34 Meperidine Not recommended in any population for pain control Nor-meperidine (active metabolite) accumulates Risk of neurotoxicity (seizures, tremors) Safer alternatives Tramadol Morphine Oxycodone/acetaminophen J Am Geriatr Soc Nov;63(11): J Am Geriatr Soc Dec;63(12):e8-e18.

35 Antispasmodics Dicyclomine, scopolamine, belladonna alkaloids Highly anticholinergic Questionable effectiveness Alternatives for chronic constipation: fiber, fluids, polyethylene glycol, psyllium Alternatives for diarrhea: loperamide J Am Geriatr Soc Nov;63(11): Pharmacist s Letter

36 Nitrofurantoin Antibiotic for urinary tract infections AVOID if CrCl less than 30 ml/min Evidence suggests it can be used in CrCl <60 ml/min Not recommended for long-term suppression May cause pulmonary fibrosis, hepatic toxicity Consider alternative antibiotics if able J Am Geriatr Soc Nov;63(11):

37 Alpha-1 Blockers Doxazosin, prazosin, terazosin High risk of orthostatic hypotension & urinary incontinence Alternative agents have better benefit:risk ratio ACE inhibitors/arbs Beta blockers Calcium channel blockers Thiazide diuretic J Am Geriatr Soc Nov;63(11): Pharmacist's Letter. 2012

38 1 st and 2 nd Generation Antipsychotics Increased risk of stroke and mortality if dementia Acceptable uses Schizophrenia Bipolar disorder Short-tern antiemetic during chemotherapy DO NOT use for dementia-related behavioral problems unless non-pharmacological options have failed and patient threatens to harm self or others J Am Geriatr Soc Nov;63(11):

39 Non-Benzodiazepine Hypnotics Eszopiclone, zolpidem, zaleplon Side effect profile similar to benzos Only slight improvement in sleep latency & duration Increased ED visits and hospitalizations Motor vehicle crashes Avoid use - no caveats Alternatives for insomnia Non-pharmacologic interventions Low-dose trazodone or doxepin, ramelteon J Am Geriatr Soc Nov;63(11): Pharmacist s Letter

40 Oral NSAIDs Ibuprofen, naproxen, aspirin >325mg/day, ketorolac Increased risk of gastric bleed and peptic ulcer in high-risk groups: Age >75 years Corticosteroid use Antiplatelet or anticoagulant use Use of concomitant PPI reduces, but does not eliminate risk J Am Geriatr Soc Nov;63(11):

41 NSAIDs (Continued) Alternatives Pain: hydrocodone/acetaminophen, oxycodone/acetaminophen Neuropathic pain: duloxetine, venlafaxine, pregabalin, gabapentin Acute gout: NSAIDs other than ketorolac and indomethacin, colchicine, prednisone If chronic NSAID use necessary, combine with a PPI OR choose celecoxib (unless heart failure OR GI/CV risk too great) J Am Geriatr Soc Nov;63(11): Pharmacist s Letter

42 Case Question AD is an 87 YOM who presents to the ED with increased confusion. He has a history of seasonal allergies and has been taking diphenhydramine for his symptoms. Which medication would you suggest that AD try for his seasonal allergies instead of diphenhydramine? a. chlorpheniramine b. loratadine c. cetirizine d. A or B e. B or C

43 Case Question AD is an 87 YOM who presents to the ED with increased confusion. He has a history of seasonal allergies and has been taking diphenhydramine for his symptoms. Which medication would you suggest that AD try for his seasonal allergies instead of diphenhydramine? a. chlorpheniramine b. loratadine c. cetirizine d. A or B e. B or C

44 Case Question AD is an 87 YOM who presents to the ED with increased confusion and a fall with a small laceration to the head. Per his son, he has been more confused than normal over the past two days and fell and hit his head on the kitchen counter while trying to take his dishes to the sink. A urine sample is collected and it appears cloudy. Which medications could have precipitated AD s UTI? a) Diphenhydramine, amitriptyline, doxazosin b) Lisinopril, amitriptyline, doxazosin c) Losartan, diphenhydramine, acetaminophen d) Lisinopril, acetaminophen, meloxicam

45 Case Question AD is an 87 YOM who presents to the ED with increased confusion and a fall with a small laceration to the head. Per his son, he has been more confused than normal over the past two days and fell and hit his head on the kitchen counter while trying to take his dishes to the sink. A urine sample is collected and it appears cloudy. Which medications could have precipitated AD s UTI? a) Diphenhydramine, amitriptyline, doxazosin b) Lisinopril, amitriptyline, doxazosin c) Losartan, diphenhydramine, acetaminophen d) Lisinopril, acetaminophen, meloxicam

46 PIM in Older Adults with Specific Diseases

47 Heart Failure NSAIDs and celecoxib Diltiazem and verapamil Avoid in systolic heart failure only Pioglitazone, rosiglitazone Cilostazol Dronedarone severe or recently decompensated CHF May promote fluid retention and trigger an exacerbation J Am Geriatr Soc Nov;63(11):

48 Parkinson Disease Antipsychotics EXCEPT aripiprazole, quetiapine and clozapine Metoclopramide Prochlorperazine Promethazine May worsen parkinsonian symptoms J Am Geriatr Soc Nov;63(11):

49 History of Falls/Fractures Anticonvulsants Avoid except for seizure or mood disorders Opioids Excludes pain due to recent fractures or joint replacement Benzodiazepines & nonbenzodiazepine hypnotics TCAs & SSRIs May cause psychomotor impairment, ataxia, syncope, falls If must be used Reduce dose of other CNS medications with fall risk Encourage other fall reduction strategies J Am Geriatr Soc Nov;63(11):

generation antihistamines Diphenhydramine, hydroxyzine, promethazine Anticholinergics and

50 Chronic Constipation Antimuscarinics for urinary incontinence Darifenacin, oxybutynin, solifenacin, tolterodine Variable responses Calcium channel blockers Diltiazem, verapamil 1 st generation antihistamines Diphenhydramine, hydroxyzine, promethazine Anticholinergics and antispasmodics *May worsen constipation* J Am Geriatr Soc Apr;60(4): J Am Geriatr Soc Nov;63(11):

51 Case Question RH is a 68 YOM who was admitted to your hospital for shortness of breath and bilateral pitting edema in the lower extremities. Which medication likely precipitated RH s recent CHF exacerbation? a) enalapril b) metoprolol c) sitagliptin d) naproxen

52 Case Question RH is a 68 YOM who was admitted to your hospital for shortness of breath and bilateral pitting edema in the lower extremities. Which medication likely precipitated RH s recent CHF exacerbation? a) enalapril b) metoprolol c) sitagliptin d) naproxen

53 Use with Caution

54 Medications to Use with Caution Medications that are appropriate in some patients Significant risk for misuse or harm No changes from 2012 updates J Am Geriatr Soc Nov;63(11):

55 Drug-Drug Interactions

56 Drug-Drug Interactions Interactions highly associated with negative outcomes in older adults Not all-inclusive All strong recommendations J Am Geriatr Soc Nov;63(11):

High Quality Evidence Medications Interaction Recommendation Benzos/sedative hypnotics Opioids Increased risk of falls 2 other CNS-active drugs Increased risk of

57 High Quality Evidence Medications Interaction Recommendation Benzos/sedative hypnotics Opioids Increased risk of falls 2 other CNS-active drugs Increased risk of bleeding Avoid total of 3 CNS drugs Minimize # of CNS drugs Warfarin NSAIDs Avoid when possible If used, monitor closely J Am Geriatr Soc Nov;63(11):

58 Moderate Quality Evidence Medications Interaction Recommendation Antipsychotics Antidepressants Anticholinergics Lithium Peripheral alpha- 1 blockers Increased risk of falls & cognitive decline 2 other CNS-active agents Increased risk of lithium toxicity ACEIs Loop diuretics Avoid total of 3 CNS drugs Minimize # of CNS drugs Minimize # of anticholinergics Avoid Monitor lithium levels Increased risk of urinary incontinence Loop diuretics Avoid in women, unless conditions warrant both drugs J Am Geriatr Soc Nov;63(11):

59 PIMs Based on Renal Function

60 PIMs Based on Renal Function Adapted from previously published criteria CrCl cutoff Medication Recommendation < 30 ml/min Amiloride Dabigatran Rivaroxaban Spironolactone Triamterene Avoid < 30 ml/min Colchicine Reduce dose < 25 ml/min Apixaban Avoid < 50 ml/min H2 RAs Reduce dose < 60 ml/min Gabapentin Pregabalin Reduce dose 80 ml/min Levetiracetam Reduce dose J Am Geriatr Soc Nov;63(11):

61 STOPP/START Criteria

62 STOPP/START Criteria Screening Tool of Older Persons Prescriptions Screening Tool to Alert to the Right Treatment European Geriatric Medicine Deficiencies in Beers Criteria Some drugs are obsolete (in Europe) or less relevant Several drugs not contraindicated in elderly No mention of errors of omission in prescribing Do not address drug class duplication issues Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

63 STOPP/START Criteria Goals Goals : Discuss significant and common PIMs Organized into physiological systems Give special attention to PIMs in patients with fall risk, opiate use, drug class duplication Address prescribing omissions Assist in preventing hospital readmissions Criteria represents the views of a panel of geriatric experts Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

64 Differences from Beers List PIM examples not mentioned in Beers Criteria: Furosemide for ankle edema (no signs of CHF) Thiazide diuretics in patients with history of gout NSAID with moderate to severe hypertension, CHF or chronic renal failure Chronic opioids with constipation and no appropriate bowel regimen Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

65 STOPP Examples Lists medications in a certain situation STOPP examples: Aspirin with history of peptic ulcer without H2 antagonist or PPI SSRIs with history of clinically significant hyponatremia Systemic corticosteroids instead of inhaled corticosteroids for COPD maintenance therapy Corticosteroids for >3 months as monotherapy for RA or OA Beta blockers in diabetic patients with frequent hypoglycemic episodes Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

66 STOPP/START Criteria Patients prone to falls Benzodiazepines, neuroleptics, first generation antihistamines, long term opiates, vasodilators known to cause hypotension Duplicate drug classes Single agent optimization before adding a second agent from the same class example exclusion: pain management Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

67 START Examples 44-57% of elderly in the hospital lack one or more indicated medication START: consider in patients >65 with appropriate indications Warfarin in patients with chronic atrial fibrillation Statin therapy with documented history of vascular disease, independent functional status, life expectancy >5 years Home continuous oxygen in chronic respiratory failure Antidepressant with moderate to severe symptoms for >3 months Antiplatelet and statin therapy in diabetes with comorbid conditions Eur Geriatr Med 2010;1: Age Ageing Mar;44(2):213-8.

68 Case Question MM is a 72 YOF who has a history of Parkinson s, chronic lower back pain, heart failure and constipation. What may be an appropriate addition to MM s home medication list? a) Morphine SR to better control her pain b) Naproxen to help pain and inflammation c) Docusate daily to help with constipation d) Senna-S daily to help with constipation

69 Case Question MM is a 72 YOF who has a history of Parkinson s, chronic lower back pain, heart failure and constipation. What may be an appropriate addition to MM s home medication list? a) Morphine SR to better control her pain b) Naproxen to help pain and inflammation c) Docusate daily to help with constipation d) Senna-S daily to help with constipation

70 Conclusions Many physiologic changes occur in older adults May alter medication effects The Beers and STOPP/START criteria include many medications that are usually not recommended to be used in older adults, however they may be appropriate for some patients in some situations Must look at patient-specific factors and use clinical judgement

71 References Jansen PA, Brouwers JR. Clinical pharmacology in old persons. Scientifica (Cairo). 2012;2012: Shehab N, Lovegrove MC, Gellar AI, et al. US Emergency department visits for outpatient adverse drug events, JAMA. 2016;316(20): The American Geriatrics Society. American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60(4): Salvi F, Marchetti A, D Angelo F, Boemi M, Lattanzio F, Cherubini A. Adverse drug events a cause of hospitalization in older adults. Drug Saf. 2012; 35 Suppl. 1: Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: Basic principles and practical applications. Br J Clin Pharmacol. 2004; 57(1): Kaufmann CP, Tremp R, Hersberger KE, Lampert ML. Inappropriate prescribing: A systematic overview of published assessment tools. Eur J Clin Pharmacol. 2014;70(1):1-11. Steinman MA, Beizer JL, DuBeau CE, et al. How to use the American Geriatrics Society 2015 Beers criteria a guide for patients, clinicians, health systems, and payors. J Am Geriatr Soc. 2015;63(12):e1- e7. Hanlon JT, Semla TP, Schmader KE. Alternative medications for medications in the use of high-risk medications in the elderly and potentially harmful drug-disease interactions in the elderly quality measures. J Am Geriatr Soc. 2015;63(12):e8-e18. The American Geriatrics Society. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11): PL Detail-Document, potentially harmful drugs in the elderly: Beers list. Pharmacist s Letter/Prescriber s Letter. June O Mahony D, Gallagher P, Ryan C, et al. STOPP & START critieria: A new approach to detecting potentially inappropriate prescribing in old age. Eur Geriatr Med. 2010;1: O Mahony D, O Sullivan D, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 2. Age Ageing. 2015;44(2):213-8.

Katee Kindler, PharmD, BCACP

Speaker Introduction Katee Kindler, PharmD, BCACP Current Practice: Clinical Pharmacy Specialist Ambulatory Care, St. Vincent Indianapolis Assistant Professor of Pharmacy Practice, Manchester University,