1. Anthony Caprio, MD Division of Geriatric Medicine University of North Carolina at Chapel Hill Prescribing for Older Adults “Lunch and Learn” Training Module for Physicians Support for the production and design of this training module was provided by the Donald W. Reynolds Foundation All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine

2. Learning Objectives Identify risk factors for adverse drug events (ADEs). Utilize strategies for shortening medication lists and enhancing adherence. Identify and discontinue potentially harmful medications. Recognize ADEs when new symptoms are reported by older adults.

3. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Challenges of Prescribing for Older Adults Multiple medical conditions Multiple medications Multiple prescribers Different metabolisms and responses Lack of evidence for use in elderly Adherence and cost Supplements, herbals, and over-the-counter drugs Lancet. 1995;346(8966):32–36.

4. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Lots of Medications 2/3 of older adults are on regular medications. People aged >65 account for 1/3 of all prescriptions written, but they only represent 15% of the US population. Health Care Financ Rev. 1990;11:1–41. Question: How many of your older patients have… 1.More than six chronic conditions? 2.Nine or more medications? 3.Multiple medication doses?

5. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Adverse Drug Events (ADEs) Adverse symptoms Adverse clinical outcomes –Doctor visits or hospitalizations –Falls –Functional decline –Changes in cognition (delirium) –Death Poor adherence, poor quality of life Increased cost

6. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Prevalence of Adverse Drug Events (ADEs) for Older Adults in Primary Care 35% of community-dwelling older adults annually experience an ADE In the emergency department, ADEs are experienced: –2.0 per 1000 for adults under 65 –4.9 per 1000 for aged 65 years or older –6.8 per 1000 for aged 85 years or older JAMA 2006; 296:1858–1866 JAGS 1997;45:945-948. JAGS 1996;44:194–197 Am Pharm Assoc 2002;42:847–857

7. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine 1.6 per 1000 older adults require hospitalization (7 times the younger adult rate) because of ADEs. Nearly 1/3 of all geriatric hospital admissions are due to ADEs. 2/3 of nursing home patients experience an ADE (over a 4-year period) Prevalence of Adverse Drug Events (ADEs) for Older Adults in Primary Care JAMA 2006; 296:1858–1866 JAGS 1997;45:945-948. JAGS 1996;44:194–197 Am Pharm Assoc 2002;42:847–857

8. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Medications Which Account for Most Adverse Drug Events in Older Adults JAMA 2006; 296:1858–1866 JAGS 2004;52:1349–1354 NEJM 2003;348:1556–64 Antibiotics Analgesics –Opioid –NSAIDS Anticoagulants Antihistamines Anticonvulsants Antipsychotics Cardiovascular medications Diabetic medications –Insulins –Oral agent

9. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Potential Risk Factors for Adverse Drug Events (ADE) > 6 chronic disease >12 doses/day ≥ 9 medications Low BMI (<22kg/m 2 ) Age >85 years Creatinine clearance < 50 mL/min History of prior ADE Consult Pharm 1997;12:1103–11.

10. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Physiologic Changes Associated with Normal Aging Less water More fat Less muscle mass Slowed hepatic metabolism Decreased renal excretion Decreased responsiveness of the baroreceptors

11. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Case: Mr. Johnson Mr. Johnson is 83 years old. He complains of a “runny nose” during meals on a daily basis. He asks if there is a medication to stop his runny nose. Although inconvenient at mealtime, he is not bothered by this symptom at other times during the day. Question: What do you prescribe?

12. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Rhinitis Likely diagnosis is vasomotor rhinitis and may respond to ipratropium (Atrovent) nasal spray. Could be incorrectly diagnosed as allergic rhinitis and prescribed antihistamines. “Sedating” antihistamines can have significant anticholinergic effects. J Allergy Clin Immunol 1989 Jan;83(1):110–5.

13. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Do You Need to Prescribe? Does every condition need a drug? –Is it a benign or self-limiting condition? –How does this condition bother the patient? –Inconvenient, but not life-threatening –Individualize treatment plans Consider non-drug alternatives for some conditions –Diet –Exercise –Lifestyle modification Use caution with over-the-counter (OTC) medications –Not necessarily safer than prescription drugs –Uncertain safety and efficacy of herbals and supplements

14. Principle 1:“Less is More” Keep the Medication List Short ↑ number of medications = ↑ risk of ADE Question the need for new medications, stop meds if possible Prioritize treatments - Avoid under treating conditions Pain Systolic hypertension Anticoagulation and atrial fribrillation - Weigh the benefits and risks of a new medication Sedative hypnotic medications “Tight” control of parameters (blood pressure, blood sugars) Drugs Aging 2003; 20 (1): 23–57. Lancet 2000; 355: 865–872. Ann Intern Med 1999;131:492–501. J Gen Intern Med 2005; 20:116–122.

15. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Case: Mr. Connor Mr. Connor is 80 years old. He has coronary artery disease, congestive heart failure, hypertension, and Alzheimer’s dementia. His wife is the primary caregiver. He is increasingly agitated, suspicious, and verbally abusive. He has difficulty sleeping at night and has wandered from the house on two occasions. Medications: furosemide, enalapril, metoprolol, amlodipine, aspirin, atorvastatin, alprazolam, and donepezil (Aricept). Question: What do you do?

16. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Dementia and Behavioral Disturbances Atypical antipsychotics (i.e. risperdone, quetiapine, olanzepine) –FDA Black Box warning –Increased risk of stroke, death –? Efficacy (modest at best) Typical antipsychotics (i.e. haloperidol) –May also carry increased risk of death –? Efficacy Mood stabilizers (i.e. carbamazepine, valproate) –Not effective JAMA. 2005;293:596-608 NEJM 2005;353:2335-41 CMAJ 176: 627-632

17. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Dementia and Behavioral Disturbances Avoid benzodiazepines –Danger of paradoxical reaction Consider depression –Difficult to evaluate in setting of dementia –Apathy vs. depression Acetylchoinesterase inhibitors (donepezil) might be helpful Not clear if memantine (Namenda) is helpful JAMA. 2005;293:596–608

18. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Non-Pharmacologic Approach Behavioral –Identify antecedents –Behavioral and environmental interventions –Sleep hygiene Caregiver Support –Alzheimer’s association –Respite –Day programs

19. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Stopping Medications Why was it started? Is it helping? (benefit) Is it harmful? (risk) Consider interactions with other medications Is the dose within a therapeutic range? Consider underlying renal and hepatic insufficiency

20. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Stop Potentially Dangerous Drugs: The Beers Criteria The Beers criteria is a consensus-based list of potentially inappropriate medications for older adults. The Beers criteria were published 1991, revised 1997 and 2002. Statistical association with adverse drug events has been documented. Arch Intern Med 2003;163:2716–2724. Online link to this article is http:www.med.unc.edu/aging/Beerscriteria2003article.pdf http:www.med.unc.edu/aging/Beerscriteria2003article.pdf Pharmacotherapy 2005;25(6):831–838

21. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Stop Potentially Dangerous Drugs: The Beers Criteria Beers criteria have been adopted for nursing home regulation. Does not account for the complexity of the entire medication regimen. Arch Intern Med 2003;163:2716–2724. Online link to this article is http:www.med.unc.edu/aging/Beerscriteria2003article.pdf http:www.med.unc.edu/aging/Beerscriteria2003article.pdf Pharmacotherapy 2005;25(6):831–838

22. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Criteria for Potentially Inappropriate Medication Use in Older Adults: (2002 Beers Criteria) Table 1: Independent of disease or condition –Describes concern for prescribing certain drugs or classes of drugs for older adults –Gives severity rating (low or high) Table 2: Considering diagnosis or condition –Describes drugs or classes of drugs that can cause or worsen a particular disease or condition –Gives severity rating (high or low) Arch Intern Med 2003;163:2716–2724 Tables available online at http:www.med.unc.edu/aging/Beerscriteria2003article.pdfhttp:www.med.unc.edu/aging/Beerscriteria2003article.pdf

23. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Beers: Anticholinergic Medications Drug classes –Tricyclic antidepressants –Antihistamines –Antispasmodics and muscle relaxants Adverse Effects –Urinary retention –Constipation –Confusion, delirium, behavior changes –Exacerbation of dementia Beers criteria Table 1: Arch Intern Med 2003;163:2719–2720. Link to the Beers criteria is at http:www.med.unc.edu/aging/Beerscriteria2003article.pdfhttp:www.med.unc.edu/aging/Beerscriteria2003article.pdf

24. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Beers: Benzodiazepines Avoid entirely if possible Challenging to stop for patients with long-term use Long-acting –Prolonged half-life in older adults (days) –Sedation, cognitive impairment, depression –Increased risk of falls and fractures Short-acting –Increased sensitivity in older adults –If necessary, use lower doses Beers criteria Table 1: Arch Intern Med 2003;163:2719–2720. Link to the Beers criteria is http:www.med.unc.edu/aging/Beerscriteria2003article.pdfhttp:www.med.unc.edu/aging/Beerscriteria2003article.pdf

25. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Beers: Pain Medications Propoxyphene (Darvon) has limited efficacy and significant side effects Caution with non-steroidal anti-inflammatory drugs (NSAIDS) –Indomethacin has significant CNS side effects –Ketorolac (Toradol) can cause serious GI and renal effects Meperidine (Demerol) has low oral efficacy, active metabolites and CNS effects Beers criteria Table 1: Arch Intern Med 2003;163:2719–2720. Link to the Beers criteria is at http:www.med.unc.edu/aging/Beerscriteria2003article.pdfhttp:www.med.unc.edu/aging/Beerscriteria2003article.pdf BMJ 1997;315:1565–1571.

26. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Beers: Drugs Which Can Worsen Certain Diseases or Conditions  Parkinson’s disease: Metoclopramide (Reglan)  Stress incontinence: α-blockers  Hyponatremia: selective serotonin reuptake inhibitors (SSRIs)  Constipation: calcium channel blockers Beers Criteria Table 2: Arch Intern Med 2003;163:2721.

27. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Case: Mrs. Green Mrs. Green is a 92-year-old African-American woman with macular degeneration, dementia, CAD, CHF (lowEF), and atrial fibrillation. She has been prescribed an ACE inhibitor, furosemide, β-blocker, nitrates, hydralazine, digoxin, aldactone (Spironolactone), warfarin, daily aspirin, and a statin. Her daughter provides a strict low-sodium diet. Question: What else would you do for Mrs. Green?

28. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Congestive Heart Failure High risk for adverse drug events (ADEs) –Digoxin is a Beers criteria medication –Dehydration and hypotension –Electrolyte disturbance –Bleeding What is the incremental benefit of adding each medication –Life expectancy, number needed to treat, magnitude of benefit –Lipid lowering therapy, multi-drug CHF regimen? Think about goals and adherence –Decreasing hospitalizations or extending life? –Cost? –Visual impairment? –Cognitive impairment and literacy? Arch Intern Med. 1994;154(4):433–7.

29. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Increasing Adherence Keep the medication list short. Try to use once-daily medications. Encourage use of a pillbox. Review bottles of medications. Write indications for medications on prescriptions. Medication management programs

30. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Case: Mr. Jones Mr. Jones is 82 years old with a history of herpes zoster (shingles) 6 months ago. He continues to experience severe daily pain in the same dermatomal distribution as the original rash. Question: What is your diagnosis? Question: What is the treatment?

31. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Post-Herpetic Neuralgia Opiate (narcotic) medications –Effective, but constipating –Propoxyphene (Darvon) is a Beers criteria medication. Capsaicin –OTC alternative –Topical (better than systemic) –May be poorly tolerated due to local effects. Neurology 2002;59(7):1015–21. Pain 1988;33(3):333–40.

32. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Post-Herpetic Neuralgia Tricyclic antidepressants –Effective, but have anticholinergic properties. Amitriptyline > nortriptyline > desipramine –Amitriptyline is a Beers criteria medication. Gabapentin (Neurontin) –Clinical trial doses 1800–3600 mg day in divided doses. –Dose-reduce with renal insufficiency. Neurology 1998;51(4):1166–71. JAMA 1998;280(21):1837–42.

33. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Principle 2: Dosing “Start Low and Go Slow…” Start one medication at a time. Start with a low dose and increase gradually. Once daily is usually best. Monitor for response and adverse effects. Assess adherence with regimen.

34. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine “…But, Go All The Way!” Be conservative, but don’t miss the target! What is your goal? Are you achieving it? Can you keep increasing the dose or are you limited by side effects? Are you observing a clinical benefit at lower doses? Consider stopping if you can’t “go all the way” and the benefit is not clear.

35. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Case: Mrs. Smith Mrs. Smith is an 85-year-old woman with Alzheimer’s Dementia. She was titrated to 10mg of donepezil (Aricept) daily. Her daughter is now concerned about urinary incontinence and asks about treatment. Her urinalysis is normal. Question: What would you do?

36. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Prescribing Cascade: Prescribing a New Drug to Treat an Adverse Drug Event 1.Establish the correct diagnosis. –Incontinence is likely not a new diagnosis but an ADE. –Donepezil (Aricept) can worsen or precipitate urge incontinence (pro-cholinergic effects on bladder). 2.Determine if treatment is necessary. –Incontinence is leading cause of nursing home admission. –Incontinence is a significant caregiver burden. Arch Intern Med 2005;165:808–813. BMJ 1997;315:1096–1099. JAGS 2004; 52:2082–2087.

37. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Prescribing Cascade: Prescribing a New Drug to Treat an Adverse Drug Event 3.Consider drug-drug interactions (opposing effects). –Anticholinergics are often used to treat urge incontinence. –Anticholinergics can cancel the pro-cholinergic effect of donepezil. 4.Plan: Try stopping or dose-reducing donepezil. Arch Intern Med 2005;165:808–813. BMJ 1997;315:1096–1099. JAGS 2004; 52:2082–2087.

38. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Principle 3: “Think Drugs” Before Making a New Diagnosis Consider adverse drug effect as etiology of new signs/symptoms. Remember that over-the-counter drugs, supplements, and herbals can cause adverse drug effects. Consider discontinuing or dose-reducing medications rather than treating an adverse drug effect with another medication.

39. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Constipation  Incontinence  Memory loss  Syncope  Falls  Weight loss  CA Channel Blockers Alpha blockers Antihistamines Tricyclics Benzodiazepines Fluoxetine (Prozac) Common Conditions Could Really Be Adverse Drug Effects

40. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Things to Remember: Three Principles 1.Less is More! 2.Start Low and Go Slow, but Go All The Way! 3.Think Drugs! (before making a new diagnosis)

41. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Clinical Pearls Review and reconcile meds at every visit. –Indication for each medication? –Contraindications? (renal, dementia) –Can I STOP any medication? Write indications for each prescription. Beers criteria medications –Consider alternatives. –Use caution when prescribing. The Beers criteria that are referred to in this training module are on the Center for Aging and Health webpage at the following link: www.med.unc.edu/aging/Beerscriteria2003article.pdf The Center for Aging and Health has obtained written permission to give this information on our training modules. Any use of the Beers criteria by other groups is prohibited except by obtaining written permission of the authors and editors of the article. www.med.unc.edu/aging/Beerscriteria2003article.pdf

42. All Rights Reserved © 2007 The University of North Carolina at Chapel Hill School of Medicine The Center for Aging and Health, Division of Geriatric Medicine Funding:  The Donald W. Reynolds Foundation Author:  Anthony J. Caprio, MD Educational Development: Ellen Roberts, PhD, MPH William Ashley Davis, BA Christopher Osmond, MA Center for Aging and Health: Jan Busby-Whitehead, MD C. Glenn Pickard, MD Acknowledgments Online Learning Modules Available at http://www.med.unc.edu/aging/http://www.med.unc.edu/aging/