Geriatric Pharmacotherapy: Managing Older Adults on Multiple Medications

1. Geriatric Pharmacotherapy: Managing Older Adults on Multiple Medications Lynne E. Kallenbach, M.D. Asst. Professor of Medicine University of Kansas Medical Center Landon Center on Aging October 5, 2007

2. Overview • What is “polypharmacy”? • Relevant pharmacology • Medication use issues with multiple Rxs • Potentially inappropriate medications • Approach to modifying medication profiles • Quality prescribing

3. What is polypharmacy? “As older patients move through time, often from physician to physician, they are at increasing risk of accumulating layer upon layer of drug therapy, as a reef accumulates layer upon layer of coral.” Jerry Avorn, MD From Gurwitz J. Arch Intern Med Oct 11, 2004

5. Why Geriatric Pharmacotherapy Is Important • Now, people age 65+ are 13% of US population, buy 33% of prescription drugs • By 2040, will be 25% of population, will buy 50% of prescription drugs

6. The Burden of Injuries From Medications ADEs occur in 35% of community-dwelling elderly persons • Incidence of ADEs: 26/1000 hospital beds (2.6%)

7. Adverse Drug Events in Older Adults • Serious or fatal ADEs occur in 18.5% of adults aged 55-64 and in 41.9% of adults aged >85 years. • Drug related mortality is the 9th leading cause of death for people >65 years of age. • It is estimated that ~30% of ADEs are preventable.

8. Pharmacologic Changes with Aging

9. Pharmacokinetics • Absorption • Distribution • Metabolism • Excretion • Altered by changes in body make-up • Decreased lean mass, relatively increased fat

10. Aging and Absorption • Actual amount absorbed not changed • Peak concentrations may be altered

11. Effects of Aging on Volume of Distribution •  body water  lower VD for hydrophilic drugs •  lean body mass,  plasma protein (albumin)  higher percentage of drug that is unbound (active) •  fat stores  higher VD for lipophilic drugs

12. Aging and Metabolism • Metabolic clearance of a drug by the liver may be reduced because: • Aging decreases liver blood flow, size, and mass • The liver is the most common site of drug metabolism • Phase II pathways generally preferable for older patient

13. The Effects of Aging on the Kidney  kidney size  renal blood flow  number of functioning nephrons  renal tubular secretion Result: Lower glomerular filtration rate

14. Serum Creatinine Does Not ReflectClearance  lean body mass  lower creatinine production and  glomerular filtration rate (GFR) Result: In older persons, serum creatinine stays in normal range, masking change in creatinine clearance (CrCl)

15. Pharmacodynamics • Definition:Time course and intensity of the pharmacologic effect of a drug • May change with aging, eg: • Benzodiazepines may cause more sedation and poorer psychomotor performance in older adults. • Older patients may experience higher levels of morphine with longer pain relief

16. Decreased homeostatic reserve • Impacts ability to tolerate medications • Postural hypotension • Fluid and electrolyte problems • Response to hypoglycemia • Temperature regulation

17. Medication Use Issues with Multiple Prescriptions (and OTCs…herbals…etc)

18. General types of medication-related problems • Unnecessary drug • Not prescribing new needed Rx • Contraindicated drug • Dose too low or too high • Adverse drug event/ drug interaction • Nonadherence • Prescribing cascade • From Williams CM, Am Fam Phys Nov 15, 2002

19. Prescribing Cascade • Misinterpretation of an adverse drug reaction as a symptom of another condition prescribing of another Rx • Example: • Persons receiving a cholinesterase inhibitor had >50% increase risk for subsequent anticholinergic drug for incontinence Gill et al. Arch Intern Med 2005, April 11

21. Adverse Drug Events during Care Transitions • Med changes between hosp and NH • Mean # of Rx changed: • 3.1 from nursing home to hospital • 1.4 from hospital to nursing home • Most were discontinuations • ADE attributable to medication changes occurred in 20%; usually occurred after readmission to the NH

22. Characteristics of Older Adults with Medication-related Problems • 85 years and older • 6 or more active chronic conditions • Estimated creat clearance < 50 ml/min • Low body weight • Nine or more medications • More than 12 doses of medication daily • Previous adverse drug reaction • From Williams CM, Am Fam Phys 2002, adapted from Fouts, Consult Pharm, 1997

23. Risk Factors for High Risk for ADE in Older Outpatients from an Expert Consensus Panel From Hajjar et al. Am J Geriatr Pharmacother 2003, Dec

24. Drug-Drug Interactions • May lead to ADEs • Likelihood  as number of medications  • Most common: cardiovascular and psychotropic drugs

26. Case A • 75 year old woman with hypertension, diabetes mellitus, dyslipidemia, coronary heart disease, congestive heart failure, osteoporosis, arthritis and chronic back pain, depression, and seasonal allergies

27. Case A: 15 meds

28. Case B • 85 year old woman with hypertension, dependent edema, dizzy spells, chronic back pain, insomnia, and constipation

29. Case B: 15 meds

30. How many meds is too many? • Med count won’t distinguish cases A & B • Med count won’t distinguish treatment based on disease-management guidelines from symptom-management meds • Won’t distinguish prescriber decision-making from patient-generated demand • Won’t distinguish appropriate from inappropriate medication use

31. Manageable Dosing Regimens • Manageable number of dosing times/day • Once daily formulations if feasible • Reduce number of medications that can’t be taken at same time as any others • Use of reminders, medication box set-up • Feasible to keep track of and filled • Affordable so patient does not skip doses to make the supply ‘stretch’ between refills

32. Potentially Inappropriate Medication Use

33. Inappropriate Medications in Older Adults: “Beers List” • “potentially or generally inappropriate” • “suboptimal prescribing” • Overall risks outweigh potential benefits • May be ineffective and/or poorly tolerated • May be justified in some circumstances • Controversial • Expert opinion by pharmacists’ group • Limited evidence-base for many drugs

34. Beer’s List: Two Groups of Drugs • Unconditionally inappropriate • Generally best avoided regardless of circumstances • Conditioned upon disease state or dose • May only be inappropriate in specific context

35. Beer’s List • 1992—many drugs no longer used • 1997 • 2003 • Now the basis for consultant pharmacy review in nursing facilities

36. Beer’s List Selected Highlights: 1997 • Propoxyphene (but not included in Rx review guidelines for NH) • Indomethcin, phenylbutazone, pentazocine • Trimethobenzamide • Muscle relax/antispasmodics, including ditropan • Flurazepam • Amitriptyline & combinations; doxepin • Meprobamate • Particular doses of other sedative hypnotics • Chlordiazepoxide, diazepam

37. Selected 1997 drugs, continued • Disopyramide • Digoxin above 0.125 mg except for atrial arryth • Dipyridamole • Methyldopa, reserpine • Chlorpropamide • GI antispasmodics • Nonprescription & many Rx antihistamines • Meperidine • Ticlopidine • All barbiturates except phenobarbital

38. Updates to Beer’s List in 2003 (selected additions since 1997)

39. 2003: selected conditionally “inappropriate” by disease state

40. High Potential for Severe ADEs Amitriptyline Chlorpropamide Digoxin > 0.125 mg/day Disopyramide GI antispasmodics Meperidine Methyldopa Pentazocine Ticlopidine High Potential for Less Severe ADEs Antihistamines Diphenhydramine Dipyridamole Ergot mesylates Indomethacin Meperidine, oral Muscle relaxants Potentially Inappropriate Medications for Older Persons

41. Prevalence and health consequences of “inappropriate” medication use

42. Findings in Kansas Medicaid Data • Any unconditional inappropriate medication use during study year: • Community 21% • HCBS 48% • Nursing Facility 38% • Most common: propoxyphene, antihistamines, amitriptyline, muscle relaxants, and oxybutynin • Rigler et al. 2005 Ann PharmacoRx

43. Inappropriate Medication in Frail Elderly Inpatients • 11 VAMCs • 92% had at least one problem: • Expense (70%) • Impractical directions (55%) • Incorrect dosages (51%) • Most common drug types: • GI, CV, CNS • Higher risk with fair/poor self-rated health

44. Hospitalization and Death • MEPS 1996, nursing home component • Persons ≥ 65 in NH for 3 months or more • Persons receiving inappropriate Rx: • OR 1.27 for hospitalization in following month • OR 1.80 for hosp if Rx received for 2 months • OR 1.28 for death • Analyses adjusted for other key risk factors • Lau et al. Arch Intern Med Jan 10, 2005

45. Approach to the Older Patient with Multiple Medications

46. Approach to Multiple Medications • Brown bag med review at each visit • Including herbals and OTCs • Determine clinical indication for each • Motto “One disease, one drug, once daily” • Avoid the prescribing cascade • Eliminate drugs without benefit or indication • Substitute less toxic drugs where able • From Carlon JE, Geriatrics, 1996; 51:26-30

47. “NO TEARS” Approach for Medication Review • From Lewis T, BMJ Aug 21, 2004 Need and indication Open questions Tests and monitoring Evidence and guidelines Adverse events Risk reduction or prevention Simplification and switches

48. Interdisciplinary Medication Review • Ambulatory older adults • Intervention versus control groups • Regimen changes Function? Cost? • Results: reduced mean Rx by 1.5 • No impact on functioning • Savings $27 per month per person • Williams et al. JAGS Jan 2004

49. Regulatory Scrutiny • Mandated drug review already in LTC • Medicare drug benefit • Provider profiling increasingly common • Pay for performance models • Patient satisfaction monitoring • Increasing use of electronic records • Can expect increased scrutiny of the medication profiles of your patients

50. The Obvious Do’s and Don’ts • Use effective medications to treat disease • Use effective therapies to prevent disease • Do not use unsafe medications • Do not use ineffective medications