Adverse Drug Events in the Older Adult Population. Alan Lukazewski, RPh, CDE, CGP Oakwood Lutheran Senior Ministries 1

Transcription

1 Adverse Drug Events in the lder Adult Population Alan Lukazewski, RPh, CDE, CGP akwood Lutheran Senior Ministries 1

2 This educational session is possible through the generous support of the Helen Bader Foundation 2

3 Safe Communities

4 bjectives 1) Assess the impact of adverse drug events on the older adult population 2) Recite the most common adverse drug events leading to ER visits and hospitalizations 3) Recognize drug-induced geriatric syndromes 4) List the most commonly involved drugs associated with adverse drug events 5) Describe the key risk factors associated with adverse drug events 6) Identify the most common causes of adverse drug events in older adults 7) Select the tools that can be used to reduce adverse drug event risk 4

5 Adverse Drug Event (ADE) Definition: An unintended effect from a drug that produces symptoms sufficient to cause a person to seek medical attention R Produces symptoms sufficient to affect function or quality of life 5

6 Impact of ADEs lder adults are 4 to 7 times more likely to experience an ADE 13 to 30% of hospital admissions due to ADEs versus 3-6% of the population 2/3rd of hospital discharges associated with adverse medical events are ADEs 6

7 Impact of ADEs ADEs now 4th or 5th leading cause of death by disease Rate of increase in reported ADE fatalities to FDA from 2000 to 2010 was 451% 7

8 Cost of ADEs Ambulatory care- $1300 Hospital- $7000-$10,000 Increased length of hospital stay 8

9 Most Common ADEs ADEs most commonly leading to ER visit or hospitalization: Gastrointestinal bleeding Electrolyte imbalance Hypoglycemia Internal bleeding Falls Delirium Drug toxicity Renal failure 9

10 Commonly Associated Drugs Drugs most commonly implicated in ER visits and hospitalization: Warfarin (Anti-coagulants) Insulin ral anti-diabetic agents Anti-platelets ACEIs/ARBs Diuretics NSAIDs piates 10

11 Commonly Associated Drugs Drugs most commonly implicated in ER visits and hospitalization: Antibiotics Antineoplastics 11

12 Drug Induced Geriatric Syndromes The Soft ADEs Falls Memory loss Delirium Urinary Incontinence Pain Depression Insomnia 12

13 Geriatric Syndromes Functional Decline Syndrome Loss of one or more ADLs Increased morbidity Increased mortality Any ADR reduces function 13

14 What don t we know? You see only what you look for and recognize only what you know Dr. M. Chisner 14

15 Real but Unrecognized ADEs Hypomagnesemia from PPIs Memory loss from statins Renal failure from PPIs Neuropathy from statins Pain from bisphosphonates Urinary incontinence from cholinesterase inhibitors 15

16 Risk Factors Number of drugs 30% used >= 5 drugs = 4% risk of serious drug-drug interactions 2-4 drugs = baseline comparator 4-fold increase 5-7 drugs 8-fold increase 8-10 drugs 13- fold increase drugs 16

17 Risk Factors Number of co-morbid conditions Care Transitions Age Renal impairment Gender Use of PIMs Use of narrow therapeutic index drugs 17

18 ADE Causation Lack of monitoring 40-60% Drug-drug interactions 13-26% Adverse drug reaction from new drug Increased drug burden causing delirium or falls Changes in adherence patterns 18

19 Lack of Monitoring Electrolytes Blood glucose Drug levels Vital signs (BP and orthostatics) INR Patient symptoms 19

20 Drug Drug Interactions 13-26% of all ADEs Pharmacist must screen and alert prescriber and nurse 20

21 Drug Drug Interactions: Attempts to Classify Relevance 2005: consensus panel developed list of 25 serious DDI s in older adults Which one s matter? J. Hanlon Frequently narrow therapeutic index drugs 21

22 Top drug drug interactions: 20 years ago Procainamide Amiodarone Procainamide Cimetidine Procainamide Trimethoprim Cimetidine Quinidine Cimetidine - Theophyline Cimetidine Disopyramide Cimetidine - Quinidine Carbamazepine Diltiazem Phenytoin Cimetidine Phenytoin Fluoxetine Phenytoin - Warfarin Phenytoin Theophylline Phenytoin Amiodarone Digoxin Amiodarone Digoxin Quinidine Digoxin Verapamil Lithium ACE Inhibitors Lithium NSAIDs Lithium - Diuretics Theophylline Erythromycin Warfarin Amiodarone Warfarin Sulfamethoxazole Warfarin Quinolones Warfarin Macrolildes Quinidine Fluvoxamine 22

23 Top drug drug interactions: 20 years ago Procainamide Amiodarone Procainamide Cimetidine Procainamide Trimethoprim Cimetidine Quinidine Cimetidine - Theophyline Cimetidine Disopyramide Cimetidine - Quinidine Carbamazepine Diltiazem Phenytoin Cimetidine Phenytoin Fluoxetine Phenytoin - Warfarin Phenytoin Theophylline Phenytoin Amiodarone Digoxin Amiodarone Digoxin Quinidine Digoxin Verapamil Lithium ACE Inhibitors Lithium NSAIDs Lithium - Diuretics Theophylline Erythromycin Warfarin Amiodarone Warfarin Sulfamethoxazole Warfarin Quinolones Warfarin Macrolildes Quinidine Fluvoxamine 23

24 Top drug drug interactions ACEIs potassium-sparing diuretics ACEI s - potassium supplements Anti-hypertensives NSAIDs NSAIDs - corticosteroids Diuretics NSAIDs Verapamil Beta-blockers Digoxin Macrolides Warfarin Aspirin Warfarin Antiplatelets Warfarin NSAIDs ARBs potassium-sparing diuretics ARBs potassium supplements SSRIs- piates SSRIs NSAIDs SSRIs - Aspirin Sulfonylureas Sulfamethoxazole Trimethoprim ACEIs Trimethoprim - ARBs 24

25 bservational Studies: Where the data are strongest Population-based studies Nested case control Nested case crossover 25

26 Drug Interactions that Matter Most ACEIs + K+-sparing diuretic Risk for hospitalization for hyperkalemia R = 20.3 After receiving a K+ sparing diuretic within previous7 days 26

27 Drug Interactions that Matter Most verall risk for hip fracture from benzodiazepine (BZD) use R 1.2 BZDs + interacting drugs Risk for hospital admission d/t hip fracture R

28 Drug Interactions that Matter Most Calcium channel blockers (CCBs) + macrolides (erythromycin, clarithromycin) Risk for hospital admission d/t hypotension/shock = R After addition of macrolide within 7 days Does NT include azithromycin 28

29 Drug Interactions that Matter Most Digoxin + macrolides Risk for hospital admission d/t digoxin toxicity = R 11.7 Clarithromycin 14.83, azithromycin 3.71, erythromycin 3.69 After addition of macrolide within 7 days 29

30 Drug Interactions that Matter Most Glyburide + SMX/TMP Risk for hospital admission d/t hypoglycemia = R 6.6 After addition of SMX/TMP within 7 days 30

31 Drug Interactions that Matter Most Warfarin + SMX/TMP (sulfa) Risk of hospitalization d/t GI bleeding = R After addition of SMX/TMP within 14 days Many antibiotics showed increased Rs; SMX/TMP most pronounced 31

32 Drug Interactions that Matter Most Warfarin + NSAIDs Risk of hospitalization d/t GI bleeding = R 3.58 For those with NSAID use in prior 90 days NSAIDs = ibuprofen, naproxen, meloxicam, nabumetone, celecoxib 32

33 bservational Studies: Where the data are strongest Warfarin + aspirin Warfarin + aspirin are overused with little evidence benefit in 800,000 Estimates suggest unnecessary deaths each year Reserve for high-risk groups 33

34 SSRIs plus NSAIDs or Aspirin Increased risk for GI bleeding Adjusted risk for SSRI use alone = 2.6 (CI ) Adjusted risk for NSAIDs alone = 3.7 (CI ) Adjusted risk for SSRIs + NSAIDs = 15.6 (CI ) Adjusted risk for SSRIs + aspirin = 7.2 (CI ) 34

35 Drug Interaction Intervention Strategies Discontinue precipitant drug Change precipitant drug Alter dose of either drug Initiate target monitoring Patient education of key symptoms to monitor 35

36 ADE Detection Temporal association Any new symptom should be considered an ADE Assume the drug is responsible until proven otherwise Surrogate markers eg. Serum K+ 36

37 Temporal Association Association of time with the onset of a known adverse effect after starting a drug or increasing the dose Discontinuation of drug and abatement of symptoms supports suspected ADE Re-challenge further increases likelihood drug was responsible 37

38 Naranjo Scale Are there previous conclusive reports of this reaction? Was the reaction more severe when the dose was increased or less severe when the dose was decreased? Did the patient have a similar reaction to the same or similar drugs in any previous exposure? 38

39 Self Reporting Self-reporting of ADEs Reliable 0.70 sensitivity, 0.85 specificity 1/3rd not reported to MD 1/3rd of those reported not acted upon by MD No action led to increased severity of ADEs 39

40 Prescribing Cascades Definition: The addition of a drug that is used to treat a side-effect from an existing drug assuming the side-effect is a new medical condition 40

41 Prescribing Cascades NSAIDs HCTZ Amlodipine HTN Gout Anti-HTN Allopurinol Edema Diuretic BisP4 Pain Aricept Incontinence Analgesic Detrol 41

42 Prescribing Cascades Statin Neuropathy Statin Memory loss Gabapentin Aricept 42

43 ADE Prevention 26-95% preventable 50-55% in most references Increase monitoring Avoid serious drug-drug interactions Adjust drug doses based on renal function Managing care transitions Medication minimization 43

44 Screening Tools (explicit criteria) Beer s AGS updated Beer s criteria 2012 STPP ARS and Drug Burden Index 44

45 45

46 ADE Prevention in Care Transitions Care transitions associated with high risk for ADEs 50% of ADEs will have occurred by 14th day post-discharge New medications Lack of monitoring Changes in adherence patterns Poor patient education 46

47 ADE Prevention in Care Transitions Create a Medication Action Plan Pharmacists: Use screening tools to identify risk and create MAP for nursing to follow up Nursing: Use MAP to incorporate monitoring for ADEs and learn! Build your working knowledge-base 47

48 Medication Minimization Doron Garfinkel, MD Community-based older adults average age 82 y/o Protocol for medication discontinuation 58% of drugs recommended for discontinuation 88% acceptance rate (4.2 drugs per patient) 2% restarted due to re-emergence of condition 81% overall success rate No adverse medical events or deaths 88% reported global improvement in health 56 out of 64 had measured improvement in cognition MMSE scores went from 14 to 24; 14 to 23; 14 to 30 48

49 Medication Minimization Doron Garfinkel, MD LTC residents (N=119) Average age approx. 82 y/o Discontinued 2.8 drugs per resident 18% failure rate 1-year mortality in control group = 45% 21% in study group Hospitalization rate in control group = 30% 11.8% in study group 49

50 Summary ADEs are more common in older adults ADEs can cause serious harm or death ADEs can lead to decline in function and quality of life Many ADEs can be prevented through: Improving monitoring Avoiding serious drug-drug interactions Provider and patient education 50

51 Summary Self-reporting of ADEs is a valid tool in their detection and our ability to mitigate their effects Medication minimization may improve function and quality of life Medication minimization may reduce the incidence of ADEs United Way of Dane County:

52 Abbreviations ACEI = ACE inhibitor- enalapril, lisinopril, captopril, fosinopril ARB = angiotenson receptor blocker SMX/TMP = Bactrim DS, Septra DS (sulfa drug or sulfonamide) Sulfonylurea = glyburide, glipizide, glimepiride (HA or oral htypoglycemia agent) NSAID = non-steroidal anti-inflammatory drug (ibuprofen, naproxen, nabumetone, or Motrin, Aleve, Celebrex) CCB = calcium channel blocker (verapamil, amlodipine, diltiazem, nifedipine) R = odds ratio: Any R over 1.0 is significant, but >2.0 is most significant. The higher the R, the greater the chance of an ADE. CI = confidence interval: Statistical measure when narrow means data are more reliable. ARS = anti-cholinergic risk scale DBI = drug burden index 52

53 References Field TS, Gurwitz JH, Harrold LR, et al. Risk factors for adverse drug events among older adults in the ambulatory setting. J Am Geriatric Soc. 2004;52(8): Rochon RA, Schmader KE, Sokol HN. Drug Prescribing for lder Adults. UpToDate September Gu Q, Dillon C, Burt V. Prescription Drug Use Continues to Increase: U.S. Prescription Drug Data NCHS Data Brief No 42, September Beijer HJ, de Blaey CJ. Hospitalizations Caused by Adverse Drug Reactions (ADR): A meta-analysis of observational studies. Pharm World Sci 2002;24:46. Pirmohamed M, Meakin J, et asl. Adverse drugs reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ 2004; Hanlon JT, SCHmader KE, Koronkowski MJ, et al. Adverse drug events in high-risk older outpatients. J Am Geriatr Soc, 45, Denham MJ (1990) Adverse Drug Reactions. Brit Med Bull, 46, Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med 2007;167:781. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med 2008; 168:508. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of non-steroidal antiinflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993; 153:

54 References American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in lder Adults. Am Geri Society Marcum ZA, Hanlon JT. Recognizing the risks of Chronic Nonsteroidal Anti-inflammatory Drug Use in lder Adults. Annals of Long Term Care. 2010; 18(9): Zhang M, Holman CDJ, Breen DB, Brameld K. Repeat adverse drug reactions causing hospitalization in older Australians: a population-based longitudinal study Brit Journ Clin Pharmacol; 63: nder G, Petrovic M, Tangiisuran B, et al. Development and validation of a score to assess the risk of adverse drug reactions among in-hospital patients 65 years or older: the Gerontonet ADR risk score. Arch Intern Med 2007; 170:1142. McDonnell PJ. Controlling Adverse Drug Reactions Through Improved Monitoring. AJMC May 1, Coleman, Eric A., MD MPH, et al, The Care Transitions Intervention, Arch Int Med. 2006;166: Novak, Christopher J. et al, Reducing Unnecessary Hospital Readmissions: The Pharmacist s Role in Care Transitions, ASCP Consultant Pharmacist ASCP 2012; 27: Pretorius RW, Gataric G, Swedlund SK, Miller JR. Reducing the risk of adverse drug events in older adults. American Family Physician 2013; 87(5): Corsonello A, et al. Potentially Inappropriate Medications and Functional Decline in Elderly Hospitalized Patients. JAGS

55 References Hamilton H, et al. Potentially Inappropriate Medications Defined by STPP Criteria and the Risk of Adverse Drug Events in lder Hospitalized Patients. Arch Intern Med 2011;171(11): American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in lder Adults. Am Geri Society Wynne HA. Adverse drug reactions in old age. Adverse Drug Reaction Bulletin. 2006; 237. nder G, Pedone C, Landi F, et al. Adverse drug reactions as a cause of hospital admissions: results from the Italian Group of Pharmacoepidemiology in the Elderly. JAGS 2002; 50: Manesse C, Derkx FHM, de Ridder MA, et al. Adverse drug reactions in elderly patients as contributing factor for hospital admission: cross sectional study. BMJ. ct 1997, Vol. 315; Weingart SN, Gandhi TK, et al. Patient-reported medication symptoms in primary care. Arch Intern Med 2005; 165: Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30: Coleman, Eric A., MD MPH, et al, The Care Transitions Intervention, Arch Int Med. 2006;166: Novak, Christopher J. et al, Reducing Unnecessary Hospital Readmissions: The Pharmacist s Role in Care Transitions, ASCP Consultant Pharmacist ASCP 2012; 27: Garfinkel D, Mangin D. Feasibility study of a systematic approach for discontinuation of multiple medications in older adults. Arch Intern Med 2010, 170: Juurlink DN, Mamdani M, Kopp A, et al. Drug-drug interactions among elderly patients hospitalized for drug toxicity. JAMA 2003;289: