Navigating the Beers Criteria: Balancing Medication Safety and Efficacy in the Geriatric Patient Kimberly Grant, Pharm.D

NAVIGATING THE BEERS CRITERIA: BALANCING MEDICATION SAFETY AND EFFICACY IN THE GERIATRIC PATIENT KIMBERLY GRANT, PHARM.D. DISCLOSURE STATEMENT

 I, the speaker, have no relative financial relationships to disclose.

LEARNING OBJECTIVES

At the conclusion of this presentation, the audience will be able to: 1. Identify updates made to the American Geriatrics Society (AGS) Beers Criteria for Potentially Inappropriate Medication Use in Older Adults 2. Recommend alternatives to medications not recommended for use in the older adult 3. Identify supporting research and rationale for Beers recommendations 4. Discuss the role of the pharmacist to improve patient safety and wellness in the geriatric population

BACKGROUND: PIM

 Potentially Inappropriate Medication (PIM)  Risk > Benefit  The Beers Criteria is the most cited resource in regards to PIMs

Beers List/Criteria. American Society of Consultant Pharmacists. Online. Available at: https://www.ascp.com/articles/beers-list-criteria

Hanlon JT, et al. Geriatric Pharmacotherapy and Polypharmacy. Brocklehurst’s Textbook of Geriatric Medicine. 2010:880-885. BACKGROUND

. Two-thirds of those over age 65 use 3 or more prescription drugs a month  42% of older adults have at least one medication filled that meets the requirement of a Potentially Inappropriate Medication (PIM)  NSAIDs  Sulfonylureas  Estrogens  Use of PIMs is associated with poor outcomes  Falls  Increased confusion  Increased mortality

The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2012;60:616-631. http://www.americangeriatrics.org/files/documents/beers/2012BeersCriteria_JAGS.pdf

National Center for Health Statistics. Health, United States, 2011: With Special Feature on Socioeconomic Status and Health. Hyattsville, MD. 2012 http://www.cdc.gov/nchs/data/hus/hus11.pdf BACKGROUND

 Medication-related problems in community-dwelling seniors cost over $177 billion per year  Hospital admission: $121.5 billion  Long-term care admissions: $32.8 billion  Physician costs: $13.8 billion  Emergency department visit costs: $5.8 billion

Estimated Annual Cost of Medication Related Problems. American Society of Consultant Pharmacists. 2014. Available at: https://www.ascp.com/articles/about-ascp/ascp-fact-sheet Ernst F. R., A. J. Grizzle. Drug-related morbidity and mortality: updating the cost-of-illness model. J Am Pharm Assoc 2001;41:192–9. BACKGROUND

 Up to 25% of hospital admissions in the elderly may be drug-related  ~16 % due to adverse drug reactions (ADRs) 5-11% due to therapeutic failures 1-9% due to adverse drug withdrawal effect (ADWEs)

Hanlon JT, et al. Geriatric Pharmacotherapy and Polypharmacy. Brocklehurst’s Textbook of Geriatric Medicine. 2010:880-885. Cahir C, Fahey T, Teeling M, Teljeur C, Feely J, Bennett K. Potentially inappropriate prescribing and cost outcomes for older people: a national population study. Br J Clin Pharmacol. 2010;69:543-552. Abstract BACKGROUND: AGE RELATED CHANGE

Pharmacokinetics Pharmacodynamics  Absorption  Homeostatic Regulation  Distribution  Disease States  Metabolism  Body Weight  Excretion  Adherence BACKGROUND: AGE RELATED CHANGES

 Liver  Decrease in size  Decrease in blood flow  Kidneys  Decrease in mass  Decrease in secretory function  Decrease in blood flow  Decrease in filtration rate

Image available at: http://www.news-medical.net/image.axd?picture=2009%2f12%2fch3_liver.jpg BACKGROUND: AGS BEERS CRITERIA

 The American Geriatrics Society (AGS) first released The Beers List in 1991 under the direction of Dr. Mark Beers . Consensus list of potentially inappropriate medications for long-term care facility residents . Incorporated into CMS (Centers for Medicare & Medicaid Services’) Interpretive Guidelines in 1999

Beers List/Criteria. American Society of Consultant Pharmacists. Online. Available at: https://www.ascp.com/articles/beers-list-criteria BACKGROUND: AGS BEERS CRITERIA

 Who is included?  Age ≥ 65  Excludes palliative care  Excluded hospice care

BACKGROUND: AGS BEERS CRITERIA TIMELINE

The Beers List is first released AGS assumes responsibility for Beers CMS adopts Beers Criteria Update

1991 1997 1999 2003 2012 2015

• Added new PIMS • Added strength and • 6 panelists quality ratings • Added PIMS • Medications to avoid • Maximum dose • 12 panelists • Drug-disease interactions • Drugs with safer alternatives

Beers List/Criteria. American Society of Consultant Pharmacists. Online. Available at: https://www.ascp.com/articles/beers-list-criteria BACKGROUND: AGS BEERS CRITERIA

 Literature search August 1, 2011- July 1, 2014  Reviewed by 13 member interdisciplinary panel of geriatric experts  1,188 citations were chosen for full panel review  Focusing on adverse drug events or adverse drug reactions

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. BACKGROUND: AGS BEERS CRITERIA

 2015 Update: Literature search August 1,2011- July 1, 2014  Systematic reviews  Meta-analyses  Randomized controlled trials  Observational studies . 1,188 citations were chosen for full panel review . AGS members also contributed evidence: 342 studies, 49 RCT, 233 other publications 2015 UPDATES AGS BEERS CRITERIA AGS BEERS CRITERIA

2015 Update  Added guidance on renally-dose adjusted medications  Added section regarding drug-drug interactions  Enhanced section regarding drug-disease interactions  Incorporated new evidence for listed Potentially Inappropriate Medications (PIMS)  Companion guide article

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015.

AGS BEERS CRITERIA: RENAL DOSING RECOMMENDATIONS

 2015 update provides drugs to be avoided or dose-adjusted according to renal function  Not to be utilized as a comprehensive list  Anti-infectives are not included  Adapted from published consensus guidelines organized by two Beers panelists +/- some medications

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. Hanlon JT, Aspinall SL, Semla TP et al. Consensus guidelines for oral dosing of primarily renally cleared medications in older adults. J Am Geriatr Soc 2009;57:335–340. AGS BEERS CRITERIA: RENAL DOSING RECOMMENDATIONS

 Estimated Cockcroft-Gault

 Estimated MDRD

Hanlon JT, et al. Geriatric Pharmacotherapy and Polypharmacy. Brocklehurst’s Textbook of Geriatric Medicine. 2010:880-885 AGS BEERS CRITERIA: RENAL DOSING RECOMMENDATIONS

 Drugs to avoid in reduced renal function Drugs Estimated CrCl (mL/min) NOACS

Amiloride < 30 Drugs Est CrCl Colchicine 10-29 (mL/min) Duloxetine <30 Apixaban <15 Fondaparinux <30 Dabigatran <30 Probenecid <30

Spirinolactone <30 Edoxoban <30

Tramadol (ER) <30 Rivaroxaban <30 Triamterene <30 Drugs Est CrCl (mL/min): ADJUST Est CrCl (mL/min): AVOID Amiloride 30-50: Administer ½ normal dose < 30 (or SCr > 1.5 mg/dL, or BUN >30mg/dL) Apixaban 15-25 (SCr ≥ 1.5 mg/dL + ≥ 80 yo or BW ≤ 60 kg <15 AGSCimetidine BEERS CRITERIA: RENAL<50: Administer DOSING ½ of normal doseRECOMMENDATIONS Colchicine <30: Monitor for adverse effects <10 Dabigatran 30-50 + P-gp inhibitor: 75 mg BID <30: *75 mg BID based upon PK data Edoxaban 30-50: 30 mg once daily (Mft labeling): DVT, PE, Afib. <30 or >95 Enoxaparin <30 * Not FDA approved in dialysis Famotidine <50: Administer 50% of normal dose or increase interval (q36h or q48h) Fondaparinux 30-50: Administer 50% of normal dose or heparin <30 Gabapentin <60: Increase dosing interval Levetiracetam <80: Reduce dose Pregabalin <60: Dosing chart based on indication Ranitidine <50: Administer 150 mg q24h Rivaroxaban 30-50: 15 mg once daily (A.fib) <30 Spirinolactone 30-50: Maximum dose 25 mg daily <30 Tramadol <30: Increase dosing interval to q12h (IR) <30 Avoid (ER) Triamterene <30 QUESTION 1

For a patient with a creatinine clearance = 36mL/min using a total daily dose of 900 mg of gabapentin, which choice would represent a safe and effective dose of gabapentin?

A. 300 MG TID B. 300 MG BID C. 400 MG BID D. 400 MG QAM + 500 MG QPM E. 500 MG QAM + 400 MG QPM CASE EXAMPLE: GABAPENTIN

 Gabapentin Dosing recommendations  Seizures >60 mL/minute 300 to 1,200 mg 3 times daily

 Diabetic neuropathy 30-59 mL/minute 200 to 700 mg twice daily  Neuropathic pain  Restless legs syndrome 15-29 mL/minute 200 to 700 mg once daily

 Anxiety <15 mL/minute Reduce daily dose in proportion to creatinine clearance Dialysis Dose based on CrCl plus a single supplemental dose of 125 to 350 mg (given after each 4 hours of hemodialysis)

LexiComp Online. 2016. CASE EXAMPLE: GABAPENTIN

 Resident receiving Gabapentin 300 mg BID for anxiety. (Estimated CrCl ~ 36 mL/min)  Increased behaviors noted  Increase gabapentin 300 mg TID  Resident experiences 3 falls within 2 weeks CASE EXAMPLE: GABAPENTIN

 Increase the dose, not the interval  Total daily dose = 300mg + 300 mg + 300 mg= 900 mg  Recommend gabapentin 400 mg in the morning and 500 mg at bedtime.

AGS BEERS CRITERIA: RENAL DOSING RECOMMENDATIONS

 Dosing of primarily renally cleared anti-infectives Drug Est CrCl (mL/min) Maximum Dosage Acyclovir 10-29 800 mg q8h <10 800 mg q12h Amantadine 30-59 100 mg qd 15-29 100 mg q48h <15 100 mg q7d Ciprofloxacin <30 500 mg q24h Nitrofurantoin <30 Avoid

Valacyclovir 30-49 1000 mg q12h 10-29 1000 mg q24h <10 500 mg q24h

Hanlon JT et al., JAGS 2009;57:335–340

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. AGS BEERS CRITERIA: RENAL DOSING RECOMMENDATIONS

 Narrow therapeutic range drugs: renal elimination is impaired with age  Aminoglycosides  Digoxin  Lithium  Methotrexate  Vancomycin

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. AGS BEERS CRITERIA: DRUG-DRUG INTERACTIONS

 Drug-drug interactions associated with harmful outcomes included in 2015 update  Excluding anti-infectives . Described as selective and not comprehensive . Highlight drug-drug interactions studied specifically in the elderly population

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. AGS BEERS CRITERIA: DRUG-DRUG INTERACTIONS

Drug Interacting drug(s) Effect Management

Lithium ACE inhibitors, Increased lithium toxicity • Decrease ACE or Loop dose Loop diuretics • Minimize therapy changes • Monitor serum lithium 4-6 weeks after change

Theophylline Cimetidine Increased theophylline toxicity • Change interacting drug therapy Ciprofloxacin • Anticipate change and decrease theophylline dose

Warfarin NSAIDs Increased bleeding • Switch Acetaminophen for NSAID Antibiotics • Increase INR monitoring • Decrease warfarin dose

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. CASE EXAMPLE: WARFARIN

Increased INR = Increased bleeding risk Decreased INR = Decreased effectiveness

 Aspirin  Rifampin  NSAIDs: Ibuprofen, Naproxen  Colestyramine  Antibiotics: Sulfamethoxazole-trimethoprim,  Herbal supplements: St. John’s wort Ciprofloxacin  Dietary supplements AGS BEERS CRITERIA: DRUG-DRUG INTERACTIONS

Drug Interacting Drug(s) Effects Management Benzodiazepines CYP3A4 Inhibitors Increased risk of hip fracture • Use shorter-acting BZDs Calcium channel blockers Macrolides (excluding azithromycin) Increased risk of hypotension • Increased monitoring • Medication alternatives

Digoxin Amiodarone Increased risk of digoxin • Increased monitoring Macrolides toxicity • Appropriate dosing Verapamil

Phenytoin SMX/TMP Increased risk of phenytoin • Antibiotic choice toxicity • Increased monitoring

Sulfonylureas SMX/TMP Hypoglycemia • Alter therapy Macrolides • Patient education Quinolones

Tamoxifen Paroxetine Breast cancer • Medication choice

Hines LE, Murphy J. AJGP 2011; 9:364-7 AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. QUESTION 2

Which of the following choices represents a safe therapeutic alternative to lorazepam in a patient with dementia displaying sundowning behaviors?

A. Temazepam 15 mg QHS PRN B. Melatonin 3 mf QHS C. Acetaminophen/diphenhydramine 1 tablet QHS D. Quetiapine 12.5 mg QHS PRN

CASE EXAMPLE: BENZODIAZEPINES

 Resident admitted following hospitalization for UTI receiving Ciprofloxacin 250 mg every 12 hours x 5 days. Resident has had increased confusion and wandering with baseline dementia.  Lorazepam 0.5 mg every 6 hours PRN is ordered.  Lorazepam 0.5 mg given at 2:39 am  Resident falls at 4:30 am  Lorazepam at 5:00 pm  Resident falls at 7:25 pm

AGS BEERS CRITERIA: DRUG-DRUG INTERACTIONS

Drug Interacting drug(s) Effect Management

ACE/ARB Potassium supplements Increase in K+ • Medication alternatives

Alpha-1 blockers Loop diuretics Increase in urinary retention • Medication alternatives (peripheral)

Anticholinergic Anticholinergic Increased confusion • Medication alternatives

Antiplatelet NSAID Increased bleeding • Medication alternatives Warfarin • Increased monitoring (INR) Corticosteroid NSAID Increased bleeding • Limit duration of use • Medication alternatives CNS medications 2+ CNS medications Increase in falls • Medication alternatives • Falls prevention measures AGS BEERS CRITERIA: DRUG-DISEASE INTERACTIONS

Disease Drug Delirium/Dementia • Anticholinergics, BZDs, H2 Blockers, Steroids Falls/Fractures • AED, Antipsychotic, BZD, Opioids, SSRI, TCAs Heart Failure • CCBs (non-dihydropyridine, Cilostazol, Dronedarone, Glitazones, NSAIDs

Insomnia • Amphetamines, Caffeine, Decongestants, Methylphenidate, Modafinil, Theophylline LUTS (Lower urinary tract • Anticholinergics symptoms) Parkinson’s Disease • Antipsychotics (except clozapine), Metoclopramide Peptic Ulcer Disease • NSAIDs Seizures • Antipsychotics, Bupropion Syncope • ACHE inhibitors, Alpha blockers, Antipsychotics, TCAs Urinary Incontinence • Alpha blockers, Estrogen AGS BEERS CRITERIA 2015 PIMS CHANGES

 Nitrofurantoin in individuals with creatinine clearance <30 mL/min  Amiodarone as first-line treatment for Atrial fibrillation  Nonbenzodiazepine and benzodiazepine hypnotics and consider duration of use  Sliding scale insulin  Proton-pump inhibitors beyond 8 weeks without justification for use  Desmopressin for treatment of nocturia or nocturnal polyuria

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. NITROFURANTOIN

 Historically warned against use if creatinine clearance < 40 mL/min  In 2003 warning was changed to < 60 mL/min  4 studies between 1958-1971 included patients with “poor” renal function  Recently, 3 retrospective trials have looked at nitrofurantoin use in presence of impaired renal functioning 1. 2009: hospitalized patients CrCl <50 mL/min vs. > 50 mL/min 2. 2013: outpatient women CrCl 50 mL/min 3. 2015: large retrospective review women > 65 yo median CrCl ~ 69 mL/min

Oplinger M, Andrews CO. Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for evidence. Ann Pharmacother. 2013;47:106-111. Bains A, Buna D, Hoag NA. A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment. Can Pharm J. 2009;142:248-252. Geerts AFJ, Eppenga WL, Heerdink R, et al. Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. Eur J Clin Pharmacol. 2013;69:1701-1707. Singh N, Gandhi S, McArthur E, et al. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women. CMAJ. 2015 Jun 16;187(9):648-56. doi: 10.1503/cmaj.150067. Epub 2015 Apr 27. 2015 PIMS CHANGES

 Avoid nitrofurantoin in individuals with creatinine clearance <30 mL/min  Long term use in suppression therapy should still be avoided Irreversible pulmonary fibrosis Liver toxicity Peripheral neuropathy

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. NITROFURANTOIN

 Utilize appropriate antibiotic stewardship  Suppression therapy?

Guidelines for Antimicrobial Treatment of Acute Uncomplicated Cystitis and Pyleonephritis in Women. Infectious Disease Society of America. 2011; 52;52:e03-e120. 2015 PIMS CHANGES

 Avoid amiodarone as first-line treatment for Atrial fibrillation  Dronedarone  Disopyramide  Digoxin

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. Hon-Chi L, Huang KT, Win-Kuang S. Use of antiarrhythmic drugs in elderly patients. J Geriatr Cardiol. 2011 Sep; 8(3): 184-194 ANTIARRHYTHMICS IN THE ELDERLY

 Increased risk of drug-drug interactions  Age-related changes in ADME processes  Individualize use  Device therapy  Anticoagulation  Ablation

2015 PIMS CHANGES

 Avoid non-benzodiazepine and benzodiazepine hypnotics without consideration of duration of use  Diagnosis/ behavior intended to be treated  Half-life/Metabolism  Pharm versus Nonpharm

AGS 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS. 2015. 2015 PIMS CHANGES

 Avoid use of sliding scale insulin  Refers to use of short-acting or bolus insulin  Does not apply to titration schedules

2015 PIMS CHANGES

 Avoid use of proton-pump inhibitors beyond 8 weeks without justification for use  Bone loss  Fracture  Clostridium difficile infection (CDI)

Image available at: http://www.nps.org.au/medicines/digestive-system/indigestion-reflux-and-stomach-ulcer-medicines/heartburn-and-reflux-medicines/for-health-professionals/pharmacology Recommendations & Rationale RISK FACTOR: PPI USE IDSA . No recommendation . “…other well controlled studies have suggested this association is the result of confounding with underlying severity of illness and duration of hospital stay.”

FDA . Use lowest dose & shortest duration of therapy as appropriate to the condition being treated . “The role of PPI use cannot be definitively ruled out in these reviewed reports…the weight of evidence suggests a positive association between the use of PPIs and C. difficile infection and disease…”

Beers . Avoid use of proton-pump inhibitors beyond 8 weeks without justification. . “Multiple studies and 5 systematic reviews and meta-analyses support an association between PPI exposure and CDI, bone loss, and fractures.”

Cohen et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31(5): 431-455. FDA Drug Safety Communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). February 8, 2012. Available online at: http://www.fda.gov/drugs/drugsafety/ucm290510.htm#hcp American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS 2015.

HOW TO UTILIZE THE BEERS CRITERIA? PRACTICE APPLICATION APPLICATION OF BEERS CRITERIA

 Improve medication selection  Decrease number of adverse drug events  Improve quality of care  Cost avoidance

RESOURCES

 Companion article  AGS iGeriatrics  Educational materials  National Library of Medicine’s Medline Plus www.nlm.nih.gov/medlineplus/druginformation.html  www.nursinghometoolkit.com  www.hospitalelderlifeprogram.org

2015 COMPANION ARTICLE KEY PRINCIPLES TO APPLICATION

 Medications are potentially inappropriate  Caveats are listed  Understand the rationale  Balance safer options: nonpharmacologic versus pharmacologic  Starting point  Provide access

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. JAGS. 2015;63: e1-e7. KEY PRINCIPLES TO APPLICATION

 Clinical  Health System  Payor

Journal of the American Geriatrics SocietyVolume 63, Issue 12, pages e1-e7, 8 OCT 2015 DOI: 10.1111/jgs.13701http://onlinelibrary.wiley.com/doi/10.1111/jgs.13701/full#jgs13701-fig-0002 APPLICATION

“Any symptom in an older adult is a medication side effect until proven otherwise”

PRACTICE CASE

An 89 yof is admitted to your facility following a Past medical history: Medication list: hospitalization due to overall deconditioning and an episode of acute kidney injury. The patient has •CHF • Allopurinol 100 mg BID been living alone in a 2-story home, but has a •Diabetes- type II • Aspirin 81 mg chewable QD large, supportive family. •Hypothyroidism • Digoxin 0.125 mg QD Her family claims she has a past history of •Gout • Diltiazem CD 120 mg QD frequent falls. •Atrial fibrillation • Levothyroxine 100 mcg QAM •Hypertension • Metformin 500 mg QAM Serum creatinine = 1.06 mg/dL •Hyperlipidemia • Metoprolol tartrate 50 mg BID •Osteopenia Potassium = 5..2 • Pantoprazole 40 mg QD •DJD • Simvastain 20 mg QHS Sodium = 139 •Hx. Heart attack • Rivaroxaban 20 mg QPM •Hx. Breast cancer Vital signs= 119/64 (80) Weight = 167 pounds Height= 65 inches

CASE QUESTIONS 1-3:

Which medication(s) would warrant discontinuation according to the 2015 Beers Criteria?

A. Aspirin 81 mg B. Digoxin 0.125 mg C. Pantoprazole 40 mg D. Metformin 500 mg

CASE QUESTIONS 1-3

According to the 2015 Beers Criteria, Rivaroxaban 20 mg QPM is an appropriate choice for treating this patient’s atrial fibrillation?

True or false?

CASE QUESTIONS 1-3

The nursing staff reports that your patient has been eating <25% of her meals during the past few days and doesn’t want to eat in the dining room with the other residents. She also declined activities yesterday. Are there any medications that could be contributing to this behavior?

THANK YOU