High Risk Medications in Older Adults Key Principles

High Risk Medications in Older Adults – Key Principles You Need to Know for Your Practice Todd P. Semla, MS, Pharm. D. , BCPS, FCCP, AGSF National PBM Clinical Pharmacy Program Manager – Mental Health & Geriatrics U. S. Dept. of Veterans Affairs Associate Professor Depts. of Medicine, and Psychiatry & Behavioral Sciences Northwestern University Feinberg School of Medicine 1

Disclosures • Dr. Semla has received honorarium for his services as an editor for Lexi. Comp, Inc. and the American Geriatrics Society as a Section/Associate Editor to the Journal of the American Geriatrics Society, author of the Geriatrics At Your Fingertips, and for cochairing the AGS Beers Criteria panel. • Dr. Semla’s spouse is an employee of Abbvie and owns stock in Abbvie and Abbott Labs. • Dr. Semla’s views are his own and do not necessarily reflect those of the U. S. Department of Veterans Affairs or the U. S. Government. 2

Objectives 1. What is a high risk medication? Where do they come from? 2. How can best avoid or use high risk medications in my practice? 1. Identify alternatives to high risk medications. 3

What is a High Risk Medication? • Potential harms >>> potential benefits • Determined by National Committee for Quality Assurance (NCQA) and Pharmacy Quality Alliance (PQA) • HEDIS Quality Measures (Health Effectiveness Data and Information Set) – High-risk Medications in the Elderly – Potentially Harmful Drug-Disease Interactions in the Elderly • HEDIS measures used by CMS and others 4

Examples of HEDIS High Risk Medications Anticholinergics • 1 st generation antihistamines – diphenhydarmine • Anti-Parkinson agents – benzotropine • Tertiary TCAs – amitriptyline Sulfonylureas, long-acting • Chlorpropamide • Glyburide Skeletal muscle relaxants – Cyclobenzaprine 5

Examples of HEDIS High Risk Medications Days Supply – not >90 days • Nitrofurantoin • Nonbenzodiazepine, hypnotics Average Daily Dose • Reserpine >0. 1 mg/day • Digoxin >0. 125 mg/day • Doxepin >6 mg/day 6

Examples of HEDIS Potentially Harmful Drug-Disease Interactions in the Elderly History of Falls • Anticonvulsants • Selective Serotonin Reuptake Inhibitors (SSRIs) History of Dementia • H 2 receptor antagonists • Anticholinergics 7

Examples of HEDIS Potentially Harmful Drug-Disease Interactions in the Elderly History of Dementia and/or Falls • Antipsychotics • Benzodiazepines • Nonbenzodiazepine hypnotics • Tricyclic antidepressants (TCAs) Chronic Kidney Disease • Nonsteroidal antiinflammatory drugs (NSAIDs) 8

From Where do NCQA and PQA Get Their List? J Am Geriatr Soc 63: 2227– 2246, 2015 9

Intent of the AGS 2015 Beers Criteria • • • Goals: Improve care by ↓ exposure to PIMS Educational tool Quality measure Research tool Prescribing measure vs. Quality measure 10

Tables § § § § § Table 2 – PIM list (with some selective caveats) Table 3 – PIMs due to Drug – Disease/Syndrome Interaction Table 4 – Medications to be used with caution Table 5 – Non-Anti-infective Drug-Drug Interactions Table 6 – Non-Anti-Infective Medications that should be avoided or have dosage reduced with varying levels of kidney function Table 7 – Drugs with strong anticholinergic properties Table 8 – Medications Moved or Modified Table 9 – Medications Removed Table 10 – Medications Added 11

Table 2. Drugs to Avoid (except if…) Organ System or TC or Drug Rationale Recommend. Quality of Evidence Strength of Recommend. Nitrofurantoin Pulmonary and hepatic toxicity, peripheral neuropathy; Lack of efficacy <30 m. L/min Avoid long term suppression; avoid if Cr. Cl <30 m. L/min Moderate Strong Antipsychotics (conventional or atypical) Increase CVA risk; increased cognitive decline and mortality in dementia Avoid unless danger to self/others and non pharm has failed Moderate Strong Insulin, sliding scale Hypoglycemia risk Avoid Moderate Strong Chlorpropamide Glyburide Hypoglycemia risk Avoid High Strong 12

Table 2. Drugs to Avoid (except if…) Organ System or TC or Drug Rationale Recommend. Quality of Evidence Strength of Recommend. Benzodiazepines Short and long acting Risk cognitive effects and injury (fall/MVA); may be appropriate, eg Et. OH withdrawal Avoid High Strong Megestrol Minimal effect on weight; risk of thrombotic events and death Avoid Moderate Strong Proton –pump inhibitors Risk of C. diff Avoid use for >8 High infection, bone loss weeks unless and fractures high-risk Strong Non-COX NSAIDs, oral GI bleeding; Protection w/ PPIs or misoprostol Strong Avoid chronic use Moderate 13

Table 2. Drugs to Avoid (except if…) Organ System or TC or Drug Rationale Recommend. Quality of Evidence Strength of Recommend. Non Benzodiazepines Hypnotics (“Z” drugs) Risk cognitive effects and injury (fall/MVA); same ADE as benzo’s Avoid Moderate Strong Estrogens with or w/o progestin Carcinogenic potential, lack of efficacy in dementia/CV disease prevention Avoid oral and topical patch. Vaginal cream and tablets safe and effective for vaginal symptoms Oral and patch: high strong Vaginal crm/tab: moderate Vaginal crm/tab: weak Ineffective at tolerated doses, antichol, falls Avoid Moderate Strong Muscle Relaxants 14

Table 3. Drug-disease/syndrome Interactions Disease or Syndrome Drug Rationale Recomm. Quality of Evidence Strength of Recomm. Syncope ACh. EIs Peripheral αblockers Tert. TCAs Orthostatic hypotension or bradycardia Avoid α- blockers: High TCAs, ACh. EIs, antipsych: Moderate ACh. EIs, TCAs: Strong CNS stimulant effects Avoid Moderate Strong Chlorpromazine Thioridazine Olanzapine Insomnia Oral decongestants Stimulants Theobromines α- blockers, antipsych. : Weak 15

Table 4. Use with Caution Drug Rationale Recommend Quality of Evidence Dabigatran Risk of bleeding; lack of evidence if Cr. Cl < 30 m. L/min Use with Moderate caution if >75 or if Cr. Cl < 30 m. L/min Weak Drugs linked to SIADH/ Hyponatremia (eg SSRI, TCA, CBZ, antipsychotics) May exacerbate or cause SIADH/ hyponatremia; monitor Use with caution Strong Moderate Strength of Recommend 16

Table 5. 2015 AGS Beers Criteria for Potentially Clinically Important Non-anti-infective Drug– Drug Interactions That Should Be Avoided in Older Adults Object Drug and Class Interacting Drug and Class Risk Rationale Recommendation Quality of Strength of Evidence Recommendation ACEIs Amiloride or triamterene Increased risk of Avoid routine use; hyperkalemia reserve for patients with demonstrated hypokalemia while taking an ACEI Moderate Strong Anticholinergic Increased risk of Avoid, minimize cognitive number of decline anticholinergic drugs (Table 7) Moderate Strong Antidepressants (ie, ≥ 2 other CNSTCAs and SSRIs) active drugsa Increased risk of Avoid total of ≥ 3 CNS- Moderate Strong falls active drugsa; minimize number of CNS-active drugs Antipsychotics Increased risk of Avoid total of ≥ 3 CNS- Moderate Strong falls active drugsa; minimize number of CNS active drugs ≥ 2 other CNSactive drugsa 17

Table 5, continued Object Drug and Class Interacting Drug and Class Risk Rationale Recommendation Quality of Evidence Benzodiazepines and ≥ 2 other CNS-active Increased risk of Avoid total of ≥ 3 CNS- High nonbenzodiazepine, drugsa falls and active drugsa; minimize benzodiazepine fractures number of CNS active receptor agonist drugs hypnotics Corticosteroids, oral NSAIDs Increased risk of Avoid; if not possible, Moderate or parenteral peptic ulcer provide disease or gastrointestinal protection bleeding Lithium ACEIs Increased risk of Avoid, monitor lithium Moderate lithium toxicity concentrations Lithium Loop diuretics Increased risk of Avoid, monitor lithium Moderate lithium toxicity concentrations Opioid receptor agonist analgesics ≥ 2 other CNS-active Increased risk of Avoid total of ≥ 3 CNS- High drugsa falls active drugsa; minimize number of CNS drugs Strength of Recommendati on Strong Strong 18

Table 6. 2015 American Geriatrics Society Beers Criteria for Non-Anti-Infective Medications That Should Be Avoided or Have Their Dosage Reduced with Varying Levels of Kidney Function in Older Adults Medication Class Cr. CL, m. L/min, at and Medication Which Action Required Rationale Recommendation Quality of Strength of Evidence Recommenda tion Cardiovascular or hemostasis Amiloride <30 Increased potassium Avoid and decreased sodium Moderate Strong Apixaban <25 Increased risk of bleeding Avoid Moderate Strong Dabigatran <30 Increased risk of bleeding Avoid Moderate Strong Edoxaban 30– 50 <30 or >95 Increased risk of bleeding Reduce dose Avoid Moderate Strong Enoxaparin <30 Increased risk of bleeding Reduce dose Moderate Strong Fondaparinux <30 Increased risk of bleeding Avoid Moderate Strong 19

Table 6, continued Medication Class Cr. CL, m. L/min, at and Medication Which Action Required Rivaroxaban 30– 50 <30 Spironolactone Triamterene <30 Rationale Recommendation Increased risk of bleeding Reduce dose Avoid Quality of Strength of Evidence Recommenda tion Moderate Strong Increased potassium Avoid and decreased sodium Moderate Strong Avoid Moderate Weak Reduce dose Moderate Strong Central nervous system and analgesics Duloxetine <30 Gabapentin <60 Increased gastrointestinal adverse effects (nausea, diarrhea) CNS adverse effects Levetiracetam ≤ 80 CNS adverse effects Reduce dose Moderate Strong Pregabalin <60 CNS adverse effects Reduce dose Moderate Strong Tramadol <30 CNS adverse effects Immediate release: reduce dose Extended release: avoid Low Weak 20

Table 6, continued Medication Cr. CL, m. L/min, at Class and Which Action Medication Required Gastrointestinal Rationale Recommendation Quality of Evidence Strength of Recommendati on Cimetidine <50 Mental status changes Reduce dose Moderate Strong Famotidine <50 Mental status changes Reduce dose Moderate Strong Nizatidine <50 Mental status changes Reduce dose Moderate Strong Ranitidine <50 Mental status changes Reduce dose Moderate Strong Colchicine <30 Gastrointestinal, neuromuscular, bone marrow toxicity Reduce dose; monitor Moderate for adverse effects Strong Probenecid <30 Loss of effectiveness Avoid Strong Hyperuricemia Moderate 21

APPLICATION AND INTENT OF THE AGS 2015 BEERS CRITERIA J Am Geriatr Soc 63: e 1–e 7, 2015 – FREE! 22

Seven Key Principles on How To Use the Beers Criteria 1. Medications in the Beers Criteria are potentially inappropriate, not definitely inappropriate. 2. Read the rationale and recommendations statements for each criterion. The caveats and guidance listed there are important. 3. Understand why medications are included in the Beers Criteria, and adjust your approach to those medications accordingly 4. Optimal application of the Beers Criteria involves identifying potentially inappropriate medications, and where appropriate offering safer non-pharmacologic and pharmacologic therapies 23

Seven Key Principle on How To Use the Beers Criteria continued. . 5. The Beers Criteria should be a starting point for a comprehensive process of identifying and improving medication appropriateness and safety 6. Access to meds in the Beers Criteria should not be excessively restricted by prior authorization and/or health plan coverage policies 7. The Beers Criteria are not equally applicable to all countries 24

Beers Criteria only Part of Quality Prescribing § Quality prescribing includes • Correct drug for correct diagnosis • Appropriate dose (label; dose adjustments for comorbidity, drug-drug interactions) • Avoiding underuse of potentially important medications (e. g. , bisphonates for osteoporosis) • Avoiding overuse (e. g. , antibiotics) • Avoiding potentially inappropriate drugs • Avoiding withdrawal effects with discontinuation • Consideration of cost 25

What are the challenges of using them in clinical care? § § § All of the above perceived barriers RN/Family Request Lack of Tested Non Drug Alternatives Multiple prescribers Risk of drug is less than risk of condition Palliative Care and other special cases and populations 26

Alternatives to High Risk Medications in the Elderly J Am Geriatr Soc 63: e 8–e 18, 2015 - FREE! 27

Recommendations • Two tables & three appendices • Table 1 - Alternatives to High-Risk Medications • Table 2 - Alternatives to Potentially Harmful Drug-Disease Interactions • Appendix I – References for Table 1 • Appendix II – References for Table 2 • Appendix III – Resources for Non Pharmacological Alternatives for Tables 1 & 2 28

Table 1. Alternatives to High-Risk Medications Therapeutic Class High-Risk Medications Alternatives First-generation antihistamines e. g. , Chlorpheniramine Diphenhydramine Intranasal saline 2 nd generation antihistamine Intranasal steroid Parkinson disease Benzotropine (oral) Trihexyphenidyl Carbidopa/levodopa Tertiary tricyclic antidepressants e. g. , Amitriptyline Imipramine Depression: SSRI, SNRI, bupropion Neuropathic pain: *SNRI, *gabapentin, capsaicin topical, pregabalin, topical lidocaine Nonbenzodiazepine hypnotics Eszopilclone, zaleplon, zolpidem No medications, nonpharmacologic approach; 2 nd line – doxepin 3 mg Estrogens (oral or patch) Conjugated or esterified estrogen, estradiol Vaginal – okay *Vasomotor Sxs – SSRIs, SNRIs, gabapentin Hanlon JT, et al. JAGS 2015; 63(12): e 8 -e 18 FREE! *off-label use 29

Table 1. Alternatives to High-Risk Medications Therapeutic Class High-Risk Medications Alternatives Skeletal muscle relaxants Carisoprodol Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine Acute mild or moderate pain – APAP, nonacetylated salicylate, propionic acid derivative NSAID (ibuprofen, naproxen) if no HF or e. GFR>30 m. L/min with PPI if >7 days Barbiturates Phenobarbital, others For epilepsy - lamotrigine, levetiracetam Sulfonylureas, longduration Chlorpropamide Glyburide Glipizide, metformin Hanlon JT, et al. JAGS 2015; 63(12): e 8 -e 18 FREE! *off-label use 30

Table 2. Potential Drug-Disease Interactions: Alternative Medications DISEASE STATE High-Risk Medications Alternatives Falls Benzodiazepines, Z-drugs For anxiety – buspirone, *SNRI TCAs For depression – SNRI, bupropion Antipsychotics • Delirium • Dementia Nonpharmacologic, if fails lowest dose need nonanticholinergic antipsychotic (*risperidone, *quetiapine) or shortest duration possible Anticonvulsants New onset epilepsy – lamotrigine, levetiracetam and calcium + vit. D Neuropathic pain: *SNRI, *gabapentin, capsaicin topical, pregabalin, topical lidocaine Hanlon JT, et al. JAGS 2015; 63(12): e 8 -e 18 FREE! *potential off-label use 31

Table 2. Potential Drug-Disease Interactions: Alternative Medications DISEASE STATE High-Risk Medications Alternatives Dementia Chronic kidney disease or chronic renal failure (e. GFR<30 m. L/min) TCAs For depression – SSRI, SNRI, bupropion Neuropathic pain: *SNRI, *gabapentin, capsaicin topical, pregabalin, topical lidocaine Antipsychotics See above H 2 blockers PPI Anticholinergics For allergy – 2 nd gen. antihistamine, nasal steroid For Parkinson disease – levodopa with carbidopa All nonaspirin nonsteroidal antiinflammatories (NSAIDs) including cycloxygenase-2 selectives Neuropathic pain: APAP, *SNRI, *gabapentin, capsaicin topical, pregabalin, topical lidocaine *potential off-label use 32

Take homes § Don’t let the perfect be the enemy of the good § Beers PIMs are only part of appropriate prescribing § Target initiatives to high prevalence/high severity meds (based on local data, where possible) § Stopping meds should be done with same consideration as starting § Beers Criteria = Patient-centered care 33

Conclusions • Elderly patients are likely to benefit when highrisk medications are eliminated from their regimen. • HEDIS quality measures on medication use in the elderly are based on the AGS Beers Criteria. • The AGS Beers Criteria should be used with clinical judgment and common sense. Use the key principles to help you best use Beers Criteria in practice. • Alternatives to high-risk medications are available; however, the search for alternative treatments for older persons is limited by a lack of quality evidence. 34

“The trend of multiple drug use by elderly people will likely increase in the future as a result of an increasing burden of chronic disease and success of researchers who develop new drugs. ” Ron Stewart, MS Pharm. The Annals of Pharmacotherapy, 1990 35