Medication Use and Safety in the Elderly Amy N. Thompson, PharmD, BCPS ACOVE 5

Objectives Understand the physiologic changes associated with aging Understand the physiologic changes associated with aging Recognize potentially dangerous medications for the elderly Recognize potentially dangerous medications for the elderly Identify risk factors for adverse drug events in the elderly Identify risk factors for adverse drug events in the elderly Identify proper monitoring parameters for high risk medications in the elderly Identify proper monitoring parameters for high risk medications in the elderly

Challenges of Prescribing for Older Adults Multiple medical conditions Multiple medical conditions Multiple prescribers Multiple prescribers Adherence and cost Adherence and cost Lack of evidence Lack of evidence Supplements, herbals and over-the- counter medications Supplements, herbals and over-the- counter medications Different metabolisms and distribution Different metabolisms and distribution

Physiologic Changes Less body water more body fat Less body water more body fat Less muscle mass Less muscle mass Decreased hepatic metabolism and renal excretion Decreased hepatic metabolism and renal excretion Decreased responsiveness and sensitivity of the baroreceptor reflex Decreased responsiveness and sensitivity of the baroreceptor reflex

Distribution Decreased body water Decreased body water –Decreased volume of distribution Higher concentration of water soluble agents Higher concentration of water soluble agents Increased body fat Increased body fat –Increased volume of distribution Increased half-life of fat soluble agents Increased half-life of fat soluble agents Decreased serum proteins Decreased serum proteins –Increased concentration of agents that are highly protein bound

Metabolism Slowed phase I metabolism Slowed phase I metabolism –Oxidation, reduction, dealkylation Unchanged phase II metabolism Unchanged phase II metabolism –Conjugation, acetylation, methylation

Excretion Reduced kidney clearance Reduced kidney clearance –30-40% fall in functioning glomeruli by 80 –1% (at age 20) ->30% sclerotic glomeruli Serum creatinine not accurate predictor of renal function due to decreased muscle mass Serum creatinine not accurate predictor of renal function due to decreased muscle mass –Creatinine secretion reduced ~40%

Pharmacodynamics Alterations are complex and poorly studied Generally the elderly are more sensitive to drug effects – –Anticholinergics – –Benzodiazepines Homeostasis is more effected by drugs – –Postural BP – –EPS – –Cognition

Therapeutic Response Toxic Response Therapeutic Window Age

Medication Use People over the age of 65 consume 30% of all prescriptions in the US and 40% of all over-the-counter medications People over the age of 65 consume 30% of all prescriptions in the US and 40% of all over-the-counter medications –While they only represent 15% of the US population Clinical trials Clinical trials –Elderly frequently not included due to unpredictable drug metabolism and effects

GF is a 68 y/o AAF – –PMH: Type 2 Diabetes, HTN, GERD, HLP – –Medications: Metformin, glipizide, and hydrochlorothiazide, simvastatin Diagnosed today with AFib – –Started on warfarin 5 mg daily – –Diltiazem 240 mg daily

One week later: – –GF presents to the ER with bilateral LE edema – –Given a prescription for Lasix 20 mg daily What is going on?

Medication Safety Think about the medication regimen before making a new diagnosis Think about the medication regimen before making a new diagnosis –Consider ADE as etiology of new s/sx –Consider reducing dose or stopping medications before treating a ADE with another medication

Risk Factors for Adverse Drug Events >6 chronic disease states >6 chronic disease states >12 doses/day >12 doses/day >9 Medications >9 Medications Low BMI (<22 kg/m 2 ) Low BMI (<22 kg/m 2 ) Creatinine clearance <50 mL/min Creatinine clearance <50 mL/min Female Female

Arch Intern Med.2003;163: Adverse Drug Events Linked to preventable problems in the elderly, such as: Linked to preventable problems in the elderly, such as: –Depression –Constipation –Falls –Immobility –Confusion –Hip fractures

Arch Intern Med.2003;163: Avoiding Potentially Dangerous Drugs: Beers Criteria Consensus-based list of potentially inappropriate medications for older adults Consensus-based list of potentially inappropriate medications for older adults Published 1991; revised in 1997, 2002 Published 1991; revised in 1997, 2002 Criteria covered 2 types of statements: Criteria covered 2 types of statements: –Medications that should generally be avoided because they are either ineffective or they pose a high risk –Medications that should not be used in older persons known to have specific medical conditions

Beers Criteria: Anticholinergic Agents Drug classes Drug classes –Tricyclic antidepressants –Antihistamines –Antispasmodics and muscle relaxants Adverse events Adverse events –Urinary incontinence –Constipation –Confusion, delirium, behavior changes –Exacerbation of dementia

Beers Criteria: Benzodiazepines Avoid entirely if at all possible Avoid entirely if at all possible Challenging to stop for patients with long-term use Challenging to stop for patients with long-term use Long-acting Long-acting –Prolonged half-life in older adults (days) –Sedation, cognitive impairment, depression –Increased risk of falls and fractures Short-acting Short-acting –Increased sensitivity in older adults –If necessary, use lower doses

Beers Criteria: Pain Medications Propoxyphene (Darvon) has limited efficacy and significant side effects Propoxyphene (Darvon) has limited efficacy and significant side effects Non-steroidal anti-inflammatory drugs (NSAIDS) that should be avoided completely: Non-steroidal anti-inflammatory drugs (NSAIDS) that should be avoided completely: –Indomethacin has significant CNS side effects –Ketorolac (Toradol) can cause serious GI and renal effects

Beers Criteria: Pain medications Long-term use of NSAIDS – –Potential for GI bleed – –Renal failure – –Heart failure – –High blood pressure Meperidine (Demerol) has low oral efficacy, active metabolites and CNS effects Meperidine (Demerol) has low oral efficacy, active metabolites and CNS effects

Beers Criteria: Cardiovascular Agents Digoxin – –Should not exceed mg/day except when treating atrial arrhythmias – –Decreased renal clearance, increase in toxic effects Amiodarone – –Associated with QT interval problems – –Lack of efficacy in older adults

Beers Criteria: Disease Specific Parkinson’s disease: Parkinson’s disease: –metoclopromide and anti-psychotics Stress incontinence Stress incontinence –alpha-blockers Hyponatremia Hyponatremia –SSRIs Constipation Constipation –calcium channel blockers Cognitive impairment Cognitive impairment –Anticholinergics, antispasmodics, and muscle relaxants

JAMA. 2006;296: Adverse Drug Events National surveillance of ED visits for outpatient ADE National surveillance of ED visits for outpatient ADE –2 year study, 21,000 ADEs reported 3,500 required hospitalization 3,500 required hospitalization –People >65 ED visits were twice that of those younger ED visits were twice that of those younger –4.9 per 1,000 vs. 2.7 per 1,0000 Hospitalizations nearly 7 times higher Hospitalizations nearly 7 times higher –1.6 per 1,000 vs per 1,000

Adverse Drug Events Drugs for which regular outpatient monitoring is used to prevent acute toxicity accounted for 54% of hospitalizations Drugs for which regular outpatient monitoring is used to prevent acute toxicity accounted for 54% of hospitalizations Three medications caused 1/3 of ED visits Three medications caused 1/3 of ED visits –Insulin –Warfarin –Digoxin

Adverse Drug Events Cardiovascular medications Psychotropic medications Antibiotics Anticoagulants NSAIDS Anti-seizure medications

JAGS.2007; 55:S383–S391. NSAID Use and GI Bleeds Several risk factors place the elderly population at increased risk for GI bleeds – –>75 years of age – –History of PUD – –History of GI bleed – –Concomitant use of warfarin – –Long term glucocorticoid use These patients warrant treatment with misoprostol or PPI

Medication Safety Prescribe one medication at a time Prescribe one medication at a time Start the dose low and titrate up slowly Start the dose low and titrate up slowly Use once daily dosing if possible Use once daily dosing if possible –Increases patient adherence Monitor the patient for response and adverse effects Monitor the patient for response and adverse effects

3 weeks later…. GF falls in the middle of the night while trying to get to the bathroom, she is subsequently admitted to the hospital Upon discharge her medications have been changed – –D/C lasix, diltiazem – –Start amiodarone 400 mg BID

Given her current treatment plan would you recommend any changes? Most current medication list – –Warfarin 5 mg daily – –Hydrochlorothiazide 25 mg daily – –Simvastatin 40 mg daily – –Amiodarone 400 mg BID

J Am Geriatr Soc. 1996;44(8):944–948 Medication Safety Avoid drug-drug interactions that are associated with hospitalizations Avoid drug-drug interactions that are associated with hospitalizations –ACE Inhibitor plus Potassium sparing diuretic or potassium supplement Potassium sparing diuretic or potassium supplement –Benzodiazepine Antidepressant and antipsychotics Antidepressant and antipsychotics –Warfarin New antibiotic, potent CYP inhibitors/inducers New antibiotic, potent CYP inhibitors/inducers

It has been 1 month since hospital discharge and GF is returning to clinic for follow-up She complains today of feeling very weak and have dark stools for the past week What is the most likely cause?

Medication Safety Educate the patient – –Indication – –Why it is being used – –What they need to watch for – –Provide the patient with an up-to-date medication list at each visit Always assess compliance

Medication Safety Always assess the Risk vs. Benefit Always assess the Risk vs. Benefit –Appropriate medication use requires that benefits of therapy clearly outweigh the associated risks –Benefit-to-risk ratio is unique to an individual; the very medication and dosage that helps one patient may harm another Remember that supplements, herbal and OTC agents can cause ADE Remember that supplements, herbal and OTC agents can cause ADE Know what your patient is taking Know what your patient is taking

Its been three months and GF has been doing well. After her last discharge her amiodarone was stopped and metoprolol 25 mg BID was started Her INR has been stable between 2 and 2.5 since her GI bleed

She presents to the ER today with signs and symptoms of a stroke – –INR on presentation 1.4 Current medications – –Warfarin 5 mg daily – –Simvastatin 20 mg daily – –Hydrochlorothiazide 25 mg daily – –Metoprolol 25 mg BID – –St Johns Wort 1 tablet daily What is going on?

Medication Safety Common herbal agents that can be hazardous Common herbal agents that can be hazardous –Garlic, gingko, green tea Increased bleeding time Increased bleeding time –St. John’s Wort Increased clearance of medications metabolized by CYP-3A4 Increased clearance of medications metabolized by CYP-3A4 –Chromium, gingko, nettle Hypoglycemia Hypoglycemia

Quality Indicators All elders should have an up-to-date medication list in the medical record All elders should have an up-to-date medication list in the medical record If an elder is prescribed a drug, then the prescribed drug should have a defined indication If an elder is prescribed a drug, then the prescribed drug should have a defined indication If an elder is prescribed a drug, then they should receive appropriate education about its use If an elder is prescribed a drug, then they should receive appropriate education about its use

Quality Indicators If an elder receives a new prescription for a medication known to be high risk, proper monitoring should be performed If an elder receives a new prescription for a medication known to be high risk, proper monitoring should be performed

Skills Medication reconciliation done at patient visit and hospitalization Medication reconciliation done at patient visit and hospitalization –All prescribed medications –Topical agents/transdermal patches –OTC medications –Herbal products and supplements –Eye and ear drops –Inhalers Drug list will be printed from Oacis each day when on inpatient service Drug list will be printed from Oacis each day when on inpatient service

Medication Safety Is patient taking any over-the-counter medications or herbal supplements? Is patient taking any over-the-counter medications or herbal supplements? –Did you evaluate for harm and drug interactions?

Skills Dose advisor should be used to ensure proper dosing for any new medication Dose advisor should be used to ensure proper dosing for any new medication

Skills Anytime a new medication is started the patient will be given a patient education sheet from Micromedex ® Anytime a new medication is started the patient will be given a patient education sheet from Micromedex ®

Skills Any new medication prescribed to an elder will have the indication written in the directions Any new medication prescribed to an elder will have the indication written in the directions –This will aid in patient education and adherence

Skills Any high risk medication will be appropriately monitored Any high risk medication will be appropriately monitored

Medication Safety Is the patient currently on amiodarone therapy? Is the patient currently on amiodarone therapy? –Is the patient on warfarin? Has the dose been appropriately adjusted? Has the dose been appropriately adjusted? –Is the patient on digoxin? Has the dose been appropriately adjusted? Has the dose been appropriately adjusted? –Is the patient on simvastatin? Is the patient on 20mg/or less a day? Is the patient on 20mg/or less a day?

Medication Safety If warfarin is prescribed If warfarin is prescribed –PT/INR should be drawn within 4 days for new starts –Has a PT/INR been drawn in the past 30 days? If not, did you schedule an appointment with the PharmD today? If not, did you schedule an appointment with the PharmD today?

Medication Safety If a hypoglycemic agent is prescribed If a hypoglycemic agent is prescribed –Has an A1C been checked within the last 6 months? If not, have you ordered one to be drawn today? If not, have you ordered one to be drawn today? –Did you ask the patient about s/sx of hypoglycemia? If patient is experiencing s/sx of hypoglycemia, what did you do to address this issue? If patient is experiencing s/sx of hypoglycemia, what did you do to address this issue? –Reduce the dose of the hypoglycemic agent –Refer to a CDE for further management

Medication Safety Is patient currently receiving NSAID therapy? Is patient currently receiving NSAID therapy? –Did you ask about the signs/symptoms of GI bleeding? –Does patient have a history of PUD? Are they being treated with a PPI? Are they being treated with a PPI? –If not, did you start one today?

Medication Safety Is patient currently receiving digoxin? Is patient currently receiving digoxin? –Did you ask the patient about s/sx of digoxin toxicity? Did patient have s/sx of toxicity? Did patient have s/sx of toxicity? –If so, did you order a digoxin level today?

Skills Each patient will receive an Aging Q3 pillbox to aid in patient adherence

Patient Survey Surveyors to randomly select elders after check-out process occurs: – –Do you know who your doctor is? – –Were you given a medication list today? – –Were you started on a new medicine today? – –If so, were you given an information sheet on this medication? – –Do you know what this medicine is for?

Take Home Points Review and reconcile medications at each visit: Review and reconcile medications at each visit: –Indication for each medication? –Contraindications? (renal, dementia) –Can I STOP any medication? –Is the patient on any OTCs, herbals or supplements? Write indications on prescriptions Write indications on prescriptions –Increase patient knowledge and compliance

Take Home Points Avoid high-risk medications if possible Avoid high-risk medications if possible –Beers criteria –If high-risk medications is used, monitor appropriately When prescribing new medication When prescribing new medication –Are there any drug-drug interactions? –Is it appropriately dosed? Remember to look for ADE Remember to look for ADE

Questions???????????