PHARMACOTHERAPY UPDATE Benjamin Gross, Pharm D, BCPS, BCACP, BC ADM, CDE Associate Professor Director of Residency Programs Lipscomb University College of Pharmacy and Health Sciences 1
DISCLOSURE I DO NOT HAVE ANY DISCLOSURES TO REPORT 2
Contact Email: ben.gross@lipscomb.edu gross.ben@gmail.com Office One University Park Drive Nashville, TN 37204 Phone: 615.966.7195 3
Objectives Discuss common medication issues in the elderly Discuss adverse effects of medications and their impact on treatment plans Discuss new medications and their impact on the elderly Discuss new medications, adverse effects, or restrictions for the general population 4
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Drug Therapy in the Elderly Among people 65 years of age 90% use at least one medication per week 40% use at least 5 different medications per week 12% use 10 different medications per week Women take more medications Medication use greatest among frail elderly, hospitalized patients, and nursing home residents Nursing home resident 7 to 8 different drugs 6
Drug Therapy in the Elderly Elderly Patients Use more drugs than any other age group More likely to have chronic disorders Physiologic reserves are reduced Aging alters pharmacodynamics and pharmacokinetics Less able to obtain or afford drugs 7
Pharmacokinetics in the Elderly Absorption Distribution Metabolism Excretion 8
Pharmacokinetics in the Elderly Class or Category Decreased Hepatic Metabolism Decreased Renal Elimination Analgesics and anti inflammatory drugs Antibiotics Cardiovascular Drugs Naproxen Ibuprofen Morphine Meperidine Amlodipine Diltiazem Lidocaine Nifedipine Propranolol Quinidine Theophylline Verapamil Amikacin Ciprofloxacin Gentamicin Nitrofurantoin Streptomycin Tobramycin Captopril Digoxin Enalapril Lisinopril Procainamide Quinapril 9
Pharmacokinetics in the Elderly Class or Category Decreased Hepatic Metabolism Decreased Renal Elimination Diuretics Psychoactive Drugs Alprazolam Chlordiazepoxide Desipramine Diazepam Imipramine Nortriptyline Trazadone Triazolam Amiloride Furosemide Hydrochlorothiazide Triamterene Risperidone Others Levodopa Amantadine Chlorpropramide Cimetidine Glyburide Lithium Metoclopramide Ranitidine 10
Pharmacodynamics in the Elderly What the drug does to the body or the response of the body to the drug Effects of similar drug concentrations at the site of action may be greater or smaller in the elderly compared to younger patients Particularly sensitive to anticholinergic drug effects Those with dementia: prone to CNS adverse effects of anticholinergic drugs Anticholinergic drugs» Commonly cause: constipation, urinary retention, blurrred vision, orthostatic hypotension, and dry mouth 11
Effect of Aging on Drug Response Class Drug Action Effect of Aging Analgesics Morphine Acute analgesic effect Anticoagulants Warfrain PT Bronchodilators Albuterol Bronchodilation Cardiovascular Angiotensin II receptor blockers Diltiazem, Enalapril, Felodipine, Verapamil Decreased BP Acute antihypertensive effect Psychoactive Diazepam Sedation Diphenhydramine Psychomotor function Haloperidol Acute Sedation Others Levodopa Adverse effects 12
Drug Related Problems in the Elderly Inappropriate medications Overdosage Underprescribing Drug/Disease Interactions Inadequate monitoring Poor communication Lack of adherence 13
Beers Criteria Avoid Indomethacin First generation antihistamines Alpha blockers Treatment hypertension Antiarrhythmic drugs (Class Ia, Ic, III) Benzodiazepines Treatment for insomnia, agitation, or delirium Digoxin > 0.125 mg/day Tertiary TCAs Glyburide Complete list: http://www.americangeriatrics.org/files/documents/beers/printableb eerspocketcard.pdf J AM Geriatr Soc 2012. doi:10.1111/j.1532 5414.2012.03923.x 14
Drug Categories of Concern in Elderly Analgesics NSAIDs May be prone to adverse effects of these drugs Anticoagulant Increase sensitivity to the anticoagulant effect of warfarin Antidepressants Fluoxetine: long elimination half life Paroxetine: more sedating, more drug interactions, anticholinergic effects Sertraline: diarrhea most common adverse effect 15
Aspirin and Macular Degeneration Aspirin: Increased risk of age related macular degeneration (AMD) Liew, G. et al. JAMA intern Med. 2013; 258 264 16
Liew, G. et al. JAMA intern Med. 2013; 258 264 Klein, et al. JAMA 2012; 2469 2478 17
Aspirin and Macular Degeneration Prospective observational study 5000 patients over period 20 years Age: 43 86 99% white 56% women Regular aspirin use At least twice weekly use for more than three months Mean duration of follow up almost 15 years Klein, et al. JAMA 2012; 2469 2478 18
Aspirin and Macular Degeneration Results Regular aspirin use ten years prior was associated with an increase risk of AMD Incidence of AMD in aspirin users was 1.76% compared to 1.03% in nonusers Increased risk with neovascular or wet AMD Klein, et al. JAMA 2012; 2469 2478 19
Aspirin and Macular Degeneration Prospective observational study 2389 patients 15 years of follow up Mean age: 65 years Regular Aspirin Use At least once weekly use for the past year Klein, et al. JAMA 2012; 2469 2478 20
Aspirin and Macular Degeneration Liew, G. et al. JAMA intern Med. 2013; 258 264 21
Aspirin and Macular Degeneration Christen, W.G., et al. Ophthalmology 2009: 2386 92. 22
Azithromycin and Risk of Potentially Fatal Heart Rhythms FDA MedWatch Safety Alert Azithromycin Abnormal changes in the electrical activity of the heart Fatal irregular heart rhythm At risk Patients QT interval prolongation Low blood levels of potassium and magnesium Slower than normal heart rate Medications used for arrhythmias http://www.fda.gov/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm343 350.htm 23
Ray, W.A. et al. NEJM 2012; 366:1881 90. 24
Ray, W.A. et al. NEJM 2012; 366:1881 90. 25
Ray, W.A. et al. NEJM 2012; 366:1881 90. 26
Zolpidem Containing Products FDA recommends lower doses New data show that blood levels high enough the next morning to impair activities that require alertness Ambien, Ambien CR, Edluar, and ZolpiMist Highest risk With extended release forms Women Intermezzo (Zolpidem tartrate): no change 27
Zolpidem Containing Products Ambien, Edluar, ZolpiMist Ambien CR Dosing recommendation in current drug label for zolpidem Men and Women: 10 mg once daily, immediately before bedtime Men and Women: 12.5 mg once daily, immediately before bedtime FDA s proposed new dosing recommendations for zolpidem Women: 5 mg once daily, immediately before bedtime Men: 5 or 10 mg once daily, immediately before bedtime Women: 6.25 mg once daily, immediately before bedtime Men: 6.25 or 12.5 mg once daily, immediately before bedtime 28
Vitamin D and Calcium Supplementation U.S. Preventive Services Task Force (USPSTF) recommendation statements Recommends against daily supplementation with 400 IU or less of Vitamin D 3 and 1000 mg or less of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women (Recommendation D) Insufficient data to assess balance of the benefits and harms of daily supplementation greater than 400 IU of vitamin D 3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm 29
http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm 30
Vitamin D and Calcium Supplementation http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm 31
Vitamin D and Calcium Supplementation National Osteoporosis Foundation. 2013. Clinician s guide to prevention and treatment of osteoporosis 32
Vitamin D and Calcium Supplementation Warensjo, E., et al. BMJ: 2011; 343:d1473 33
Vitamin D and Calcium Supplementation Michaelsson, K., et al. BMJ: 2013;346:f228 34
Glucagonlike peptide 1 based therapies Singh, S., et al. JAMA Intern Med. 2013 doi:10.1001/jamainternmed.2013.2720 35
Glucagonlike peptide 1 based therapies Population based case control study Seven Blue Cross Blue Shield Plans 1,269 cases Mean age: 52 years Male: 57% Sitagliptin and Exenatide Increased odds of hospitalizations for acute pancreatitis 36
Glucagonlike peptide 1 based therapies 37
Statins and Acute Kidney Injury Dormuth, C.R., et al. BMJ 2013;346:f880 38
NEW DRUG/INDICATION/DOSE APPROVALS Exelon (rivastigmine transdermal system) Abilify Maintena Nesina, Oseni, Kazano Eliquis (apixaban) Xarelto (rivaroxaban) Fycompa (perampanel) Prolia (denosumab) Lucentis (ranibizumab) Nucynta (tapentadol) Qsymia (phentermine/topiramate) Horizant (gabapentin enacarbil) Belviq (lorcaserin) Dymista (azelastine and fluticasone) 39
New Medication Alogliptin (Nesina ) Dipeptidyl peptidase 4 (DPP 4) inhibitor Type 2 diabetes Dose 25 mg once daily CrCL 30 60 ml/min: 12.5 mg CrCl < 30 ml/min or hemodialysis: 6.25 mg 40
New Medication Alogliptin Adverse effect Nasopharyngitis Headache Upper respiratory tract infection Pancreatitis (0.2%) Drug interactions No significant drug drug interactions 41
New Medication Alogliptin and Pioglitazone (Oseni ) How supplied 12.5/15, 12.5/30,12.5/45 25/15, 25/30, 25/45 Dosage Congestive Heart Failure (Class I or II) 25mg/15mg CrCl 30 60 ml/min 12.5 mg/15 mg, 12.5 mg/30 mg, 12.5 mg/45 mg Severe renal impairment Not recommended but can use 6.25 mg dose Adverse effects Nasopharyngitis Back pain Upper respiratory tract infection 42
New Medication Alogliptin and Metformin (Kazano ) 12.5 mg/500 mg 12.5 mg/1000 mg Adverse Effects Upper respiratory tract infections Nasopharyngitis Diarrhea Hypertension Headache Back pain Urinary Tract Infections 43
New Medicaiton Phentermine and Topiramate extendedrelease (Qsymia ) BMI >30 or BMI >27 plus hypertension or diabetes or dyslipidemia Dosage 7.5 mg/46 mg After 12 weeks escalate dose or discontinue Higher dose: 15mg/92mg Take one dose every other day for at least one week to discontinue 44
Qsymia Davidson, MH, et al. Am J Cardiol 2013 45
New Indication Denosumab (Prolia ) Treatment of increased bone mass in men with osteoporosis at high risk of fracture ADAMO study 12 months Significant increase in BMD at all skeletal sites RANK Ligand inhibitor 60 mg subcutaneous injection every 6 months Orwol, E., et al. J Clin Endocrin Metab. 2012 46
New Indication Denosumab Adverse effects GI: Diarrhea (20%), nausea (8.6 31%), vomiting (15%) Musculoskeletal Arthralgia, backache, limb pain Fatigue Nasopharyngitis Upper respiratory infection Dyspnea 47
New Dose Rivastigmine transdermal system (Exelon Patch) Alzheimer's disease treatment New Dose: 13.3 mg/24 h OPTIMA study Higher dose reduced deterioration compared to lower dose Well tolerated Dement Geriatr Cogn Disord. 2012;33(5):341 53. doi: 10.1159/000340056. Epub 2012 Jul 11. 48
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