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4/1/2013
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
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DISCLOSURE
• I DO NOT HAVE ANY DISCLOSURES TO REPORT
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Contact
• Email:
– [email protected]
– [email protected]
• Office
– One University Park Drive
– Nashville, TN 37204
– Phone: 615.966.7195
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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
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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
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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
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Pharmacokinetics in the Elderly
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Absorption
Distribution
Metabolism
Excretion
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Pharmacokinetics in the Elderly
Class or Category
Decreased Hepatic Metabolism
Analgesics and anti‐inflammatory
drugs
Naproxen
Ibuprofen
Morphine
Meperidine
Antibiotics
Cardiovascular Drugs
Decreased Renal Elimination
Amikacin
Ciprofloxacin
Gentamicin
Nitrofurantoin
Streptomycin
Tobramycin
Amlodipine
Diltiazem
Lidocaine
Nifedipine
Propranolol
Quinidine
Theophylline
Verapamil
Captopril
Digoxin
Enalapril
Lisinopril
Procainamide
Quinapril
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Pharmacokinetics in the Elderly
Class or Category
Decreased Hepatic Metabolism Diuretics
Decreased Renal Elimination
Amiloride
Furosemide
Hydrochlorothiazide
Triamterene
Psychoactive Drugs
Alprazolam
Chlordiazepoxide
Desipramine
Diazepam
Imipramine
Nortriptyline
Trazadone
Triazolam
Risperidone
Others
Levodopa
Amantadine
Chlorpropramide
Cimetidine
Glyburide
Lithium
Metoclopramide
Ranitidine
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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
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Effect of Aging on Drug Response
Class
Drug
Action
Effect of Aging
Analgesics
Morphine
Acute analgesic effect
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Anticoagulants
Warfrain
PT
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Bronchodilators
Albuterol
Bronchodilation
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Cardiovascular
Angiotensin II receptor blockers
Decreased BP
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Diltiazem, Enalapril, Felodipine, Verapamil
Acute antihypertensive effect
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Diazepam
Sedation
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Diphenhydramine
Psychomotor function
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Haloperidol
Acute Sedation
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Levodopa
Adverse effects
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Psychoactive Others
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Drug‐Related Problems in the Elderly
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Inappropriate medications
Overdosage
Underprescribing
Drug/Disease Interactions
Inadequate monitoring
Poor communication
Lack of adherence
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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
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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
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Aspirin and Macular Degeneration
• Aspirin: Increased risk of age‐related macular degeneration (AMD)
Liew, G. et al. JAMA intern Med. 2013; 258‐264
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Liew, G. et al. JAMA intern Med. 2013; 258‐264
Klein, et al. JAMA 2012; 2469‐2478
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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
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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
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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
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Aspirin and Macular Degeneration
Liew, G. et al. JAMA intern Med. 2013; 258‐264
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Aspirin and Macular Degeneration
Christen, W.G., et al. Ophthalmology 2009: 2386‐92.
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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
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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
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Ray, W.A. et al. NEJM 2012; 366:1881‐90.
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Ray, W.A. et al. NEJM 2012; 366:1881‐90.
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Ray, W.A. et al. NEJM 2012; 366:1881‐90.
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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
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Zolpidem‐Containing Products
Dosing recommendation in FDA’s proposed new current drug label for dosing recommendations zolpidem
for zolpidem
Ambien, Edluar, ZolpiMist
Men and Women: 10 mg once daily, immediately
before bedtime
Women: 5 mg once daily, immediately before bedtime
Men: 5 or 10 mg once daily, immediately before bedtime
Ambien CR
Men and Women: 12.5 mg Women: 6.25 mg once daily, immediately before once daily, immediately bedtime
before bedtime
Men: 6.25 or 12.5 mg once daily, immediately before bedtime
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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 D3 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 D3 and greater than 1000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women
http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm
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http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm
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Vitamin D and Calcium Supplementation
http://www.uspreventiveservicestaskforce.org/uspstf/uspsvitd.htm
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Vitamin D and Calcium Supplementation
National Osteoporosis Foundation. 2013. Clinician’s guide to prevention and treatment of osteoporosis
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Vitamin D and Calcium Supplementation
Warensjo, E., et al. BMJ: 2011; 343:d1473 33
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Vitamin D and Calcium Supplementation
Michaelsson, K., et al. BMJ: 2013;346:f228
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Glucagonlike peptide 1‐based therapies
Singh, S., et al. JAMA Intern Med. 2013 doi:10.1001/jamainternmed.2013.2720
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Glucagonlike peptide 1‐based therapies
• Population‐based case‐control study
• Seven Blue Cross Blue Shield Plans
– 1,269 cases
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Mean age: 52 years
Male: 57%
Sitagliptin and Exenatide
Increased odds of hospitalizations for acute pancreatitis
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Glucagonlike peptide 1‐based therapies
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Statins and Acute Kidney Injury
Dormuth, C.R., et al. BMJ 2013;346:f880
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NEW DRUG/INDICATION/DOSE APPROVALS
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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)
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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
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New Medication
• Alogliptin
– Adverse effect
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Nasopharyngitis
Headache
Upper respiratory tract infection
Pancreatitis (0.2%)
– Drug interactions
• No significant drug‐drug interactions
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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
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New Medication
• Alogliptin and Metformin (Kazano®)
– 12.5 mg/500 mg
– 12.5 mg/1000 mg
– Adverse Effects
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Upper respiratory tract infections
Nasopharyngitis
Diarrhea
Hypertension
Headache
Back pain
Urinary Tract Infections
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New Medicaiton
• Phentermine and Topiramate extended‐
release (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
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Qsymia®
Davidson, MH, et al. Am J Cardiol 2013
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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
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New Indication
• Denosumab
– Adverse effects
• GI:
– Diarrhea (20%), nausea (8.6‐31%), vomiting (15%)
• Musculoskeletal
– Arthralgia, backache, limb pain
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Fatigue
Nasopharyngitis
Upper respiratory infection
Dyspnea
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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.
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Questions
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