High Risk Medications and Safe Treatment Alternatives

Use of High-Risk Medications in the Elderly

and Safer Alternate Treatments

Certain medications are more likely to have adverse effects for people over the age of 65. There are often safer alternate treatments that are highly effective. Below is a list of high risk medications compiled by the PHP Plan Pharmacist. These are the medications included in the Plan formulary, as well as potential risks and alternative treatment options. Please consider these recommendations when prescribing for patients 65 and older.

The Use of High-Risk Medications in the Elderly is a HEDIS (Healthcare Effectiveness Data and Information Set) performance measure that assesses the percentage of Plan Members 65 years of age and older who received at least one or two different high-risk medications.

Therapeutic Class High Risk Medications Potential Risks Safer Treatment Options† Alpha-Blockers, Central Guanabenz May cause bradycardia, sedation, ACE inhibitors / ARBs Guanfacine orthostatic hypotension, and Beta-blockers Methyldopa exacerbate depression. Calcium channel blockers Reserpine (>0.1 mg/day) Thiazide diuretics Anti-Anxiety Agents Meprobamate Meprobamate has a high risk of Buspirone abuse, and is highly sedating. Use SSRIs (Fluoxetine, Citalopram, in the elderly may result in Paroxetine) confusion, falls/fractures,and SNRIs (Venlafaxine, duloxetine) respiratory depression. Anti-emetics Promethazine Elderly patients are more For N/V: Ondansetron (QL = 45/30) Trimethobenzamide (Tigan) susceptible to anticholinergic adverse events including urine retention, confusion, and sedation. Antiparkinson Agents Benztropine Elderly patients are more Carbidopa / levodopa, Trihexyphenidyl susceptible to anticholinergic Pramipexole, Ropinirole, adverse events including urine Bromocriptine, Amantadine, retention, confusion, Selegiline

† Treatment alternatives may require prior authorization or step therapy. For the most current formulary listings, please consult: positivehealthcare.net/california/php/for-members/drug-benefit/formulary/ March 2014

hallucinations and psychotic-like symptoms Anti-Psychotics Thioridazine (Mellaril) Thioridazine has a high potential Atypical antipsychotics: Mesoridazine for CNS and extrapyramidal Risperidone, Olanzapine, adverse events. It has been Ziprasidone, Abilify, Saphris, associated with tremor, slurred quetiapine speech, muscle rigidity, dystonia, (Please note, all antipsychotics bradykinesia, and akathisia. have been associated with increased mortality when used to treat psychosis related to dementia.) Antithrombotics Dipyridamole (Persantine, NOTE: These agents been shown to be no For prevention of thromboembolic does NOT include combination better than aspirin in preventing complications of cardiac valve product with aspirin) clotting and may be considerably replacement: Warfarin Ticlopidine (Ticlid) more toxic. Dipyridamole is For prevention of stroke: associated with an increased risk Clopidogrel, Aggrenox, Aspirin of orthostatic hypotension in the elderly. Ticlopidine is associated with an increased risk of hematologic effects (e.g., neutropenia, thrombocytopenia, aplastic anemia), increased cholesterol and triglycerides, and GI bleed). Barbiturates Phenobarbital (Luminal) These medications are highly PLEASE NOTE: Patients being Mephobarbital (Mebaral) addictive and cause more adverse switched off barbiturates should Secobarbital (Seconal) effects than most other sedatives be tapered slowly over a Butabarbital (Butisol) in the elderly, greatly increasing prolonged period of time. Pentobarbital (Nembutal) cognitive impairment, confusion, For seizures: Divalproex, Butalbital and Butalbital and risk of falls. Levetiracetam, Lamotrigine, combinations (Fioricet/Codeine) Carbamazepine For sleep: Consider non- pharmacologic interventions, focusing on proper sleep hygiene. Rozerem may be considered as a safer option with less abuse

potential. Trazodone, Mirtazapine, Gabapentin, Nortriptyline For headache: Sumatriptan Calcium Channel Blockers Nifedipine immediate-release Immediate release nifedipine may Amlodipine, Felodipine (Adalat, Procardia) cause excessive hypotension and Extended-release Nifedipine constipation in the elderly. Cardiovascular, Other Disopyramide Disopyramide may induce heart For disopyramide: Beta-blockers, Digoxin (>0.125 mg/day) failure in elderly patients. It is also Calcium channel blockers, strongly anticholinergic, and may Flecainide cause urine retention, confusion, - For digoxin > 0.125 mg/day: In and sedation. heart failure, digoxin dosages Digoxin is substantially excreted by >0.125 mg/day have been the kidney. Because elderly associated with no additional patients are more likely to have benefit and may have increased decreased renal function, there is toxic effects. an increased risk of toxicity at doses exceeding 0.125 mg/day. Estrogens and Estrogen / Conjugated estrogen (Premarin) Elderly patients on long-term oral For Hot Flashes: Progesterone Products (Oral and Conjugated estrogen / medroxy- estrogens are at increased risk for Continuously re-evaluate the need Transdermal) progesterone (Prempro, breast and endometrial cancer. In for long-term estrogen therapy; Premphase) addition, results from the evaluate non-drug therapy. Estradiol, oral (Estrace, Femtrace) Women’s Health Initiative (WHI) Postmenopausal women should Estradiol patch (Alora, Climara, hormone trial suggest these avoid using oral estrogens for Estraderm, Estradiol, Menostar, medications may increase the risk more than 3 years. After 3 years Vivelle-Dot) of heart attack, stroke, blood clots, patients should be titrated off Estradiol / drospirenone (Angeliq) and dementia. therapy due to the risks Estradiol / levonorgestrel outweighing the benefits. (ClimaraPro) **SSRIs, Gabapentin, and Estradiol / norethindrone Venlafaxine have non-FDA labeled (CombiPatch) indications (medically accepted Estradiol / norgestimate (Prefest) use) for hot flashes. Estropipate (Ogen, Ortho- Est)Esterified estrogen (Menest) For Bone Density: Alendronate, Esterified estrogen / Actonel, Evista, Prolia methyltestosterone (Covaryx,

Estratest) Ethinyl estradiol / norethindrone (Activella, FemHRT) First Generation Antihistamines Brompheniramine Elderly patients are more For Allergic Rhinitis: Carbinoxamine (Arbinoxa, Palgic) susceptible to anticholinergic Desloratadine, Chlorpheniramine adverse events including urine Azelastine (nasal), Fluticasone Clemastine retention, confusion, and sedation. (nasal), Flunisolide (nasal), and Cyproheptadine Nasonex Dexbrompheniramine For N/V: Ondansetron (QL = Dexchlorpheniramine 45/30) Diphenhydramine (Benadryl) For Pruritus: Desloratadine, Doxylamine (Doxytex) Topical steroids Hydroxyzine (Vistaril) For Anxiety: SSRIs, buspirone, Promethazine (Phenergan) venlafaxine Triprolidine In addition, there are OTC Options All combination products for which coverage may vary containing one of these depending on benefit plan: medications Loratadine (Claritin)

Narcotic Analgesics Meperidine (Demerol) These specific medications are less For Moderate Pain: NSAIDs*, Pentazocine / APAP (Talacen) effective than other narcotics and Tramadol, APAP with codeine Pentazocine / naloxone (Talwin have more CNS adverse effects For Severe Pain: NX) such as confusion and hallucina- Hydrocodone/APAP, Oxycodone, tions. Also, their use increases the Oxycodone/APAP, Morphine risk of falls and seizures. * Gastroprotective therapy with a PPI recommended in chronic NSAID use Oral Hypo-glycemics Chlorpropamide (Diabinese) Associated with an increased risk Glipizide Glyburide (Diabeta) of hypoglycemia compared to Glimepiride other oral diabetes agents. Chlorpropamide has also been associated with hyponatremia and SIADH in the elderly. Peripheral Vasodilators Ergoloid mesylates These agents are associated with For prevention of stroke: Isoxsuprine increased risk of orthostatic hypo- Clopidogrel, Aggrenox, Aspirin tension in the elderly. In addition, Peripheral Vascular Disease:

they have not been shown to be cilostazol effective for stroke prevention. For treatment of Alzheimer’s / dementia: Galantamine Donepezil

Progestins Megestrol (Megace, Megace ES) Megestrol is substantially excreted Medroxyprogesterone by the kidney. Because elderly Dronabinol patients are more likely to have decreased renal function, there is an increased risk of toxicity, including adrenal suppression and thrombosis. Sedative Hypnotics Chloral hydrate Impaired motor and/or cognitive Consider non-pharmacologic Eszopiclone (Lunesta) performance after repeated interventions, focusing on proper Zolpidem (Ambien, Ambien CR) exposure. sleep hygiene. Zaleplon (Sonata) Rozerem may be considered as a safer option with less abuse potential. Trazodone Mirtazapine Gabapentin Nortriptyline Skeletal Muscle Relaxants Carisoprodol (Soma) Most muscle relaxants are poorly For Spasticity: Baclofen, Cyclobenzaprine (Flexeril) tolerated in the elderly due to anti- Tizanidine, and Dantrolene Methocarbamol (Robaxin) cholinergic effects, sedation and For Muscluloskeletal Pain: oral Orphenadrine (Norflex) cognitive impairment. In addition, NSAIDs*, Voltaren gel, duloxetine; Metaxalone (Skelaxin) these agents have abuse potential. May consider non-pharmacologic Chlorzoxazone (Parafon Forte) treatments, such as cryotherapy, All combination products heat, massage, containing one of these stretching/exercise, and medications transcutaneous electrical nerve stimulation (TENS) * Gastroprotective therapy with a PPI recommended in chronic NSAID use

Tertiary Amine Tricyclic Amitriptyline Elderly patients are more For Depression / Anxiety / OCD: Antidepressants (TCAs) Clomipramine susceptible to anticholinergic - Secondary Amine TCAs Doxepin (>6 mg/day) adverse events including urine (Nortriptyline, Protriptyline, Imipramine retention, confusion, and sedation. Desipramine, Amoxapine) Trimipramine - SSRIs (Fluoxetine, Citalopram, Paroxetine, Sertraline) - SNRIs (Venlafaxine, Cymbalta) - Bupropion For neuropathic pain / fibromyalgia: - Gabapentin, duloxetine, Lyrica For prevention of migraine: Propranolol, Divalproex sodium, Topiramate Thyroid Hormones Dessicated thyroid (Armour Dessicated thyroid may increase Levothyroxine, Levoxyl, Levothroid thyroid, NP Thyroid, Nature- the risk of cardiovascular events in Current guidelines recommend Throid, Westhroid) the elderly, especially those with starting at a low dose and, once coronary artery disease. cardiovascular tolerance is established, slowly increasing until adequate replacement is achieved. Urinary Anti-Infectives Nitrofurantoin (Furadantin) Nitrofurantoin is substantially For treatment of acute UTI: Nitrofurantoin monohydrate/ excreted by the kidney. Since Ciprofloxacin, Trimethoprim / macrocrystals (Macrobid) elderly patients are more likely to sulfamethoxazole (TMP/SMX), Nitrofurantoin macrocrystals have decreased renal function, Amoxicillin/clavulanate, Cefdinir, (Macrodantin) nitrofurantoin use is associated Cefaclor, Cefpodoxime, Suprax with an increased risk of For prevention of recurrent UTIs: pulmonary toxicity, neuropathy, Prescription options include: and hepato-toxicity. In addition, TMP/SMX there is a lack of efficacy in Non-prescription options include patients with a CrCl <60 mL/min practicing good personal hygiene, due to inadequate drug avoiding baths, and wearing cotton concentration in the urine. underwear.

References: 1. The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially † Treatment alternatives may require prior authorization or step therapy. For the most current formulary listings, please consult: positivehealthcare.net/california/php/for-members/drug-benefit/formulary/ March 2014

Inappropriate Medication Use in Older Adults. JAGS. 2012; 60: 616-31. 2. PQA. Use of High-Risk Medications in the Elderly: Review and Revision of Performance Measure. June 2012. 3. Lovell P, Vender RB. Management and Treatment of Pruritus. Skin Therapy Letter. 2007. 12(1). 4. Nadler SF. Non-pharmacologic Treatment of Pain. J Am Osteopath Assoc. 2004; 104(11 suppl): 6S-12S. 5. Radbruch L, Elsner F, Trottenberg P, Strasser F, Fearon K: Clinical practice guidelines on cancer cachexia in advanced cancer patients. Aachen, Department of Palliative Medicinen/ European Palliative Care Research Collaborative; 2010. 6. Rossouw JE, Anderson GL, Prentice RL, et. al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principle results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-33. http://jama.ama-assn.org/content/288/3/321.full.pdf+html 7. Juthani-Mehta M. Urinary Tract Infections in Elderly Person. American Society of Nephrology - Online Geriatric Nephrology Curriculum, Chapter 32. 2009: 1-3. 8. Centers for Medicare &Medicaid Services. Memo to Part D Sponsors. Transition to Part D Coverage of Benzodiazepines and Barbiturates Beginning in 2013. October 2, 2012. 9. Kim, MI, Ladenson PW. Hypothyroidism in the Elderly. 2007. In Endotext.com. Available online: http://www.endotext.org/aging/aging9/agingframe9.htm