Organ System, Therapeutic Category, Drugs |
Rationale |
Recommendation |
Quality of Evidence |
Strength of Recommendation |
Anticholinergics |
First-generation antihistamines Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbrompheniramine DexchlorpheniramineDimenhydrinate Diphenhydramine (oral) Doxylamine Hydroxyzine Meclizine Promethazine Triprolidine |
Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity Use of diphenhydramine in situations such as acute treatment of severe allergic reaction may be appropriate |
Avoid |
Moderate |
Strong |
Antiparkinsonian agents Benztropine (oral) Trihexyphenidyl |
Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more-effective agents available for treatment of Parkinson disease |
Avoid |
Moderate |
Strong |
Antispasmodics Atropine (excludes ophthalmic) Belladonna alkaloids Clidinium-Chlordiazepoxide Dicyclomine Hyoscyamine Propantheline Scopolamine |
Highly anticholinergic, uncertain effectiveness |
Avoid |
Moderate |
Strong |
Antithrombotics |
Dipyridamole, oral short-acting (does not apply to the extended-release combination with aspirin) |
May cause orthostatic hypotension; more effective alternatives available; intravenous form acceptable for use in cardiac stress testing |
Avoid |
Moderate |
Strong |
Ticlopidine |
Safer, effective alternatives available |
Avoid |
Moderate |
Strong |
Anti-infective |
Nitrofurantoin |
Potential for pulmonary toxicity, hepatoxicity, and peripheral neuropathy, especially with long-term use; safer alternatives available |
Avoid in individuals with creatinine clearance <30 mL/min or for long-term suppression of bacteria |
Low |
Strong |
Cardiovascular |
Peripheral alpha-1 blockers Doxazosin Prazosin Terazosin |
High risk of orthostatic hypotension; not recommended as routine treatment for hypertension; alternative agents have superior risk–benefit profile |
Avoid use as an antihypertensive |
Moderate |
Strong |
Central alpha blockers Clonidine Guanabenz Guanfacine Methyldopa Reserpine (>0.1 mg/d) |
High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension |
Avoid clonidine as first-line antihypertensive Avoid others as listed |
Low |
Strong |
Disopyramide |
Disopyramide is a potent negative inotrope and therefore may induce heart failure in older adults; strongly anticholinergic; other antiarrhythmic drugs preferred |
Avoid |
Low |
Strong |
Dronedarone |
Worse outcomes have been reported in patients taking dronedarone who have permanent atrial fibrillation or severe or recently decompensated heart failure |
Avoid in individuals with permanent atrial fibrillation or severe or recently decompensated heart failure |
High |
Strong |
Digoxin |
Use in atrial fibrillation: should not be used as a first-line agent in atrial fibrillation, because more-effective alternatives exist and it may be associated with increased mortality |
Avoid as first-line therapy for atrial fibrillation |
Atrial fibrillation: moderate |
Atrial fibrillation: strong |
|
Use in heart failure: questionable effects on risk of hospitalization and may be associated with increased mortality in older adults with heart failure; in heart failure, higher dosages not associated with additional benefit and may increase risk of toxicity |
Avoid as first-line therapy for heart failure |
Heart failure: low |
Heart failure: strong |
|
Decreased renal clearance of digoxin may lead to increased risk of toxic effects; further dose reduction may be necessary in patients with Stage 4 or 5 chronic kidney disease |
If used for atrial fibrillation or heart failure, avoid dosages >0.125 mg/d |
Dosage >0.125 mg/d: moderate |
Dosage >0.125 mg/d: strong |
Nifedipine, immediate release |
Potential for hypotension; risk of precipitating myocardial ischemia |
Avoid |
High |
Strong |
Amiodarone |
Amiodarone is effective for maintaining sinus rhythm but has greater toxicities than other antiarrhythmics used in atrial fibrillation; it may be reasonable first-line therapy in patients with concomitant heart failure or substantial left ventricular hypertrophy if rhythm control is preferred over rate control |
Avoid amiodarone as first-line therapy for atrial fibrillation unless patient has heart failure or substantial left ventricular hypertrophy |
High |
Strong |
Central nervous system |
Antidepressants, alone or in combination Amitriptyline Amoxapine Clomipramine Desipramine Doxepin >6 mg/d Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine |
Highly anticholinergic, sedating, and cause orthostatic hypotension; safety profile of low-dose doxepin (≤6 mg/d) comparable with that of placebo |
Avoid |
High |
Strong |
Antipsychotics, first- (conventional) and second- (atypical) generation |
Increased risk of cerebrovascular accident (stroke) and greater rate of cognitive decline and mortality in persons with dementia Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacological options (e.g., behavioral interventions) have failed or are not possible and the older adult is threatening substantial harm to self or others |
Avoid, except for schizophrenia, bipolar disorder, or short-term use as antiemetic during chemotherapy |
Moderate |
Strong |
Barbiturates Amobarbital Butabarbital Butalbital Mephobarbital Pentobarbital Phenobarbital Secobarbital |
High rate of physical dependence, tolerance to sleep benefits, greater risk of overdose at low dosages |
Avoid |
High |
Strong |
Benzodiazepines Short- and intermediate- acting Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam |
Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents; in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults |
Avoid |
Moderate |
Strong |
Long-acting Clorazepate Chlordiazepoxide (alone or in combination with amitriptyline or clidinium) Clonazepam Diazepam Flurazepam Quazepam |
May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesia |
|
|
|
Meprobamate |
High rate of physical dependence; very sedating |
Avoid |
Moderate |
Strong |
Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics Eszopiclone Zolpidem Zaleplon |
Benzodiazepine-receptor agonists have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures);increased emergency department visits and hospitalizations; motor vehicle crashes; minimal improvement in sleep latency and duration |
Avoid |
Moderate |
Strong |
Ergoloid mesylates (dehydrogenated ergot alkaloids) Isoxsuprine |
Lack of efficacy |
Avoid |
High |
Strong |
Endocrine |
Androgens Methyltestosterone Testosterone |
Potential for cardiac problems; contraindicated in men with prostate cancer |
Avoid unless indicated for confirmed hypogonadism with clinical symptoms |
Moderate |
Weak |
Desiccated thyroid |
Concerns about cardiac effects; safer alternatives available |
Avoid |
Low |
Strong |
Estrogens with or without progestins |
Evidence of carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women Evidence indicates that vaginal estrogens for the treatment of vaginal dryness are safe and effective; women with a history of breast cancer who do not respond to nonhormonal therapies are advised to discuss the risk and benefits of low-dose vaginal estrogen (dosages of estradiol <25 μg twice weekly) with their healthcare provider |
Avoid oral and topical patch Vaginal cream or tablets: acceptable to use low-dose intravaginal estrogen for management of dyspareunia, lower urinary tract infections, and other vaginal symptoms |
Oral and patch: high Vaginal cream or tablets: moderate |
Oral and patch: strong Topical vaginal cream or tablets: weak |
Growth hormone |
Impact on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, impaired fasting glucose |
Avoid, except as hormone replacement after pituitary gland removal |
High |
Strong |
Insulin, sliding scale |
Higher risk of hypoglycemia without improvement in hyperglycemia management regardless of care setting; refers to sole use of short- or rapid-acting insulins to manage or avoid hyperglycemia in absence of basal or long-acting insulin; does not apply to titration of basal insulin or use of additional short- or rapid-acting insulin in conjunction with scheduled insulin (i.e., correction insulin) |
Avoid |
Moderate |
Strong |
Megestrol |
Minimal effect on weight; increases risk of thrombotic events and possibly death in older adults |
Avoid |
Moderate |
Strong |
Sulfonylureas, long-duration Chlorpropamide |
Chlorpropamide: prolonged half-life in older adults; can cause prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion |
Avoid |
High |
Strong |
Glyburide |
Glyburide: higher risk of severe prolonged hypoglycemia in older adults |
|
|
|
Gastrointestinal |
Metoclopramide |
Can cause extrapyramidal effects, including tardive dyskinesia; risk may be greater in frail older adults |
Avoid, unless for gastroparesis |
Moderate |
Strong |
Mineral oil, given orally |
Potential for aspiration and adverse effects; safer alternatives available |
Avoid |
Moderate |
Strong |
Proton-pump inhibitors |
Risk of Clostridium difficile infection and bone loss and fractures |
Avoid scheduled use for >8 weeks unless for high-risk patients (e.g., oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett's esophagitis, pathological hypersecretory condition, or demonstrated need for maintenance treatment (e.g., due to failure of drug discontinuation trial or H2 blockers) |
High |
Strong |
Pain medications |
Meperidine |
Not effective oral analgesic in dosages commonly used; may have higher risk of neurotoxicity, including delirium, than other opioids; safer alternatives available |
Avoid, especially in individuals with chronic kidney disease |
Moderate |
Strong |
Non-cyclooxygenase-selective NSAIDs, oral: Aspirin >325 mg/d Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen Ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin |
Increased risk of gastrointestinal bleeding or peptic ulcer disease in high-risk groups, including those aged >75 or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents; use of proton-pump inhibitor or misoprostol reduces but does not eliminate risk. Upper gastrointestinal ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3–6 months and in ~2–4% of patients treated for 1 year; these trends continue with longer duration of use |
Avoid chronic use, unless other alternatives are not effective and patient can take gastroprotective agent (proton-pump inhibitor or misoprostol) |
Moderate |
Strong |
Indomethacin |
Indomethacin is more likely than other NSAIDs to have adverse CNS effects. Of all the NSAIDs, indomethacin has the most adverse effects. |
Avoid |
Moderate |
Strong |
Ketorolac, includes parenteral |
Increased risk of gastrointestinal bleeding, peptic ulcer disease, and acute kidney injury in older adults |
|
|
|
Pentazocine |
Opioid analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other opioid analgesic drugs; is also a mixed agonist and antagonist; safer alternatives available |
Avoid |
Low |
Strong |
Skeletal muscle relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine |
Most muscle relaxants poorly tolerated by older adults because some have anticholinergic adverse effects, sedation, increased risk of fractures; effectiveness at dosages tolerated by older adults questionable |
Avoid |
Moderate |
Strong |
Genitourinary |
Desmopressin |
High risk of hyponatremia; safer alternative treatments |
Avoid for treatment of nocturia or nocturnal polyuria |
Moderate |
Strong |