| Anticholinergics (excludes TCAs) |
First-generation antihistamines (as single agent or as part of combination products) | Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity. Use of diphenhydramine in special situations such as acute treatment of severe allergic reaction may be appropriate | Avoid | Hydroxyzine and promethazine: high; | Strong |
| Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more-effective agents available for treatment of Parkinson disease | Avoid | Moderate | Strong |
Clidinium-chlordiazepoxide | Highly anticholinergic, uncertain effectiveness | Avoid except in short-term palliative care to decrease oral secretions | Moderate | Strong |
| Antithrombotics |
| Dipyridamole, oral short actinga (does not apply to 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 |
| Ticlopidinea | Safer effective alternatives available | Avoid | Moderate | Strong |
| Anti-infective |
| Nitrofurantoin | Potential for pulmonary toxicity; safer alternatives available; lack of efficacy in patients with CrCl < 60 mL/min due to inadequate drug concentration in the urine | Avoid for long-term suppression; avoid in patients with CrCl < 60 mL/min | Moderate | Strong |
| Cardiovascular |
| 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 |
| High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension | Avoid clonidine as a first-line antihypertensive. | Low | Strong |
Antiarrhythmic drugs (Class Ia, Ic, III) | Data suggest that rate control yields better balance of benefits and harms than rhythm control for most older adults. Amiodarone is associated with multiple toxicities, including thyroid disease, pulmonary disorders, and QT- interval prolongation | Avoid antiarrhythmic drugs as first-line treatment of atrial fibrillation | High | Strong |
| Disopyramidea | 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 heart failure. In general, rate control is preferred over rhythm control for atrial fibrillation | Avoid in patients with permanent atrial fibrillation or heart failure | Moderate | Strong |
| Digoxin > 0.125 mg/d | In heart failure, higher dosages associated with no additional benefit and may increase risk of toxicity; slow renal clearance may lead to risk of toxic effects | Avoid | Moderate | Strong |
| Nifedipine, immediate releasea | Potential for hypotension; risk of precipitating myocardial ischemia | Avoid | High | Strong |
| Spironolactone > 25 mg/d | In heart failure, the risk of hyperkalemia is higher in older adults especially if taking > 25 mg/d or taking concomitant NSAID, angiotensin converting-enzyme inhibitor, angiotensin receptor blocker, or potassium supplement | Avoid in patients with heart failure or with a CrCl < 30 mL/min | Moderate | Strong |
| Central nervous system |
Tertiary TCAs, alone or in combination: Chlordiazepoxide-amitriptyline Perphenazine-amitriptyline | Highly anticholinergic, sedating, and cause orthostatic hypotension; safety profile of low-dose doxepin (≤6 mg/d) is comparable with that of placebo | Avoid | High | Strong |
| Antipsychotics, first (conventional) and second (atypical) generation (see Table 8 for full list) | Increased risk of cerebrovascular accident (stroke) and mortality in persons with dementia | Avoid use for behavioral problems of dementia unless nonpharmacological options have failed and patient is threat to self or others | Moderate | Strong |
| Highly anticholinergic and risk of QT-interval prolongation | Avoid | Moderate | Strong |
| High rate of physical dependence; tolerance to sleep benefits; risk of overdose at low dosages | Avoid | High | Strong |
Short and intermediate acting: Chlordiazepoxide-amitriptyline Clidinium-chlordiazepoxide | Older adults have increased sensitivity to benzodiazepines and slower metabolism of long-acting agents. In general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents in older adults May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia, end-of-life care | Avoid benzodiazepines (any type) for treatment of insomnia, agitation, or delirium | High | Strong |
| Chloral hydratea | Tolerance occurs within 10 days, and risks outweigh benefits in light of overdose with doses only 3 times the recommended dose | Avoid | Low | Strong |
| Meprobamate | High rate of physical dependence; very sedating | Avoid | Moderate | Strong |
Nonbenzodiazepine hypnotics | Benzodiazepine-receptor agonists that have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures); minimal improvement in sleep latency and duration | Avoid chronic use (> 90 days) | Moderate | Strong |
| Lack of efficacy | Avoid | High | Strong |
| Endocrine |
| Potential for cardiac problems and contraindicated in men with prostate cancer | Avoid unless indicated for moderate to severe hypogonadism | 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 that vaginal estrogens for treatment of vaginal dryness is safe and effective in women with breast cancer, especially at dosages of estradiol < 25 μg twice weekly | Avoid oral and topical patch. Topical vaginal cream: acceptable to use low-dose intravaginal estrogen for the management of dyspareunia, lower urinary tract infections, and other vaginal symptoms | | |
| Growth hormone | Effect 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 | 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: prolonged half-life in older adults; can cause prolonged hypoglycemia; causes syndrome of inappropriate antidiuretic hormone secretion. Glyburide: greater risk of severe prolonged hypoglycemia in older adults | Avoid | High | Strong |
| Gastrointestinal |
| Metoclopramide | Can cause extrapyramidal effects including tardive dyskinesia; risk may be even greater in frail older adults | Avoid, unless for gastroparesis | Moderate | Strong |
| Mineral oil, oral | Potential for aspiration and adverse effects; safer alternatives available | Avoid | Moderate | Strong |
| Trimethobenzamide | One of the least effective antiemetic drugs; can cause extrapyramidal adverse effects | Avoid | Moderate | Strong |
| Pain |
| Meperidine | Not an effective oral analgesic in dosages commonly used; may cause neurotoxicity; safer alternatives available | Avoid | High | Strong |
Non–COX-selective NSAIDs, oral | Increases risk of GI bleeding and 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 GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3–6 months and in approximately 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 |
Ketorolac, includes parenteral | Increases risk of GI bleeding and peptic ulcer disease in high-risk groups. (See above Non-COX selective NSAIDs.) Of all the NSAIDs, indomethacin has most adverse effects | Avoid | | Strong |
| Pentazocinea | Opioid analgesic that causes CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs; is also a mixed agonist and antagonist; safer alternatives available | Avoid | Low | Strong |
Skeletal muscle relaxants | Most muscle relaxants are poorly tolerated by older adults because of anticholinergic adverse effects, sedation, risk of fracture; effectiveness at dosages tolerated by older adults is questionable | Avoid | Moderate | Strong |