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Drug Categories of Concern in the Elderly

By J. Mark Ruscin, PharmD, FCCP, BCPS, Professor and Chair, Department of Pharmacy Practice, Southern Illinois University Edwardsville School of Pharmacy
Sunny A. Linnebur, PharmD, BCPS, BCGP, Professor of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences

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Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for elderly patients. Some drugs, although reasonable for use in younger adults, are so risky they should be considered inappropriate for the elderly. The Beers Criteria are most commonly used to identify such inappropriate drugs (see Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update)). The 2012 American Geriatrics Society updates to the Beers criteria further categorize potentially inappropriate drugs into 3 groups:

Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update)


Prescribing Concern/Recommendations


First-generation antihistamines, as single agents or in combination products (brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, dexbrompheniramine,dexchlorpheniramine, diphenhydramine [oral], doxylamine, hydroxyzine, promethazine, triprolidine)

Highly anticholinergic; greater risk of confusion, dry mouth, constipation, and other anticholinergic effects and toxicity

Clearance reduced with advanced age; tolerance develops when used as hypnotics

Avoid, except use of diphenhydramine in special situations (eg, severe allergic reaction) may be appropriate

Antiparkinson drugs (benztropine [oral], trihexyphenidyl)

Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease

Antispasmodics (belladonna alkaloids, clidinium-chlordiazepoxide, dicyclomine, hyoscyamine, propantheline, scopolamine)

Highly anticholinergic, uncertain effectiveness

Avoid except short-term use in palliative care to decrease oral secretions



May cause pulmonary toxicity; safer alternatives available; lack of efficacy in patients with creatinine clearance < 60 mL/min due to inadequate drug concentration in the urine; do not use for long-term suppression or in patients with creatinine clearance < 60 mL/min


Dipyridamole, oral short-acting (does not apply to extended-release combination with aspirin)

Possible orthostatic hypotension; more effective alternatives available; avoid, except IV form acceptable for cardiac stress testing


Safer effective alternatives available; avoid

Cardiovascular drugs

Alpha-1 blockers (doxazosin, prazosin, terazosin)

High risk of orthostatic hypotension; alternative drugs have better risk/benefit ratio; avoid use as an antihypertensive

Alpha agonists, central (clonidine, guanabenz, guanfacine, methyldopa, reserpine [> 0.1 mg/day])

High risk of adverse CNS effects; may cause bradycardia and orthostatic hypotension; avoid clonidine as first-line hypertensive; others not recommended

Antiarrhythmic drugs, classes Ia, Ic, and III (amiodarone, dofetilide, dronedarone, flecainide, ibutilide, procainamide, propafenone, quinidine, sotalol)

Rate control preferred over rhythm control; avoid as first-line treatment for atrial fibrillation

For amiodarone, increased risk of thyroid disease, pulmonary disorders, and QT interval prolongation


Potent negative inotrope (may induce heart failure); strongly anticholinergic; avoid, other antiarrhythmic drugs preferred


Worse outcomes in patients who have permanent atrial fibrillation or heart failure; avoid

Rate control preferred over rhythm control for atrial fibrillation

Digoxin (> 0.125 mg/day)

In patients with heart failure and/or low creatinine clearance, higher dosages associated with no additional benefit and increased risk of toxicity; avoid

Nifedipine, immediate release

Risk of hypotension and myocardial ischemia; avoid

Spironolactone (> 25 mg/day)

In patients with heart failure, risk of hyperkalemia especially if also taking an NSAID, ACE inhibitor, angiotensin receptor blocker, or K supplement; avoid in heart failure or if creatinine clearance < 30 mL/min


Tertiary TCAs, alone or in combination (amitriptyline, chlordiazepoxide-amitriptyline, clomipramine, doxepin [> 6 mg/day], imipramine, perphenazine-amitriptyline, trimipramine)

Highly anticholinergic and sedating and cause orthostatic hypotension; avoid

Antipsychotics, 1st (conventional) and 2nd (atypical) generations

Increased risk of stroke and mortality in patients with dementia

Avoid in patients with dementia-related behavior problems unless nonpharmacologic options have failed and patients are a threat to themselves or others



Highly anticholinergic; risk of QT interval prolongation; avoid

Barbiturates (amobarbital, butabarbital, butalbital, mephobarbital, pentobarbital, phenobarbital, secobarbital)

High rate of physical dependence and tolerance; risk of overdose at low dosages; avoid

Benzodiazepines, short- and intermediate-acting (alprazolam, estazolam, lorazepam, oxazepam, temazepam, triazolam)

Benzodiazepines, long-acting (clorazepate, chlordiazepoxide, chlordiazepoxide-amitriptyline, clidinium-chlordiazepoxide, clonazepam, diazepam, flurazepam, quazepam)

Increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes

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 use for insomnia, agitation, or delirium

Chloral hydrate

Can overdose at only 3 times recommended dose; tolerance occurs within 10 days; risks outweigh benefits; avoid


High rate of physical dependence; very sedating; avoid

Nonbenzodiazepine hypnotics (eszopiclone, zolpidem, zaleplon)

Similar to benzodiazepines (eg, delirium, falls, fractures); minimal improvement in sleep latency and duration

Not to be used for > 90 days

Ergot mesylates


Lack of efficacy; avoid

Endocrine therapy

Androgens (methyltestosterone, testosterone)

Potential for cardiac problems; exacerbation of prostate cancer

Avoid except for moderate to severe hypogonadism

Desiccated thyroid

Possible cardiac effects; safer alternatives available; avoid

Estrogens with or without progestins

Possible carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women

Topical vaginal cream low dose can be used for dyspareunia, lower UTIs, and other vaginal symptoms; evidence that low doses (estradiol < 25 mcg twice/wk) may be safe in women with breast cancer

Avoid topical patch and oral

Growth hormone

Little effect on body composition; associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, impaired fasting glucose

Avoid except for hormone replacement after pituitary gland removal

Insulin, sliding scale

Higher risk of hypoglycemia without improvement in glucose control regardless of care setting; avoid


Minimal effect on weight; increases risk of thrombotic events and possibly death; avoid

Sulfonylureas, long duration (chlorpropamide, glyburide)

Chlorpropamide: Prolonged half-life; can cause prolonged hypoglycemia, syndrome of inappropriate antidiuretic hormone secretion; avoid

Glyburide: Greater risk of severe prolonged hypoglycemia; avoid

GI therapy


Can cause extrapyramidal effects including tardive dyskinesia; risk may be greater in frail older adults; avoid except for gastroparesis

Mineral oil, oral

Potential for aspiration; safer alternatives available; avoid


One of the least effective antiemetics; can cause extrapyramidal effects; avoid

Pain management


Not an effective oral analgesic in common dosages; may cause neurotoxicity; safer alternatives available; avoid

Non–COX-selective NSAIDs, oral (aspirin [> 325 mg/day], diclofenac, diflunisal, etodolac, fenoprofen, ibuprofen, ketoprofen, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin)

Increased 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

Upper GI ulcers, gross bleeding, or perforation occur in about 1% of patients treated for 3–6 mo and in about 2–4% of patients treated for 1 yr; these trends continue with longer duration of use

Avoid chronic use unless other alternatives are ineffective and patients are able to take a proton pump inhibitor or misoprostol (which reduce but do not eliminate risk)


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


CNS adverse effects, including confusion and hallucinations, more common than with other opioids; is also a mixed agonist and antagonist; safer alternatives available; avoid

Skeletal muscle relaxants (carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine)

Poorly tolerated because of anticholinergic effects; sedation; risk of fracture; effectiveness at dosages tolerated by older adults is questionable; avoid

*TCAs are excluded.

These drugs are used infrequently.

TCAs = tricyclic antidepressants.

Adapted from The American Geriatrics Society 2012 Beers Criteria Update Expert Panel: American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society 60: 616–631, 2012.

Drugs to Be Used With Caution in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update)


Reason for Caution

Aspirin for primary prevention of cardiac events

Use with caution in patients ≥ 80 yr.

Lack of evidence regarding benefit vs risk in patients > 80 yr


Use with caution in patients ≥ 75 yr or with creatinine clearance < 30 mL/min. Greater risk of bleeding than warfarin in patients ≥ 75 yr

Lack of evidence regarding efficacy and safety in patients with creatinine clearance < 30 mL/min


Use with caution in patients ≥ 75 yr. Increased risk of bleeding; benefit may offset risk in highest-risk elderly (eg, those with previous MI or diabetes mellitus)






Serotonin–norepinephrine reuptake inhibitors


Tricyclic antidepressants


May worsen or cause syndrome of inappropriate antidiuretic hormone secretion or hyponatremia

Monitor Na level closely when starting or changing dosages.


May increase episodes of syncope in patients with history of syncope

Adapted from The American Geriatrics Society 2012 Beers Criteria Update Expert Panel: American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society 60: 616–631, 2012.


NSAIDs are used by > 30% of people aged 65 to 89, and half of all NSAID prescriptions are for people > 60. Several NSAIDs are available without prescription.

The elderly may be prone to adverse effects of these drugs, and adverse effects may be more severe because of the following:

  • NSAIDs are highly lipid-soluble, and because adipose tissue increases with age, distribution of the drugs is extensive.

  • Plasma protein is often decreased, resulting in higher levels of unbound drug and exaggerated pharmacologic effects.

  • Renal function is reduced in many of the elderly, resulting in decreased renal clearance and higher drug levels.

Serious adverse effects include peptic ulceration and upper GI bleeding; risk is increased when an NSAID is begun and when dose is increased. Risk of upper GI bleeding increases when NSAIDs are given with warfarin, aspirin, or other antiplatelet drugs (eg, clopidogrel). NSAIDs may increase risk of cardiovascular events and can cause fluid retention and, rarely, nephropathy.

NSAIDs can also increase BP; this effect may be unrecognized and lead to intensification of antihypertensive treatment (a prescribing cascade—see Drug-disease interactions). Thus, clinicians should keep this effect in mind when BP increases in elderly patients and ask them about their use of NSAIDs, particularly OTC NSAIDs.

Selective COX-2 (cyclooxygenase-2) inhibitors (coxibs) cause less GI irritation and platelet inhibition than other NSAIDs. Nonetheless, coxibs still have a risk of GI bleeding, especially for patients taking warfarin or aspirin (even at a low dose) and for those who have had GI events. Coxibs, as a class, appear to increase risk of cardiovascular events, but risk may vary by drug; they should be used cautiously. Coxibs have renal effects comparable to those of other NSAIDs.

Lower-risk alternatives (eg, acetaminophen) should be used when possible. If NSAIDs are used in the elderly, the lowest effective dose should be used, and continued need should be reviewed frequently. If NSAIDs are used long-term, serum creatinine and BP should be monitored closely, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use).


Age may increase sensitivity to the anticoagulant effect of warfarin. Careful dosing and routine monitoring can largely overcome the increased risk of bleeding in elderly patients taking warfarin. Also, because drug interactions with warfarin are common, closer monitoring is necessary when new drugs are added or old ones are stopped; computerized drug interaction programs should be consulted if patients take multiple drugs. Patients should also be monitored for warfarin interactions with food, alcohol, and OTC drugs and supplements. The newer anticoagulants (dabigatran, rivaroxaban, apixaban) may be easier to dose and have fewer drug-drug interactions and food-drug interactions than warfarin, but still increase the risk of bleeding in elderly patients, particularly those with impaired renal function.


Tricyclic antidepressants are effective but should rarely be used in the elderly. SSRIs and mixed reuptake inhibitors, such as serotonin-norepinephrine reuptake inhibitors (SNRIs), are as effective as tricyclic antidepressants and cause less toxicity; however, there are some concerns about some of these drugs:

  • Paroxetine: This drug is more sedating than other SSRIs, has anticholinergic effects, and, like some other SSRIs, can inhibit hepatic cytochrome P-450 2D6 enzyme activity, possibly impairing the metabolism of several drugs, including tamoxifen, some antipsychotics, antiarrhythmics, and tricyclic antidepressants.

  • Citalopram: Doses in the elderly should be limited to a maximum of 20 mg/day because QT prolongation is a concern.

  • Venlafaxine: This drug may increase BP.

  • Mirtazapine: This drug can be sedating and may stimulate appetite/weight gain.


Doses of antihyperglycemics should be titrated carefully in patients with diabetes mellitus. Risk of hypoglycemia due to sulfonylureas may increase with age. As described in see Table: Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update), chlorpropamide is not recommended in elderly patients because of the increased risk of hypoglycemia and of hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Risk of hypoglycemia is also greater with glyburide than with other oral antihyperglycemics because its renal clearance is reduced in the elderly.

Metformin, a biguanide excreted by the kidneys, increases peripheral tissue sensitivity to insulin and can be effective given alone or with sulfonylureas. Risk of lactic acidosis, a rare but serious complication, increases with degree of renal impairment and with patient age. Heart failure is a contraindication.


In many elderly patients, lower starting doses of antihypertensives may be necessary to reduce risk of adverse effects; however, for most elderly patients with hypertension, achieving BP goals requires standard doses and multidrug therapy. Initial treatment of hypertension in the elderly typically involves a thiazide-type diuretic, ACE inhibitor, angiotensin II receptor blocker, or dihydropyridine Ca channel blocker, depending on comorbidities. β-blockers should be reserved for 2nd-line therapy. Short-acting dihydropyridines (eg, nifedipine) may increase mortality risk and should not be used. Sitting and standing BP can be monitored, particularly when multiple antihypertensives are used, to check for orthostatic hypotension, which may increase risk of falls and fractures.

Antiparkinsonian drugs

Levodopa clearance is reduced in elderly patients, who are also more susceptible to the drug’s adverse effects, particularly orthostatic hypotension and confusion. Therefore, elderly patients should be given a lower starting dose of levodopa and carefully monitored for adverse effects (see Parkinson Disease : Levodopa). Patients who become confused while taking levodopa may also not tolerate dopamine agonists (eg, pramipexole, ropinirole). Because elderly patients with parkinsonism may be cognitively impaired, drugs with anticholinergic effects should be avoided.


Antipsychotics should be used only for psychosis. In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than placebo and can have severe adverse effects. In people with dementia, studies showed antipsychotics increased mortality and risk of stroke, leading the FDA to issue a black box warning on their use in such patients. Generally, dementia-related behavior problems (eg, wandering, yelling, uncooperativeness) do not respond to antipsychotics.

When an antipsychotic is used, the starting dose should be about one quarter the usual starting adult dose and should be increased gradually with frequent monitoring for response and adverse effects. Once the patient responds, the dose should be titrated down, if possible, to the lowest effective dose. The drug needs to be stopped if it is ineffective. Clinical trial data relating to dosing, efficacy, and safety of these drugs in the elderly are limited.

Antipsychotics can reduce paranoia but may worsen confusion (see also Schizophrenia : Conventional antipsychotics). Elderly patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. Sedation, orthostatic hypotension, anticholinergic effects, and akathisia (subjective motor restlessness) can occur in up to 20% of elderly patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6 to 9 mo after the drug is stopped.

Extrapyramidal dysfunction can develop even when 2nd-generation antipsychotics (eg, olanzapine, quetiapine, risperidone) are used, especially at higher doses. Risks and benefits of using an antipsychotic should be discussed with the patient or the person responsible for the patient's care. Antipsychotics should be considered for behavior problems only when nonpharmacologic options have failed and patients are a threat to themselves or others.

Anxiolytics and hypnotics

Treatable causes of insomnia should be sought and managed before using hypnotics (see also Approach to the Patient With a Sleep or Wakefulness Disorder : Hypnotics). Nonpharmacologic measures, such as cognitive-behavioral therapy, and sleep hygiene (eg, avoiding caffeinated beverages, limiting daytime napping, modifying bedtime) should be tried first. If they are ineffective, nonbenzodiazepine hypnotics (eg, zolpidem, eszopiclone, zaleplon) are options for short-term use. These drugs bind mainly to a benzodiazepine receptor subtype and disturb the sleep pattern less than benzodiazepines. They have a more rapid onset, fewer rebound effects, fewer next-day effects, and less potential for dependence. As described in see Table: Potentially Inappropriate Drugs in the Elderly (Based on the American Geriatrics Society 2012 Beers Criteria Update), short-, intermediate-, and long-acting benzodiazepines are associated with increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in the elderly and should be avoided for the treatment of insomnia. Benzodiazepines may be appropriate for treatment of anxiety or panic attacks in the elderly.

Duration of anxiolytic or hypnotic therapy should be limited if possible because tolerance and dependence may develop; withdrawal may lead to rebound anxiety or insomnia.

Antihistamines (eg, diphenhydramine, hydroxyzine) are not recommended as anxiolytics or hypnotics because they have anticholinergic effects, and tolerance to the sedative effects develops quickly.

Buspirone, a partial serotonin agonist, can be effective for general anxiety disorder; elderly patients tolerate doses up to 30 mg/day well. The slow onset of anxiolytic action (up to 2 to 3 wk) can be a disadvantage in urgent cases.


Digoxin, a cardiac glycoside, is used to increase the force of myocardial contractions and to treat supraventricular arrhythmias. However, it must be used with caution in elderly patients. In men with heart failure and a left ventricular ejection fraction of 45%, serum digoxin levels > 0.8 ng/mL are associated with increased mortality risk. Adverse effects are typically related to its narrow therapeutic index. One study found digoxin to be beneficial in women when serum levels were 0.5 to 0.9 ng/mL but possibly harmful when levels were 1.2 ng/mL. A number of factors increase the likelihood of digoxin toxicity in the elderly. Renal impairment, temporary dehydration, and NSAID use (all common among the elderly) can reduce renal clearance of digoxin. Furthermore, digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Also, if lean body mass is reduced, as may occur with aging, volume of distribution for digoxin is reduced. Therefore, starting doses should be low (0.125 mg/day) and adjusted according to response and serum digoxin levels (normal range 0.8 to 2.0 ng/mL). However, serum digoxin level does not always correlate with likelihood of toxicity.


Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension in many elderly patients and have less risk of hypokalemia and hyperglycemia than other diuretics (see also Drugs for Hypertension : Diuretics). Thus, K supplements may be required less often.

K-sparing diuretics should be used with caution in the elderly; the K level must be carefully monitored, particularly when these diuretics are given with ACE inhibitors or angiotensin II receptor blockers or when the patient has impaired kidney function.

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