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Drug Categories of Concern in Older Adults

By

J. Mark Ruscin

, PharmD, FCCP, BCPS, Southern Illinois University Edwardsville School of Pharmacy;


Sunny A. Linnebur

, PharmD, BCPS, BCGP, University of Colorado Anschutz Medical Campus

Last full review/revision Dec 2018| Content last modified Dec 2018
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Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for older adults. Some drugs, although reasonable for use in younger adults, are so risky they should be considered inappropriate for older adults. The American Geriatric Society Beers Criteria are most commonly used to identify such inappropriate drugs (see table Potentially Inappropriate Drugs in Older Adults) (1). The Beers Criteria categorize potentially inappropriate drugs into 3 groups:

  • Inappropriate: Always to be avoided

  • Potentially inappropriate: To be avoided in certain diseases or syndromes

  • To be used with caution: Benefit may offset risk in some patients

Table
icon

Potentially Inappropriate Drugs in Older Adults (Based on the American Geriatrics Society 2015 Beers Criteria Update)

Drug

Prescribing Concern/Recommendations

Anticholinergics*

First-generation antihistamines (brompheniramine, carbinoxamine, chlorpheniramine, clemastine, cyproheptadine, dexbrompheniramine, dexchlorpheniramine, dimenhydrinate, diphenhydramine [oral], doxylamine, hydroxyzine, meclizine, 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 (atropine [excludes ophthalmic], belladonna alkaloids, clidinium-chlordiazepoxide, dicyclomine, hyoscyamine, propantheline, scopolamine)

Highly anticholinergic, uncertain effectiveness

Anti-infectives

Nitrofurantoin

Potential for pulmonary toxicity, hepatotoxicity, and peripheral neuropathy, especially with long-term use; safer alternatives available

Avoid in patients with creatinine clearance < 30 mL/min or for long-term suppression of bacteria

Antithrombotics

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

Ticlopidine

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

Amiodarone

Effective for maintaining sinus rhythm but has greater toxicities than other antiarrhythmics used in atrial fibrillation; 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 as first-line therapy for atrial fibrillation unless patient has heart failure or substantial left ventricular hypertrophy

Disopyramide

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

Dronedarone

Worse outcomes in patients taking dronedarone who have permanent atrial fibrillation or severe or recently decompensated heart failure

Avoid in patients with permanent atrial fibrillation or severe or recently decompensated heart failure

Digoxin

Use in atrial fibrillation: Should not be used as a first-line agent, because more effective alternatives exist and digoxin may be associated with increased mortality; avoid as first-line therapy

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

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 doses > 0.125 mg/day

Nifedipine, immediate release

Risk of hypotension and myocardial ischemia; avoid

CNS

Antidepressants: Tertiary TCAs, alone or in combination (amitriptyline, amoxapine, clomipramine, desipramine, doxepin [> 6 mg/day], imipramine, nortriptyline, protriptyline, trimipramine), paroxetine

Highly anticholinergic and sedating and cause orthostatic hypotension; avoid

Safety profile of low-dose doxepin (≤ 6 mg/day) comparable with that of placebo

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

Increased risk of stroke and greater rate of cognitive decline and mortality in patients with dementia

Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacologic options (eg, behavioral interventions) have failed or are not possible and older adults is threatening substantial harm to self or others

Avoid, except for schizophrenia, bipolar disorder, or short-term use as antiemetic during chemotherapy

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

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

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

Benzodiazepines, short- and intermediate-acting: Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting drugs; in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults; avoid

Benzodiazepines, long-acting: May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, periprocedural anesthesia

Meprobamate

High rate of physical dependence; very sedating; avoid

Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (eszopiclone, zolpidem, zaleplon)

Benzodiazepine-receptor agonists have adverse events similar to those of benzodiazepines in older adults (eg, delirium, falls, fractures); increased emergency department visits and hospitalizations; motor vehicle crashes; minimal improvement in sleep latency and duration; avoid

Ergot mesylates (dehydrogenated ergot alkaloids)

Isoxsuprine

Lack of efficacy; avoid

Endocrine therapy

Androgens (methyltestosterone, testosterone)

Potential for cardiac problems; exacerbation of prostate cancer

Avoid except for confirmed moderate to severe hypogonadism

Desiccated thyroid

Possible cardiac effects; safer alternatives available; avoid

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 practitioner

Avoid topical patch and oral

Vaginal cream or tablets: Acceptable to use low-dose intravaginal estrogen for management of dyspareunia, lower urinary tract infections, and other vaginal symptoms

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

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 (ie, correction insulin)

Megestrol

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

Metoclopramide

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

Proton-pump inhibitors

Risk of Clostridium difficile infection and bone loss and fractures

Avoid scheduled use for > 8 wk unless for high-risk patients (eg, oral corticosteroids or chronic NSAID use), erosive esophagitis, Barrett esophagitis, pathologic hypersecretory condition, or demonstrated need for maintenance treatment (eg, due to failure of drug discontinuation trial or H2 blockers)

Pain management

Meperidine

Not an effective oral analgesic in common dosages; may cause neurotoxicity; safer alternatives available; avoid, especially in individuals with chronic kidney disease

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)

Indomethacin

Ketorolac, includes parenteral

Indomethacin: Increased risk of adverse CNS effects; avoid

Ketorolac, includes parenteral: Increased risk of GI bleeding, peptic ulcer disease, and acute kidney injury in older adults; avoid

Pentazocine

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

Genitourinary (desmopressin)

High risk of hyponatremia; safer alternative treatments; avoid for treatment of nocturia or nocturnal polyuria

*TCAs are excluded.

These drugs are used infrequently.

TCAs = tricyclic antidepressants.

Table
icon

Drugs to Be Used With Caution in Older Adults (Based on the American Geriatrics Society 2015 Beers Criteria Update)

Drug

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

Dabigatran

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

Prasugrel

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

Antipsychotics

Carbamazepine

Carboplatin

Cyclophosphamide

Cisplatin

Diuretics

Mirtazapine

Oxcarbazepine

Serotonin–norepinephrine reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs)

Tricyclic antidepressants

Vincristine

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

Monitor Na level closely when starting or changing dosages

Vasodilators

May increase episodes of syncope in patients with history of syncope

Analgesics

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.

Older adults 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 older adults, 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). Thus, clinicians should keep this effect in mind when BP increases in older adults 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 older adults, 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).

Anticoagulants

Age may increase sensitivity to the anticoagulant effect of warfarin. Careful dosing and routine monitoring can largely overcome the increased risk of bleeding in older adults 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, edoxaban) may be easier to dose and have fewer drug-drug interactions and food-drug interactions than warfarin. Compared to warfarin, the newer anticoagulants are as or more effective at reducing the risk of stroke and intracranial hemorrhage in patients with atrial fibrillation, but still increase the risk of bleeding in older adults, particularly those with impaired renal function.

Antidepressants

Tricyclic antidepressants are effective but should rarely be used in older adults. Selective serotonin reuptake inhibitors (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 and escitalopram: Doses in older adults should be limited to a maximum of 20 mg/day and 10 mg/day, respectively, because QT prolongation is a concern.

  • Venlafaxine: This drug may increase BP.

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

Antihyperglycemics

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 the table Potentially Inappropriate Drugs in Older Adults, chlorpropamide is not recommended in older adults 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 older adults.

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. Symptomatic heart failure is a contraindication.

Antihypertensives

In many older adults, lower starting doses of antihypertensives may be necessary to reduce risk of adverse effects; however, for most older adults with hypertension, achieving BP goals requires standard doses and multidrug therapy. Initial treatment of hypertension in older adults 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. Clinicians must balance the goals for BP targets and risk of adverse effects in older adults (such as inducing orthostatic hypotension or increasing the risk for falls).

Antiparkinsonian drugs

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

Antipsychotics

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 older adults are limited.

Antipsychotics can reduce paranoia but may worsen confusion (see also Antipsychotic Drugs: Conventional antipsychotics). Older adults, 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 older adults 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 patient behaviors pose a threat to themselves or others.

Anxiolytics and hypnotics

Treatable causes of insomnia should be sought and managed before using 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 the table Potentially Inappropriate Drugs in Older Adults, short-, intermediate-, and long-acting benzodiazepines are associated with increased risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults and should be avoided for the treatment of insomnia. Benzodiazepines may be appropriate for treatment of anxiety or panic attacks in older adults.

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; older adults 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

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 older adults. 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 older adults. Renal impairment, temporary dehydration, and NSAID use (all common among older adults) can reduce renal clearance of digoxin. Furthermore, digoxin clearance decreases an average of 50% in older adults 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. In addition, the American Geriatric Society Beers Criteria suggest avoiding doses > 0.125 mg/day (1).

Diuretics

Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension in many older adults and have less risk of hypokalemia and hyperglycemia than other diuretics. Thus, K supplements may be required less often.

K-sparing diuretics should be used with caution in older adults; 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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