Drug Categories of Concern in Older Adults

Oral nonsteroidal anti-inflammatory drugs (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:

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

NSAIDs can also increase blood pressure; this effect may be unrecognized and lead to intensification of antihypertensive treatment (a prescribing cascade Drug-disease interactions ). Thus, clinicians should keep this effect in mind when blood pressure increases in older adults and ask them about their use of NSAIDs, particularly over-the-counter 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, topical diclofenac gel) 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 blood pressure should be monitored closely, especially in patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use), and a gastroprotective drug (eg, proton-pump inhibitor or misoprostol) should be considered for concomitant 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 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 over-the-counter 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.

Tricyclic antidepressants (TCAs) 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 TCAs and cause less toxicity; however, there are some concerns about some of these drugs (below). In addition, all SSRIs, SNRIs, and TCAs can increase the risk of falls and hyponatremia in older adults.

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 Potentially Inappropriate Drugs in Older Adults (Based on the American Geriatrics Society 2019 Beers Criteria® Update) , 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 and glimepiride than with other oral antihyperglycemics because 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.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors (canagliflozin, dapagliflozin, and empagliflozin) can increase risk of urinary tract infections, fungal infections, and hypovolemia with orthostatic hypotension; they should be avoided in patients with impaired renal function.

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 blood pressure goals requires standard doses and multidrug therapy. Initial treatment of hypertension in older adults typically involves a thiazide-type diuretic, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker, or dihydropyridine calcium channel blocker, depending on comorbidities. Beta-blockers should be reserved for those with heart disease or for rate control of atrial fibrillation. Short-acting nifedipine may increase mortality risk and should not be used. Sitting and standing blood pressure should be monitored, particularly when multiple antihypertensives are used, to check for orthostatic hypotension, which may increase risk of falls and fractures. Ambulatory or home blood pressure monitoring may also be more accurate in older adults than in-clinic blood pressures because many older adults suffer from white-coat syndrome (an increase in blood pressure while at a doctor's office) or masked hypertension (a decrease in blood pressure while at a doctor's office). Clinicians must balance the goals for blood pressure targets and risk of adverse effects in older adults (such as inducing orthostatic hypotension or increasing the risk for falls).

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 Levodopa Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more 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 (eg, diphenydramine, trihexyphenidyl) 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 U.S. Food and Drug Administration (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. Antipsychotics should not be used merely because a behavioral problem (eg, yelling, repeating phrases) is annoying to people other than the patient.

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 Conventional antipsychotics Antipsychotic drugs are divided into conventional antipsychotics and 2nd-generation antipsychotics (SGAs) based on their specific neurotransmitter receptor affinity and activity. SGAs may offer... read more ). 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 months 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' behaviors pose a threat to themselves or others.

Treatable causes of insomnia should be sought and managed before using hypnotics Hypnotics Almost half of all people in the US report sleep-related problems. Disordered sleep can cause emotional disturbance, memory difficulty, poor motor skills, decreased work efficiency, and increased... read more . 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, but lower doses are indicated for older adults. Nonbenzodiazepine hypnotics and 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 weeks) 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 older adults. In men with heart failure and a left ventricular ejection fraction of ≤ 45%, serum digoxin levels > 0.8 ng/mL (1.0 nmol/L) 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 (0.6 to 1.2 nmol/L) but possibly harmful when levels were ≥ 1.2 ng/mL (1.5 nmol/L). A number of factors increase the likelihood of digoxin toxicity in older adults. Renal impairment, temporary dehydration, and nonsteroidal anti-inflammatory drug (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 [1.0 to 2.6 nmol/L]). 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 Reference Some drug categories (eg, analgesics, anticoagulants, antihypertensives, antiparkinsonian drugs, diuretics, hypoglycemic drugs, psychoactive drugs) pose special risks for older adults. Some... read more ) and avoiding digoxin for first-line treatment of heart failure and atrial fibrillation.

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, potassium supplements may be required less often.

Potassium-sparing diuretics should be used with caution in older adults; the potassium level must be carefully monitored, particularly when these diuretics are given with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers or when the patient has impaired kidney function.