10 Risky Drugs for Elders

Pharmacists should be familiar with the fact that the number of elders is growing, and so is the use of OTC and prescription drugs among elders. Of the US population, 15% is over age 65, and this segment consumes about one third of all prescription drugs.¹ Almost all seniors (~90%) use at least one prescription medication weekly, more than 40% use 5 to 9, and 12% use 10 or more.² Seniors are a burgeoning presence in the health care system, and these patients often seek emergency treatment for drug-related problems.³ Experts estimate that pharmacists fill ~320,000 questionable prescriptions annually for community-dwelling elders.⁴ Medication-related risks occur with age-related changes in metabolism and excretion, and these risks are compounded as the number of drugs taken increases.¹ The outcomes may be unnecessary functional decline, delirium, falls, or suboptimal care.⁵

Since 1991, the Beers criteria have provided guidance concerning drugs that are risky for nursing home residents.⁶ The article "Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults,"by Fick et al,⁷ can help pharmacists understand specific concerns for all older patients, not just nursing home residents.¹ Up to one half of all adverse drug events (ADEs) among seniors are preventable.⁸ Therefore, all clinicians who see elderly patients should screen them routinely for inappropriate drug use.⁹ Awareness of risk factors for likely and preventable ADEs is critical (Table 1).

The Infamous Five Risky Drugs

Five drugs account for ~85% of inappropriate prescribing,⁴ and their use in seniors should raise questions immediately.

Amitriptyline

Amitriptyline (and also doxepin)^1,3 has anticholinergic properties that produce adverse effects in elders. Many better alternatives are available for depression, including the selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors, and bupropion.⁴ If these drugs are intended to be used for insomnia, better choices are available (Table 2).^5,10

Diazepam and Chlordiazepoxide

These drugs can have half-lives measured in days in elders.^1,4,7 Sedation may be prolonged, and fall or fracture risk is increased. Short-acting benzodiazepines, given in the lowest possible doses, are preferred.

Propoxyphene

Propoxyphene,⁴ in combination with acetaminophen, ranked number 8 in 2002 and number 10 in 2003 in terms of generic drug units.¹¹ Some experts think that its use actually is increasing.¹² Propoxyphene is a mild synthetic opiate; 65 mg is approximately equivalent to 100 mg of propoxyphene napsylate, which in turn is equivalent to slightly less than 650 mg of acetaminophen or aspirin.^11,13 Its metabolite, norpropoxyphene, lingers for 30 to 36 hours.¹³ Its frequent combination with aspirin or acetaminophen raises additional issues for seniors using analgesics alone or in combination products. The alternative is acetaminophen alone; patients should be monitored to ensure that they take <4 g daily (or <2.6 g in the frail elderly).

Short-Acting Dipyridamole

This drug makes the list because of its association with orthostatic hypotension.⁴ Its long-acting form should be used only in patients with artificial heart valves.⁷ Low-dose aspirin may be an acceptable alternative.

Five More Risky Drugs

Meperidine

This drug, which is metabolized to active metabolites that accumulate in patients with declining renal function, is a problem for elders.⁵ Orally, it is poorly effective.⁷ Meperidine increases the likelihood of anxiety, tremors, twitching, myoclonus, and seizures. Morphine is a better alternative for severe pain.

Cyclobenzaprine and Carisoprodol

Cyclobenzaprine and carisoprodol¹ and other muscle relaxants are poorly tolerated by the elderly. They tend to cause sedation and weakness. At doses tolerated by elders, their efficacy is questionable.⁷ Carisoprodol, metabolized to meprobamate, may be especially impairing and potentially addictive.¹⁴

Nonsteroidal Anti-Inflammatory Drugs and Cyclooxygenase-2 Inhibitors

These agents increase the risk of gastrointestinal ulcers^1,4 to ~2%, which translates to 107,000 hospitalizations and 16,500 deaths in the United States annually?exceeding the number of deaths caused by AIDS.¹⁵ These drugs also endanger elders with renal failure, heart failure, and hypertension.⁴ Indomethacin produces the most adverse central nervous system (CNS) events.⁷

Heavily anticholinergic diphenhydramine and hydroxyzine are associated with lingering sedation.^1,5 Diphenhydramine raises special concerns because of its common presence in OTC medications for assorted complaints (insomnia, allergies, nausea, itching, etc). A large study of hospitalized elders associated diphenhydramine with cognitive decline, urinary catheter placement, and increased length of stay, in a dose-dependent manner.¹⁶ Alternatives include newer, less-sedating antihistamines for allergies or interventions for insomnia (Table 2).

Included with the muscle relaxants and antispasmodics in the Beers list,⁷ oxybutynin is used widely in elders with or without a toileting protocol for urinary incontinence and overactive bladder. The drug is a problem among institutionalized and community-dwelling adults.^1,9 Better alternatives are in clinical trials.

Fluoxetine

Fluoxetine, given daily, can accumulate in the body, due to its long half-life. Excessive CNS stimulation, sleep disturbances, and increasing agitation may follow. Other SSRIs with shorter half-lives are better choices.⁷

Why Are Risky Drugs Still Used in the Elderly?

A recent study of 13,003 community- dwelling elderly found that clinicians prescribed 1 of 5 inappropriate medications (propoxyphene, hydroxyzine, diazepam, amitriptyline, or oxybutynin) during 58% of visits. The odds of receiving an inappropriate drug were double for women.⁹ With good guidance about drugs to be avoided in the elderly available, what drives the continued use of these drugs?

The use of certain of these drugs may be clinically justified, because the Beers list has never been validated in a research setting, and not all elderly persons are identical. Also, general practitioners may be unaware of the Beers list.¹ Attempts to educate prescribers using continuing education or grand-rounds formats often fail.¹⁷ Cost can be a significant driver; many offending drugs are older and less costly. For several agents, prescription drug addiction is a possible driver; physicians may be reticent to begin the weaning process, or patients may insist on certain drugs. In addition, patients may have high expectations and pressure prescribers to continue these drugs.¹⁷

The solution may be to include pharmacists in the prescribing process in a more meaningful way. Restricting prescribing, employing protocols, or removing some agents from the formulary also may help.¹⁷ Nevertheless, monitoring patients carefully has been and will continue to be the cornerstone of pharmaceutical counseling and care.

Ms. Yeznach Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health. The views expressed are those of the author and not those of any governmental agency.

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