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American Pain Society
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Glenview, IL 60025
Stephen W. Harkins, Department Editor
Daniel T. Kennedy, PharmD BCPS; Ralph E. Small, PharmD FCCP FASHP
Authors' note: Nonsteroidal anti inflammatory drugs (NSAIDs) are an excellent choice for elderly patients, due to the high incidence of inflammatory conditions seen in this population. Arthritis and other musculoskeletal inflammatory diseases respond adequately to the anti inflammatory and analgesic properties of NSAIDs, administered as either monotherapy or in combination with narcotic agents. No NSAID has proven to be superior for elderly patients. Individual response may vary with different NSAID agents, so healthcare professionals must determine the optimal drug choice for their patients. Consideration must be given to adverse side effects of various NSAIDs in elderly patients. This article answers current questions regarding the use of NSAIDs for elderly patients.
The adverse side effects of NSAIDs merit strong concern in elderly patients (Shirk, 1997). Diagnoses of NSAID-induced gastropathy, renal impairment, hypersensitivity, and prolonged bleeding are common in older persons. Of these, the gastrointestinal side effects of NSAIDs raise particular concerns in the elderly population. Elderly patients who take NSAIDs are almost five times as likely to die from gastrointestinal bleeding as those who do not (Griffin, Ray, & Schaffner, 1988). Patients older than 60 years of age, especially those having concomitant disease states or taking multiple drug therapy, are at high risk for NSAID-induced gastropathy (Pitner, Wiley, & Pennypacker, 1994). With this in mind, do the safety profiles of currently available NSAIDs differ? Aspirin is most likely to promote gastropathy, with piroxicam (Feldene®), indomethacin (Indocin®), sulindac (Clinoril®), meclofenamate (Meclomen®), tolmetin (Tolectin®), and naproxen (Naprosyn®) close behind (Pitner et al.; Wade, 1995). If an elderly patient requires an NSAID, choose one not listed above and ensure that the patient takes it with food to counteract the direct irritant effects on the stomach lining. Alternative therapy such as acetaminophen, nonacetylated salicylates (e.g., salsalate, sodium salicylate, magnesium salicylate), capsaicin topical analgesic cream (Zostrix®), low-dose opioid analgesics, tricyclic antidepressants (amitriptyline), skeletal muscle relaxants (Baclofen®), and nondrug therapies (i.e., heat, exercise, physical therapy) sometimes work well for elderly patients poorly suited for NSAID therapy due to lack of response or adverse side effects.
If an elderly patient needs long-term NSAID therapy and has other risk factors for NSAID-induced gastropathy (i.e., previous history of any gastrointestinal condition, concomitant corticosteroid therapy, tobacco use, alcohol abuse, higher doses of NSAIDs), the physician should implement pharmacologic prophylaxis (Pitner et al., 1994). Misoprostol (Cytotec®) is the only agent currently indicated and proven to prevent NSAID-induced gastric and duodenal ulceration (Higa, 1997). Dosing of misoprostol should start at 100 mg twice daily after meals for 1 week, then increase to 200 mg twice daily after meals. Dosing of misoprostol four times daily may be unnecessary (Raskin et al., 1995). The main side effect of misoprostol is diarrhea, which usually is transient and minimal with drug administration after meals and twice-daily dosing. If gastrointestinal ulceration occurs and discontinuing the NSAID is impossible, omeprazole (Prilosec®) may be the only drug that can speed healing (Pearson & Kelberman, 1996). High-dose famotidine (40 mg twice daily) may also be an option for both the prevention and healing of NSAID-induced gastric and duodenal ulceration (Taha et al., 1996; Hudson et al., 1997). However, total cost must be considered when selecting a high-dose H2 antagonist, proton pump inhibitor, or misprostol (Graham, 1997).
The primary age-related pharmacokinetic change with NSAIDs in elderly people involves protein binding (Erwin, Briesacher, & Franic, 1995). NSAIDs are highly protein bound (> 90%). In the elderly population, serum albumin tends to decrease, resulting in fewer binding sites and higher free fractions of NSAIDs in the blood. An increase in unbound or free fractions of the drug may enhance the clinical effect of pain relief in elderly patients, but it also increases toxicity (Murray & Brater, 1990).
On the whole, elderly patients are at greater risk for drug-drug and drug-disease interactions with NSAIDs because many take numerous medications to treat comorbid chronic conditions (Erwin et al., 1995). This is of particular concern for an older patient who uses medications for hypertension. NSAIDs may inhibit the effects of all loop diuretics by 20% (Erwin et al.). Other drugs, such as beta-blocking agents, thiazide diuretics, and angiotensin-converting enzyme inhibitors may have compromised antihypertensive effects when combined with NSAIDs (Murray & Brater, 1990).
Because the analgesic effects of NSAID therapy are variable, each patient has individual requirements. The physician must titrate dosing to achieve optimal therapeutic benefits while minimizing adverse side effects. The highest risk for NSAID-induced gastropathy occurs within the first 90 days of continuous drug therapy (Pitner et al., 1994). Close monitoring of serum hematocrit and hemoglobin, as well as testing for occult blood in the stool, are vital during this period. This should include monitoring for black, tarry stools and any subjective changes indicative of gastrointestinal bleeding. Increased use of over-the-counter antacids and H2 blockers may indicate the onset of NSAID-induced gastropathy. Because many older patients consider these symptoms "normal," a thorough interview by the healthcare professional is important. Once the patient is stabilized on NSAID therapy, monitoring will ensure his or her continuing safety. This entails a complete blood count, liver function tests, and a renal function profile every 6 to 12 months (Bush, Shlotzhauer, & Imai, 1991). However, healthcare professionals should order these tests more frequently if symptoms develop or if the patient's status changes in any way.
Several studies suggest a risk-lowering effect of NSAIDs in patients susceptible to Alzheimer's disease. Recent data from the Baltimore Longitudinal Study of Aging support this claim (Stewart, Kawas, Corada, & Metter, 1997). This prospective study observing the incidence of Alzheimer's disease in approximately 1,700 patients began in 1958 and continued through 1980. Results revealed a reduced risk of Alzheimer's disease in patients who took nonaspirin NSAIDs. It showed that the risk was lower for patients who used NSAIDs for more than 2 years rather than for shorter periods of time. The risk of Alzheimer's disease was not significantly lower in patients who took aspirin or acetaminophen. Although this study shows promise for NSAID use in preventing Alzheimer's disease, lack of information on drug dosing and frequency of NSAID use makes applicability difficult. Further research is needed before NSAID dosing to prevent Alzheimer's disease becomes common practice, because of the side effects these drugs produce--especially in an elderly population.
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Stewart, W.F., Kawas, C., Corrada, M., & Metter, E.J. (1997). Risk of Alzheimer's disease and duration of NSAID use. Neurology, 48, 626-632.
Taha, A.S., Hudson, N., Hawkey, C.J., Swannell, A.J., Trye, P.N., Cottrell, J., Mann, S.G., Simon, T.J., Sturrock, R.D., & Russell, R.I. (1996). Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. New England Journal of Medicine, 334, 1435-1439.
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Elderly patients are at greater risk for drug-drug and drug-disease interactions with NSAIDs because many take numerous medications to treat comorbid chronic conditions.
Daniel T. Kennedy is assistant professor and Ralph E. Small is professor at the School of Pharmacy of Virginia Commonwealth University/Medical College of Virginia in Richmond, VA.
