To obtain CE credit for this activity, go to www.aanp.org and click on the CE Center. Locate the listing for this article and complete the post-test. Follow the instructions to print your CE certificate.
Use of nonsteroidal anti-inflammatory drugs in the older adult
Article first published online: 23 JUN 2014
©2014 American Association of Nurse Practitioners
Journal of the American Association of Nurse Practitioners
Volume 26, Issue 8, pages 414–423, August 2014
How to Cite
Fowler, T. O., Durham, C. O., Planton, J. and Edlund, B. J. (2014), Use of nonsteroidal anti-inflammatory drugs in the older adult. American Assoc Nurse Prac, 26: 414–423. doi: 10.1002/2327-6924.12139
Disclosure The authors report no competing interests.
- Issue published online: 21 JUL 2014
- Article first published online: 23 JUN 2014
- Manuscript Accepted: MAR 2014
- Manuscript Received: OCT 2013
- Older adult;
- pain management;
- geriatric, NSAIDs
Annually, approximately 90 million prescriptions are filled for nonsteroidal anti-inflammatory drugs (NSAIDs) with the number prescribed for older adults approximately three times higher than for younger adults. This article examines the benefits and risk of NSAID use in older adults.
Electronic data collection of research studies, evidence-based reviews, consensus statements, and guidelines related to the purpose of this article were analyzed if published between 2000 and 2013 in English from Ovid, MEDLINE, and PubMed databases.
While NSAIDs are commonly used to treat pain and inflammation in older adults, strong consideration must be given to the potential adverse effects. A lack of consistency in the guidelines regarding NSAID use poses further challenges for clinicians in the selection of the best pharmacological approach. When prescribing NSAIDs, adverse events, polypharmacy, comorbidities, and treatment guidelines must be considered. NSAIDs are an appropriate option for pain management in select older adults, often after a trial of acetaminophen and if benefits outweigh risks. Alternative pharmacological and nonpharmacological therapies may be more appropriate in many older adults.
Implications for practice
The challenge for clinicians prescribing NSAIDs in the treatment of pain in older adults is to utilize safe, individualized, and evidenced-based pain management regimens.
Pain affects people of all ages; however, pain prevalence is higher in the older adult, with estimates often exceeding 50% (Barkin et al., 2010). A more recent study in independent adults over the age of 60 estimates 85% experience moderate to severe pain and over 28% experience continuous pain (Brown, Kirkpatrick, Swanson, & McKenzie, 2011). In the older adult, chronic pain is found to diminish quality of life by increasing depression, social isolation, immobility, and falls, while also associated with weight loss, poor appetite, cognitive impairment, and decreased quality of sleep. Chronic pain also increases overall healthcare utilization and cost (American Geriatrics Society (AGS), 2009; The International Association for the Study of Pain, 2012). With the prevalence of pain and its impact on the older adult, clinicians must effectively and safely manage pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are common treatments for pain and inflammatory conditions in the older adult. An understanding of the pharmacology, side effects, and drug–drug interactions of NSAIDs is essential for the clinician managing pain in this population.
NSAID use in the older adult
Musculoskeletal problems, such as osteoarthritis, rheumatoid arthritis, and gout, increase with age and lead to chronic pain. As the 60 and older population will almost double in the next 20 years, the number of people with chronic pain and NSAID utilization will increase (Administration on Aging, 2008; Centers for Disease Control and Prevention, 2011; Lawrence et al., 2008; U.S. Census Bureau, 2011). NSAIDs are an effective analgesic for many chronic pain conditions and serve a valuable role in the treatment of inflammatory musculoskeletal conditions. Currently, there is a high rate of NSAID use; these drugs are among the most common prescriptions in the United States with over 98 million prescriptions filled and an estimated 23 million Americans using over-the-counter (OTC) NSAIDs in 2012 (Alliance for Rational Use of NSAIDs, 2012). The rate of NSAID use is somewhat difficult to assess in the older adult secondary to OTC and as-needed use. Nevertheless, over 20% of older adults over the age of 65 use prescription NSAIDs and a much larger percentage use OTC NSAIDs (Friedewald et al., 2010). With an aging population, an increasing rate of chronic pain and recognition of NSAIDs as effective therapy, clinicians must utilize NSAIDs safely and appropriately.
However, NSAIDs have potential toxicities and side effects with use, and recommendations for NSAID therapy vary. The American College of Rheumatology (ACR) recommends NSAID therapy only after a trial of maximum dose acetaminophen (4 g/24 h) because of potential adverse events with NSAIDs that has only a modest benefit in pain reduction over acetaminophen (ACR, 2008; Hochberg et al., 2012). An update in the management of knee osteoarthritis guidelines in 2013 by the American Academy of Orthopaedic Surgeons (AAOS) recommends NSAIDs as first line pharmacological therapy. The recommendations are based on strong evidence for the benefit of NSAIDs in knee osteoarthritis and inconclusive evidence for the benefit of acetaminophen compared to placebo (Brown, 2013). Unlike the AAOS (2013) recommendations, the AGS Beers Criteria that focuses on inappropriate prescribing and adverse events associated with medications, recommends caution, and even avoidance of NSAIDs in older adults with certain other medications and comorbidities (2012a). Overall, the guidelines recognize NSAIDs as modestly more effective than acetaminophen for chronic inflammatory conditions (AAOS, 2013; ACR, 2008). However, the lack of consistency in the above guidelines for the use of NSAIDS in this population creates a dilemma for the clinician faced with managing pain in the older adult.
Pharmacology of NSAIDs
Consideration should be given to the pharmacology of NSAIDs when assessing a patient's appropriateness for therapy. NSAIDs have analgesic, anti-inflammatory, and antipyretic properties because of their mechanism of action. NSAIDs inhibit the COX enzyme that blocks the biosynthesis of prostaglandins responsible for multiple functions, including the inflammatory response, platelet aggregation, body temperature regulation, and gastrointestinal mucosal protection (Barkin et al., 2010; Vane & Botting, 1998). The COX enzyme has various forms within the body, including the two isoenzymes COX-1 and COX-2. Of the two isoenzymes, COX-2 inhibition has been credited with the anti-inflammatory properties of NSAIDs. In addition to the benefits, inhibition of COX-1 or COX-2 also increases the risk of certain adverse events. NSAIDS are divided into two classes based on their inhibition of COX-1 or COX-2. Currently, there are over 20 different NSAIDs belonging to one of two classes, nonselective cyclooxygenase (COX) inhibitors (nonselective NSAIDs) or selective COX-2 inhibitors (selective NSAIDs) (Barkin et al., 2010; Vane & Botting, 1998). Aspirin is a salicylate and considered a nonselective NSAID; however, because of the high doses required for anti-inflammatory and analgesic properties (1–4 g/day) and high gastrointestinal risk associated with higher doses, aspirin is most often used for antiplatelet and cardiovascular protection (Katzung, Masters, & Trevor, 2012).
Nonselective and selective NSAIDs offer anti-inflammatory effects as they both inhibit COX-2; how-ever, the side effects associated with each subclass vary. Specifically, COX-1 inhibition (nonselective NSAIDs) increases the risk for gastrointestinal bleeding, vasoconstriction, decreased glomerular filtration rate, sodium retention, edema and antiplatelet effects. COX-2 inhibition (most notably selective NSAIDs) leads to an increased risk for edema, heart failure, hypertension, and thrombotic events, such as myocardial infarction (Barkin et al., 2010; Vane & Botting, 1998). Selective NSAIDs were introduced to mitigate gastrointestinal risks because they do not inhibit COX-1 that is responsible for these side effects. However, selective NSAIDs increase the risk for cardiovascular events (Chan, Abraham, Scheiman, Laine, & First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents, 2008).
NSAIDs are well absorbed and metabolized through the liver via the CYP3A and CYP2C of the P450 pathway and excreted via the renal system (Katzung, Masters, & Trevor, 2012). The half-life is variable, and NSAIDs, such as ibuprofen, ketoprofen, diclofenac, and indomethacin, have a short half-life of less than 6 hours NSAIDs, such as naproxen, meloxicam, and celecoxib, have a longer half-life of greater than 6 hours (Katzung et al., 2012). NSAIDs with a shorter half-life require greater compliance by the patient because of frequent administration, but have the advantage of decreased hepatic circulation, lowering the risk for adverse events. NSAIDs with a longer half-life require less frequent dosing, but bring increased hepatic circulation and the risk for adverse events (Katzung et al., 2012).
Benefits of NSAID use
NSAIDs are effective analgesics, but also provide anti-inflammatory properties beneficial in the management of many chronic inflammatory pain conditions found in the older adult. Studies demonstrate that NSAIDs improve pain, stiffness, and function when compared to acetaminophen and placebo and are often preferred by patients to other pharmacological therapies (Case, Baliunas, & Block, 2003; Golden, Moskowitz, & Minic, 2004; Lee et al., 2004; Wegman, van der Windt, van Tulder, Stalman, & de Vries, 2004). In two randomized controlled trials, a significant improvement in pain, stiffness, and weight bearing was associated with NSAIDs as compared to acetaminophen (Case et al., 2003; Golden et al., 2004). Compared to opioids, NSAIDs have fewer negative associations with use and no significant concerns for abuse or addiction. NSAIDs also do not have the concerning side effects of respiratory depression, sedation, confusion, and constipation. Finally, NSAIDs are available in a topical formulation. This provides an option for those who have difficulty ingesting medication, prefer topical over oral, and for isolated pain in a superficial joint. Topical NSAIDs also decrease systemic absorption and risk for adverse events and drug–drug interactions.
Risks of NSAID use
NSAIDs have the potential for a number of side effects in multiple systems within the body and the risk varies with age, comorbidities, class of NSAIDs, and dosing (Table 1). Gastrointestinal side effects related to NSAID use has been well documented and may range from dyspepsia to life-threatening bleeding and/or perforated gastric ulcer because of the inhibition of COX-1 and gastroprotective prostaglandins (Barkin et al., 2010; Lanza, Chan, Quigley, & Practice Parameters Committee of the American College of Gastroenterology, 2009). Prior history of gastrointestinal bleeding, nonselective NSAID use, high-dose NSAIDs, older age, alcohol use, tobacco use, other antithrombotic drugs, and corticosteroid therapy are also major risk factors for gastrointestinal adverse events when combined with NSAID use (Laine, 2006). NSAID use has a two to four times increase in the risk for gastrointestinal complications (Coxib and traditional NSAID Trialists’ [CNT] Collaboration, 2013). Upper gastrointestinal symptoms, such as dyspepsia, are the most common adverse events. Pilotto, Franceschi Leandro, Di Mario, and Geriatric Gastroenterology Study Group (Societe Italiana Gerontologie Geriatria) (2003) found, in patients 65 and older, that 25% of NSAID users reported upper gastrointestinal symptoms as compared to 17% of those not treated with NSAIDs. Higher NSAID doses also increase the risk for dyspepsia (Ofman et al., 2003). Gastrointestinal bleeding is the most concerning adverse event, as bleeding can have a sudden onset with significant complications. NSAID use is associated with a fourfold increase in the risk for gastrointestinal bleeding, with the highest risk associated with nonselective NSAID use and higher NSAID dosing (CNT Collaboration, 2013; Tarone, Blot, & McLaughlin, 2004). In 2002, Ofman noted the risk for additional gastrointestinal complications through a systematic review comparing NSAID users to placebo in randomized trials. A risk ratio of 5.36 (95% CI: 1.79, 16.1) for gastrointestinal perforations, ulcers, and bleeds was noted in NSAID users as compared to placebo (Ofman et al., 2002). Major gastrointestinal complications also lead to hospitalizations. The published mortality rates associated with NSAID use vary with time, location, and source; however, a recent study notes a mortality rate of 5.6% (95% CI: 4.9, 6.7) with hospital admissions for gastrointestinal events (Lanas et al., 2005). As a result of the gastrointestinal adverse events, the United States Federal Food and Drug Administration (FDA) has mandated that all NSAIDs have a black box warning for the risk for gastrointestinal events, including dyspepsia, bleeding, ulcer, and perforation.
|Common NSAID Side Effects|
|Gastrointestinal*||▪ Dyspepsia, abdominal pain, gastric ulcers, bleeding, perforation|
|▪ Greater risk with nonselective NSAIDs versus selective NSAIDs|
|Cardiovascular*||▪ Increased blood pressure, myocardial infarction, congestive heart failure, cerebrovascular accident|
|▪ Greater risk with selective NSAIDs versus nonselective NSAIDs|
|Hematologic||▪ Increased risk for bleeding and anemia|
|Renal||▪ Water and sodium retention, decreased renal blood flow, electrolyte imbalances, prerenal azotemia, hyporeninemic hypoaldosteronism|
|Hepatic||▪ Elevated transaminases, hepatitis|
All NSAIDs also carry an FDA black box warning regarding the risk for cardiovascular events, which may be life-threatening. The highest risk is with selective NSAIDs. The exact mechanism is not well understood, but thought to be secondary to increased platelet aggregation, reduction in vasodilation, and possible destabilization of atherosclerotic plaque through COX-2 inhibition (ACR, 2008). The higher the COX-2 selectivity of an NSAID, the higher the risk for cardiovascular side effects (Grosser, Fries, & FitzGerald, 2006; Figure 1). Two highly selective COX-2 inhibitors, rofecoxib and valdecoxib, were removed from the U.S. market because of numerous side effects, including the significant increase in cardiovascular risk (Bresalier et al., 2005; Nussmeier et al., 2005). Currently, celecoxib is the only selective COX-2 inhibitor available in the United States, but still has an increased risk for cardiovascular events that appears to be dose dependent when compared to nonselective NSAIDs (Farkouh & Greenberg, 2009).
The most common hematologic adverse events are related to the anticoagulant effects of NSAIDs. The risk is highest in nonselective NSAIDs and with concurrent anticoagulant or antiplatelet pharmacological therapy. Anemia may also be seen with NSAID use, but this is most commonly secondary to gastrointestinal bleeding and a work-up for bleeding should be initiated (ACR, 2008). Renal adverse events include increased fluid retention, electrolyte abnormalities, and an increase in blood pressure by an average of 5 mmHg (Barkin et al., 2010). NSAIDs also have the potential to be nephrotoxic, with linkages to prerenal azotemia and hyporeninemic hypoaldosteronism. Liver toxicity is a rare side effect of NSAID use and is unpredictable; currently, no solid risk factors have been identified (ACR, 2008). The CLASS study demonstrated that liver toxicity related to NSAID use was secondary to diclofenac in 97% of the cases (Silverstein et al., 2000).
Common NSAID drug–drug interactions
Polypharmacy is common in older adults, with over 90% of adults over the age of 65 using at least one medication per week, almost 60% using five or more medications, and almost 20% using 10 or more medications a week (Slone Epidemiology Center, 2006). NSAIDs are one of the most commonly used medications in adults, with 7%–10% use in adults over the age of 65 (Slone Epidemiology Center, 2006). In addition to high utilization, NSAIDs also have a high risk for adverse drug events and are one independent risk factor for preventable adverse drug events along with advanced age, comorbidities, and polypharmacy (Field et al., 2004). Drug–drug interactions often precipitate the adverse effects of NSAIDs (Table 2).
|Common NSAID Drug–Drug Interactions|
|Drug||Adverse Drug Interaction|
|Aspirin (ASA)||▪ Nonselective NSAIDs (most notably ibuprofen) blocks antiplatelet affect|
|▪ Combined use with selective and nonselective NSAIDs increases risk for gastrointestinal event and bleeding.|
|Anticoagulants and antiplatelets||▪ Increased risk for bleeding through an additive effect|
|Glucocorticoids||▪ Increased risk for gastrointestinal ulcer, bleeding, fluid retention, and edema through an additive effect|
|Angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)||▪ Increase risk for nephrotoxicity and decrease antihypertensive effect because of blockage of prostaglandins responsible for vasodilation and natriuresis|
|Diuretics||▪ Decreased diuretic effect because of inhibition of prostaglandins responsible for natriuresis|
|▪ Increased risk for hyperkalemia with potassium-sparing diuretic|
|Beta blockers||▪ Impedes antihypertensive effect through inhibition of prostaglandins, sodium and fluid retention|
|Pentoxifylline (Trental)||▪ Increased risk for bleeding|
|SSRIs||▪ Increased risk for bleeding and hyponatremia/SIADH|
|Lithium||▪ Increase lithium levels and risk for toxicity secondary to decreased renal excretion|
|Cidofovir||▪ Increased risk for nephrotoxicity|
|Probenecid||▪ Decreased renal excretion of NSAID, increasing the risk for NSAID side effects|
|Ginkgo biloba||▪ Increased risk for bleeding|
Anticoagulants, antiplatelets, diuretics, corticosteroids, and cardiovascular medications are common medications associated with adverse drug events (Table 2; Field et al., 2004). These drug classes also have a high potential for drug–drug interactions with NSAIDs. Concurrent use of anticoagulants (warfarin, heparin, enoxaparin, direct thrombin inhibitors) increases the risk for bleeding, notably gastrointestinal bleeding, through an additive effect and is one of the most common drug–drug interactions in older adults (Malone et al., 2005). Cheetham, Levy, Niu, and Bixler (2009) noted an increase in hospitalization secondary to gastrointestinal bleeding in patients taking warfarin plus nonselective NSAIDs or selective NSAIDs (COX-2 inhibitors).
Angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), and diuretics are three common medications among older adults (Slone Epidemiology Center, 2006). In combination with NSAIDs, their antihypertensive effect maybe negated with a potential increase in nephrotoxicity. A recent study also highlights the dangers associated with a triple therapy combination of an ACEI or ARB, diuretic, and NSAID (Lapi, Azoulay, Yin, Nessim, & Suissa, 2013). Triple therapy combinations produce a 31% higher risk for acute renal failure, with the greatest risk in the first 30 days of therapy. The acute renal failure stems from renal hypovolemia through the effects of diuretics, exacerbated by a combination of NSAID and ACEI or ARB therapy. The diuretic decreases blood flow to the glomerulus, while the NSAID constricts the renal afferent arteriole. Glomerular filtration is likely maintained by angiotensin II, which increases sodium retention and allows for efferent arteriolar vasoconstriction; however, with triple therapy, the ACEI or ARB prevents activation of angiotensin II, increasing renal hypovolemia and the risk for acute renal failure (Lapi et al., 2013).
Anticoagulants, diuretics, ACEI, and ARBs are potentially serious and life-threatening drug–drug interactions with NSAID use. Table 2 lists several other common drug–drug interactions with NSAIDs and other medications common among older adults.
Prescribing NSAIDs in the older adult
A thorough medical history and complete medication list should be obtained and reviewed to identify any potential comorbidities or drug–drug interactions before initiating NSAID therapy. When prescribing NSAIDs for the older adult, it is important to initially consider the class of NSAID (nonselective vs. selective), the dosage, frequency, and duration. To reduce the risk for adverse events, the lowest dose, frequency, and duration is ideal. Also, with the vast number of NSAIDs from which to choose, it is important to consider such factors as nonselective versus selective NSAIDs, COX-1 and COX-2 affinity, and the half-life. Those NSAIDs with a higher affinity for COX-1 inhibition (nonselective NSAIDs) produce an increased risk for gastrointestinal and renal side effects, but potentially lower cardiovascular risk. Of the nonselective NSAIDs, those with the lowest COX-2 affinity have the lowest risk for cardiovascular events and are therefore best for those with cardiovascular risk; naproxen is the nonselective NSAID of choice with cardiovascular risk (ACR, 2008; Antman et al., 2007; Chan et al., 2008; Friedewald et al., 2010; Figure 1). NSAIDs with a higher COX-2 affinity (selective NSAIDs) have lower COX-1 affinity, therefore lower gastrointestinal risk, but an increased cardiovascular risk.
Gastrointestinal adverse events must be considered when initiating NSAID therapy in older adults. Factors that increase the risk for gastrointestinal adverse events include age, prior history of peptic ulcer or gastrointestinal bleeding, active Helicobacter pylori infection, tobacco and alcohol use, concurrent use of high-risk medications (anticoagulants, antiplatelets, corticosteroids, aspirin), high-dose NSAID therapy, and long-term NSAID therapy. Selective NSAIDs (celecoxib) have lower COX-1 affinity, decreasing the risk for adverse gastrointestinal events. They are therefore valuable for patients with an increased gastrointestinal risk. Screening for Helicobacter pylori infection and eradication has potential benefits in decreasing the gastrointestinal risk with long-term NSAID therapy (Lanza et al., 2009). Administration of NSAIDs with food and adequate fluid can minimize gastrointestinal distress for most patients; however, the predictability of food/liquid intake in the older adult population is often variable. With lower gastrointestinal risk, nonselective NSAIDs are appropriate. However, with increasing age (particularly over the age of 70) and increasing gastrointestinal risk, the addition of a proton pump inhibitor (PPI) or misoprostol should be considered (Lanza et al., 2009). PPIs and misoprostol have also been found to be effective in minimizing gastrointestinal risk in patients using NSAIDs (Lanza at al., 2009). Histamine 2 receptor antagonists (H2RA) are effective at protecting against adverse gastrointestinal events at higher doses (Lanza et al., 2009). In patients with significantly elevated gastrointestinal risk, a selective NSAID plus a PPI or misoprostol is a treatment option; however, avoiding NSAID therapy altogether is the best recommendation (ACR, 2008; Chan et al., 2008; Lanza et al., 2009).
Cardiovascular risks are also of concern. The higher the COX-2 affinity, the higher the cardiovascular risk. Therefore, selective NSAIDs (celecoxib) are inappropriate for patients with increased cardiovascular risk. Patients at higher risk include those with a history of coronary artery disease, cardiovascular disease requiring low-dose aspirin, or an estimated 10-year cardiovascular risk greater than 20% (Chan et al., 2008). In patients with a recent (6 months) cardiovascular event (acute myocardial infarction, percutaneous coronary angioplasty with stent placement, coronary artery bypass grafting), all NSAIDs should be avoided because of increased risk for morbidity (Friedewald et al., 2010). Combination therapy with NSAIDs and other anticoagulants should be avoided, but if the patient cannot be managed appropriately with other analgesic therapies, such as acetaminophen or opioids, gastroprotective agents, such as PPIs or misoprostol, should be prescribed and providers and patients must closely monitor for bleeding, recognizing the increase risk for gastrointestinal events and adverse events (Chan et al., 2010; Cheetham et al., 2009; Friedewald et al., 2010). Providers should consider avoiding triple therapy with ACEI or ARB, diuretics, and NSAIDs. However, if no effective alternatives to NSAIDs exist, the provider should review patients’ comorbidities, concurrent medications, and renal function. This combination of NSAIDs with diuretics and ACEI or ARB requires increased vigilance and close monitoring for renal injury. When initiating NSAID therapy in patients with cardiovascular disease, blood pressure should be monitored closely, particularly within the first 3 months and if concurrently used with ACEIs, ARBs, and beta-blockers. The NSAID dose should be decreased or discontinued with an increase in blood pressure; however, if dose reduction or discontinuation is not feasible, the elevated blood pressure should be managed with antihypertensives (Friedewald et al., 2010). Heart failure risk also increases with NSAIDs, making their use inadvisable in those with a history or high risk for heart failure (ACR, 2008).
Low-dose aspirin is commonly prescribed in older adults for cardiovascular protection benefits, as aspirin is the only NSAID that provides primary cardiac and secondary stroke prevention (Friedewald et al., 2010). Concomitant use of a nonselective NSAID with aspirin can negate the cardioprotective effects of low-dose aspirin. Nonselective NSAIDs competitively bind to the COX-1 enzyme responsible for the antithrombotic effect and block the binding of aspirin, eliminating cardio protective effects (Barkin et al., 2010). Ibuprofen appears to have the greatest effect on aspirin, and no effect has been found with selective NSAIDs (celecoxib) (Farkouh & Greenberg, 2009; Friedewald et al., 2010). In 2006, the United States FDA released recommendations based on current data analysis to dose ibuprofen at least 30 minutes after or 8 hours before immediate-release aspirin (United States FDA, 2013). Sufficient data are lacking regarding enteric-coated aspirin and the effects of other nonselective NSAIDs on low-dose aspirin; therefore, the same timing precautions should be implemented as with ibuprofen and immediate release aspirin (Friedewald et al., 2010).
Nonselective and selective NSAID therapy should be carefully monitored or avoided in patients with renal insufficiency because of an increased risk for impaired natriuresis , edema, blood pressure elevation, and electrolyte abnormalities. Caution also should be demonstrated in those patients with unexplained anemia, liver failure, and bleeding disorders (ACR, 2008; Friedewald et al., 2010).
Essential in the decision of whether to prescribe an NSAID, is the consideration of the AGS Beers Criteria (2012a) identifying NSAIDs as a potentially inappropriate medicine in older adult. These consensus driven criteria, recently revised in 2012, are increasingly being used to monitor quality of care for older adults. Table 3 adapts the Beers Criteria supporting the recommendations discussed in this section, noting the quality of evidence and strength of recommendation.
|Drug and Related Comorbidity||Recommendation||Quality of Evidence||Strength of Recommendation|
|Nonselective NSAIDs||Avoid chronic use unless alternative therapies are not effective and can take a gastroprotective agent||Moderate||Strong|
|Indomethacin/Ketorolac (oral or parenteral)||Avoid||ModerateKetorolac: High||Strong|
|NSAIDs in patients with heart failure||Avoid||Moderate||Strong|
|NSAIDs in patients with Stage IV or V chronic kidney disease||Avoid in patients with a CrCl < 30 mL/min||Moderate||Strong|
|NSAIDs in patients with history of gastric or duodenal ulcers||Avoid||Moderate||Strong|
|NSAIDs in patients with hypertension||Avoid||Moderate||Strong|
Alternatives to NSAIDs
While NSAIDs are an effective pharmacological therapy for chronic pain management, not all patients are appropriate for NSAID therapy. Alternative nonpharmacological and pharmacological therapies should be considered in older adults with pain.
Various alternative pharmacological options are appropriate to consider when treating pain in older adults (Table 4). Acetaminophen is often recommended as first line therapy because of its lower risk for adverse events and drug–drug interactions. The FDA currently recommends a maximum dose of 4 g/day with recent restrictions to a maximum dose of 325 mg of acetaminophen per unit of drug in combination medications (United States FDA, 2011). The manufacturer of OTC Extra Strength Tylenol has lowered the maximum dose on the packaging instructions to 3 g/day. When taking acetaminophen, all OTC medications and any other pain medication should be reviewed, with patient education to avoid unintentional overdosing, which can lead to liver damage and failure (United States FDA, 2011). If acetaminophen is ineffective in controlling pain, opioids and tramadol should be considered. Often the old adage of “start low and go slow” helps reduce side effects associated with opioids. Despite their widespread use, nutritional supplements such as glucosamine and chondroitin sulfate are not recommended as alternative therapies, specifically in the management of osteoarthritis (Hochberg et al., 2012). Alternative therapies, such as serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclics, anticonvulsants, and topical analgesics may also be options when treating neuropathic pain (Table 4; AGS, 2009).
|Alternative Pharmacological Therapy|
|Acetaminophen||Effective analgesia and first line recommendation because of low risk for adverse events.||Inadvertent overdose when combined with other medications. Caution with a history of liver disease and alcohol abuse. Maximum of 325 mg acetaminophen in prescription drug products. Maximum daily dose of 4 g/24 h.|
• Oxycodone (OxyContin, Roxicodon)
• Oxymorphone (Opana)
• Morphine (MS Contin, Kadian, Avinza)
• Hydromorphone (Dilaudid) Phenylpiperidines
• Transdermal fentanyl (Duragesic) Phenylheptanones
|Appropriate therapy if not responding to more conservative approaches. Diminished addiction risk in older adults. May receive pain control at lower doses, without opioid side effects and the risk associated with other nonopioid therapy, such as NSAIDs. Various options to include short-acting/breakthrough preparations and long-acting/extended-release preparations.||Carefully consider the frequency and severity of pain, comorbidities, other medications, and risk for opioid side effects. Opioid adverse events include respiratory depression, sedation, fall risk, confusion, constipation, and dependency risk. Stigma with opioids that often inhibits patient use. Do not prescribe fentanyl in opioid naïve patients because of risk for over sedation and death.|
|Tramadol||Recommended for moderate to severe pain not controlled with NSAIDs or acetaminophen. Less stigma than opioid therapy and may be more readily acceptable by the patient.||Potential for dependency and abuse. Avoid with history or risk for addiction. Monitor for sedation and respiratory depression. Lowers seizure threshold and should be avoided in patients with a history of seizures. Increase risk for serotonin reuptake syndrome especially with use of SSRIs and SNRIs.|
• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)
• Desvenlafaxine (Prestiq)
• Milnacipran (Savella)
|Effective therapy for neuropathic pain, such as fibromyalgia and peripheral neuropathy. Nonsedating||Nausea, diaphoresis, dizziness, hypertension, tachycardia.|
Tricyclics Secondary amine
• Nortriptyline (Pamelor)
• Despiramine (Norpramine)
|Therapy for neuropathic pain in fibromyalgia, peripheral neuropathy, and postherpetic neuralgia.||Not recommended in older adults secondary to anticholinergic effects, sedating, orthostatic hypotension, and increased risk for falls.|
• Gabapentin (Neurontin)
• Pregabalin (Lyrica)
|Effective therapy for neuropathic pain. Newer anticonvulsants (pregabapentin and gabapentin) have a lower side effect profile than older anticonvulsants.||In older adults with a risk for falls or fractures, anticonvulsants not recommended. Side effects include ataxia, falls, sedation, and peripheral edema.|
• Lidocaine patch
• Topical NSAID
|Decreased risk for side effects because of decreased systemic absorption. Topical lidocaine is effective for neuropathic pain.||Skin irritation is the most common side effect. Patients may find difficult to apply and maintain applications because of moisture or movement.|
Much has been written about the role of nonpharmacological therapies in the management of pain. Some of these regimens provide an alternative to pain relieving medications. These alternatives, many with short-term efficacy and good tolerance, may decrease medication dosages, lowering side effects and adverse events (Carpenter, 2012). Both the ACR and the AGS recommend the use of nonpharmacological measures to augment or replace medication management (ACR, 2008; AGS, 2012b). There is evidence to support the benefits of physical exercise, patient education, formal cognitive behavioral therapy (CBT), and other approaches, such as thermal modalities, chiropractic measures, assistive devices, and transcutaneous electrical nerve stimulation (ACR, 2008; Carpenter, 2012; Hochberg et al., 2012).
Exercise is the essential nonpharmacological treatment for individuals with arthritis, regardless of age, comorbidity, pain severity, or disability (Ringdahl & Pandit, 2011). Patients should be encouraged to remain active and advised to participate in an exercise program that considers exercise capacity and physical limitations. Exercise modalities may include water and land-based activities that improve functional status, gait, and pain management (Hochberg et al., 2012). Additionally, weight management along with exercise is vital.
CBT and patient education are useful tools for chronic pain management and include skills, such as relaxation, meditation, goal setting, and expectation management (Carpenter, 2012). CBT is recommended by the American Geriatric Society for the management of chronic pain in the older adult as an alternative treatment modality (AGS, 2009).
Patients frequently benefit from a combination of pharmacological and nonpharmacological modalities in the management of pain. Whenever possible and appropriate, a combination of modalities should be prescribed in the treatment of pain. Such an approach encourages patient involvement in self-care, an essential component in the management of any chronic problem.
Persistent pain in the older adult is a frequent problem that has the potential to dramatically influence function and quality of life. Treating pain in the older adult is a challenge for clinicians, particularly given the variety of issues to consider, from age, comorbidities, and polypharmacy, to NSAID pharmacology and varying guideline recommendations. The ACR (ACR, 2008; Hochberg et al., 2012) and the AAOS (2013) have contrasting recommendations about how soon to resort to NSAIDs. However, the AGS Beers Criteria (2012a) cautions against NSAID therapy in any older adult. Despite the challenges and lack of consistent recommendations, clinicians can provide effective pain management for the older adult through the careful use of appropriate pharmacologic (including NSAID therapy) and nonpharmacologic strategies. These strategies should be chosen on an individualized basis balancing safety and efficacy. Strong consideration should be given to acetaminophen as a first-line therapy because of its safety and efficacy profile. If acetaminophen is not effective in managing pain, NSAIDs should be considered with careful thought given to the potential for adverse events. Because of this risk, long-term NSAID use should be avoided and should only be maintained at the lowest possible dose and for the shortest effective time (<18 months). However, long-term NSAID therapy may be necessary in select older adults with the clinician minimizing risk by considering the class of NSAID, comorbidities, polypharmacy, and monitoring for potential adverse events.
- Administration on Aging. (2008). Projected future growth of the older population. Retrieved from http://www.aoa.gov/Aging_Statistics/future_growth/future_growth.aspx
- Alliance for Rational Use of NSAIDs. (2012). Information about an important public health initiative. Retrieved from http://www.nsaidalliance.com/downloads/NSAID-Alliance-HCP-Brochure-Web.pdf
- American Academy of Orthopaedic Surgeons (AAOS). (2013). Treatment of osteoarthritis of the knee; evidence based guideline (2nd ed.). Retrieved from http://www.aaos.org/Research/guidelines/TreatmentofOsteoarthriti-softheKneeGuideline.pdf
- American College of Rheumatology (ACR). (2008). Recommendations for use of selective and nonselective nonsteroidal antiinflammatory drugs: An American College of Rheumatology white paper. Arthritis & Rheumatism, 59(8), 1058–1073.
- American Geriatrics Society (AGS). (2009). Pharmacological management of persistent pain in older persons. Journal of the American Geriatrics Society, 57(8), 1331–1346.
- American Geriatrics Society (AGS). (2012a). American Geriatrics Society updated Beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 60(4), 616–631.
- American Geriatrics Society (AGS). (2012b). Statement on the use of opioids in the treatment of persistent pain in older adults. Retrieved from http://www.americangeriatrics.org/files/documents/Opioid_Statement_April_2012.pdf
- American Heart Association (2007). Use of nonsteroidal antiinflammatory drugs: An update for clinicians—A scientific statement from the American Heart Association. Circulation, 115(12), 1634–1642. , , , , , , &
- 2010). Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult? Drugs & Aging, 27(10), 775–789. , , , , , & (
- 2005). Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. New England Journal of Medicine, 352(11), 1092–1102. , , , , , , … (
- 2013). AAOS clinical practice guideline: Treatment of osteoarthritis of the knee—Evidence-based guideline, 2nd edition. Journal of the American Academy of Orthopaedic Surgeons, 21(9), 577–579. (
- 2011). Pain experience of the elderly. Pain Management Nursing, 12(4), 190–196. , , , & (
- 2012). An online self-help CBT intervention for chronic lower back pain. Clinical Journal of Pain, 28(1), 14–22. (
- 2003). Lack of efficacy of acetaminophen in treating symptomatic knee osteoarthritis: A randomized, double-blind, placebo-controlled comparison trial with diclofenac sodium. Archives of Internal Medicine, 163(2), 169–178. , , & (
- Centers for Disease Control and Prevention. (2011). Osteoarthritis. Retrieved from http://www.cdc.gov/arthritis/basics/osteoarthritis.htm
- First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents. (2008). Management of patients on nonsteroidal anti-inflammatory drugs: A clinical practice recommendation from the first international working party on gastrointestinal and cardiovascular effects of nonsteroidal anti-inflammatory drugs and anti-platelet agents. American Journal of Gastroenterology, 103(11), 2908–2918.Direct Link:, , , , &
- 2010). Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): A randomised trial. Lancet, 376(9736), 173–179. , , , , , & (
- 2009). Gastrointestinal safety of nonsteroidal antiinflammatory drugs and selective cyclooxygenase-2 inhibitors in patients on warfarin. Annals of Pharmacotherapy, 43(11), 1765–1773. , , , & (
- Chisholm-Burns, M., Wells, B., Schwinghammer, T., Malone, P., Kolesar, J., Rotschafer, J., & DiPrio, J. (Eds.). (2008). Pharmacotherapy principles & practice. United States of America: McGraw Hill Medical. New York, NY.
- Coxib and traditional NSAID Trialists’ (CNT) Collaboration. (2013). Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: Meta-analyses of individual participant data from randomised trials. Lancet, 382, 769–779.
- 2009). An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs. American Journal of Cardiology, 103(9), 1227–1237. , & (
- 2004). Risk factors for adverse drug events among older adults in the ambulatory setting. Journal of the American Geriatrics Society, 52(8), 1349–1354. , , , , , , … (
- 2010). AJC editor's consensus: Selective and nonselective nonsteroidal anti-inflammatory drugs and cardiovascular risk. American Journal of Cardiology, 106(6), 873–884. , , , , , , … (
- 2008). The antiplatelet effect of six non-steroidal anti-inflammatory drugs and their pharmacodynamic interaction with aspirin in healthy volunteers. American Journal of Cardiology, 101(7), 1060–1063. , , , , , & (
- 2004). Analgesic efficacy and safety of nonprescription doses of naproxen sodium compared with acetaminophen in the treatment of osteoarthritis of the knee. American Journal of Therapeutics, 11(2), 85–94. , , & (
- 2006). Biological basis for the cardiovascular consequences of COX-2 inhibition: Therapeutic challenges and opportunities. Journal of Clinical Investigation, 116(1), 4–15. , , & (
- American College of, R. (2012). American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care & Research, 64(4), 455–474. , , , , , , &
- 2012). Drugs used to treat diseases of the blood, inflammation & gout. Basic & clinical pharmacology (12th ed.). United States of America: The McGraw-Hill Companies, Inc, New York, NY. , , & (
- 2006). GI risk and risk factors of NSAIDs. Journal of Cardiovascular Pharmacology, 47(Suppl 1), S60–S66. (
- 2005). A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. American Journal of Gastroenterology, 100, 1685–1693.Direct Link:, , , , , , … (
- Practice Parameters Committee of the American College of Gastroenterology. (2009). Guidelines for prevention of NSAID-related ulcer complications. American Journal of Gastroenterology, 104(3), 728–738. , , , &
- 2013). Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: Nested case-control study. BMJ, 346, e8525, 1–11. , , , , & (
- National Arthritis Data Workgroup. (2008). Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis & Rheumatism, 58(1), 26–35. , , , , , , …
- 2004). A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: A meta-analysis. Arthritis & Rheumatism, 51(5), 746–754. , , , , , & (
- 2005). Assessment of potential drug-drug interactions with a prescription claims database. American Journal of Health-System Pharmacy, 62(19), 1983–1991. , , , , , , … (
- 2005). Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. New England Journal of Medicine, 352(11), 1081–1091. , , , , , , … (
- 2002). A meta-analysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. Journal of Rheumatology, 29(4), 804–812. , , , , , , & (
- 2003). Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs. Arthritis & Rheumatism, 49(4), 508–518. , , , , , , & (
- Geriatric Gastroenterology Study Group (Societe Italiana Gerontologie Geriatria). (2003). NSAID and aspirin use by the elderly in general practice: Effect on gastrointestinal symptoms and therapies. Drugs & Aging, 20(9), 701–710. , , , , &
- 2011). Treatment of knee osteoarthritis. American Family Physician, 83(11),1287–1292. , & (
- 2000). Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: The CLASS study—A randomized controlled trial. Celecoxib long-term arthritis safety study. JAMA, 284(10), 1247–1255. , , , , , , … (
- Slone Epidemiology Center. (2006). Patterns of medication use in the United States 2006. Retrieved from http://www.bu.edu/slone/research/studies/slone-survey/
- 2004). Nonselective nonaspirin nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding: Relative and absolute risk estimates from recent epidemiologic studies. American Journal of Therapeutics, 11(1), 17–25. , , & (
- The International Association for the Study of Pain. (2012). Facts on “pain in older persons.” Retrieved from http://www.iasp-pain.org/AM/Template.cfm?Section=Home&Template=/CM/ContentDisplay.cfm&ContentID=3611
- United States Food and Drug Administration. (2011). FDA drug safety communication: Prescription acetaminophen products to be limited to 325 mg per dose unit; boxed warning will highlight potential for severe liver failure. Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm239821.htm#sa
- United States Food and Drug Administration. (2013). Information for healthcare professionals: Concomitant use of ibuprofen and aspirin. Retrieved from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafety-InformationforPatientsandProviders/ucm125222.htm
- U.S. Census Bureau. (2011). The older population: 2010. Retrieved from http://www.census.gov/prod/cen2010/briefs/c2010br-09.pdf
- 1998). Mechanism of action of nonsteroidal anti-inflammatory drugs. American Journal of Medicine, 104(3A), 2S–8s. , & (
- 2004). Nonsteroidal antiinflammatory drugs or acetaminophen for osteoarthritis of the hip or knee? A systematic review of evidence and guidelines. Journal of Rheumatology, 31(2), 344–354. , , , , & (
- 2002). Celecoxib does not affect the antiplatelet activity of aspirin in healthy volunteers. Journal of Clinical Pharmacology, 42(9), 1027–1030. , , , , , , & (