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Comparative Effectiveness Review Summary Guides for Clinicians [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007-.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

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Comparative Effectiveness Review Summary Guides for Clinicians [Internet].

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Choosing Non-Opioid Analgesics for Osteoarthritis

Clinician's Guide

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Issued: .

This guide summarizes clinical evidence on the effectiveness and safety of non-opioid analgesics for osteoarthritis. It covers most available over-the-counter (OTC) medications and prescription non-steroidal anti-inflammatory drugs (NSAIDs). The reviewed drugs are listed below. This guide does not address non-pharmacologic therapies such as diet, exercise, acupuncture, or surgical interventions.

Clinical Issue

Twenty-one million Americans have osteoarthritis. It is a chronic condition associated with pain and substantial disability. Managing pain can assist in maintaining mobility and improving quality of life. Choosing among the available prescription and over-the-counter medications requires careful consideration of benefits, risks, and cost.

The categories of non-opioid drug treatments for osteoarthritis are:

Clinical Bottom Line

  • Acetaminophen relieves mild pain but is inferior to NSAIDs for reducing moderate or severe pain. Acetaminophen has fewer systemic side effects than NSAIDs.
    Level of confidence: Image clinoafu1.jpg
  • All non-aspirin NSAIDs work equally well for pain reduction.
    Level of confidence: Image clinoafu1.jpg
  • NSAIDs increase the risk of GI bleeding. The risk increases with higher doses and with age. People older than 75 have the highest risk.
    Level of confidence: Image clinoafu1.jpg
  • Celecoxib, high dose ibuprofen, and high dose diclofenac increase the risk of myocardial infarction. Naproxen does not increase the risk of myocardial infarction.
    Level of confidence: Image clinoafu3.jpg
  • Capsaicin cream relieves chronic osteoarthritic pain, but about half of the people using it will experience local burning sensations. The burning diminishes over time.
    Level of confidence: Image clinoafu3.jpg
  • OTC topical creams containing salicylates do not reduce osteoarthritic pain.
    Level of confidence: Image clinoafu3.jpg

Confidence Scale

The confidence ratings in this guide are derived from a systematic review of the literature. The level of confidence is based on the overall quantity and quality of clinical evidence.

High Image clinoafu1.jpg

There are consistent results from good quality studies.

Medium Image clinoafu2.jpg

Findings are supported, but further research could change the conclusions.

Low Image clinoafu3.jpg

There are very few studies, or existing studies are flawed.

Assessing Risk of Complications

GI Bleeding Risk

The most frequent serious complication is gastrointestinal (GI) bleeding due to gastric irritation. Age is one important factor that affects a person’s risk, as shown in the box below.

Risk of NSAID-Associated GI Bleeding Increases With Age

For people age 16–44:

5 of 10,000 people on NSAIDs will have a serious GI bleed

1 of 10,000 people on NSAIDs will die from a GI bleed

For people age 45–64:

15 of 10,000 people on NSAIDs will have a serious GI bleed

2 of 10,000 people on NSAIDs will die from a GI bleed

For people age 65–74:

17 of 10,000 people on NSAIDs will have a serious GI bleed

3 of 10,000 people on NSAIDs will die from a GI bleed

For people age 75 or older:

91 of 10,000 people on NSAIDs will have a serious GI bleed

15 of 10,000 people on NSAIDs will die from a GI bleed

Strategies to Lower the Risk of GI Bleeding

  • Avoid NSAIDs for people with a history of GI bleeding.
    Level of confidence: Image clinoafu1.jpg
  • Avoid NSAIDs for people on anticoagulant therapy.
    Level of confidence: Image clinoafu2.jpg
  • Consider acetaminophen. It is associated with a lower risk of GI bleeding than NSAIDs.
    Level of confidence: Image clinoafu1.jpg
  • Consider co-prescribing proton pump inhibitors (PPIs) or misoprostol. These drugs are effective in reducing GI bleeding for people on NSAIDs. Misoprostol is poorly tolerated by many individuals due to its GI side effects.
    Level of confidence: Image clinoafu1.jpg
  • Consider celecoxib. Results from short-term trials indicate it has a lower risk of GI bleeding than other NSAIDs. Concomitant use of aspirin (even low dose) reduces or negates the benefit of using celecoxib.
    Level of confidence: Image clinoafu2.jpg

Cardiovascular Risk

The cardiovascular risk of NSAIDs has received considerable attention. In general, the increased risk of myocardial infarction for any of the NSAIDs other than naproxen is about 30 per 10,000 people taking NSAIDs per year.

  • Celecoxib, ibuprofen at high doses (800 mg three times a day), and diclofenac at high doses (75 mg twice a day) have a higher risk of myocardial infarction compared to not taking these medications.
    Level of confidence: Image clinoafu2.jpg
  • Naproxen, even at high doses (500 mg twice a day), does not increase the risk of myocardial infarction.
    Level of confidence: Image clinoafu2.jpg
  • For other oral NSAIDs, we do not have enough data on cardiovascular risks to make reliable judgments.

Hepatotoxicity Risk

  • Clinically significant hepatotoxicity is rare for all the NSAIDs in this guide.
    Level of confidence: Image clinoafu1.jpg
  • Diclofenac is associated with higher rates of aminotransferase elevations (compared to other NSAIDs) but not with a higher incidence of serious liver disease.
    Level of confidence: Image clinoafu2.jpg

Renal Risk

  • All NSAIDs, including COX-2 inhibitors, can cause or aggravate hypertension, congestive heart failure, edema, and kidney problems.
    Level of confidence: Image clinoafu2.jpg
  • 5 mm Hg is the average increase in mean blood pressure for nonselective NSAIDs.
    Level of confidence: Image clinoafu2.jpg
  • 2 out of 1,000 people stop taking an NSAID because of renal problems.
    Level of confidence: Image clinoafu2.jpg
  • Long-term, regular acetaminophen use is associated with a small decrease in renal function in women but not in men. In people without underlying renal disease, this decrease is unlikely to progress to clinically significant renal failure.
    Level of confidence: Image clinoafu2.jpg

Alternatives to Oral NSAIDs

  • Consider glucosamine and chondroitin. Pharmaceutical grade glucosamine hydrochloride (1500 mg a day) plus chondroitin sulfate (1200 mg a day) reduces moderate to severe pain without serious side effects, but this combination has no effect on mild pain. The Food and Drug Administration (FDA) does not regulate these supplements as drugs, so the purity may vary.
    Level of confidence: Image clinoafu2.jpg
  • Consider acetaminophen. For mild pain, it is an effective alternative to NSAIDs.
    Level of confidence: Image clinoafu1.jpg
  • Consider capsaicin cream. It relieves chronic osteoarthritic pain, but about half of the people using it will experience local burning sensations. The burning diminishes over time.
    Level of confidence: Image clinoafu2.jpg
  • Consider topical creams containing prescription NSAIDs. They work as well as oral NSAIDs for osteoarthritic pain relief and have fewer systemic side effects. Topical diclofenac and topical ibuprofen are the best studied topicals. The FDA has not approved any topical NSAID formulations, but compounding is widely available.
    Level of confidence: Image clinoafu1.jpg

Still Unknown

  • There have been few studies comparing aspirin or salsalate to other NSAIDs for the treatment of osteoarthritis.
  • We do not have enough data to make reliable judgments about the cardiovascular risks of many oral NSAIDs. The drugs most studied are celecoxib, ibuprofen, diclofenac, and naproxen.
  • There is insufficient evidence to assess whether therapeutic doses (up to 4 grams a day) of acetaminophen lead to liver abnormalities in people without underlying liver disease.
  • Results from recent observational studies suggest an increased cardiovascular risk with heavy use of acetaminophen, but large, long-term trials of acetaminophen and associated cardiovascular safety are lacking.
  • It is not known whether using celecoxib is a better strategy than adding a PPI or misoprostol to a conventional NSAID for lowering the risk of GI bleeding.

Doses and Price

NON-PRESCRIPTION ANALGESICS

PRICE FOR 100 TABLETS/1 TUBE3
DRUG NAME1BRAND NAMES2STRENGTHGENERICBRAND
AcetaminophenTylenol®325 mg$2$7
500 mg$3$8
ORAL NSAIDs
AspirinBayer®, Ecotrin®325 mg$2NA
325 mg EC$2$5
IbuprofenAdvil®, Motrin®200 mg$4$10
NaproxenAleve®220 mg$7$8
TOPICAL PAIN RELIEVERS
CapsaicinTheragen®, Zostrix®60-gram tube (.025%)$8$12
60-gram tube (.075%)NA$17
SUPPLEMENTS
Glucosamine hydrochloride plus chondroitin sulfate500 mg/400 mg tid$55NA

PRESCRIPTION NSAIDs

PRICE FOR 1-MONTH SUPPLY3
DRUG NAME1BRAND NAMESDOSEGENERICBRAND
TRADITIONAL NSAIDs
DiclofenacCataflam®, Voltaren®75 mg bid$70$160
50 mg tid$85$175
100 mg XR daily$85$160
EtodolacLodine®400 mg bid$90$110
400 mg tid$130$170
IbuprofenMotrin®400 mg tid$20$30
800 mg tid$35$45
IndomethacinIndocin®50 mg tid$65NA
75 mg SR bid$130$140
KetoprofenOruvail®75 mg tid$95$115
200 mg ER daily$85$100
MeloxicamMobic®7.5 mg dailyNA$100
15 mg dailyNA$155
NabumetoneRelafen®1000 mg daily$85$125
1500 mg daily$100$150
NaproxenAnaprox®, Naprelan®, Naprosyn®250 mg tid$70$105
500 mg bid$80$110
500 mg tid$120$165
PiroxicamFeldene®20 mg daily$75$115
COX-2 INHIBITOR
CelecoxibCelebrex®100 mg bidNA$125
200 mg bidNA$200
400 mg bidNA$300
SALICYLATES
SalsalateAmigesic®, Salflex®750 mg bid$20$30
1

These drugs were evaluated in the systematic review.

2

OTC brand names were selected based on OTC sales in 2005.

3

Average Wholesale Price from Drug Topics Redbook, 2006.

EC = enteric coated, XR/ER = extended release, SR = sustained release, bid = twice a day, tid = three times a day, NA = not available.

Resource for Patients

Choosing Pain Medicine for Osteoarthritis: A Guide for Consumers is a companion to this Clinician’s Guide. It can help people talk with their health care professional about pain relief options. It provides information about:

  • Types of over-the-counter and prescription pain relievers.
  • Benefits, risks, and price of pain relievers.

For More Information

For electronic copies of the consumer’s guide, this clinician’s guide, and the full systematic review, visit this Web site: www.effectivehealthcare.ahrq.gov

For free print copies call:

The AHRQ Publications Clearinghouse (800) 358-9295

Consumer’s Guide, AHRQ Pub. No. 06(07)-EHC009-2A

Clinician’s Guide, AHRQ Pub. No. 06(07)-EHC009-3

Source

The source material for this guide is a systematic review of 351 research publications. The review, Comparative Effectiveness and Safety of Analgesics for Osteoarthritis (2006), was prepared by the Oregon Evidence-based Practice Center. The Agency for Healthcare Research and Quality (AHRQ) funded the systematic review and this guide. The guide was developed using feedback from clinicians who reviewed preliminary drafts.

AHRQ created the John M. Eisenberg Center at Oregon Health & Science University to make research useful for clinicians. This guide was prepared by David Hickam, M.D., Roger Chou, M.D., Valerie King, M.D., Theresa Bianco, Pharm.D., Sandra Robinson, M.S.P.H., and Martha Schechtel, R.N., of the Eisenberg Center.

Bookshelf ID: NBK63966PMID: 21977522

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