The nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used medicines to treat osteoarthritis-the most common form of arthritis- and mild to moderate pain. They cost around $4 to more than $1,500 a month. This report shows how you could save hundreds of dollars a month or more. Since individual needs vary, use the information in this report to talk with your doctor about the medicine and dose that is right for you, and the possible risks.

NSAIDs should be used with caution. They all increase the risk of serious side effects, including stomach ulcers, gastrointestinal bleeding, kidney failure, heart attacks, and strokes. Except for low-dose aspirin and naproxen, NSAIDs might not be appropriate for people at risk of heart disease or stroke. Don't take them for long periods of time without consulting a doctor.

Taking effectiveness, safety, and cost into account, we have chosen two NSAIDs as Consumer Reports Best Buy Drugs:

  • Naproxen-generic prescription and over-the-counter
  • Ibuprofen-generic prescription and over-the-counter

These are inexpensive medicines that are as effective as other NSAIDs when used in comparable doses. Naproxen may be a better choice for people who have higher risk of heart attacks or strokes, since the available evidence indicates it does not increase the risk of these conditions. If you are at increased risk of bleeding due to older age, use of aspirin or other blood thinners, or a history of prior bleeding or ulcers, talk to your doctor before starting an NSAID. Celecoxib (Celebrex) may be an alternative in some situations, or taking an acid blocker to help protect the stomach. Celecoxib is no more effective at relieving pain than ibuprofen or naproxen, but is more expensive, so it is not a top choice for most people. NSAIDs applied to the skin (topical) can be as effective as NSAID tablets or capsules for localized arthritis pain, but it is not yet clear if they cause fewer, serious side effects than oral NSAIDs. Also, they are more expensive. Our advice:

  • If you have had a stomach ulcer or bleeding, or are at high risk of either, talk with your doctor about the potential risks of taking NSAIDs and treatment alternatives. The risk of bleeding from NSAID use increases with age.
  • If you have heart disease or are at risk of a heart attack or stroke, talk with your doctor about the potential risks of taking any NSAID.
  • If you have kidney disease or high blood pressure, talk with your doctor about the risks of taking NSAIDs for long periods of time.
  • Take the lowest dose of an NSAID that brings relief and do not take any longer than necessary.
  • NSAIDs can interact with other medicines, including other NSAIDs, such as aspirin, and increase the risk of serious side effects. If your doctor prescribes an NSAID, tell him or her about any other medicines or dietary supplements you are taking, including daily aspirin to reduce your risk of heart attack or stroke.

Published in July 2013

Welcome

This report on the pain relievers called nonsteroidal anti-inflammatory drugs, or NSAIDs, is part of a Consumer Reports project to help you find safe, effective medicine that gives you the most value for your health-care dollar. To learn more about the project and other drugs we've evaluated, go to www.CRBestBuyDrugs.org.

NSAIDs are used to treat mild and moderate pain due to certain conditions, including osteoarthritis- the most common type of arthritis which involves breakdown of cartilage in the joints leading to pain, stiffness, and immobility-headaches and migraines, menstrual pain, and muscle soreness. With more than 98 million prescriptions in 2012 in the U.S., according to IMS Health, a healthcare technology and information company, NSAIDs are one of the most commonly used classes of medications. But they should be used with caution because they can cause serious bleeding, heart attacks, and strokes. The Arthritis, Rheumatism, and Aging Medical Information System estimates that adverse effects due to NSAIDs are responsible for more than 100,000 hospitalizations and more than 16,000 deaths in the U.S. each year.

NSAIDs are available as tablets or capsules that can be taken by mouth (oral), as well as gel, drops, and patches (topical) that can be applied directly to the skin at the painful areas of the body. See the chart on section 1 for a list of the available NSAIDs.

Most oral forms of NSAIDs are now available as less expensive generic drugs. And three are available in lower-dose formulations, as nonprescription over-thecounter drugs: acetylated salicylates (Aspirin, Bayer, Bufferin, and generic), ibuprofen (Advil, Motrin IB, and generic), and naproxen (Aleve and generic).

In addition, many combination products for treating cold symptoms and combination prescription painkillers contain an NSAID, such as ibuprofen or naproxen, or another medication called acetaminophen (Tylenol and various generics, discussed below). If you already take an NSAID for pain and need to take a cold remedy, check to make sure it does not interact with your NSAID and that you are not exceeding the maximum daily amount for the particular NSAID.

Other over-the-counter and prescription medicines are available to treat osteoarthritis and mild to moderate pain. Many doctors recommend that you first try acetaminophen for mild pain before an NSAID and consider an NSAID only if acetaminophen doesn't work for you.

But acetaminophen comes with its own caveats. It's not as effective at relieving pain as NSAIDs, and high doses can damage the liver. People with cirrhosis of the liver, those with hepatitis, and those who are heavy drinkers should use it with caution. Do not take more than the maximum daily amount, which is 4,000 mg per day-the equivalent of eight extra-strength 500 mg capsules daily. Acetaminophen can cause liver problems even at doses lower than 4,000 mg per day, so it's important to limit the dose to what you need. Certain Tylenol products have instructions to limit your daily maximum to no more than 3,000 mg. This is a voluntary reduction from the manufacturer. To date, the U.S. Food and Drug Administration's maximum daily limit for acetaminophen remains at 4,000 mg. In particular, older persons should consider limiting use of acetaminophen to less than the daily maximum amount.

And as we noted above, many combination products for treating cold symptoms contain acetaminophen. According to the FDA, more than 600 prescription and over-the-counter medications contain acetaminophen. So if you're unsure what's in your medications, check the labels to be sure you don't unknowingly take too much acetaminophen.

List of Available NSAIDs
Generic name Brand name(s) Available as a generic prescription drug?
Prescription and Nonprescription Pills
Acetylsalicylic acid Aspirin, Bayer, Bufferin Yes
Ibuprofen Advil, Motrin Yes
Naproxen Aleve, Anaprox, Naprosyn, Naprelan Yes (No generic version of Naprelan)
Prescription-Only Pills
Celecoxib Celebrex No
Diclofenac Cataflam, Zipsor, Voltaren XR Yes
Diflunisal Generic only Yes
Etodolac Generic only Yes
Fenoprofen Nalfon Yes (600 mg strength)
Flurbiprofen Ansaid Yes
Indomethacin Generic only Yes
Ketoprofen Generic only Yes
Meclofenamate Generic only Yes
Mefenamic acid Ponstel Yes
Meloxicam Mobic Yes
Nabumetone Generic only Yes
Nonacetylated Salicylates Generic only Yes
Oxaprozin Daypro Yes
Piroxicam Feldene Yes
Sulindac Clinoril Yes
Tolmetin Generic only Yes
Topical Formulations
Diclofenac 1.0 % Gel Voltaren No
Diclofenac 1.3 % Patch Flector No
Diclofenac 1.5 % Solution Pennsaid No

This report focuses primarily on the use of NSAIDs to treat osteoarthritis. But the information can also be helpful if you use these drugs occasionally to relieve aches and pains, including headaches and muscle soreness. In fact, if you take an over-the counter NSAID several times a week or more, this report will give you some important information about the risks and safe use of these medicines.

The report is based on a comprehensive expert analysis of the medical evidence available on NSAID medication. There's more information on section 6 and at www.CRBestBuyDrugs.org about how we conducted our evaluation.

What Are NSAIDs and Who Needs Them?

NSAIDs can help reduce fever and are often used to treat mild to moderate pain due to a variety of conditions, such as arthritis, back aches, bursitis, dental procedures, headaches, muscle spasms, menstrual cramps, sprains, and tendinitis.

NSAIDs are the most frequently prescribed treatment for osteoarthritis. The drugs don't cure the disease, but they can help relieve its symptoms. Your doctor will probably consider an NSAID if you have osteoarthritis symptoms that aren't helped by exercise, other nondrug treatments, or acetaminophen (Tylenol and generic).

About 27 million adults in the U.S. have osteoarthritis, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases. It's more common in older people, with up to a third of adults 65 and older suffering from the condition. Obesity also increases the risk of arthritis.

The best way to ward off the pain, stiffness, and joint "creakiness" of osteoarthritis and aging is regular exercise, stretching, muscle strengthening, and losing weight if necessary. In some cases, keeping active and limber can eliminate or sharply reduce the need to take medicine. But be careful: Some exercises might be inappropriate for your condition and you can injure yourself if you do an exercise incorrectly. Ask your doctor or physical therapist to help you develop an appropriate and safe exercise program.

Don't confuse osteoarthritis with other forms of arthritis, such as rheumatoid arthritis. Although the names sound similar, they are two very different diseases. Rheumatoid arthritis is an autoimmune disease in which the body attacks the lining of its own joints and causes inflammation (pain, redness, and swelling). It tends to worsen over time and can damage and deform the joints. It usually strikes people between the ages of 30 and 50. NSAIDs are sometimes used to relieve the pain and inflammation associated with rheumatoid arthritis. But the underlying disease often requires additional treatment with other kinds of drugs. (For more about that, see our Best Buy Drug report on biologics for rheumatoid arthritis: www.consumerreports.org/health/best-buy-drugs/ rheumatoid_arthritis.htm)

How NSAIDs Work

NSAIDs block the production of substances in the body called "prostaglandins." Those chemicals play a role in pain, inflammation, fever, and muscle cramps and aches. At low doses, NSAIDs work mainly as pain relievers. At higher doses, they may also reduce the body's inflammatory response to tissue damage as well as relieve pain. However, the clinical importance of any anti-inflammatory effects is uncertain, and for osteoarthritis, inflammation is usually not a major issue.

More specifically, NSAIDs block two different enzymes, called COX-1 and COX-2, which the body uses to make prostaglandins. (COX stands for cyclooxygenase). While this results in reduced pain and inflammation, it can also lead to serious gastrointestinal bleeding, heart attacks, and strokes. The gastrointestinal bleeding problems can be traced specifically to the blocking of COX-1. Prostaglandins produced by the COX-1 enzyme help protect the lining of the stomach from acid, so blocking this enzyme increases the risk of stomach bleeding and ulcers. Some people have an especially high risk of this problem, but it's difficult to tell in advance who they are.

NSAIDs differ in how much they block the COX-1 enzyme relative to the COX-2 enzyme. NSAIDs that block both enzymes are referred to as "nonselective" NSAIDs and those that mainly block the COX-2 enzyme are called "selective" NSAIDs. One selective NSAID, Vioxx, was withdrawn from the market in 2004 because it was linked to an increased risk of heart attacks and strokes. Another selective NSAID, Bextra, was withdrawn in 2005 because it was associated with an increased risk of serious cardiovascular problems in people who had undergone coronary artery bypass graft surgery as well as a higher risk of life-threatening skin reactions than other NSAIDs. The only selective NSAID currently available in the U.S. is Celebrex (celecoxib).

Heart Risk

All NSAIDs carry a warning on the package insert that says they can increase the risk of heart attacks and strokes. Those problems appear to be related to blocking the COX-2 enzyme, which all NSAIDs do, though to varying degrees. This has led to some troubling questions, such as: At what dose and over what period of time do NSAIDs become unsafe and the dangers outweigh the benefits? And given that the various NSAIDs have differing effects on the COX-2 enzyme, what does that mean regarding their relative safety?

The available evidence indicates that other than aspirin and naproxen, NSAIDs in general are associated with an increased risk of heart attacks or strokes. This includes selective as well as nonselective NSAIDs. Though it isn't clear why naproxen would affect heart attack risk differently than other NSAIDs, it may be related to the specific structure of the drug. Although the FDA issued a warning about possible heart attack risk with naproxen in 2004 based on results from one trial that was stopped early, subsequent analyses of all of the available evidence have found no increase in risk with it.

For NSAIDs other than naproxen, it is unclear from the available studies whether low doses used for short periods increase the risk of heart attacks or strokes. So if you are at higher risk for heart disease, you should talk to your doctor first before taking an NSAID. If you are not at higher risk and use NSAIDs only occasionally-just a few times a month or less-for, say, headache relief or to ease sore muscles, there is probably no reason to worry or stop using them.

If you have heart failure, do not take NSAIDs without discussing it with your doctor first, since using NSAIDs can worsen heart failure.

NSAIDs can also cause high blood pressure or worsen it if you already have the condition, which can lead to heart problems. NSAIDs can also reduce the effectiveness of certain high blood pressure medications. So avoid NSAIDs if you have high blood pressure, unless your doctor has said it is appropriate for your situation. If you take an NSAID regularly, check your blood pressure frequently and tell your doctor if it rises.

There's more information below on how to assess your own risk and use NSAIDs wisely and safely. Most relevant here is that some people might be more prone than others to the heart and stroke risks posed by the NSAIDs, so knowing your heart disease risk is important for making informed decisions about NSAID use. Find out your 10-year risk of having a heart attack or stroke by using our free risk calculator: http://www.consumerreports.org/heartrisk.

Aspirin-the oldest and best known NSAID-is unique because it is the only NSAID with well-known blood-thinning (antiplatelet) effects that has been proven to actually lower the risk of heart attacks and strokes in people with an elevated risk. The U.S. Preventative Services Task Force advises that the benefits of daily aspirin use outweigh the risks for men ages 45 to 79 who are at a high risk of having a heart attack in the next 10 years. For women, the benefits don't tip in aspirin's favor until age 55, and are limited to those at high risk of having a stroke in the next decade. Also, regardless of gender, the therapy should be limited to those who are not at increased risk of gastrointestinal bleeding.

What if you take aspirin to protect your heart but want to take another NSAID for pain? Aspirin plus another NSAID can be a dangerous combination. Taken together, they can increase the risk of ulcers and gastrointestinal bleeding. Also, there is some evidence that ibuprofen might reduce the heartprotective effects of aspirin. However, other research has not found that to be the case. Given this conflicting evidence, if you take aspirin to protect your heart, you might want to avoid ibuprofen and possibly try acetaminophen or naproxen instead for pain relief.

Stomach Risk

Taking NSAIDs can increase your risk for stomach bleeding. More than 100,000 Americans are hospitalized each year and more than 16,000 die from ulcers and gastrointestinal bleeding linked to NSAID use, according to The Arthritis, Rheumatism, and Aging Medical Information System. People who have previously had stomach bleeding and/or ulcers are at higher risk. Additional risk factors include older age and taking other NSAIDs, corticosteroids, or blood thinners-for example, clopidogrel (Plavix and generic) or warfarin (Coumadin and generic). Talk with your doctor about how to assess your risk.

Evidence indicates that Celebrex poses a lower bleeding risk than other NSAIDs.

Another strategy to reduce the risk of bleeding is to use an NSAID along with a stomach acid blocker, such as the proton pump inhibitors (PPIs) omeprazole (Prilosec OTC and generics) or lansoprazole (Prevacid 24HR and generics). In people at very high risk of bleeding, NSAIDs are not recommended even with these strategies, as the risk of bleeding cannot be lowered enough for NSAIDs to be considered "safe."

Although aspirin does not carry the heart risks of the other NSAIDs, it can cause gastrointestinal problems. Even at low doses it can cause stomach bleeding. And at higher doses aspirin poses the same gastrointestinal risk as other NSAIDs, and possibly even a greater risk than some of them.

Salsalate is a chemical cousin to aspirin that some studies indicated might be less harsh on the stomach than aspirin and other NSAIDs. However, those studies had issues that give us doubt about the reliability of their results. So to date, there is still no solid evidence that salsalate poses less risk of gastrointestinal problems than other NSAIDs.

The topical NSAID formulations-diclofenac gel (Voltaren), drops (Pennsaid), and patches (Flector)- were designed to be safer than oral NSAIDs, since the medication is mainly delivered directly to the joints where the pain is located, and theoretically should not have much blocking action on COX enzymes throughout the body. However, studies have not been large or long enough to know for certain whether they actually reduce the risk of bleeding or heart attacks and strokes, though they appear to cause less stomach upset and are as effective as NSAID pills for relieving pain that is localized to a single or a few joints.

Because the topicals result in reduced levels of the NSAID medication in the body, they should theoretically have a reduced risk of heart attack and stroke, but studies are needed to confirm this.

The topical formulations listed above are the only ones approved by the FDA. Some pharmacies will make topical formulations of NSAIDs by crushing pills and mixing them with an ointment or other carrier.

However, whether such formulations are effective is unknown.

The ability of NSAIDs to penetrate the skin to get to the joint varies depending on the specific NSAID and the carrier used. In addition, the concentration of NSAID varies, and the quality control process may not be adequate. Because of these uncertainties, we don't recommend using such compounded NSAIDs.

Table 1. Who Needs an NSAID?
May Need an NSAID May Want to Take NSAIDs With Extra Caution May Want to Avoid NSAIDs
  • If you have osteoarthritis with pain, joint inflammation and stiffness unrelieved by an exercise regimen, other nondrug treatments, or acetaminophen.
  • If you have rheumatoid arthritis and need symptom relief.
  • If you have moderate pain due to a headache, joint or muscle injury; use short-term only. May want to try acetaminophen first.
  • If you have low-grade, chronic pain, for example, back pain, unrelated to osteoarthritis.
  • If you have frequent stomach upset or a "sensitive" stomach.
  • If you are 50 years of age or older or have previously suffered ulcers or GI1 problems; and/or a family history of early heart disease, especially if a parent has died of a heart attack at a young age; or you smoke, have high cholesterol or high blood pressure, or kidney problems.
  • If you take steroids or blood thinners, such as clopidogrel (Plavix and generic) or warfarin (Coumadin and generic).
  • If you have taken NSAIDs regularly for pain relief or osteoarthritis for many years and still need to, especially if you have ever had an ulcer, or GI pain and bleeding associated with NSAID use.
  • If you have ever had stomach ulcers or bleeding.
  • If you have coronary artery disease or any other form of heart disease or heart failure.2
  • If you have ever had a heart attack.2
  • If you have uncontrolled high blood pressure.
  • If you have kidney disease.
  • If you have ever had a stroke or a transient ischemic attack (a ministroke).2
  • If you are undergoing coronary artery bypass graft (CABG) surgery.
  • If you take aspirin to protect your heart.
  • If you are in your third trimester of pregnancy.
  1. GI stands for gastrointestinal.
  2. With the exception of aspirin for people with heart disease or who have had a heart attack.

Kidney Risk

NSAIDs have been associated with kidney failure, so people with kidney disease due to diabetes or other causes should not take NSAIDs unless your doctor has said it is appropriate for your situation.

Bottom Line

NSAIDs are effective pain relievers. But even the nonprescription forms like ibuprofen (Advil, Motrin IB, and generic) and naproxen (Aleve and generic) can be dangerous when taken too often or in high doses regularly.

Although there are no studies that quantify the extent of the inappropriate or unsafe use of NSAIDs, many doctors and our medical consultants think that Americans overuse them, taking both the nonprescription and prescription versions too often for mild headaches and everyday aches and pains, especially those associated with exercise and sports.

Given that, we offer the following recommendations to reduce your risk:

  • Take NSAIDs with caution, and avoid regular use if possible.
  • Consider trying acetaminophen first. But be sure to follow the product label directions carefully.
  • Don't take NSAIDs on a regular basis to treat osteoarthritis or chronic pain without seeing a doctor to assess your risk for heart problems and gastrointestinal bleeding.

Table 1 gives you guidance on when an NSAID might be appropriate for your situation and when you should avoid them or use only with caution.

Choosing an NSAID - Our Best Buy Picks

All NSAIDs ease the pain and other symptoms of osteoarthritis, and other types of pain, too. At equivalent doses, their effectiveness is essentially the same. No study, to date, shows that one NSAID is superior to others in relieving pain. That includes brand-name NSAIDs such as Celebrex and Mobic.

NSAIDs likely differ in the risks they pose to your stomach or heart. But as already discussed, there is no NSAID associated with having both a low risk of bleeding as well as low heart attack or stroke risk, so your choice of an NSAID and its dose depends on the safety profile of the NSAID and on your individual risk profile. Tables 1 and 2, respectively, will help gauge your risk and treatment options.

NSAIDs differ substantially in price, so cost might be an important factor in which one you choose. Some generic prescription versions cost $4 or less for a month's supply, while more expensive brand names can run as high as $1,500 or more monthly. The only COX-2 selective drug available in the U.S., Celebrex (celecoxib), costs $181 to $282 monthly, depending on the dose.

Thus, our choice of the following two Best Buy NSAIDs is based primarily on their relatively low cost but also takes into account the evidence on their effectiveness and safety:

  • Naproxen-generic prescription and over the counter
  • Ibuprofen-generic prescription and over the counter

Both of these medications have been on the market for more than 20 years. Ibuprofen and naproxen are widely prescribed by doctors and are also used heavily (perhaps too heavily) as nonprescription pain relievers. Naproxen is not associated with increased heart risk. So for people at increased risk for heart attacks or strokes or a prior history of them, naproxen may be a better choice, especially if you take it frequently for a long period of time or at higher (prescription strength) doses.

Like other nonselective NSAIDs, both naproxen and ibuprofen are associated with increased risk of gastrointestinal bleeding. If you are at increased risk of bleeding due to older age, use of aspirin or other blood thinners, or a history of prior bleeding or ulcers, talk to your doctor before starting an NSAID. Celecoxib (Celebrex) may be an alternative in some situations. You may be able to take an acid blocker to help protect the stomach.

Celecoxib is no more effective at relieving pain than ibuprofen or naproxen, but is more expensive, so it is not a top choice drug for most people. For people with a very high bleeding risk, even taking Celebrex or using an acid-blocker may not make taking an NSAID safe, so discuss alternative treatments for pain with your doctor.

Both of our Best Buys-ibuprofen and naproxen-are also available as nonprescription drugs. Prescription strength doses may cost as little as $4 for a month's supply through generic drug programs run by major chain stores, such as Kroger, Sam's Club, Target, and Walmart. For an even better bargain if you are going to be on those drugs long-term, you may be able to get a three-month supply for as little as $10 through these programs. We note in the price chart starting on the NSAIDs Cost Comparison table under the Drug Comparison tab which NSAIDs are available through these programs. Some stores, such as CVS and Walgreens, require a membership fee to participate and might charge higher prices. There might be other restrictions too, so check the details carefully to make sure your drug and dose are covered.

If you need higher doses of an NSAID due to osteoarthritis or other conditions, your best bet is to get a prescription NSAID under a physician's care. He or she should monitor your response and your risk of any side effects, including stomach, heart, and kidney problems.

If your pain is localized to one or a few joints or muscles, one of the topical formulations-gel (Voltaren), drops (Pennsaid), or patches (Flector)- might be good options to consider. But they aren't cheap: A month's supply can cost between $196 and $478 or even more, depending on how much and how often they are applied. Although the idea of these topical formulations was to reduce the risk of ulcers and gastrointestinal bleeding, this has not yet been proven definitively, though the medications do cause less stomach upset. And since the topicals result in reduced levels of the NSAID medication in the body, they should theoretically pose a reduced risk of heart attack and stroke, but studies are needed to confirm this. So unless you need the convenience of a patch, drops or gel, and are willing to pay the extra cost, for most people a pill is still your best bet.

For occasional use-for example, if your arthritis or pain symptoms are mild or intermittent-you can probably get the pain relief you need by taking nonprescription aspirin, ibuprofen, or naproxen.

Remember, however, that regular (and especially everyday) use of NSAIDs-prescription or nonprescription- can lead to complications, especially at high doses. That's why the instructions on the packaging of all nonprescription NSAIDs state that you should not take them for longer than 10 days without consulting a physician. Unfortunately, many people ignore those recommendations.

If you take a nonprescription NSAID several times a week (or more) because of chronic pain, stiffness, or to prevent sports injuries or muscle soreness after sports activities, you should consider seeing a doctor. There might be better strategies for managing your pain that could also help reduce the amount of medication you take.

For Osteoarthritis Patients: Your Treatment Options

Table 2 offers another way of looking at treatment options based on your risk if a physical therapy or exercise program has not given you enough relief. To find the medicine and dose that's right for you, your physician should ask about and assess your gastrointestinal and heart risk. Don't take high doses of any NSAID without such an assessment, and don't start an NSAID on your own (e.g., an over-the-counter NSAID or taking a friend or family member's NSAID) if you know you are at higher risk, without talking to a doctor first.

If you have ever had an ulcer or stomach bleeding, you might want to avoid NSAIDs altogether and try acetaminophen. If that doesn't relieve your pain or other symptoms, you should talk to your doctor about whether to take low doses of an NSAID only when you need one, and always along with a stomach acid reducer, such as the over-the-counter proton pump inhibitors (PPIs) omeprazole (Prilosec OTC and generics) and lansoprazole (Prevacid 24HR and generics).

Acid reducers can lower the incidence of ulcers and GI bleeding in people taking NSAIDs. And this combination has become a frequently prescribed (and advertised) dual treatment. But the combination does not eliminate the risk completely. So be alert to the signs of an ulcer or GI bleeding, such as burning stomach pain. Bleeding can also occur without preceding stomach pain, so also look for other signs of bleeding, such as lightheadedness, weakness, blood in your stool, or black and tarry stools.

Table 2. Options in Treating Osteoarthritis
Health Status and Risks Options
  • No or low GI risk1
  • No heart or stroke risk
  • Generic ibuprofen or naproxen
  • Other NSAID with lowest out-of-pocket cost for you
  • Acetaminophen
  • GI risk2
  • No or low heart or stroke risk
  • Acetaminophen
  • Lowest effective dose of ibuprofen or naproxen (or other generic NSAID) plus a stomach acid reducer
  • Celecoxib, with or without a proton pump inhibitor
  • Topical NSAID
  • Heart or stroke risk
  • No or low GI risk
  • Acetaminophen
  • Naproxen
  • Aspirin plus a stomach acid reducer. Lowest effective dose of each drug
  • Topicals3
  • Heart or stroke risk
  • GI risk2
  • Acetaminophen plus aspirin for heart protection, with a stomach acid reducer
  • Naproxen, with a stomach acid reducer
  • Topicals3
  • Use lowest effective dose of drugs
  • Stay alert for signs of an ulcer: burning stomach pain, blood in stool, or black, tarry stools
  1. GI stands for gastrointestinal.
  2. Patients with a history of prior bleeding should talk to their doctor before taking an NSAID.
  3. Because the topicals result in reduced levels of the NSAID medication in the body, they should theoretically have a reduced risk of heart attack and stroke, but studies are needed to confirm this.

Of course, if you do take an acid reducer, you will have to pay for another medicine. Most prescription and nonprescription acid reducers are relatively inexpensive. Our Best Buy picks-generic omeprazole and generic lansoprazole-cost as little as $17 a month. (Our Best Buy Drugs report on Proton Pump Inhibitors is available at www.CRBestBuyDrugs.org.)

Another option to reduce the risk of bleeding is celecoxib (Celebrex), either with or without a PPI. Celebrex is no more effective than other NSAIDs for relieving pain and costs more than generic NSAIDs; unless you are at higher risk for bleeding, the extra cost of Celebrex is unnecessary for most people.

If you have heart disease, uncontrolled high blood pressure, or had a heart attack or stroke, you might want to try acetaminophen first, with your doctor's permission. That is also a good option if you are at high risk for those conditions because you smoke, have high cholesterol, or high blood pressure. Take the lowest dose that provides adequate pain relief. If you take aspirin, especially at higher doses, talk with your doctor about taking a stomach acid reducer, such as omeprazole or lansoprazole, at the same time.

Another option is to take naproxen, since it does not appear to increase heart attack risk like other nonaspirin NSAIDs.

What if you are taking aspirin to protect your heart but want to take another NSAID for pain? As we previously noted, that can be a dangerous combination that can increase the risk of ulcers and gastrointestinal bleeding. And ibuprofen might reduce the heart-protective effects of aspirin. So if you are taking aspirin to protect your heart, you might want to avoid ibuprofen and possibly try acetaminophen or naproxen instead for pain relief.

The Evidence

This section presents more information on the effectiveness and safety of the NSAIDs.

Studies show that NSAIDs are effective pain relievers, but they have serious risks. Most NSAIDs increase the risk of bleeding and ulcers in the stomach, particularly when used at high doses for long periods, and most increase the risk of heart attacks and strokes. NSAIDs also have other risks, such as increasing blood pressure, causing fluid retention, and reducing kidney function.

When used only periodically at low doses to relieve aches, pains, or soreness, there's no evidence that NSAIDs pose any significant stomach risk. It's not entirely clear if heart risks only occur at higher doses or with longer duration of use; if you are at higher risk for heart attacks or strokes talk to your doctor before taking an NSAID. If you are not at higher risk, using the lowest dose for the shortest period of time necessary is still probably the safest strategy.

How Effective Are NSAIDs?

In general, oral NSAIDs reduce pain by an average of about 50 percent in people who benefit from them. And studies show they enhance mobility in about 60 percent of the people with osteoarthritis. The degree of pain relief you get will depend primarily on the intensity of your pain. But other factors also come into play. For example, some people are more tolerant of pain than others. Also, some people might respond to some oral NSAID drugs better than other drugs because of genetic differences.

Hundreds of studies have been done on oral NSAIDs, with many comparing one to another. Overall, the differences between them appear to be negligible, and study findings do not consistently show any one oral NSAID to be better than another. Studies have shown, for example, that on average, typical doses of generic ibuprofen, naproxen, and diclofenac are just as effective at relieving pain as celecoxib (Celebrex). Some people report more pain relief with one NSAID than another, so not responding to one NSAID doesn't necessarily mean that a person won't respond to a different one.

In contrast, relatively few head-to-head studies have directly compared one topical NSAID with another or to one of the oral NSAIDs for osteoarthritis. Among the topical NSAIDs approved by the FDA, only the diclofenac solution (Pennsaid drops) has been directly compared with an oral NSAID (diclofenac) in two studies of adults with osteoarthritis of the knee. Pain relief was similar with the Pennsaid drops and oral diclofenac.

The other topical NSAIDs approved by the FDA, diclofenac gel (Voltaren) and diclofenac patches (Flector), have not been directly compared with an oral NSAID. However, they have been compared against placebo and found to be more effective for decreasing knee or hand pain related to osteoarthritis-by around 25 to 40 percent, or similar to what would be expected with an oral NSAID.

How Safe Are NSAIDs?

As discussed throughout this report, it is well-known that oral NSAIDs can cause life-threatening gastrointestinal bleeding, usually from the stomach. The risk increases with age, which is important to note because the majority of people who take NSAIDs for long periods are 60 years or older. As shown in Table 4, a person who is over the age of 75 and takes an NSAID has about a one in 110 chance of having gastrointestinal bleeding, and a one in 647 chance of dying from that complication.

Table 4. Serious Risks Associated With NSAIDs
Age Risk of GI1 bleeding each year Risk of dying from GI1 bleeding each year
Risk in any one year is:
16-44 1 in 2,100 1 in 12,353
45-64 1 in 646 1 in 3,800
65-74 1 in 570 1 in 3,353
>75 1 in 110 1 in 647
  1. GI stands for gastrointestinal

Source: Blower A, Brooks A, Fenn G, Hill A, Pearce M, Morant S. Emergency admissions for upper gastrointestinal disease and their relation to NSAID use. Aliment Pharm Ther. 1997(11):283-291.

When applied to the population as a whole, NSAID-related deaths are substantial. The Arthritis, Rheumatism, and Aging Medical Information System estimates that adverse effects due to NSAIDs may be responsible for more than 100,000 hospitalizations and more than 16,000 deaths in the U.S. each year.

Celecoxib (Celebrex), the only COX-2 selective NSAID available in the U.S., has consistently shown an advantage in lowering the risk of serious ulcer complications in the short-term (six months or less) compared with other NSAIDs. Although one major study that compared Celebrex with two other NSAIDs-ibuprofen and diclofenac-over a year found that overall, Celebrex was not any less likely to cause serious ulcer complications, analyses of all of the available studies indicate that Celebrex is effective at reducing the risk of ulcers with longer-term use.

For certain people with osteoarthritis who are at a higher risk of stomach ulcers and bleeding-due to being over 60, taking additional medication, such as aspirin, which is also known to cause stomach problems, or having a history of stomach ulcers and bleeding-current guidelines on pain management recommend either dual treatment with an NSAID plus an acid-reducing medication, such as a proton pump inhibitor (PPI), or treatment with celecoxib (Celebrex), possibly with a proton pump inhibitor. Because even these strategies may not reduce the risk of bleeding to safe levels in someone at high risk, it's important to talk to your doctor before taking an NSAID.

A majority of studies found that dual treatment with an NSAID plus a proton pump inhibitor was fairly similar to celecoxib (Celebrex) in the reduction in risk of ulcer complications in the upper GI tract of highrisk patients. One large observational study did find an advantage for celecoxib when it was compared to diclofenac plus a different kind of acid reducing medication, misoprostol, in people who were 66 or older. Celebrex was less likely to cause dangerous upper GI bleeding than diclofenac plus misoprostol.

In patients with a recent bleeding ulcer, the risk of rebleeding is high with either celecoxib or a nonselective NSAID. Based on a recent randomized trial, the best strategy in this situation would be celecoxib plus a proton pump inhibitor, if an NSAID is used.

Compared to taking an NSAID alone, studies also show that adding an acid-reducing medication (such as a PPI, an H2 receptor antagonist, or misoprostol) to an NSAID reduces the risk of "endoscopic ulcers." One acid-reducing medication, misoprostol (Cytotec and generic), has been shown to reduce short-term risk of serious ulcer complications in older patients taking NSAIDs for rheumatoid arthritis. But, since there are no longer-term studies, how well they work beyond six months is unknown.

In addition, misoprostol has to be taken four times a day and is difficult for many patients to tolerate because of GI side effects like nausea, vomiting, and diarrhea. PPIs have fewer side effects, only need to be taken once or twice daily, are stronger acid blockers than H2 receptor antagonists-such as famotidine (Pepcid AC and generics) and ranitidine (Zantac 150 and generics)-and some are available over-the-counter. Because of that, PPIs are currently the main acid-reducing medication used to prevent ulcers related to NSAIDs.

One trial evaluated whether adding a PPI to celecoxib (Celebrex) would provide even more protection from stomach ulcers and bleeding than taking celecoxib alone after hospitalization for upper GI bleeding. The addition of the PPI esomeprazole (Nexium) to celecoxib reduced risk of recurrent GI bleeding over 13 months following initial hospitalization.

Although based on the results of several older observational studies, salsalate has often been considered to be easier on the stomach and gastroinstestinal tract than other NSAIDs, the analysis upon which this Best Buy Drug report is based considers the strength of evidence with these studies to be low because they had several limitations. The studies did not take into account whether people who participated were taking other medications or had other medical conditions. The studies also did not clearly define how they assessed toxicity, how they selected people to participate, or how long the people were followed after taking salsalate.

One of the primary ideas behind the development of topical NSAIDs was to minimize the risk of serious ulcer complications by reducing the amount of the medication circulating in the body, since topical NSAIDs produce lower blood levels of the drug than oral NSAIDs. But so far, no randomized, controlled trial has evaluated the long-term risk of serious ulcer or stomach-bleeding complications with the topical forms of diclofenac. Only one short-term study found that compared to oral diclofenac, topical diclofenac (Pennsaid) lowered-by 66 percent-the risk of "severe" gastrointestinal events-those that produced impairment or incapacitation and were a clear hazard to the patient's health. But the advantage of topical diclofenac beyond 12 weeks has not yet been evaluated in a randomized trial. In an observational study based on a well-known database in the U.K., topical NSAIDs were associated with lower risk of GI bleeding than oral NSAIDs, but more research is needed to verify this finding. Diclofenac is the only NSAID available in FDA-approved topical formulations, to date.

Heart Attacks and Strokes

All NSAIDs carry a warning on their labeling that if used in certain ways they have the potential to raise the risk of heart attacks and strokes.

So far, for the older, nonselective, nonaspirin NSAIDs, a meta-analysis of primarily short-term trials found that all except naproxen were associated with similar increased risks of heart attack compared with placebo. Celecoxib (Celebrex) has also been found to increase the risk of heart attack compared to placebo, though most of the trials evaluated patients taking celecoxib for colon polyp prevention or for prevention of Alzheimer's disease, not for treating osteoarthritis. The trials generally evaluated higher doses of NSAIDs. Taking all of the available studies together, all NSAIDs, besides aspirin and naproxen, appear to nearly double the risk of heart attacks and related complications.

No randomized controlled trial has evaluated the risk of heart attacks and strokes with topical NSAIDs.

Hypertension, Heart Failure, and Kidney Problems

NSAIDs can aggravate high blood pressure, which is one way they could raise the risk of heart attack. They cause fluid retention, which can lead to slight weight gain or swollen legs even in healthy individuals. In people who have a "weak heart" (due to congestive heart failure or left ventricular dysfunction), fluid retention due to NSAIDs could make your symptoms worse and increase your risk of being sent back to the hospital if you have previously been hospitalized for heart failure.

NSAIDs also reduce kidney function in some individuals, especially those who already have kidney disease from diabetes or other causes. The risk of these problems is similar for different NSAIDs.

No randomized, controlled trial has evaluated the risk of hypertension, heart failure, and kidney problems with topical forms of diclofenac.

Liver problems

All products containing diclofenac carry a warning that they can increase the risk of abnormal liver-function tests. And there have been some reports to the FDA about cases of severe liver damage and related deaths that occurred in people taking oral diclofenac. Although a 2005 systematic review of 65 published and unpublished short-term randomized controlled trials found a 3.5-fold increase in risk of abnormal liver-function tests with oral diclofenac compared with a placebo, the degree of increased risk of clinical issues (such as liver failure) is much less certain. So far, only one published study has evaluated the long-term risk of serious liver problems due to diclofenac. That study looked at more than 17,000 patients who took oral diclofenac over 18 months and did not find any cases of liver failure, transplant, or death.

As for topical NSAIDs, short-term trials found that the risk of abnormal liver-function tests were reduced with the diclofenac topical solution (Pennsaid) compared with oral diclofenac over 12 weeks. But no randomized, controlled trial has evaluated the long-term risk of serious liver problems with any of the topical forms of diclofenac.

Fracture

The risk of bone fractures with NSAIDs is uncertain. In 2006, preliminary evidence emerged from a large observational study that found that ibuprofen, diclofenac, and naproxen were associated with an increased risk of fracture. However, there are several drawbacks to this study. One is that it is unclear whether the increase in fractures was due to actual weakening of the bone structure, changes in balance, increased clumsiness, or something else entirely. More studies are needed to better assess the relationship between NSAIDs and fracture risk.

Tolerability

Oral NSAIDs can cause other minor side effects, including upset stomach, abdominal pain, and diarrhea. Their frequency is about the same no matter which NSAID you take. About one in five people who take prescription doses of oral ibuprofen, naproxen, or diclofenac regularly, for example, have experienced one of these side effects, according to an analysis done by the Oregon Health & Science University's Drug Effectiveness Review Project, or DERP. However, most people taking the older oral NSAIDs don't stop taking the medicine because of side effects. Oral NSAIDs can also cause skin rashes, but these are rare.

With topical NSAIDs, one of the most common side effects is irritation of the skin where the drops, gel, or patch is applied. For diclofenac topical solution (Pennsaid), dry skin at the application site was the most common type of skin irritation and occurred in up to 36 percent of the adults treated for osteoarthritis. The risk of dry skin at the application site with diclofenac topical solution was 30 times greater than with a placebo.

In contrast, skin irritation might not be as much of a problem with diclofenac gel (Voltaren gel). Overall, application-site reactions only occurred in four to five percent of the patients using the topical gel for osteoarthritis of the hand or knee, which was only slightly higher than the two percent of patients using a placebo. However, it remains unclear whether the gel offers any real side effect advantage over the solution.

Age, Race, and Gender Differences

Age is an important factor when considering NSAID treatment, especially long-term. The risk of GI bleeding and stomach ulcers with oral NSAIDs increases with age, as seen in Table 4. So does heart disease risk. The older you are the more cautious your doctor should be in treating you with NSAIDs for long periods of time. Some doctors now routinely prescribe a stomachacid reducer to people 65 and over taking an oral NSAID.

There is scant data on any differences by gender or race in response to oral NSAIDs. But an important recent study found that aspirin's heart- and stroke-protective effect was different in men and women. It found that while women taking low-dose aspirin regularly had fewer strokes than men, they did not get the same benefit as men in preventing a first heart attack. The reason for this difference is unknown. It raises the possibility that women and men might also respond differently to other NSAID drugs.

Whether there are any differences in the benefits and risks of topical NSAIDs based on age, race, or gender is not yet known because their effects in patient subgroups have not yet been evaluated in any studies

5 Tips to Talking With Your Doctor

It's important for you to know that the information we present here is not meant to substitute for a doctor's judgment. But we hope it will help you and your doctor arrive at a decision about which NSAID and dose is best for you, if one is warranted at all, and which gives you the most value for your health-care dollar.

1. Mention cost to your doctor.

Bear in mind that many people are reluctant to discuss the cost of medicines with their doctor, and that studies have found that doctors do not routinely take price into account when prescribing medicines. Unless you bring it up, your doctor may assume that cost is not a factor for you.

2. Ask about older medications.

Many people (including physicians) think that newer drugs are better. While that's a natural assumption to make, it's not always true. Studies consistently find that many older medicines are as good as, and in some cases better than, newer medicines. Think of them as "tried and true," particularly when it comes to their safety record. Newer drugs have not yet met the test of time, and unexpected problems can and do crop up once they hit the market. Of course, some newer prescription drugs are indeed more effective and safer. Talk with your doctor about newer vs. older medicines, including generic drugs.

3. Consider generic drugs.

Prescription medicines go "generic" when a company's patents on them have lapsed, usually after about 12 to 15 years. At that point, other companies can make and sell the drugs. Generics are much less expensive than newer brand-name medicines, but they are not lesser quality drugs. Indeed, most generics remain useful medicines even many years after first being marketed. That is why more than 75 percent of all prescriptions in the U.S. today are written for generics.

4. Keep up-to-date records.

Another important issue to talk with your doctor about is keeping a record of the drugs you take. There are several reasons for this:

  • First, if you see several doctors, each may not be aware of medicines the others have prescribed.
  • Second, since people differ in their response to medications, it's common for doctors today to prescribe several medicines before finding one that works well or best.
  • Third, many people take several prescription medications, nonprescription drugs, and dietary supplements at the same time. They can interact in ways that can either reduce the benefit you get from the drug or be dangerous.
  • Fourth, the names of prescription drugs-both generic and brand-are often hard to pronounce and remember.

For all these reasons, it's important to keep a written list of all the drugs and supplements you take and periodically review it with your doctors.

5. Know the facts.

Finally, always be sure that you understand the dose of the medicine being prescribed and how many pills you are expected to take each day. Your doctor should tell you this information. When you fill a prescription at a pharmacy, or if you get it by mail, check to see that the dose and the number of pills per day on the bottle match the amounts your doctor told you.

How We Picked the Best Buy NSAIDs

Our evaluation is primarily based on an independent scientific review of the evidence on the effectiveness, safety, and adverse effects of NSAIDs. A team of physicians and researchers at the Oregon Health & Science University Evidence-Based Practice Center conducted the analysis as part of the Drug Effectiveness Review Project, or DERP. DERP is a first-of-its-kind multi-state initiative to evaluate the comparative effectiveness and safety of hundreds of prescription drugs.

A synopsis of DERP's analysis of the NSAIDs forms the basis for this report. A consultant to Consumer Reports Best Buy Drugs is also a member of the Oregon-based research team, which has no financial interest in any pharmaceutical company or product.

The full DERP review of NSAIDs is available at http://derp.ohsu.edu/about/final-document-display.cfm. (This is a long and technical document written for physicians.)

Some of the drug costs we cite were obtained from a health-care information company that tracks the sales of prescription drugs in the U.S. Prices for a drug can vary quite widely, even within a single city or town. The prices are national averages based on sales of prescription drugs in retail outlets. They reflect the "cash" or retail price paid for a month's supply of each drug in March 2013. As noted in the NSAIDs Cost Comparison table, other prices for prescription drugs are based on discount generic drug programs run by chain stores. However, the medications covered by these programs can change regularly, we found, so those prices are not used when selecting the Best Buy picks. Although, we do indicate when a drug is likely to be covered by one or more discount generic drug programs. Prices for nonprescription drugs were obtained by Consumer Reports secret shoppers from several large drugstore chains. They reflect average or typical prices in January 2013.

Consumer Reports Best Buy Drugs selected the Best Buy Drugs using the following criteria. The drug (and dose) had to:

  • Be approved by the FDA for treating at least one form of arthritis.
  • Have a safety record equal to or better than other NSAIDs.
  • Have an average price for a 30-day supply that was substantially lower than the most costly NSAID meeting the first two criteria.

The Consumer Reports Best Buy Drugs methodology is described in more detail in the Methods section at www.CRBestBuyDrugs.org.

Sharing This Report

This copyrighted report can be downloaded free, reprinted, and disseminated for individual noncommercial use without permission from Consumers Union or Consumer Reports® magazine as long as it is clearly attributed to Consumer Reports Best Buy Drugs™. We encourage its wide dissemination as well for the purpose of informing consumers. But Consumers Union does not authorize the use of its name or materials for commercial, marketing, or promotional purposes. Any organization interested in broader distribution of this report should email wintwe@consumer.org. Consumer Reports Best Buy Drugs™ is a trademarked property of Consumers Union. All quotes from the material should cite Consumer Reports Best Buy Drugs™ as the source.

2013 Consumers Union of U.S., Inc.

About Us

Consumer Reports is an independent and nonprofit organization whose mission since 1936 has been to provide consumers with unbiased information on goods and services and to create a fair marketplace. Its website is www.ConsumerReports.org.

Consumer Reports Best Buy Drugs is a public-education project administered by Consumers Union. These materials were made possible by the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer-fraud claims regarding the marketing of the prescription drug Neurontin.

The Engelberg Foundation provided a major grant to fund the creation of the project from 2004 to 2007. Additional initial funding came from the National Library of Medicine, part of the National Institutes of Health. A more detailed explanation of the project is available at www.CRBestBuyDrugs.org.

We followed a rigorous editorial process to ensure that the information in this report and on the Consumer Reports Best Buy Drugs website is accurate and describes generally accepted clinical practices. If we find an error or are alerted to one, we will correct it as quickly as possible. But Consumer Reports and its authors, editors, publishers, licensers, and suppliers cannot be responsible for medical errors or omissions, or any consequences from the use of the information on this site. Please refer to our user agreement at www.CRBestBuyDrugs.org for further information.

Consumer Reports Best Buy Drugs should not be viewed as a substitute for a consultation with a medical or health professional. This report and the information on www.CRBestBuyDrugs.org are provided to enhance your communication with your doctor rather than to replace it.

References

  1. Altman RD, Dreiser R-L, Fisher CL, Chase WF, Dreher DS, Zacher J. Diclofenac sodium gel in patients with primary hand osteoarthritis: a randomized, double-blind, placebo-controlled trial. Journal of Rheumatology. Sep 2009;36(9):1991-1999.
  2. Barthel HR, Haselwood D, Longley S, 3rd, Gold MS, Altman RD. Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis. Seminars in Arthritis & Rheumatism. Dec 2009;39(3):203-212.
  3. Bjordal JM, Ljunggren AE, Klovning A, Slordal L. Nonsteroidal anti-inflammatory drugs, including cox-2 inhibitors, in osteoarthritic knee pain; meta-analysis of randomized placebo controlled trials. British Medical Journal Online 2004 (November 23); 10.1136.
  4. Blower A, Brooks A, Fenn G, Hill A, Pearce M, Morant S. Emergency admissions for upper gastrointestinal disease and their relation to NSAID use. Aliment Pharm Ther. 1997(11):283- 291.
  5. Bombardier C. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. New England Journal of Medicine 2000;343:1520.
  6. Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R. Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis. Journal of the Royal Society of Medicine. 2006;99:132-140.
  7. Chan F, Lanas A, Scheiman J, Berger M, Nguyen H, Goldstein J. Celecoxib vs. omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomized trial. Lancet. 2010;376(9736):173-179.
  8. Chan FK, Hung LC, Suen BY, et al. Celecoxib vs. diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. New England Journal of Medicine 2002; 347(26):2104-10.
  9. Chan FKL, Wong VWS, Suen BY, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet. May 12 2007;369(9573):1621-1626.
  10. Dubois RW, Melmed GY, Henning JM, Laine L. Guidelines for the appropriate use of nonsteroidal anti-inflammatory drugs, cox-2 inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy. Alimentary Pharmacologic Therapy 2004; 19 (2)197-208.
  11. Farkouh ME, Kirshner H, Harrington RA, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomized controlled trial. Lancet 2004;364(9435):675-84.
  12. FDA Advisory Committee Briefing Document: Celecoxib and Valdecoxib Cardiovascular Safety. http://www.fda.gov/ohrms/ dockets/ac/05/briefing/2005-4090B1_03_Pfizer-Celebrex- Bextra.pdf. Accessed 21 Dec 2005.
  13. Fitzgerald GA, COX-2 and beyond: approaches to prostaglandin inhibition in human disease. Nat. Rev. Drug Discov. 2003;2:879-90.
  14. Fitzgerald GA. Coxibs and cardiovascular disease. New England Journal of Medicine 2004;351(17):1709-11.
  15. Food and Drug Administration. Medical Officer review, 1999: Vioxx. NDA 21- 042. http://www.fda.gov/cder/foi/nda/99/021042_52_vioxx.htm (accessed Nov.12, 2004).
  16. Garcia Rodriguez LA, Varas-Lorenzo C, Maguire A, et al. Nonsteroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population. Circulation 2004;109(24):3000-6.
  17. Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med 2009; 169:141-149.
  18. Goldstein JL, Cryer B, Amer F, Hunt B. Celecoxib plus aspirin vs. naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial. Clinical Gastroenterology & Hepatology. Oct 2007;5(10):1167-1174.
  19. Gøtzsche PC. Reporting of outcomes in arthritis trials measured on ordinal and interval scales is inadequate in relation to metaanalysis. Ann. Rheum. Disease 2001;60:349-352.
  20. Hopper L, Brown TJ, Elliot RA et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by nonsteroidal anti-inflammatory drugs: a review. British Medical Journal Online 2004 (October 8); 10.1136.
  21. Jenkins, JK and Seligman, PJ, FDA Memorandum-Analysis and recommendations for agency action regarding nonsteroidal anti-inflammatory drugs and cardiovascular risk. April 6, 2005. Available at www.fda.gov/cder/drug/infopage/cox2/NSAIDdecisionmemo.pdf.
  22. Kearney PM, Baigent C, Godwin J, Halls H, Emberson J R, Patrono C. Do selective cyclo-oxygenase-2 inhibitors and traditional nonsteroidal anti-inflammatory drugs increase the riskof atherothrombosis: meta-analysis of randomised trials (Structured abstract). BMJ. 2006;332:1302.
  23. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C. Do selective cyclooxygenase-2 inhibitors and traditional nonsteroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. BMJ. 2006;332:1302-1308.
  24. Krum H, Liew D, Aw J, Haas S. Cardiovascular effects of selective cyclooxygenase-2 inhibitors. Expert Review of Cardiovascular Therapy 2004;2(2):265-70.
  25. Lai KC, Chu KM, Hui WM, et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. American Journal of Medicine. 2005;118:1271-1278.
  26. Laine L, Goldkind L, Curtis SP, Connors LG , Yanqiong Z, Cannon CP. How common is diclofenac-associated liver injury? Analysis of 17,289 arthritis patients in a long-term prospective clinical trial. American Journal of Gastroenterology. Feb 2009;104(2):356-362.
  27. Mamdani M, Rochon PA, Juurlink DN, et al. Observational study of upper gastrointestinal hemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional nonsteroidal anti-inflammatory drugs. BMJ. 2002;325:624.
  28. Moore R. Quantitative systematic review of topically applied nonsteroidal anti-inflammatory drugs. British Medical Journal1998;316:333-338.
  29. Moore RA, Derry S, Makinson GT, McQuay HJ. Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports. Arthritis Research & Therapy. 2005;7:R644-R655.
  30. Mukherjee D. Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events. Biochemical Pharmacolog. 2002;63(5):817-21.
  31. Niculescu L, Li C, Huang J, Mallen S. Pooled analysis of GI tolerability of 21 randomized controlled trials of celecoxib and nonselective NSAIDs. Curr Med Res Opin. 2009; 25(3):729-40. PMID: 19210159.
  32. Rahme E, Barkun AN, Toubouti Y, et al. Do proton pump inhibitors confer additional gastrointestinal protection in patients given celecoxib? Arthritis & Rheumatism. Jun 15 2007;57(5):748-755.
  33. Ray WA, Stein CM, Daugherty JR, Hall K, Arbogast PG, Griffin MR. Cox-2 selective nonsteroidal anti-inflammatory drugs and risk of serious coronary heart disease. Lancet 2002;360(9339):1071-3.
  34. Ray WA, Stein CM, Hall K, Daugherty JR, Griffin MR. Nonsteroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational cohort study. Lancet 2002;359(9301):118-23.
  35. Rostom A, Goldkind L, Laine L. Nonsteroidal anti-inflammatory drugs and hepatic toxicity: a systematic review of randomized controlled trials in arthritis patients. Clinical Gastroenterology & Hepatology. May 2005;3(5):489-498.
  36. Schnitzer T, Update of ACR guidelines for osteoarthritis: role of the coxibs. J. Pain Symptom Management 2002;23(4 Suppl):S24-30; discussion S31-4.
  37. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. Journal of the American Medical Association 2000;284(10):1247-1255.
  38. Simon LS, Grierson LM, Naseer Z, Bookman AAM, Zev Shainhouse J. Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis. Pain. Jun 2009;143(3):238-245.
  39. Solomon DH, Schneeweiss S, Glynn RJ, et al. Relationship between selective cyclooxygenase-2 inhibitors and acute myocardial infarction in older adults. Circulation 2004;109(17):2068-73.
  40. Strand V, Hochberg MC. The risk of cardiovascular thrombotic events with selective cyclooxygenase-2 inhibtors. Arthritis Rheum 2002;47:349-355.
  41. Topol EJ, Falk GW. A coxib a day won't keep the doctor away. Lancet 2004; 364: 639-640.
  42. Topol, EJ. Failing the public health-refecoxib, Merck, and the FDA. New England Journal of Medicine 2004; 351 (17): 1707-1709.
  43. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011; 342:c7086.
  44. Tugwell PS, Wells GA, Shainhouse JZ. Equivalence study of a topical diclofenac solution (Pennsaid) compared with oral diclofenac in symptomatic treatment of osteoarthritis of the knee: a randomized controlled trial. Journal of Rheumatology. Oct 2004;31(10):2002-2012.
  45. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk associated with use of nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and acetaminophen and the effects of rheumatoid arthritis and osteoarthritis. Calcified Tissue International. Aug 2006;79(2):84-94.
  46. White WB, Strand V, Roberts R, Whelton A. Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal anti-inflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis. American Journal of Therapeutics. Jul-Aug 2004;11(4):244-250.
  47. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen) reduce the pain of osteo arthritis? A metaanalysis of randomized controlled trials. Ann Rheum Disease 2004;63(8):901-7.

NSAIDs Cost Comparison

Note: If the price box contains a , that indicates the dose of that drug is likely available for a low monthly cost through discount programs offered by large chain stores. For example, Kroger, Sam's Club, Target, and Walmart offer a month's supply of selected generic drugs for $4 or a three-month supply for $10. Other chain stores, such as Costco, CVS, Kmart, and Walgreens, offer similar programs. Some programs have restrictions or membership fees, so check the details carefully for restrictions and to make sure your drug is covered.

Narrow your list

CR
Best Buy
Generic Name and Dose Brand Name(s)A Drug is a Generic Frequency of Dose (per Day)B Average Cost for Month's SupplyC
Celecoxib 100 mg capsule Celebrex No Two $219
Celecoxib 200 mg capsule Celebrex No One $181
Celecoxib 400 mg capsule Celebrex No One $282
Diclofenac 25 mg capsule Zipsor No Four $412
Diclofenac 50 mg tablet Generic Yes Three $46
Diclofenac 25 mg delayed-release tablet Generic Yes Three $110
Diclofenac 50 mg delayed-release tablet Generic Yes Three $109
Diclofenac 75 mg delayed-release tablet Generic Yes Two $100
Diclofenac 100 mg extended-release tablet Generic Yes Two $155
Diclofenac 1% topical gel Voltaren gel No Maximum dose of 32 grams per day $196
Diclofenac 1.3% topical patch Flector patch No Two patches $478 per area
Diclofenac 1.5% topical solution Pennsaid solution No 40 drops per knee,four times per day $220 per area
Diflunisal 500 mg tablet Generic Yes Two $96
Etodolac 200 mg tablet Generic Yes Three $82
Etodolac 300 mg tablet Generic Yes Two $92
Etodolac 400 mg capsule Generic Yes Two $82
Etodolac 500 mg capsule Generic Yes Two $81
Etodolac 400 mg extended-release tablet Generic Yes One $41
Etodolac 500 mg extended-release tablet Generic Yes One $44
Etodolac 600 mg extended-release tablet Generic Yes One $81
Fenoprofen 400 mg capsule Nalfon No Three $250
Fenoprofen 600 mg tablet Generic Yes Three $169
Flurbiprofen 50 mg tablet Generic Yes Three $65
Flurbiprofen 100 mg tablet Generic Yes Two $91
Ibuprofen 200 mg tablet AdvilD OTCE Six $18
Ibuprofen 200 mg tablet MotrinD OTCE Six $21
1 Ibuprofen 200 mg tablet GenericD OTCE Six $11
Ibuprofen 200 mg liquid-filled capsule Advil LiquigelD OTCE Six $31
Ibuprofen 200 mg liquid-filled capsule GenericD OTCE Six $24
1 Ibuprofen 400 mg tablet Generic Yes Four $15
1 Ibuprofen 600 mg tablet Generic Yes Four $19
1 Ibuprofen 800 mg tablet Generic Yes Three $18
Indomethacin 25 mg capsule Generic Yes Three $21
Indomethacin 50 mg capsule Generic Yes Two $35
Indomethacin 75 mg extended-release capsule Generic Yes One $88
Ketoprofen 50 mg capsule Generic Yes Three $119
Ketoprofen 75 mg capsule Generic Yes Three $128
Ketoprofen 200 mg extended-release capsule Generic Yes One $211
Meclofenamate 100 mg capsule Generic Yes Three $608
Mefenamic acid 250 mg capsule Generic Yes Four $1,588
Meloxicam 7.5 mg tablet Mobic No One $187
Meloxicam 7.5 mg tablet Generic Yes One $95
Meloxicam 15 mg tablet Mobic No One $288
Meloxicam 15 mg tablet Generic Yes One $147
Nabumetone 500 mg tablet Generic Yes Two $35
Nabumetone 750 mg tablet Generic Yes Two $42
Naproxen 220 mg tablet AleveD OTCE Three $13
1 Naproxen 220 mg tablet GenericD OTCE Three $10
1 Naproxen 250 mg tablet Generic Yes Two $45
1 Naproxen 275 mg tablet Generic Yes Two $52
1 Naproxen 375 mg tablet Generic Yes Two $61
1 Naproxen 500 mg tablet Generic Yes Two $70
1 Naproxen 375 mg delayed-release tablet Generic Yes One $59
1 Naproxen 500 mg delayed-release tablet Generic Yes Two $71
1 Naproxen 550 mg tablet Generic Yes Two $39
Naproxen 375 mg extended-release tablet Naprelan No One $310
Naproxen 500 mg extended-release tablet Naprelan No One $308
Naproxen 750 mg extended-release tablet Naprelan No One $307
Oxaprozin 600 mg tablet Generic Yes Two $104
Piroxicam 10 mg capsule Generic Yes One $71
Piroxicam 20 mg capsule Generic Yes One $126
Salsalate 500 mg tablet Generic Yes Six $135
Salsalate 750 mg tablet Generic Yes Four $118
Sulindac 150 mg tablet Generic Yes Two $52
Sulindac 200 mg tablet Generic Yes Two $65
  1. "Generic" means this is a generic drug, as noted in column three as well.
  2. As commonly recommended or prescribed. Many NSAIDs must be taken multiple times per day. Convenience of dosing might be a factor for some patients. If switching from one NSAID to another, talk with your doctor about equivalency of dosing between the different NSAIDs. They come in a wide variety of recommended doses.
  3. Monthly cost reflects national average retail prices for March 2013, rounded to the nearest dollar. Data provided by Symphony Health Solutions, which is not involved in our analysis or recommendations.
  4. This is a nonprescription medicine. Generic versions or store brand might be less expensive. Prices for these medications were obtained by Consumer Reports secret shoppers from five major chain pharmacies (CVS, Rite Aid, Target, Walgreens, and Walmart) and local supermarkets across the U.S. in January 2013. The prices from the various stores were averaged to yield perpill prices, which were then converted into a monthly price based on the maximum recommended number of pills per day.
  5. OTC stands for over-the-counter, meaning it is a nonprescription drug.