Ibuprofen: Risk, Comorbidities, and Pain Management

By Jennifer Anderson

Despite warnings, ibuprofen users believe it to be harmless, but its use should be carefully monitored.

For more than a decade Yvonne D'Arcy, MS, CRNP, CNS, pain and palliative care outcomes manager at Suburban Hospital in Maryland, has lectured and educated nurse practitioners and other medical professionals about the risks associated with ibuprofen, a common over-the-counter pain medication. 

Commonly marketed as Advil or Motrin, ibuprofen is a type of NSAID. An alternative to NSAIDs is acetaminophen, usually sold as Tylenol.

NSAIDs do alleviate pain and inflammation. But they also can increase the risk of heart attack and stroke and cause other potential side effects. D'Arcy says concerns about NSAIDs spiked in the early 2000s when the National Institutes of Health terminated a study because of fatalities among participants given higher-than-average doses of the medications.

"It perked up everyone's thinking about these drugs," D'Arcy says.

Despite the warnings, people continue to use ibuprofen and believe it to be harmless. After participating in one of D'Arcy's seminars on the dangers of NSAIDs, nurses invariably ask whether they should take Advil for soreness or headaches after a difficult shift.

By comparison, patients believe Tylenol is "like taking water," D'Arcy says. "I think acetaminophen has been around for so long, people believe [the newer NSAIDs] are more effective." NSAIDs also have been well marketed, she says, and they have an anti-inflammatory component that acetaminophen does not.

For general pain, both medications tend to work well, and when D'Arcy recommends acetaminophen, she encourages patients to take the medication for several days to give it a chance to work. If a patient decides to take a NSAID instead, "it should be a very thoughtful choice," she says.

NSAIDs, including ibuprofen and naproxen, which is sold as Aleve, are available over the counter and by prescription.  

FDA Safety Review
In a July 2015 release posted on its website, the FDA alerted patients about a "comprehensive review of new safety information" on NSAIDs it had recently completed. As a result, the FDA states that it will request updates to the warning labels on all over-the-counter NSAIDs. 

Among other concerns, the FDA warns NSAIDs can increase the risk of heart attack and stroke.  While patients who have heart disease or risk factors for heart disease have an increased chance of a heart attack or stroke after taking NSAIDs, the risk also is elevated for those patients who do not have heart disease or its risk factors.

"A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied," the FDA states.

The FDA also reports that patients treated with NSAIDs after a first heart attack were more likely to die within the first year after the heart attack compared with patients who were not treated with NSAIDs after a first heart attack.

NSAIDs also increase the risk of heart failure, the FDA states. The American Heart Association (AHA) advises patients with cardiovascular disease to talk with their physicians before taking over-the-counter NSAIDs.

According to the American College of Rheumatology, NSAIDs can help particularly with arthritis pain by blocking enzymes in the body that produce chemicals linked to pain and inflammation. But as with the FDA and AHA, the American College of Rheumatology also warns of side effects with NSAIDs. These can include the following:

• heart failure and kidney failure;

• bleeding and ulcers in the stomach and intestine;

• low red blood cells (anemia);

• life-threatening skin and allergic reactions; and

• swelling around the hands, feet, and ankles.

Stomach pain, constipation, diarrhea, heartburn, nausea, and dizziness also have been associated with NSAIDs, according to the various associations. The American College of Rheumatology suggests patients with heart disease might be better off with acetaminophen. 

Likewise the AHA also encourages a stepped-up approach to pain management and, as D'Arcy explains, this includes starting with acetaminophen. If an NSAID is prescribed, the AHA states, "It is important to take it exactly as prescribed, at the lowest dose possible for your treatment, and for the shortest time needed."

Evolving Pain Management
D'Arcy says she sympathizes with patients who are suffering from pain. Exacerbating the problem is the fact that there are not enough pain specialists to help everyone. The pain management field is dwindling, she says, in part because anesthesiologists have moved away from medications, focusing instead on spinal injections and other interventions. 

Thus the role of pain management has fallen largely on primary care physicians and nurse practitioners, who do their best but don't always fully understand the risks.

At the same time, the entire field of pain management is growing more complex as more and more Americans are developing comorbid conditions—notably cardiovascular disease. And as D'Arcy points out, cardiovascular disease increasingly affects adults of all ages, including 40% of men and 35% of women in their 40s and 50s.

When recommending over-the-counter pain medications, physicians and nurse practitioners need to be aware of whether a patient has kidney disease, liver disease, high blood pressure, or asthma, is aged 60 or older, or takes steroids, diuretics, or anticoagulants.

Even short-term NSAID use can increase a patient's risk of stroke or other side effects, D'Arcy says, defining short-term as a week or less. "The impact on the patient's body can happen with just a few doses," she says. 

Patients with comorbid conditions are not the only ones who need to be aware of the risks associated with NSAIDs, D'Arcy says. Healthy older people also increase their risk of cardiovascular disease, high blood pressure, stroke, gastrointestinal bleeding, and impaired kidney function in connection with NSAID use.

For older people who already have cardiovascular disease, the increased risk of heart attack and stroke associated with NSAIDs is "quite significant," she says. "You have to be very careful using them." NSAIDs also will increase the risk of heart attack in patients who have had cardiac surgery, she says.

While acetaminophen is not without risk and can cause serious liver damage if used in excessive doses, D'Arcy says she believes the drug is underutilized as a pain medication. As a pain and fever reducer, acetaminophen works just as quickly and well as ibuprofen but without all of the potential side effects, she says.

Patients need to understand that chronic pain from arthritis and other diseases and conditions can be difficult to manage and completely alleviate, regardless of the medication. 

Topical NSAIDs
For patients with inflammation from osteoarthritis or those who do not benefit from acetaminophen, D'Arcy rarely turns to oral NSAIDs, but she will prescribe topical NSAIDs.

Topical medications are applied to the skin directly on the joint and are potentially less harmful because they remain localized and do not impact the entire system in the same way tablets and capsules do.

Topical pain medications are relatively new and have been refined within the past five years, she says. They come in a variety of applications, including patches for strains or sprains, as well as liquids, gels, and creams. 

Among other studies, a June review that appeared in Cochrane Database Systematic Reviews by researchers from Oxford found that topical NSAIDs worked well on pain associated with sprains, strains, and injuries from overuse.

The authors report that gel formulations of diclofenac, ibuprofen, and ketoprofen provided the best results, according to an abstract of the study, "Topical NSAIDs for Acute Musculoskeletal Pain in Adults."

The authors also report that adverse events were minimal and that their review included randomized double-blind trials dating to February 2015 of adult participants with acute pain resulting from strains, sprains, or sports-related injuries. Treatment had to occur at least daily.

A potential downside of topical medications is the relatively high cost of copayments, often as much as $40, which is significant for people on fixed incomes, D'Arcy says. Compounds can be less expensive, she says, and physical therapy is another option for joint pain.

Patients and medical providers considering NSAIDs need to understand the potential risks, D'Arcy says. Nurse practitioners, primary care providers, orthopedic surgeons, and cardiologists, especially, need to be educated about the risks and benefits of NSAIDs and their alternatives.

"It is important everyone is educated so that providers and patients can make informed choices," she says.

— Jennifer Anderson is a freelance health and science writer based in Falls Church, Virginia.