The Gastrointestinal Dangers You Don’t Know About NSAIDs: Louis Clay Tharp talks about how common, over-the-counter ibuprofen, naproxen, acetaminophen and others could be harmful if taken incorrectly.

Louis Clay Tharp (shown right), a healthcare and fitness expert, recently completed a special report on NSAIDs for the popular arthritis website www.CreakyJoints.org. He focuses on the gastrointestinal risk of NSAIDs when they are misused.

When Debby Smith from Madison, Wisconsin, (real name and location withheld) has a bad day – a day when the ever-present pain she feels as an osteoarthritis sufferer is magnified – she immediately rummages through her medicine cabinet and pulls out a bottle of ibuprofen. She takes the non-steroidal anti-inflammatory drug (NSAID) as directed and waits for it to help pacify her pain. She promptly resumes her daily routines after washing the medication down with a glass of water. Instead of helping her pain subside as usual, on this particular day the pain amplifies and causes an intense, acute pain in her abdomen. Her daughter sees her pain and volunteers to drive her to see Debby’s primary care physician. Had she been familiar with Louis Clay Tharp and his work with www.CreakyJoints.org, or www.ConnectToProtect.com, a site sponsored by the American Gastroenterological Association and Horizon Pharma, she might have been alerted to the dangers of NSAIDs to her gastrointestinal system.

Debby is not alone – she makes up part of the approximately 60 million Americans who use NSAIDs regularly. Every day more than 30 million Americans take NSAIDs to relieve pain resulting from various conditions, yet few are aware that there are certain risks associated with their use, including potentially serious gastrointestinal (GI) side effects that include hospitalization, permanent chronic conditions and death. Over five billion dollars are spent in the United States alone on prescription NSAIDs, and another two billion dollars are spent on over-the-counter (OTC) NSAIDs every year. NSAIDs are commonly sold under the brand names of Tylenol, Advil, Aleve, Motrin and others. Generically, they are called aspirin, naproxen, ibuprofen, acetaminophen, and other less well-known names. NSAIDs, like ibuprofen, are available either by prescription or OTC at any drugstore nationwide. There is a good chance that there is a bottle of one of these NSAIDs in your medicine cabinet right now.

Once Debby arrives at her doctor’s office, she is asked a routine question, “What medications are you currently taking?” She thinks about what prescription medications she is currently taking to treat her chronic pain, but she makes a common, yet dangerous mistake. Debby forgets to mention that she has taken OTC ibuprofen, but her story is not an isolated one. Debby has developed an ulcer, and there are many other patients across America who make the same mistake.

Robin K. Dore, MD, Clinical Professor of Medicine at the Division of Rheumatology at UCLA explains, “Patients not telling their doctors they are taking OTC medication is a major problem. They believe that since they can obtain the NSAID over-the-counter, they do not need to disclose it to their doctors.”

When an injury is sustained or tissue is damaged, the body sends a chemical known as prostaglandins to the affected area causing the affected area to swell and inflame. This inflammation can cause further cause pain to the initial injury. Doctor Robin Dore explains that NSAIDs work by interfering with these prostaglandins. There are two different kinds of prostaglandins, one that protects the stomach against irritants and another that affects inflammation. Typically, it is this inflammation that is targeted by patients who use NSAIDs, but some patients might not realize that the NSAID could also be preventing the body from protecting itself from GI irritants.

Dr. Byron Cryer, a gastroenterologist, spokesman for the American Gastroenterological Association and an associate professor at the University of Texas Southwestern Medical Center warns, “Serious GI complications involve bleeding, ulcers and perforations. Other symptomatic GI manifestations include: dyspepsia, upset stomach, abdominal pain and indigestion. Serious complications, although less frequent than GI symptoms, are still extremely common considering the number of patients taking NSAIDs.” GI symptoms are frequent – 25-50 percent of patients will have some type of GI upset after taking NSAIDs. Also, having a GI symptom does not identify who is at risk for a serious GI complication. In fact, 80 percent of patients who have these GI complications have had no prior symptoms or warning signals of risk.

Dr. Cryer explains that 2-4 percent of patients who take NSAIDs will develop a serious GI complication. In the U.S., as a consequence of an adverse effect of an NSAID (including renal and cardiovascular complications), there are over 100,000 people per year who are hospitalized and greater than 15,000 each year who die. This affects the over 14 million people with arthritis who are taking NSAIDs, regularly, or for long periods of time, as directed by their physicians. Patients with Rheumatoid Arthritis (RA) and osteoarthritis (OA) need to take a higher dose of these NSAIDs for other conditions, and so their GI risk is higher. Up to 60 percent of arthritis patients who take NSAIDs will develop a GI side-effect, and 10 percent of these patients will stop taking the NSAID as a result.

Since doctors are aware of the higher GI risks involved with patients on NSAIDs, they tend to prescribe co-therapies to counter the risk, such as misoprostol, an H2 receptor antagonist, or proton pump inhibitor.

COX-2 inhibitors are prescription NSAIDs that do not affect the prostaglandins protecting the stomach. Celebrex and Vioxx (also known as celecoxib and rofecoxib respectively) were the two main COX-2 inhibitors on the market, until Vioxx was taken off the market in 2004 as a result of concerns over increases cardiovascular issues after long-term use. Vimovo™ is the only new COX-2 inhibitor which has been introduced since Vioxx was pulled from the market. Dr. Robin Dore explains that many people prefer to take only one pill, in contrast to taking a medication to counter the negative effects of another. Vimovo™ is one such prescription NSAID which has gastric ulcer reduction built into the pill, which combines naproxen and esomeprazole magnesium. Other combination medications are in development that combine ibuprofen and famotidine.

Access to care is also a problem for patients needing NSAIDs. Patients who suffer from chronic diseases such as OA or RA are already at elevated risk of developing GI complications. Patients who have had GI problems before are at least 13 percent more likely to have another GI complication when taking NSAIDs. Even if there hasn’t been a complication, just having had an ulcer puts a patient in the “high risk” category for life. Knowing this, a physician may prescribe a high-risk patient a COX-2 inhibitor only to have the insurance company make the patient start what is known as step therapy. Step therapy or ‘fail first’ requires a patient to try other less-expensive medications and “failing” on those medications before having access to the original medication prescribed by the doctor. Advocacy groups like Fail First Hurts (http://www.FailFirstHurts.org) fight for patients’ rights in regard to insurance companies overriding doctor’s orders. (Failfirsthurts.org is part of the Global Healthy Living Foundation, the same non-profit organization that CreakyJoints.org belongs to.)

Doctors today are taking greater steps to educate their patients about the GI dangers of taking NSAIDs. Whenever Dr. Dore prescribes a patient a COX-2 inhibitor, she hands them a patient education guide. She states that even though there are warnings on the boxes of COX-2 inhibitors about cardiovascular and other dangers associated with taking or mixing NSAIDs, sometimes patients do not read them. She makes sure to go over the patient education guide with them and always keeps a laminated version of it in her office (shown left). Dr. Cryer is also very involved in the reduction and mitigation of the risks of taking NSAIDs. He works closely with Connect to Protect, a program done in collaboration with Horizon Pharma, which educates physicians and patients to better understand and manage the risks associated with NSAIDs. Part of the Connect to Protect campaign is to address the issue of helping patients better understand the risk and to help them manage the risk. The program promotes public awareness and starts the dialogue between physicians and patients.