Common painkillers combined with other drugs may cause high risk of GI bleeding

Nonsteroidal anti-inflammatory drugs (NSAIDs) — such as ibuprofen and aspirin — increase one’s risk of upper gastrointestinal bleeding.

When taken in combination with other drugs, this risk is significantly higher, according to new research appearing in the October issue of Gastroenterology, the official journal of the American Gastroenterological Association.

“These findings may help clinicians tailor therapy to minimize upper gastrointestinal bleeding, and are especially valuable in elderly patients who are likely to use multiple drugs at the same time,” said Gwen Masclee, MD, lead study author from Erasmus Medical Center in Rotterdam, the Netherlands. “Defining risk factors is a critical step towards improving care and decreasing NSAID-associated complications and deaths.”

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Researchers performed a self-controlled case series analysis of data from 114,835 patients with upper GI bleeding. Drug exposure was determined based on prescriptions of NSAIDs, cyclooxygenase 2 (COX-2) inhibitors — such as Bextra®, Celebrex® and Vioxx® — or low-dose aspirin, alone and in combination with other drugs that affect risk for internal bleeding. This study identified that:

    • Single therapy with non-selective NSAIDs (the commonly found NSAIDs, which contain both COX-1 and COX-2 enzymes) is more likely to cause upper GI bleeding than single therapy with COX-2 inhibitors or low-dose aspirin.
    • Combination therapy significantly increases the risk for internal bleeding, with simultaneous use of non-selective NSAIDs and steroid therapies increasing the risk to the greatest extent.
    • The risk of upper GI bleeding is always higher for drug combinations with non-selective NSAIDs than that for low-dose aspirin or COX-2 inhibitors.
    • Simultaneous use of non-selective NSAIDs or low-dose aspirin, but not COX-2 inhibitors, with corticosteroids, aldosterone antagonists (diuretic drugs) or anticoagulants (which prevent the blood from clotting) produces significant excess risk of upper GI bleeding.

      In patients with increased risk, the researchers recommend first reassessing the need for NSAID therapy (or for the concomitant medication). If feasible, discontinuation of NSAIDs is the preferred strategy in high-risk patients. When NSAIDs are necessary, they should be used at the lowest effective dose for the shortest possible duration.

      “Importantly, we found that risk varies dramatically from patient to patient based on underlying characteristics, necessitating careful review to assess risk in each individual using NSAIDs,” added Dr. Masclee.

      NSAIDs act as pain relievers and fever reducers. Prescription NSAIDs can also work to reduce inflammation. There are currently more than 500 over-the-counter and prescription NSAIDs, including ibuprofen (Advil®, Motrin IB®), naproxen sodium (Aleve®) and aspirin (Bayer®).

      Patients should always disclose all of their medications to their physician and work together to determine a safe plan for medication use. The American Gastroenterological Association has created the Gut Check: Know Your Medicine educational campaign to motivate and empower individuals to engage in the safe use of medication and prevent unnecessary deaths from GI bleeding. To learn more about this campaign, explore

      1. Masclee, et al. Risk of Upper Gastrointestinal Bleeding From Different Drug Combinations. Gastroenterology 2014: 147(4): 784-792.e9

      About the AGA Institute

      The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to include 17,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization.

      About Gastroenterology

      Gastroenterology, the official journal of the AGA Institute, is the most prominent scientific journal in the specialty and is in the top 1 percent of indexed medical journals internationally. The journal publishes clinical and basic science studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition. The journal is abstracted and indexed in Biological Abstracts, Current Awareness in Biological Sciences, Chemical Abstracts, Current Contents, Excerpta Medica, Index Medicus, Nutrition Abstracts and Science Citation Index. For more information, visi t Like AGA and Gastroenterology on Facebook. Join AGA on LinkedIn. Follow us on Twitter @AmerGastroAssn. Check out our videos on YouTube.

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