DUEXIS(®) (ibuprofen 800 mg, famotidine 26.6 mg): a new approach to gastroprotection for patients with chronic pain and inflammation who require treatment with a nonsteroidal anti-inflammatory drug

Abstract

Chronic pain conditions affect at least 116 million US adults and more than one-third of adults worldwide. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively for the treatment of chronic pain due to their efficacy as anti-inflammatory and analgesic agents. Gastrointestinal toxicity is the most well known adverse effect of NSAID therapy and it may manifest as dyspepsia, ulcers, or bleeding. Current guidelines for the management of patients who require NSAIDs for chronic pain and inflammation recognize the potential toxicity associated with these drugs and the need for gastroprotection. DUEXIS(®) (ibuprofen 800 mg, famotidine 26.6 mg) is a proprietary combination, immediate release tablet containing 800 mg of ibuprofen and 26.6 mg of famotidine. The efficacy of DUEXIS(®) taken three times daily has been demonstrated in two large-scale controlled clinical trials (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared with Ibuprofen: Efficacy and Safety Studies (REDUCE) and REDUCE-2) which showed that this new formulation significantly reduced the risk of endoscopic upper gastrointestinal ulcers compared with ibuprofen alone (REDUCE-1, p < 0.0001, REDUCE-2, p <0.05). DUEXIS(®) was also superior to ibuprofen in decreasing the risk for gastric ulcers (REDUCE-1, p < 0.001, REDUCE-2, p < 0.05) as well as duodenal ulcers (REDUCE-1, p < 0.05, REDUCE-2, p < 0.05). Safety results from these two studies indicated that treatment-emergent adverse events occurred in 55% of patients treated with DUEXIS(®)versus 58.7% for ibuprofen, and serious adverse events were recorded for 3.2% of patients treated with DUEXIS(®)versus 3.3% of those on ibuprofen. Adverse events leading to discontinuation occurred in 6.7% of patients treated with DUEXIS(®) and 7.6% for ibuprofen. The combination of ibuprofen and famotidine in a single tablet has the potential to improve adherence to gastroprotective therapy in patients who require NSAID treatment and the use of a histamine type 2 receptor antagonist rather than a proton-pump inhibitor may decrease the risk for clinically significant drug interactions and adverse events (e.g. interaction with clopidogrel, fracture, pneumonia, Clostridium difficile infection).

Keywords: chronic pain; famotidine; gastrointestinal; ibuprofen; proton-pump inhibitor; ulcer.

Figure 1.

Overall incidence rate of patients who developed at least one gastric or upper gastrointestinal ulcer in REDUCE-1 and REDUCE-2 (adapted from DUEXIS^® Prescribing Information [2011]). DUEXIS^®, 800 mg of ibuprofen, 26.6 mg of famotidine.

Figure 2.

Forest plots of the relative risk (95% confidence interval) of upper gastrointestinal ulcers for HZT-501 versus ibuprofen in subgroup analyses [Laine et al. 2012]. HZT-501, DUEXIS^® (ibuprofen 800 mg, famotidine 26.6 mg); IBU, ibuprofen.