LAS VEGAS, NV—A single tablet combining ibuprofen plus a high-dose H2-receptor antagonist (H2RA) such as famotidine may decrease ibuprofen-induced ulcer disease and improve patient compliance, according to a study presented at PAINWeek 2012.

When nonsteroidal anti-inflammatory drugs (NSAIDs) are used for osteoarthritis (OA), rheumatoid arthritis (RA), and chronic pain, gastrointestinal (GI) toxicity is a major concern. Because of this, co-therapy that has other gastroprotective agents is prescribed, such as prostaglandin analogues, proton pump inhibitors, and H2RAs, and NSAIDs with a lower GI risk, such as coxibs.

Merrell Magelli, PharmD, from Horizon Pharma, Northbrook, IL, and colleagues presented the results of two multicenter, randomized, double-blind, parallel Phase 3 studies (REDUCE-1 and REDUCE-2) of the single-tablet combination. They evaluated whether a single-tablet combination of 800 mg ibuprofen and 26.6 mg famotidine administered three times a day would significantly decrease upper-GI ulcerations compared with  ibuprofen alone in patients who require NSAIDs for OA, RA, or chronic pain. During the studies, patients were randomized in approximately a 2:1 ratio to treatment with either famotidine/ibuprofen or ibuprofen alone.

Patients (n=930 in REDUCE-1 and n=452 in REDUCE-2; aged 40–80 years) were stratified based on two risk factors for developing upper GI ulcers: the use of concomitant low-dose aspirin (≤325 mg daily) and/or other oral anticoagulant therapy, and a history of upper GI ulcer. Endoscopies were performed at 8, 16, and 24 weeks, and the primary endpoint was gastric ulcers identified on endoscopy during the 24-week study. A GI ulcer was endoscopically diagnosed if it had unequivocal depth and an ulcer diameter ≥3 mm.

Dr. Magelli and colleagues stated that these results demonstrate that famotidine/ibuprofen reduced NSAID-associated upper-GI ulcers overall, along with reducing upper GI ulcers in the subset of patients taking NSAIDs for OA, RA, and chronic pain. The incidence of treatment-associated adverse effects was balanced across both treatment groups, except for dyspepsia, which was statistically lower for the famotidine/ibuprofen group (4.7%) compared with the ibuprofen group (8.0%) (P=0.009). Dr. Magelli noted that the serious adverse effects were reported in 3.2% and 3.3% of patients in the famotidine/ibuprofen and ibuprofen groups, respectively.