Single-Tablet Ibuprofen-Famotidine Reduces NSAID-Associated Upper GI Ulcers

PALM SPRINGS, CA — A single-tablet combination of ibuprofen 800mg and famotidine 26.6mg (HZT-501) administered three times daily was found to reduce nonsteroidal antiinflammatory drug (NSAID)-associated upper gastrointestinal (GI) ulcers in patients overall, as well as in each subset for those taking NSAIDs for osteoarthritis, rheumatoid arthritis, and chronic pain, a study presented during the 2012 American Academy of Pain Medicine Annual Meeting has found.

Michael H. Schiff, MD, University of Colorado School of Medicine, Greenwood Village, CO, and colleagues conducted REDUCE-1 and REDUCE-2, two 24-week double-blind trials of HZT-501 in patients expected to require daily NSAID therapy ≥6 months. Patients were 40–80 years of age (approximately 68% female) with no history of ulcer complications, a negative H. pylori test, and a baseline endoscopy showing no ulcers and <5 erosions in the upper GI tract. In the primary analysis population, 761 patients had been taking ibuprofen for osteoarthritis (OA) and rheumatoid arthritis (RA) and 521 for chronic pain.

REDUCE-1 enrolled 906 patients and REDUCE-2, 627 patients who were randomized 2:1 to HZT-501 (n=1,022) or ibuprofen (n=511). Concomitant low-dose aspirin use (LDA; ≤325mg daily) and oral anticoagulants were permitted. Evaluations (i.e., endoscopies, physical exams, assessment of adverse events) were done at Weeks 8, 16, and 24. The primary efficacy endpoint was the presence of GI ulcers ≥3mm diameter of unequivocal depth.

At Week 24, the cumulative proportion of patients who experienced an upper GI ulcer was 11% in the HZT-501 group and 21.9% in the ibuprofen group (P<0.0001) for all patients. Comparable proportions were seen when the groups were stratified by diagnosis: 11.9% vs. 20.2% (P=0.002) for OA+RA, respectively, and 9.9% vs. 23.9% (P<0.0001) for chronic pain.

Over 24 weeks of treatment, 31% of patients taking HZT-501 discontinued the drug compared with 42.9% of those taking ibuprofen. While the incidence of treatment-emergent GI disorders was not significant overall, the incidence of dyspepsia was significantly lower in HZT-501 patients (4.7% vs. 8%; P=0.009).

The investigators concluded that HZT-501 combination therapy reduces NSAID-associated upper GI ulcers and may improve adherence and compliance in patients taking NSAIDs who require gastroprotection.