One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Abstract

Objective:To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study. Research design and methods:Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs). Results:In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p ¼ 0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112-167 of treatment and remained low with continued treatment. Conclusions:One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/ famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons

“…These results are similar to previous studies that have documented the gastroprotective effects of high-dose H 2 -receptor antagonist therapy in this setting [24,[27][28][29][30]32]. For older patients requiring long-term ibuprofen therapy, early intervention with gastroprotective agents may offer the greatest benefit with respect to reducing the risk for ulcer development [18].…”

“…Generally, prevention studies can be affected by compliance differences in the study groups. Previous reports on these studies, however, indicate that adherence and exposure to the study treatments was good (~80%) [29], but compliance was not assessed for other therapies allowed in the study (LDA/OAC therapies). Moreover, results may not be generalizable to the entire population due to the exclusion/enrolment criteria of the study, such as excluding those with prior diseases that might increase the risk for upper GI ulcers.…”

“…The study design and primary efficacy and safety results of the Phase III, multicenter, REDUCE-1 (NCT00450658) and REDUCE-2 (NCT00450216) clinical studies conducted in the US from March 2008 to September 2008 and March 2007 to August 2008, respectively, have been reported previously [27][28][29]. The REDUCE trials consisted of a 24-week, randomized, double-blind, parallel-group study designed to evaluate the efficacy, as measured by endoscopically diagnosed upper GI ulcers, and safety of the combination ibuprofen/famotidine tablet versus ibuprofen alone.…”

“…The REDUCE trials consisted of a 24-week, randomized, double-blind, parallel-group study designed to evaluate the efficacy, as measured by endoscopically diagnosed upper GI ulcers, and safety of the combination ibuprofen/famotidine tablet versus ibuprofen alone. Patients who completed the 24-week treatment period without developing an endoscopically diagnosed upper GI ulcer were eligible to enroll in an extension study [29] or continue to be monitored for safety for an additional 4 weeks, for a total of 28 weeks of safety monitoring. The identical-appearing tablets of ibuprofen 800 mg/famotidine 26.6 mg tablet or ibuprofen 800 mg were self-administered orally, on a double-blind basis, TID, for up to 24 consecutive weeks.…”

“…TEAEs of special interest for this analysis included events within the GI system, vascular system, investigations, blood and lymphatic systems, cardiac system, and metabolism and nutrition disorders systems organ classes. Detailed safety analyses have been reported previously [29].…”