Ibuprofen-Famotidine Combination Reduces Ulcer Risk

Laird Harrison

September 14, 2012

September 14, 2012 (Las Vegas, Nevada) — A pill that combines ibuprofen and famotidine lowers the risk for ulcers caused by ibuprofen alone, a new study shows.

Compared with patients taking only ibuprofen, half as many patients taking the combination drug had endoscopically observed ulcers after 24 weeks, researchers reported here at PAINWeek, a conference of pain specialists.

Horizon Pharma launched the new combination drug under the brand name Duexis in the United States in January 2011 and is marketing it as a more convenient alternative to taking a nonsteroidal anti-inflammatory drug (NSAID) along with a separate gastroprotective agent.

Pill Burden

More than 100,000 patients are hospitalized and 17,000 die every year in the United States as a result of gastrointestinal bleeding associated with NSAIDs, said Merrell Magelli, PharmD, vice president of medical affairs at Horizon Pharma, which funded the studies presented here.

As a result, many professional guidelines call for gastroprotection in patients taking NSAIDs who are at high risk for gastrointestinal illness. Dr. Magelli cited a 2006 consensus statement on NSAIDs published in Clinical Gastroenterology and Hepatology.

Yet only 25% of physicians prescribe gastroprotective agents in patients at high risk for ulcers from their NSAIDs, and only 25% of patients continue taking the gastroprotective medication after their third refill, said Dr. Magelli.

One reason may be that patients don't understand the need for the protection and want to cut back on the number of pills they take, she said. "A lot of patients will not adhere because they have to take multiple pills," she told Medscape Medical News.

Duexis, which combines 800 mg ibuprofen with 26.6 mg famotidine, reduces the number of pills the patient needs to take from 16 to 3 per day, she said. "We're trying to decrease the pill burden."

She argued that a combination agent could also be cheaper for patients with medical benefits because they could get 1 prescription and owe only a single copayment of $20 per month. The 2 drugs separately would cost $65 a month, and patients who purchase them with 2 prescriptions would have 2 copayments, she said.

At the meeting, Dr. Magelli reported on the combined results of 2 clinical trials, REDUCE-1 and REDUCE-2 (Registration Endoscopic Studies to Determine Ulcer Formation of HZT-501 Compared with Ibuprofen: Efficacy and Safety Studies), in which a total of 930 patients took the combination agent and 452 took ibuprofen.

The mean age of the patients was 56 years in both groups. About 6% of patients had prior ulcers, and 16% of the combination therapy group was taking low-dose aspirin, compared with 12.8% of the ibuprofen group. Patients were excluded if they had used NSAIDs for less than 31 days before randomization.

Eleven percent of patients taking the combination agent for 24 weeks had endoscopically observed ulcers compared with 21.9% of those taking ibuprofen alone, a difference that was statistically significant (P < .0001).

The ratios stayed about the same whether the patients were taking the medications for arthritis (osteoarthritis and rheumatoid arthritis were combined in the study) or other chronic pain.

About 3% of each group had serious adverse events. Treatment-emergent adverse events were similar as well: 26.0% of patients taking the combination sustained a gastrointestinal disorder compared with 28.5% of those taking ibuprofen alone, a difference that was not statistically significant (P = .326).

Dyspepsia occurred in 4.7% of the combined therapy group and 8.0% of the ibuprofen group, a statistically significant difference (P = .009).

No Surprise

Nothing about these findings comes as a surprise, Bill McCarberg, MD, an adjunct assistant clinical professor at the University of California, San Diego, told Medscape Medical News.

"It's not particularly news or noteworthy," he said. If ibuprofen and famotidine work well taken separately, one would expect them to work well in a combined drug, he said.

But he agreed that more needs to be done to address the problem of gastrointestinal bleeding in patients at risk for ulcers who are taking NSAIDs. Too many patients are taking the NSAIDs without gastroprotection.

"The interesting part of this is that despite guidelines being out there, there's a lack of uptake by primary care physicians," he said.

The study was funded by Horizon Pharma. Dr. Magelli is an employee of Horizon Pharma. Dr. McCarberg is an advisor to Iroko Pharmaceuticals.

PAINWeek. Abstract 52.

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