FDA To Complete Prilosec, Nexium Safety Review In November, CDER Says

FDA is continuing to investigate safety data on AstraZeneca's proton pump inhibitors Prilosec and Nexium (omeprazole and esomeprazole, respecttively), but announced a preliminary conclusion the drugs do not present an increased cardiovascular risk.

The agency plans to complete the analysis and review of the data by early November, at which point FDA will release more information about the studies, officials said during an Aug. 9 media call.

FDA's preliminary conclusion based on available data is the PPI products do not present an increased risk of heart problems and the agency "does not believe healthcare providers or patients should change either their prescribing practices or their use of these products at this time."

This conclusion also applies to the 20 mg dose used in Procter & Gamble's Prilosec OTC , Dr. Paul Seligman, associate director, Office of Safety Policy and Communication at FDA's Center for Drug Evaluation and Research, said during the call.

The current data "coupled with the fact that Prilosec OTC has been on the market since September 2003 and more than 15 million frequent heartburn sufferers have taken it, [shows] that there's no increased cardiac safety risk," Procter & Gamble told "The Tan Sheet."

CDER released a same-day early communication about the ongoing safety review of the two PPIs after receiving data from AstraZeneca over the last several months.

FDA obtained data from AstraZeneca on May 29 outlining the results of two small long-term clinical studies in patients with severe gastroesophageal reflux disease.

The trials "raised concerns" that long-term use of the products may increase the risk of heart attacks, heart failure and heart-related sudden death compared to patients who received surgery to control their GERD.

A 14-year study of omeprazole treatment versus surgery for serious GERD found patients in the omeprazole group experienced more heart events than the surgery group.

Another ongoing study comparing esomeprazole and surgical procedures has data from five years of follow-up.

The initial data from the second study showed patients in the esomeprazole group had a higher risk of heart events compared to the surgery group, but an updated analysis shows the number of cardiovascular events is similar in both treatment groups, FDA says.

The agency points out while both studies collected data on safety, study protocols did not specify how cardiovascular events were to be defined or documented, which increases the difficulty of evaluating the safety data.

Other factors that may have skewed the study results include GERD patients randomized to the surgery groups withdrawing from the studies before undergoing the procedure, and patients who followed through with the procedure tending to be younger and less likely to have history of heart problems or cardiovascular risk factors, FDA says.

"These differences between the two groups of patients could have biased and significantly influenced the safety data from these studies," the agency says.

Since the initial submission of data, AstraZeneca has provided additional information to the agency on patient follow-up and pooled analyses of other trials, including placebo-controlled trials of up to two years in duration, according to FDA.

The data from four two-year, placebo-controlled trials showed participants treated with omeprazole actually had "fewer heart attacks or other heart problems" compared to patients receiving placebo, FDA says.

"Although these studies were not specifically conducted to assess the risk of heart problems, and patient follow-up is incomplete, they do not suggest an increased risk of heart problems with the use of omeprazole," the agency states, adding, other available data will continue to be assessed.

"Based on everything we know now, FDA's preliminary conclusion is that the observed difference in risk of heart attacks and other heart related problems seen in early analyses of the two small long-term studies is not a true effect," FDA says.

- Jessica Lake ([email protected])