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Update of Safety Review
FDA has completed its review of recently submitted safety data for the drugs Prilosec (omeprazole) and Nexium (esomeprazole) that raised concerns about a potential increased risk of heart problems for patients treated with these drugs. On August 9, 2007, FDA announced that it had received and was reviewing new safety data about Prilosec (omeprazole) and Nexium (esomeprazole) and communicated its preliminary conclusion that the available data did not suggest an increased risk of heart problems for patients treated with these drugs. At the time, FDA did not believe that healthcare providers or patients should change either their prescribing practices or their use of these products. FDA committed to communicate its conclusions and any resulting recommendations to the public at the completion of its review. FDA is issuing this follow-up communication based on a comprehensive review of the data from two studies that were submitted to FDA. FDA continues to believe that long-term use of omeprazole or esomeprazole is not likely to be associated with an increased risk of heart problems and recommends that healthcare providers continue to prescribe and patients continue to use these products in the manner described in the labeling for the two products. This follow-up communication is in keeping with FDA’s commitment to inform the public about its ongoing safety reviews of drugs. What does FDA know now about these data? Omeprazole: A 14-year study was conducted in Europe in patients with severe gastroesophageal reflux disease (GERD). In this study, 154 patients were randomly assigned to a group that would be given the drug omeprazole and 144 patients to a group that would have anti-reflux surgery. Over the course of this study, over half the patients dropped out prior to its completion. At FDA’s request, the sponsor of the study asked the investigators for follow-up information on all the patients in the study, including those that dropped out. FDA’s subsequent analysis found that 8 patients that received omeprazole died of heart-related causes (due to heart failure or sudden death) and 9 had experienced non-fatal heart attacks. In contrast, 2 patients assigned to have surgery for their severe GERD died of heart-related causes and 2 had non-fatal heart attacks. This difference in heart problems between the two groups of patients was seen within the first year of the study, and continued over time. However, there were important differences in the health of the patients between the two treatment groups. At the start of the study (baseline), 6 of the patients that were assigned to receive treatment with omeprazole had a history of heart attack; three of these patients ultimately died of heart-related causes. In contrast, none of the patients assigned to have surgery for their severe GERD had a history of heart attack, including the 2 surgery patients who died of heart-related causes. Another difference was noted in the median age of the patients in the two treatment groups at baseline. The median age of patients assigned to omeprazole was four years greater compared to the age of patients in the group assigned to surgery. By the end of the study, there was a greater percentage of patients who were treated with omeprazole that were 60 years of age or older (88%) compared to patients who had surgery (77%). These findings suggest that overall, patients in the surgery group tended to be younger and healthier. These differences between the patients in the two treatment groups could have biased and significantly influenced the safety data from this study. In addition, several of the patients who were assigned to the group that was to have surgery withdrew from the study without ever undergoing the surgical procedure and several patients received both surgery and drug treatment. These elements of the study make it difficult to assess the association between treatment with omeprazole and the development or worsening of heart problems. Esomeprazole: A second study, that is still ongoing, comparing esomeprazole to surgery had five years of follow-up information on patients. This study, also conducted in Europe, randomly assigned 266 patients with severe GERD to be treated with esomeprazole and 288 patients to have laparoscopic surgery. Forty of the patients who were to receive surgery withdrew from the study without undergoing the procedure. While the initial data from this study suggested a difference in the number of reported heart problems between the two groups of patients, FDA’s analysis found that the number of patients who experienced heart problems was similar in both treatment groups. Overall, non-fatal heart attacks were seen in 5 patients treated with esomeprazole compared to 4 patients who underwent laparoscopic surgery. There were no heart-related deaths in this study. While both of these studies collected safety data, the study protocols did not specify how heart problems, such as heart attacks, were defined or verified. As a result, evaluating the information that has been gathered about the safety of either drug in these studies is difficult. FDA’s assessment of the information from these two studies is further supported by an additional analysis of 14 comparative studies of omeprazole, four of which were placebo-controlled. 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. Based on everything we know now, FDA’s conclusion is that the reported difference in the frequency of heart attacks and other heart related problems seen in the earlier analyses of the two small long-term studies does not indicate the presence of a true effect. Prilosec and Nexium are members of a class of drugs called proton pump inhibitors (PPIs) and work by reducing the amount of acid produced by the stomach. Both drugs are used for the treatment of gastroesophageal reflux disease (GERD) including a condition where the lining of the esophagus wears away (erosions), and for maintenance of healing erosions of the esophagus. They are also used for the treatment of ulcers. Prilosec (omeprazole) and Nexium (esomeprazole) are available by prescription. Prilosec is also sold over-the-counter for frequent heartburn. Report serious adverse events to
Date created: December 10, 2007
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