FDA Reviewing Proton-Pump-Inhibitor Safety; for Now, No Call to Change Labeling

Steve Stiles

August 10, 2007 (Rockville, MD) - The FDA is reviewing the safety of omeprazole (Prilosec, AstraZeneca) and esomeprazole (Nexium, AstraZeneca), proton-pump inhibitors used for the treatment of gastroesophageal reflux disease (GERD) and ulcers, based on analyses from two clinical trials suggesting the drugs may increase cardiovascular risk, the agency announced yesterday [1,2].
But because of questions about the clinical-trial data and their inconsistency with a large amount of other data showing no such increased risks, the "FDA does not believe that healthcare providers or patients should change either their prescribing practices or their use of these products at this time," according to an "Early Communication" posted on the agency's website.
"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," it stated. But the agency said it continues to review the issue and left open the possibility of future regulatory action.
The cautions emerged from a 14-year randomized study that compared omeprazole with surgery in patients with severe GERD and from a similarly designed five-year study of esomeprazole, the latter of which is still ongoing, according to the FDA statement.
The first study showed an early and persisting omeprazole-related increase in "heart attacks, heart failure, and heart-related sudden death," and the second study hinted at an increase in "cardiovascular events" from esomeprazole.
However, "while both of these studies collected safety data, the study protocols did not specify how heart problems, such as heart attacks, were to be defined or documented." The FDA noted that patient withdrawals in the surgical arms and age differences between the randomization groups further complicated the studies' interpretation.
Also, data from 14 other studies of omeprazole, including four that were placebo-controlled, suggested that the drug, if anything, might lower cardiovascular risk. "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," according to the agency.
FDA. 2007 safety alerts for drugs, biologics, medical devices, and dietary supplements: Omeprazole, omeprazole + sodium bicarbonate. August 9, 2007. Available at: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Omeprazole.
FDA. Early communication about an ongoing safety review: Omeprazole (Prilosec), esomeprazole (Nexium). August 9, 2007. Available at: http://www.fda.gov/cder/drug/early_comm/omeprazole_esomeprazole.htm.