Are PPIs Especially Dangerous for Women?

Washington, DCThe long-term use of drugs classed as proton pump inhibitors or PPIs , and marketed variously as Prevacid, Prilosec or Nexium, is dangerous for many reasons. Kidney damage, the focus of recently consolidated multidistrict litigation, is not the only problem. Long-term PPI use has also been associated with bone fractures and dementia in women, as well as the risk of birth defects. The issue for the lawsuits to come will be whether drug makers gave patients adequate warning of the dangers associated with their products and thus the opportunity to make informed choices.

The evidence for an elevated risk of bone fractures, especially of the hip, spine and wrist, is the most compelling. PPI use has been associated with a 26 percent higher incidence of hip fracture; 58 percent higher risk of spine fracture, and 33 percent risk of fracture at any site. It was not entirely clear why PPI use increased this risk, but possibilities include an effect on calcium absorption, bone metabolism or an increased risk of falling. Women between the ages of 60 and 69 were more than three times more likely than men to suffer from broken bones.

The connection of PPIs with dementia in women is somewhat less clear. In research conducted by the German Center for Neurodegenerative Disease, the risk of dementia was found to be 44 percent higher among the 2,950 patients who received regular proton pump inhibitors. Others studies do not support a connection. Some argue that, since both PPI usage and dementia are associated with age and more women live to be elderly, the data may not demonstrate causation as much as simple statistical correlation.

The data is similarly murky about risks associated with pregnancy. Some studies suggest that taking a PPI during the first trimester of pregnancy may increase the risk of cardiac birth defects. Others reach the opposite conclusion, but raise the possibility that the use of lansoprazole, marketed as Prevacid, in the 4 weeks prior to conception might be associated with a higher risk of fetal injury.

As the medical research continues to take shape about the risk of bone fractures, dementia and birth defects associated with the PPIs, the legal landscape will focus on the adequacy of the warnings. To date, the FDA warns only of the increased risk of bone fractures for patients who take high dosages for prolonged periods of time. This may not prove to be adequate for women who take over-the-counter PPIs without medical consultation and it does not cover other risks that may have even more impact.