FDA Issues Warning About Proton Pump Inhibitors

Studies Show Link Between PPI Use, Increased Fracture Risk, Other Adverse Effects

June 01, 2010 04:45 pm News Staff

The FDA is warning physicians and consumers(www.fda.gov) about a possible increased risk for fractures of the hip, wrist and spine with high doses or long-term use of proton pump inhibitors, or PPIs.

The labeling on these products will be changed to describe these risks for both the prescription and OTC product versions, the agency said.

Prescription PPIs reduce the amount of acid in the stomach and are used to treat such conditions as gastroesophageal reflux disease, stomach and small intestine ulcers, and esophagitis. The affected products are

  • esomeprazole, which is marketed as Nexium and, in combination with naproxen, as Vimovo;
  • dexlansoprazole, which is marketed as Dexilant;
  • omeprazole, which is marketed as Prilosec and, in combination with sodium bicarbonate, as Zegerid;
  • lansoprazole, which is marketed as Prevacid;
  • pantoprazole, which is marketed as Protonix; and
  • rabeprazole, which is marketed as Aciphex.

OTC versions of the products, which are used to treat frequent heartburn, are

  • omeprazole, which is marketed as Prilosec OTC and, in combination with sodium bicarbonate, as Zegerid OTC; and
  • lansoprazole, which is marketed as Prevacid 24HR.

The FDA said patients should not stop taking the medications unless advised to do so by their physicians. However, the agency also cautioned that OTC PPIs should be used only for 14 days, and no more than three 14-day treatment courses should be used in one year.

In addition, FDA officials advised physicians to follow the dosage recommendations contained in the prescription product labeling and consider whether a lower dosage or shorter duration of PPI therapy would adequately treat a patient's condition.

Patients at risk for osteoporosis should have their bone density status managed according to current clinical practice, and, if indicated, should take vitamin D and calcium supplements, the agency said.

The FDA said its actions were based on a review of seven studies, six of which reported an increased risk of fractures of the hip, wrist and/or spine. The agency's review included one study(archinte.ama-assn.org) published May 10 in the Archives of Internal Medicine that found that postmenopausal women who used PPIs had a 26 percent increased risk for forearm and wrist fractures, a 47 percent increased risk for spine fractures, and a 25 percent increased risk for total fractures.

Another study in the same journal issue found that increasing levels of pharmacologic acid suppression are associated with increased risks for nosocomial Clostridium difficile infection(archinte.ama-assn.org); the risk was greatest among patients who used PPIs more than once per day. The drugs also are associated with recurrent C.difficile infection(archinte.ama-assn.org), according to another study in the same journal.

Yet another study(archinte.ama-assn.org) in that Archives issue found that high-dose PPIs, when compared with low-dose PPIs, do not further reduce the rates of rebleeding, need for surgical intervention or mortality after endoscopic treatment in patients with bleeding peptic ulcers.

Finally, the same journal issue also contained an editorial(archinte.jamanetwork.com) that noted that PPIs are the third-highest selling class of drugs in the United States, with $13.9 billion in annual sales. The drugs are overprescribed, the author said, with more than two-thirds of PPI prescriptions written for inappropriate indications. He urged physicians to "offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic."