The US Food and Drug Administration (FDA) has warned that high dose, long term use of a class of drugs known as Proton Pump Inhibitors (PPIs), for conditions such as heartburn, acid reflux and gastric ulcers, carries an increased risk of bone fractures in the wrist, hip and spine.

In their warning to consumers and health care professionals on Tuesday, the FDA said the product labeling will be changed to include a safety warning about the increased potential risk.

PPIs are available in the US as prescription and over the counter (OTC) drugs.

Prescription PPIs are used to treat conditions such as gastroesophageal reflux disease (GERD), ulcers of the stomach and small intestine, and inflammation of the esophagus. They include:

  • Esomeprazole (brand name Nexium, from AstraZeneca).
  • Dexlansoprazole (Dexilant, from Takeda).
  • Omeprazole (Prilosec, from AstraZeneca, Zegerid, from Santarus).
  • Lansoprazole (Prevacid, from Takeda).
  • Pantoprazole (Protonix, from Wyeth-Ayerst).
  • Rabeprazole (Aciphex, from Janssen-Cilag)

OTC versions of these drugs are approved in the US for the treatment of frequent heartburn. These include Prilosec OTC, Zegerid OTC and Prevacid 24HR.

The FDA said they decided to issue the warning after reviewing a number of epidemiological studies that reported a an increased risk of fractures of the hip, wrist and spine in patients using high doses of PPIs for one year or more. Most of the people affected were over the age of 50.

Both the Warnings and Precautions section of the prescription label and the Drug Facts label on the OTC versions will be updated.

Dr Joyce Korvick, deputy director for safety in the agency’s Division of Gastroenterology Products, said:

“When prescribing proton pump inhibitors, health care professionals should consider whether a lower dose or shorter duration of therapy would adequately treat the patient’s condition.”

The FDA urged patients and professionals to weigh up the benefits against the risks when deciding if PPIs are the appropriate treatment, and consumers should discuss their concerns with a health care professional before purchasing an OTC version.

The FDA had this advice for consumers taking PPIs:

  • Don’t stop taking your PPI unless instructed to do so by your doctor.

  • Be aware that an increased risk of hip, wrist and spine fracture have been reported by people using PPIs, and the greatest risk was among those using PPIs for a year or more at high doses.

  • Read and follow the instructions on the Drug Facts label if you buy an over the counter PPI.

  • You should only use over the counter PPIs (as directed) for heartburn and for no more than 14 days.

  • See a doctor if your heartburn persists or if you have any concerns about using PPIs.

  • Don’t take more than three 14-day courses of over the counter PPIs in a year.

  • Report side effects to the FDA’s MedWatch AER program.

PPIs are among the most widely used drugs in the world and are generally considered safe. According to a report in the Associated Press, PPIs were the third best selling group of prescription drugs in the US last year.

They work by inhibiting a particular type of proton pump, the H+/K+-ATPase pump in gastric parietal cells, thereby strongly suppressing the secretion of acid in the digestive system, easing the pain of heartburn and acid reflux, and helping to heal ulcers.

However, acid is an important tool in digestion, and too little of it means fewer nutrients are absorbed into the body.

Another other area of concern with PPIs is that they may interfere with proton pumps elsewhere in the body, where they carry out other vital functions.

Some researchers have suggested that we don’t know much about how PPIs affect the functions of cells other than parietal cells and we should do more research on the efficacy and safety of their long term use. Dr Masayuki Suzuki, a gastroenterologist with the National Hospital Organization Tokyo Medical Center in Japan, wrote a paper about this in 2008.

“Proton Pump Inhibitors and Gastritis.”
Masayuki Suzuki, Hidekazu Suzuki, and Toshifumi Hibi
J Clin Biochem Nutr. 2008 March; 42(2): 71-75.
Published online 2008 March 1. doi: 10.3164/jcbn.2008012.

Sources: FDA, AP.

Written by: Catharine Paddock, PhD