Drug Safety Oversight Board Meeting, July 15, 2010

Public Summary

The Executive Director updated the Drug Safety Oversight Board (DSB or Board) on Drug Safety Communications posted and in development since the June 17, 2010 meeting. The following is a list of the posted risk communications:

Drug Safety Communications posted since the June 17, 2010 DSB meeting:

• July 8, 2010: New risk management plan and patient Medication Guide for Qualaquin (quinine sulfate)
• July 13, 2010: New Boxed Warning for severe liver injury with arthritis drug Arava (leflunomide)

The DSB discussed two topics:

1.  Proton pump inhibitors and the risk of fractures
2.  A path forward update for the Drug Safety Oversight Board

The views expressed by non-CDER employees are those of the individual and not necessarily the opinion of their respective government agency.

Proton pump inhibitors (PPIs) and the risk of fractures

Proton pump inhibitors (PPIs) work by reducing the amount of acid in the stomach. Nexium (esomeprazole), Dexilant (dexlansoprazole), Prilosec (omeprazole), Zegerid (omeprazole/sodium bicarbonate), Prevacid (lansoprazole), Protonix (pantoprazole), Aciphex (rabeprazole), and Vimovo (naproxen and esomeprazole magnesium) are available by prescription to treat conditions such as gastroesophageal reflux disease, stomach and small intestine ulcers, and inflammation of the esophagus. Prilosec OTC, Zegerid OTC, and Prevacid 24HR are sold over-the-counter (OTC) for the treatment of frequent heartburn.

On May 25, 2010, FDA posted a Drug Safety Communication to inform health care professionals and the public about a possible increased risk of hip, wrist, and spine fractures with the use of PPIs (Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors). The Board discussed recent feedback about the Drug Safety Communication and the impact it may have had on health care professionals and the public.

The Federal Partners with hospitals and clinics provided PPI usage patterns including information on fractures occurring in their patients using PPIs. The Board invited a guest expert in osteoporosis research, Dr. Cliff Rosen, from Maine Medical Center’s Research Institute. Dr. Rosen provided a clinical perspective on the use of PPIs and the risk of fractures.

The Board discussed the following:

• A brief overview on the use of PPIs and risk of bone fractures
• The importance of using the lowest effective PPI dose
• Overview of the mechanism of action of PPIs and possible pathophysiologic pathways for fractures associated with PPI use
• Required PPI labeling change
• Current safety research on the PPIs and the risk of fractures
• Epidemiologic data reporting an association of PPIs with fractures
• The challenges associated with the clinical trial and epidemiological data for PPI and fracture risk, including the multiple confounders for both observational studies and prospective clinical trials (e.g. variation in duration of use, intermittent use, variation in PPI use, and underlying diseases, such as concomitant steroid use, smokers)
• An overview on FDA’s communication strategy for PPIs and the risk of fractures
• The May 25, 2010 Drug Safety Communication on PPIs and the risk of fractures and its main messages

Drug Safety Oversight Board Path Forward Update

The Board heard an update from the DSB staff about the progress over the past year. The DSB staff reviewed the changes made in the Board’s membership. In addition, the Board heard a summary of topics presented over the past year and compared them with the goals outlined at the September 2009 meeting. The Board had previously outlined a goal to discuss drug safety topics that broadly affect health care. Examples of broad drug safety topics discussed by the Board over the past year included safety issues associated with tablet splitting (Drug Safety Oversight Board Meeting, October 15, 2009) and CT scans, radiation exposure, and a potential risk of cancer (Drug Safety Oversight Board Meeting, April 15, 2010). The Board members offered input on how they would like to see the Board evolve over the coming year.

The Board discussed the following:

• The size and representation of the Board
• Potential topic areas the Board should explore in the coming year
• The role of the Board and DSB staff in following up on previous and current Board recommendations
• Possible actions to promote the value of the Board to areas within FDA and to the healthcare professionals and public
• A recently published article about the DSB: (The Food and Drug Administration's Drug Safety Oversight Board: An Evolving Paradigm for Clinical Input on Drug Safety Topics)

Board Update: A Feedback Conversation

The Board discussed a possible Drug Safety Communication involving a potentially fatal medication error with the use of nimodipine capsules intended for oral administration but given intravenously in certain clinical settings.