Drug Safety Oversight Board Meeting, March 15, 2012

Public Summary
The following is a list of the Drug Safety Communications (DSCs) posted shortly before or since the January 19, 2012 meeting and relayed to the Drug Safety Oversight Board (DSB or Board) via memorandum:

January 12, 2012: Cardio-Gen-82 Update- Preliminary findings from ongoing investigations of CardioGen-82: This update is in follow-up to the Drug Safety Communication alerting healthcare professionals to stop performing heart scans with CardioGen-82 due to potential for increased radiation exposure in patients issued on 7/26/2011.
January 13, 2012: New Boxed Warning and Contraindication for Adcetris (brentuximab vedotin): FDA issued a communication notifying the public that two additional cases of progressive multifocal leukoencephalopathy (PML), a rare but serious brain infection that can result in death, have been reported with the lymphoma drug Adcetris (brentuximab vedotin). Due to the serious nature of PML, a new Boxed Warning highlighting this risk has been added to the drug label. At the time of Adcetris' approval in August 2011, one case of PML was described in the Warnings and Precautions section of the label.
January 20, 2012: New risk factor for Progressive Multifocal Leukoencephalopathy (PML)associated with Tysabri (natalizumab): FDA issued a communication informing the public that testing positive for anti-JC virus (JCV) antibodies has been identified as a risk factor for progressive multifocal leukoencephalopathy (PML). PML is a rare but serious brain infection associated with use of Tysabri (natalizumab) for the treatment of multiple sclerosis (MS) or Crohn's disease.
February 08, 2012: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs): FDA issued a communication informing the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD). A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve.
February 08, 2012: Victrelis (boceprevir) and ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitor drugs: FDA issued a communication notifying healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.
February 15, 2012: Planned return of CardioGen-82 to market with new Boxed Warning: This update is in follow-up to the Drug Safety Communication: Update: Preliminary findings from ongoing investigations of CardioGen-82 issued on 1/12/2012
February 28, 2012: Important safety label changes to cholesterol-lowering statin drugs: FDA issued a communication to provide the public with more information for the safe and effective use of statins and are based on FDA’s comprehensive review of the statin class of drugs.
March 1, 2012: Interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury.
March 28, 2012: Revised recommendations for Celexa (citalopram hydrobromide) related to potential risk of abnormal heart rhythms with high doses.
April 10, 2012: Updated information about the risk of blood clots in women taking birth control pills containing drospirenone.
April 20, 2012: New Warning and Contraindication for blood pressure medicines containing aliskiren (Tekturna).
April 26, 2012: Updated information on drug interactions between Victrelis (boceprevir) and certain boosted HIV protease inhibitor drugs.
May 7, 2012: FDA Drug Safety Communication: Safety review update of cancer drug Revlimid (lenalidomide) and risk of developing new types of malignancies.

The DSB discussed three topics:

Commercial Web Sites Accessing and/or Offering FDA Adverse Event Reporting System (AERS) Data
HHS Efforts to Mitigate the Risks Associated with Prescription Drug Abuse
Department of Defense Challenges with FDA Risk Evaluation & Mitigation Strategies (REMS)

Views expressed by non-CDER employees are those of the individual and not necessarily the opinion of their respective federal agency or institution.
Commercial Web Sites Accessing and/or Offering FDA Adverse Event Reporting System (AERS) Data
The Board heard a presentation from Lauren Choi, Pharm.D., Team Leader, Division of Pharmacovigilance II, Office of Surveillance and Epidemiology, CDER, on the proliferation of commercial web sites accessing and/or offering FDA Adverse Event Reporting System (AERS) data.
These sites (for example, www.adverseevents.com

or www.drugcite.com

) purport to refine and present FDA’s AERS data in more user-friendly interfaces and platforms than might be available at www.fda.gov.
Dr. Choi reviewed the sites for content options and variations, features, limitations, specific cautions, and implications for the future.
The Board discussed the following:

Possible range and breadth of patient use of AE sites and potential impacts on drug safety and medication adherence.
Need for more information about public AE sites, some with fee-based options.
Concerns about AE information presented without adequate context or explanation.
The potential for private AE sites to present new directions for developing accessible health information for consumers that will have relevance with the continued growth of web-based information, tools, and applications.

HHS Efforts to Mitigate the Risks Associated with Prescription Drug Abuse
Peter Lurie, MD, MPH, from the Office of Policy and Planning in the Office of the Commissioner, presented on HHS efforts to mitigate risks associated with prescription drug abuse.
Dr. Lurie introduced the role and goals of the Prescription Drug Abuse Subcommittee of the HHS Behavioral Health Coordinating Committee. (Dr. Lurie co-chairs the Subcommittee with Dr. Nora Volkow of the National Institute on Drug Abuse, NIH.)

Improve federal surveillance capacity
Increase provider access to Prescription Drug Monitoring Program data
Reduce overdose deaths through secondary prevention strategies
Develop educational materials to promote appropriate use/reduce misuse
Use electronic medical records as a tool for improved clinical identification of drug abuse

The Board discussed:

Prescription drug abuse mitigation efforts currently under consideration in Federal Partner agencies.
Potential impacts that new or different requirements might have within Federal Partner agencies.
Drug Take-back Programs as a tool for risk mitigation.
State-level Prescription Drug Monitoring Programs (PDMPs) as tools for risk mitigation.

Department of Defense (DOD) Challenges with FDA Risk Evaluation & Mitigation Strategies (REMS)
The Board heard a presentation from COL Carol Labadie, PharmD, U.S. Army Pharmacy Consultant.
DOD faces an array of challenges in implementation and compliance with FDA REMS, including acquisition of drug products and related logistical concerns, documentation requirements, facility coordination, and product shipping constraints. There are also barriers to REMS compliance when using certain products in the field and/or in combat situations.
In general, REMS with ETASU (elements to assure safe use) are the most difficult to implement within DOD, given DOD’s geographically and structurally disparate organizations and missions.
In DOD regions with multiple medical facilities, “cross-pharmacy” use can create organizational and data tracking challenges.
The Board discussed:

FDA’s interest in methods to streamline, centralize, and assist all our Federal partners.
Alternative approaches to centralize and/or better track REMS requirements for all partners.