Drug Safety Oversight Board Meeting, June 17, 2010
The Executive Director updated the Drug Safety Oversight Board (DSB or Board) on Drug Safety Communications posted and in development since the April 15, 2010 meeting. The following is a list of the posted risk communications:
Drug Safety Communications Posted since the April 15, 2010 DSB meeting:
- April 21, 2010: New Boxed Warning on severe liver injury with propylthiouracil
- May 3, 2010: Ongoing safety review of GnRH agonists and possible increased risk of diabetes and certain cardiovascular diseases
- May 12, 2010: Medication errors from swallowing topical Benadryl Extra Strength Itch Stopping Gel
- May 25, 2010: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors
- May 26, 2010: Completed safety review of Xenical/Alli (orlistat) and severe liver injury
- June 2, 2010: Drug labels now contain updated recommendations on the appropriate use of long-acting inhaled asthma medications called Long-Acting Beta-Agonists (LABAs)
- June 11, 2010: Ongoing safety review of Benicar and cardiovascular events
The DSB discussed two topics:
1. Gadolinium-based contrast agents and renal adverse events and anaphylaxis
2. Meta-analysis update
The views expressed by non-CDER employees are those of the individual and not necessarily the opinion of their respective government agency.
Gadolinium-based contrast agents and renal adverse events and anaphylaxis
MRI contrast agents are a group of agents used to improve the visibility of internal body structures in magnetic resonance imaging (MRI). The most commonly used FDA-approved compounds for contrast enhancement with MRI procedures are gadolinium-based contrast agents (GBCAs). GBCAs are manufactured by a chelating process, a procedure in which large organic molecules or a ligand form a stable complex around the gadolinium - a paramagnetic metal ion. The chelate reduces the chances of toxicity that could result from exposure to gadolinium. This stable complex is eliminated predominantly by the kidneys.
Nephrogenic systemic fibrosis (NSF) is a rare but potentially debilitating and sometimes fatal condition that most often affects the skin and may also involve other organs. The condition is associated with kidney failure and the administration of large amounts of gadolinium. The FDA has released several Drug Safety Communications (Public Health Advisories and Information for Health Care Professionals) in 2006 and 2007 about the occurrence of NSF in patients with decreased renal function receiving GBCAs: Information on Gadolinium-Containing Contrast Agents. The Board discussed the differing safety profiles associated the seven FDA-approved GBCAs - Magnevist, MultiHance, Omniscan, OptiMARK, ProHance, Ablavar, and Eovist and possible revisions to the labels of these products.
The Federal Partners with hospitals and clinics presented information on GBCA usage patterns, knowledge on their differing safety profiles among their health care staff, and reports of NSF and anaphylaxis in their health care institutions. The Board was joined by a guest expert, Dr. Emmanuel Kanal, the Director of Magnetic Resonance Services and Professor of Radiology and Neuroradiology at the University of Pittsburgh Medical Center. Dr. Kanal is also the Chair of the American College of Radiology Magnetic Resonance Safety Committee. Dr. Kanal provided an overview on the safety of GBCAs, including reports of NSF and anaphylaxis
The Board discussed the following:
- An overview on the safety of GBCAs including reports of NSF and anaphylaxis
- An overview of FDA’s regulatory actions on the GBCAs since NSF was first described in the literature
- Incidence, pathogenesis, and proposed etiology of NSF and GBCA exposure in renal disease
- Whether NSF is a GBCA class related effect or adverse drug-specific experience
- The risk-benefit profiles of the seven FDA-approved GBCAs
- Post Marketing Requirements with the sponsor to study the occurrence of NSF in moderate to severe renal failure in patients undergoing clinically indicated MRI
- Published observational studies and case reports of anaphylaxis with GBCAs
- AERS cases of fatal anaphylaxis associated with GBCAs
- Disproportionality analyses of AERS data
- The new proposed labeling for the seven GBCAs
The Board heard an update from FDA’s Meta-analysis Working Group about the development of FDA’s meta-analysis best practice guidance. The group’s lead provided an overview on the issues that face the Working Group and Steering Committee, the guidance document in development, the timeline, and plan for moving the guidance document forward.
The Board was joined by Dr. Joseph Lau, a guest expert on meta-analyses. Dr. Lau is a professor of medicine at Tufts University and researcher at the Institute for Clinical Research and Health Policy Studies. Dr. Lau's research focus is evidence-based medicine and meta-analysis.
The Board discussed the following:
- What aspects of the meta-analytic update are most important
- Areas not mentioned in the update that should be addressed in the planned best-practices document
- The role for cumulative meta-analysis in the routine assessment of postmarket drug safety
Board Update: A Feedback Conversation
The Board discussed a possible Drug Safety Communication involving an off-label use of Qualaquin (quinine sulfate).