The Honorable Margaret A. Hamburg
U.S. Food and Drug Administration
White Oak Building I
I0903 New Hampshire Avenue
Silver Spring, MD 20993
Via: E-mail firstname.lastname@example.org
Dear Commissioner Hamburg:
The Project On Government Oversight is an independent, nonprofrt organization that provides oversight of the federal government. We take a keen interest in the U.S. Food and Drug Administration (FDA), which receives around $4 billion a year in federal taxpayer dollars to regulate almost twenty-frve percent of the U.S. economy.
We would like to bring to your attention a potentially dangerous interaction of the drugs Seroquel (quetiapine) and methadone that may be putting veterans at risk. According to news accounts, these drugs are now widely used in combination to treat veterans with Post-Traumatic Stress Disorder (PTSD). However, a study published in 2007, and funded by Seroquel's maker, Astra Zeneca, found that Seroquel signifrcantly increases plasma levels of methadone. This may increase the risk of a methadone overdose.
Further, between 2002 and July 2010, the FDA's Adverse Event Reporting System (AERS) received over eighty reports of patients who overdosed and often died while taking Seroquel in combination with methadone. As I'm sure you are aware, AERS reports are known to underestimate the true number of drug adverse events, so POGO is alarmed that so many reports have been filed with the FDA on Seroquel and methadone interactions.
However, despite the known interaction effect, the FDA-approved labels for Seroquel and methadone do not note the study from 2007, and the labels do not discuss this interaction in the warning section. In the interest of patients, and especially veterans, we ask that you make changes to both labels to note this drug interaction. Further, we ask that you immediately issue an alert to inform patients and prescribers.
The dangers of Seroquel and methadone were first reported in a study published in 2007 in the Journal of Clinical Psychopharmacology. I This study found that Seroquel significantly increases blood plasma levels of methadone. In one patient, Seroquel led to an 85 percent increase in blood plasma levels of methadone. The study found wide variability across patients, which the authors argue may be due to differences in genetic subpopulations.
Yet, prescriptions of Seroquel and methadone are at an all time high for veterans. An investigation by the Military Times found that military spending on Seroquel almost quadrupled between 200I and 2009.
Many of these veterans are also taking methadone for pain relief and to control anxiety caused by PTSD. The Military Times found that methadone overdose has caused at least sixty deaths in the military, more than any other drug—legal or illegal.
A separate investigation by the Associated Press noted that military expenditures on Seroquel have jumped sevenfold since the beginning of the war in Afghanistan. The military spent $8.6 million on Seroquel last year alone. Physicians said that they are prescribing it to provide relief from nightmares and anxiety caused by PTSD. The Associated Press also discovered that Seroquel has become the Department of Veterans Affairs' (VA) second biggest drug expenditure since 2007. Last year the VA spent $125 million on Seroquel compared to $14.4 million in 2001.
In the case of one soldier, Andrew White, the Associated Press reported that the interaction of Seroquel and methadone may have been deadly. To treat his PTSD, he was prescribed Seroquel, methadone, and Paxil. Mr. White's autopsy report stated, "The narcotic analgesic methadone was present in the blood at a concentration that can cause fatal respiratory depression in those who do not have adequate tolerance to opioid medications."
Again, POGO urges FDA to improve the labels of Seroquel and methadone to note the 2007 study in the Journal of Clinical Psychopharmacology. Further, we ask FDA to issue an alert to inform patients and prescribers. We also have concerns about the quality of the data in the AERS database and how the FDA uses this information to monitor for adverse drug events. To help answer our concerns, we ask that FDA provide someone to brief our staff.
We have attached a copy of the 2007 study in the Journal of Clinical Psychopharmacology and copies of the FDA's AERS reports noting an adverse reaction to Seroquel and methadone.
I appreciate your review of this letter and the attached documents. If you have any questions, please do not hesitate to contact Paul Thacker at (202) 347-1122 or email@example.com .
cc: Senator Carl Levin
Chairman, Senate Armed Services Committee
Senator John McCain
Ranking Member, Senate Armed Services Committee
Senator Daniel K. Akaka
Chairman, Senate Veterans' Affairs Committee
Senator Richard Burr
Ranking Member, Senate Veterans' Affairs Committee
The Honorable Eric K Shinseki
Department of Veterans Affairs
George Peach Taylor Jr., M.D., MPH
Acting Assistant Secretary of Defense for Health Affairs
Department of Defense
 Claude Uehlinger et al., "Increased (R)-Methadone Plasma Concentrations by Quetiapine in Cytochrome P450s and ABCB1 Genotyped Patients," Journal of Clinical Psychopharmacology, June 3, 2007. (Downloaded October 22, 2010)
 Andrew Tilghman and Brendan McGarry, "Medicating the Military: Use of Psychiatric Drugs has Spiked; Concerns Surface about Suicide, other Dangers," Army Times, March 17, 2010. (Downloaded October 22, 2010)
 Andrew Tilghman and Brendan McGarry, "Rx for Death: Troop Deaths Soar with Prescriptions for War Wounded," Navy Times, September 7, 2010. (Downloaded October 22, 2010)
 Matthew Perrone, "Questions Loom over Drug Given to Sleepless Vets," Associated Press, August 30, 2010. (Downloaded October 22, 2010) (Hereinafter Perrone, "Questions Loom")