June 18, 2007
No MedGuide for Zyprexa after Eleven Years of Death and Injury
By Evelyn Pringle
held a public hearing on June 12 and 13, 2007, to obtain feedback on
the FDA's Medication Guide program. Medication Guides contain the
FDA-approved patient information for a drug and are handed out by
pharmacists to help prevent adverse events.
Liversidge appeared at this hearing as a board member of the Alliance
for Human Research Protection to offer feedback for the Medication
Guide on Zyprexa, an atypical antipsychotic marketed by Eli Lilly. She
began her talk by explaining why the testimony that she had planned to
give had to be changed at the last minute.
"I sat down and
read over the material provided for this hearing and was all set to
speak on content as well as delivery systems," she told the FDA panel.
"However, I didn't get very far because, believe it or not, there was
no Zyprexa MedGuide."
"Nor were there MedGuides for the other atypical antipsychotics," Ellen said, "all of which have two black box warnings."
went back to ask myself why there would be no FDA MedGuide in 2007 for
Zyprexa, after all that has happened with this drug, and after all
these years," she said, "And that's when I came up with the title of
this testimony, 'Too Little, Too Late,'"
Ellen's son, Robert
Liversidge III, died of profound hyperglycemia on October 5, 2002, as a
result of taking Zyprexa. After finding that there was no MedGuide for
Zyprexa, Ellen says she searched the FDA website to see what
information was available to patients at that location and found that
the black box warning about diabetes, hyperglycemia and death, that she
and others had fought so hard to have added to the label 4 years ago,
had been watered down. The warning was not listed in a black box, she
told the panel, and it was not first on the list.
FDA briefing materials for the hearing, a MedGuide is required if a
drug has even one of the following characteristics: (1) Patient
labeling could help prevent serious adverse effects; (2) It has serious
risks (relative to benefits) which patients should be made aware
because the information could affect a patient's decisions to use, or
continue to use, the drug; or (3) It is important to health and patient
adherence to directions for use is crucial to the effectiveness of the
Experts say Zyprexa qualifies for a MedGuide under all 3
categories: (1) The labeling would definitely help prevent serious
adverse events; (2) Few patients would be willing to take the drug and
risk developing diabetes given that numerous studies have shown Zyprexa
to be no more effective than the older class of antipsychotics that do
not cause diabetes; and (3) Most patients on Zyprexa would learn that
the drug is not FDA approved to treat the condition they have.
reading the list of adverse events on the FDA website, Ellen says, she
found "high blood sugar and diabetes," mentioned in the number 4
position, even though the wording in the warning in late 2003,
specifically included diabetes, hyperglycemia, and death.
"Why was this wording changed?" she asked the panel. "And whose decision was it?"
current document on the FDA website, Ellen said, is basically useless.
Although it did mention that people should get frequent blood glucose
monitoring, "There was no indication of how often blood glucose
monitoring should take place, nor was there mention of what symptoms of
diabetes should be watched for," she noted.
There is no
mention that the CATIE study found Zyprexa to have the most lethal side
effects out of all the new atypical antipsychotics, Ellen pointed out,
or that the American Diabetes Association clearly stated that the risk
is the highest with Zyprexa.
There is also no mention, Ellen
said, that the use of the drug for treating mania should be brief. When
Lilly obtained FDA approval for the sale of Zyprexa in the US in
September 1996, the only approved indication was for the treatment of
adults with schizophrenia. In 2000, the drug was approved to treat the
manic phase of bipolar disorder.
Ellen's son was diagnosed
with bipolar disorder years before his death but had always done fine
with lithium. However, in 2000, Rob had to apply for Medicaid to help
pay his medical expenses and this was his downfall, she says.
the 1990s, Lilly and the other makers of the new class of atypical
antipsychotics, had been successful in corrupting the state Medicaid
programs by influencing top officials in state agencies all over the
country to write prescribing formularies for doctors that listed the
new expensive drugs as the first line of treatment for all patients
covered by Medicaid, and that is how Rob ever ended up on Zyprexa.
2006, Pennsylvania official Steven Fiorello, former Chief Pharmacist
and Head of the state drug formulary committee, was indicted on felony
and misdemeanor charges for his conflicts of interests with drug
companies and was charged with other ethics violations for accepting
"educational grant money" and failing to disclose the payments.
working as a fraud investigator in the Pennsylvania Office of Inspector
General, Bureau of Special Investigations, Allen Jones discovered the
off-the-books slush fund account where atypical makers were depositing
money under the guise of "educational grants," to influence state
officials and policy makers involved in developing the preferred drug
list in Pennsylvania. Mr Fiorello was in the position to approve drugs
for patients in prisons and 9 state hospitals.
from this scheme were enormous. For instance, Zyprexa was listed for
schizophrenia, and Mr Jones' estimates that Pennsylvania has roughly
9,000 schizophrenic patients in state prisons and mental hospitals at
any given time.
"And based on the average length of stay," he
reports, "an additional 4,000 patients move through the system each
year resulting in the potential recruitment of 13,000 customers, worth
about $6,000 each per year."
In addition, "when patients leave
state institutions with prescriptions for medication," he says, "many
of them continue to be supported through Medicaid."
former investigator, psychiatrist Dr Stefan Kruszewski, worked in the
Pennsylvania Bureau of Program Integrity in the Department of Public
Welfare, and says his investigations found serious abuses and
over-drugging of patients in state care. One case he reported in 2003
involved four children and one adult who died due to substandard care
and the off-label prescribing of atypical antipsychotics.
people most vulnerable to the medicating for profit scheme in
Pennsylvania," Dr Kruszewski says, "were children in state care or
involved in the juvenile justice system, the disabled, and the prison
He calls the over-prescribing that took place
polypharmacy at its worst. "Nearly all the patients," he explains,
"were prescribed a combination of drugs, an antipsychotic and an
"But worst of all," he says, "the
medical records showed that most of the patients who were receiving the
drugs had never been psychotic and had never had a seizure."
"That fact that Medicaid patients are over-medicated to the max," says patient advocate Vince Boehm, "is not debatable."
to provider's reports," he reports, "even three antipsychotics, with a
witches' brew of other preparations, is not unusual for patients being
discharged from state hospitals."
Mr Boehm says the public
system has failed these clients and "the taxpayers will be left to
subsidize the cleanup of this mess for generations to come."
ultimate goal in the drugging-for-profit scheme was to keep patients on
the drugs for life. For example, Ellen testified that, although Zyprexa
was approved only to treat the manic phase of bipolar disorder, which
is typically brief, her son "was put on this drug for two years until
he fell into a coma and died."
She pointed out that, at the
time that he was prescribed Zyprexa in 2000-2002, there was no FDA
warning guide so she was completely in the dark about the new drug
prescribed to her Rob. Also, she told the panel that the current guide
on the FDA website is almost the same as having no guide at all.
on this document would have been helpful to me," Ellen said. There is
still no description for the symptoms of hyperglycemia that might have
saved her son had she known about them the week before he died," she
When Rob suddenly lapsed into a coma and died, Ellen
was determined to find out what happened and she subsequently learned
that other countries had required warnings about the risk of
hyperglycemia, diabetes and death on the label of Zyprexa since the
spring of 2002, on the website of the consumer advocacy group, Public
During her testimony, Ellen reminded the FDA panel
that, back in 2001, before her son was killed, the FDA met with its
equivalent agencies around the world, and they all agreed to cooperate
with each other particularly on drug safety, and pointed out that this
obviously did not happen with the FDA.
"In the spring of
2002," she said, "both Japan and the UK required Lilly to put a warning
on Zyprexa for diabetes, hyperglycemia, and death."
as if the FDA didn't already know this," she testified, "because at the
end of 2001, Dr. Doriswaimey and an FDA researcher reviewed Medwatch
data for Zyprexa and found over two hundred cases of diabetes and 23
As a follow-up to Ellen's testimony, a review of the
FDA website on June 17, 2007, and the "Patient Information Sheet" on
Zyprexa revealed only one warning about the risk of diabetes which
states: "High blood sugar and diabetes. Patients with diabetes or who
have a higher chance for diabetes should have their blood sugar checked
The lack of enforcement action against Lilly over the
past 6 years by Bush appointed officials at the FDA is easily
explained. Leonard Roy Frank provides a list of many of the reasons in
the report titled, "Zyprexa: A Prescription for Diabetes, Disease and
Early Death," published in the August 2005 edition of Street Spirit,
"Eli Lilly's ties to the two Bush
administrations are a matter of public record. President George H. W.
Bush is a former member of Eli Lilly's board of directors. In 2000, Eli
Lilly made campaign contributions of $1.6 million, 82 percent of which
went to President George W. Bush and other Republicans. In 2001,
President Bush appointed Mitch Daniels, a former Eli Lilly vice
president, to be White House director of the Office of Management and
Budget. In 2002, President Bush appointed Sidney Taurel, Eli Lilly's
current chairman and CEO, to the Homeland Security Council."
the last FDA Commissioner, Lester Crawford, had to get out of dodge and
was indicted on charges of conflict of interest for secretly holding
stock in companies that were regulated by the FDA, he hopped right from
the court house into a job making big bucks off the pharmaceutical
And the revolving door between Lilly and the Bush
administration is in full swing today. In May 2007, Lilly issued a
press release to proudly announce the hiring of Alex Azar II as a new
senior vice president, a guy who was the Deputy Secretary of the US
Health and Human Services Department until February 2007.
the release, Lilly openly bragged about how Mr Azar supervised all
operations of the HHS and specifically listed the FDA as an agency
under his direction. Although the amount of his salary was not
mentioned, if based on a percentage of the profits made from Zyprexa
while he controlled the FDA, he should be set for life.
say to look for more top regulatory officials to jump ship before the
results are in from the numerous Congressional investigations into the
FDA's "cozy" relationship with the pharmaceutical industry and the
mishandling of drug safety issues.
At the moment, Congress is
investigating Lilly for ripping off Medicaid and Medicare with the
illegal marketing of Zyprexa and the criminal investigations of Lilly
by US attorneys in various states are too numerous to keep track of.
far as litigation against Lilly related to the illegal marketing of
Zyprexa, so far, 10 states have filed Medicaid Fraud lawsuits, 4 class
actions were filed by shareholders over a 9-day period in April, and
Lilly has agreed to pay more than $1 billion in out-of-court
settlements with over 28,000 private Zyprexa victims.
are additional cases filed by insurance companies and employer unions
that provide prescription drug coverage to private payers, and citizens
and entities in other countries also have also filed lawsuits against
In every case filed, the allegations include that Lilly
marketed Zyprexa for unapproved uses and concealed the serious health
risks associated with the drug, and most prominently, the complaints
list the adverse effects of abnormal blood sugar levels, extreme weight
gain and diabetes.
According to Ely Lilly's April 16, 2007 SEC Form 8-K filing for the first quarter of 2007.
everything revealed about Zyprexa in the filings of all of this
litigation, medical professionals and patient advocacy groups are
infuriated over the fact that Lilly is still profiting from the drug.
In the first quarter of 2007, sales were up 11% in the US from last
year, and Zyprexa earned Lilly more than $1.1 billion, according to the
company's April 16, 2007 SEC filing.
However, critics say they
are even more outraged that the sales of Lilly's top selling diabetes
drug, Humalog, are up 11% over last year.
"The fact that this
drug continues to be marketed," Mr Frank says, "that the media has
barely covered the story, that there have been no criminal charges
against the responsible parties and that there has been no outcry from
the psychiatric profession or the public, have only compounded the
"Lilly's introduction of Zyprexa and the FDA's
complicity," he states, "have led to one of the greatest crimes in
medical history in terms of the number of people harmed, the damage
inflicted, and the grossness of fraud in promoting and advertising the
Authors Bio: Evelyn Pringle is a columnist for OpEd News and
investigative journalist focused on exposing corruption in government
and corporate America.