Mark B. McClellan, M.D., Ph.D., Commissioner
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20854

Dear Commissioner McClellan:

Public Citizen, representing 160,000 consumers
nationwide, hereby
petitions the U.S. Food and Drug Administration (FDA)
pursuant to the
Federal Food, Drug and Cosmetic Act 21, U.S.C. Section
355(e)(3), and 21
C.F.R. 10.30, to immediately remove from the market  
rosuvastatin
(Crestor-AstraZeneca) before additional cases of
life-threatening
rhabdomyolysis and kidney failure/kidney damage occur.

We have obtained new information from the FDA and
health agencies in
Canada and the U.K. concerning serious post-marketing
adverse reactions
– including seven cases of life-threatening
rhabdomyolysis (muscle
destruction) and nine cases of kidney failure or
kidney damage – in
patients mostly using lower doses of this
recently-approved
cholesterol-lowering drug, rosuvastatin.  We have also
become aware of
decisions by major U.S. health insurers and by the
Swedish government
not to reimburse for the drug. This information
re-emphasizes the basis
for which we strongly urged the FDA not to approve it
last year and
subsequently advised people not to use the drug once
it was approved.
The urgency of this petition is heightened by the fact
that AstraZeneca
is currently launching a major direct-to-consumer
advertising campaign
to promote the drug.

In opposing the drug's approval at a July 9, 2003 FDA
advisory
committee meeting, we pointed to two cases of kidney
failure and one
case of kidney insufficiency in clinical trials prior
to approval in
which patients had also experienced both protein and
blood in the urine.
There were also a large number of patients who had
blood and/or protein
in their urine but had not suffered from kidney
failure. In addition to
this kidney toxicity, unique among all of the statin
drugs, rosuvastatin
is the only one of these drugs in which any cases of
the
life-threatening muscle destruction known as
rhabdomyolysis was found to
occur prior to approval. Even cerivastatin (Baycol),
which was
ultimately banned after at least 31 cases of fatal
rhabdomyolysis, had
not caused a single case of this adverse reaction
prior to approval. In
contrast, there were seven cases of rhabdomyolysis in
patients receiving
rosuvastatin before its approval. Although all were
receiving a dose (80
milligrams) that was not approved, a small patient
getting even the 40
milligram dose might be receiving the same amount of
drug per pound of
body weight and we were concerned that cases would
occur at this 40
milligram dose or even lower doses. We stated that it
was likely, if not
certain, that if it were approved, rosuvastatin would
have to be banned
because of post-marketing cases of rhabdomyolysis and
kidney failure
that would inevitably occur.

In the United States, where the drug has only been on
the market for a
little more than 5 months, a 39-year-old woman, taking
only 20
milligrams a day, died of rhabdomyolysis and renal
insufficiency. In
addition, a 63-year-old man in the U.S. developed
acute renal failure
using a dose of only 10 milligrams a day and another
patient in the U.S.
developed renal insufficiency and renal tubular
necrosis after using
rosuvastatin at a dose of 10 milligrams a day for only
2 weeks. The
total number of new cases of adverse reactions after
approval in the
U.S., Canada and the U.K. combined include:

? 7 patients with rhabdomyolysis (patients using doses
of 10, 20, 20,
20-40, 40, 40 and 80 milligrams per day)

? 4 patients with acute kidney failure (patients using
10, 10, 10 and
40 milligrams per day)

? 5 additional patients with kidney damage (patients
using 10, 10, 10,
20 and 40 milligrams per day)

? 6 patients with bleeding or abnormal bleeding tests
who were also
using blood-thinning drugs such as coumadin, known to
have an abnormal
interaction with rosuvastatin (patients using  10, 10,
10, 10, 20 and
unknown milligrams per day)

Two major U.S. insurers, WellPoint/Blue Cross, with 15
million patients
insured, and Group Health Cooperative of Puget Sound
(GHCPS) with more
than 500,000 members have refused to reimburse for
Crestor. "We've
already been Baycolled," said Dr. Robert Seidman,
chief pharmacy officer
for the Thousand Oaks, Calif.-based WellPoint. "There
is a level of
nervousness, and we're being conservative and we're
being cautious,"
Seidman also said.

Group Health Cooperative of Puget Sound (GHCPS)
stated, in its decision
not to reimburse for the drug, that "Rosuvastatin
offers no advantage
over current formulary HMG-CoA reductase inhibitors
[other statins] in
terms of efficacy, safety, and cost. The effect of
rosuvastatin on
cardiovascular outcomes has not yet been studied and
the safety of
rosuvastatin beyond the one-year duration of clinical
trials is unknown.
Due to the recall of cerivastatin, a statin associated
with several
cases of rhabdomyolysis, the committee recommends
using caution before
prescribing statins with limited safety data."  In
addition, a
spokesperson from GHCPS expressed some concern about
questions of safety
based on evidence from the clinical trials.

It is of particular interest that GHCPS has decided to
reject from
their formulary rosuvastatin because in the past, they
similarly
rejected other drugs that had come on the market with
serious safety
questions such as the pain-killer Duract, the high
blood pressure drug
Posicor, the diabetes drug Rezulin, and the weight
reduction drug Redux,
all of which were eventually banned by the FDA.

In Sweden, regional governmental drug advisors
recommended against the
use of the drug. The committees said in a statement
that newer drugs
such as Crestor were not recommended because they did
not meet the
criteria of documented safety and cost effectiveness.
The decision was
unusual, because the representatives for Sweden's
regional governments
were unanimous in their decision.

In an editorial in the October 25, 2003 issue of the
British medical
journal, The Lancet, editor Dr. Richard Horton wrote:

"AstraZeneca's tactics in marketing its
cholesterol-lowering drug,
rosuvastatin, raise disturbing questions about how
drugs enter clinical
practice and what measures exist to protect patients
from inadequately
investigated medicines.
…After a damaging delay over safety concerns,
rosuvastatin finally won
US FDA approval in August and was launched last month,
winning a 2%
market share after only three weeks. [AstraZeneca CEO]
McKillop has
pledged to do whatever it takes to persuade doctors to
prescribe
rosuvastatin, including launching an estimated $1
billion first-year
promotional campaign. "We've got to drive the
momentum", he said at a
recent investors meeting. "You get one shot at
launching a major new
product. This is our shot."

Why does the quality of debate about statins matter?
First, because
safety cannot be assured. Bayer withdrew cerivastatin
in August, 2001,
after the occurrence of unexpected cases of fatal
rhabdomyolysis. The 80
mg dose of rosuvastatin was withdrawn by AstraZeneca
because of safety
concerns. Some critics are even anxious about the 40
mg dose. The
finding of proteinuria [protein in the urine] and
microscopic haematuria
[blood in the urine] associated with rosuvastatin use
are additional
worries….Since there are no reliable data about
efficacy [that is,
actually decreasing heart attacks and strokes, not
merely lowering
cholesterol levels] and safety--and AstraZeneca is
facing unusually
acute commercial pressure to force rosuvastatin into
the market--doctors
should pause before prescribing this drug. Physicians
must tell their
patients the truth about rosuvastatin--that, compared
with its
competitors, rosuvastatin has an inferior evidence
base supporting its
safe use. AstraZeneca has pushed its marketing machine
too hard and too
fast. It is time for McKillop to desist from this
unprincipled
campaign."

At the FDA advisory committee meeting on July 9, 2003
concerning  the
possible approval of rosuvastatin, I stated:

       "In summary, we strongly oppose the approval of
rosuvastatin
because of its unique renal toxicity. We are also
seriously concerned
because of the seven cases of rhabdomyolysis that were
common enough to
have shown up in clinical trials, unlike the
pre-approval studies with
all previously approved statins, including
cerivastatin. The fact that
so few patients on the 20 or 40 mg doses took the drug
for a sufficient
period of time to have had a chance to develop
rhabdomyolysis seems to
have imparted a false sense of security about the
safety of these doses
concerning muscle toxicity…If this drug is approved,
it is highly likely
it will have to be removed from the market after
‘enough'  further
damage to patients occurs."

 The new information from the U.K, Canadian and U.S.
governments
documenting cases of rhabdomyolysis and kidney damage
in people using
the using lower (10, 20 and 40 milligram) doses of
rosuvastatin confirms
these concerns and emphasizes the need for banning
this drug.

Sincerely,