Letter to FDAs McClellan CRESTOR DEATH

Discussion in 'Health and medical' started by Zee, Mar 5, 2004.

  1. Zee

    Zee Guest

    March 4, 2004

    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.


    Sidney M.Wolfe M.D. Director, Public Citizen's Health Research Group 1600 20th St. NW, Washington,
    DC. 20009 202 588-7735 fax 588-7796 e-mail [email protected] Web site: www.citizen.org/hrg

  2. listener

    listener Guest

    On 5 Mar 2004 07:22:06 -0800, [email protected] (Zee) wrote:

    >March 4, 2004
    >Mark B. McClellan, M.D., Ph.D., Commissioner Food and Drug Administration 5600 Fishers Lane
    >Rockville, MD 20854
    >Dear Commissioner McClellan:

    Here's the actual link for those interested:


    Of course Pfizer will be THRILLED to see Crestor pulled, since Crestor (which has been heavily
    prescribed in Europe) has been effectively eating into Lipitor's profits.