Crestor Drug Controversy
Group Seeks Ban of Anti-Cholesterol Drug
WASHINGTON – A 39-year-old woman has died of a muscle-destroying condition linked to the controversial new anti-cholesterol drug Crestor, a consumer advocate said Thursday, citing 16 cases of serious side effects in urging a ban of the drug.
Crestor is in the popular family of cholesterol-lowering drugs called statins.
It won Food and Drug Administration approval in August, after a delay because of safety concerns: Seven cases of the potentially fatal, muscle-destroying condition called rhabdomyolysis occurred during studies involving patients on an 80-milligram dose. For that rare condition to pop up in clinical trials was unusual — and particularly worrisome since another statin, Baycol, had been pulled off the market in 2001, linked to dozens of rhabdomyolysis-caused deaths worldwide.
In studies, Crestor also was linked to some cases of kidney abnormalities not seen with other statins.
Still, FDA ultimately decided to approve Crestor, saying it appeared to be slightly more potent than other statins and thus may be important for some patients. To lower the risk of side effects, FDA recommended starting doses of 5 mg. to 10 mg, and said patients should never exceed 40 mg.
But records from the FDA and health agencies in Canada and Britain show life-threatening side effects occur even at those lower doses, said Dr. Sidney Wolfe of the consumer advocacy group Public Citizen, in a petition filed with FDA Thursday seeking a ban.
Among the records:
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Seven patients with rhabdomyolysis, including the 39-year-old American who died after using a 20-mg dose, and a second death from an unspecified country.
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Four patients with acute kidney failure, including a 79-year-old U.S. man who died.
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Five additional patients with less severe kidney damage.
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Also, among six patients, Crestor interacted dangerously with the blood-thinner Coumadin, commonly used by heart-disease patients. One had a hemorrhage, Wolfe said.
Crestor maker AstraZeneca wouldn’t comment on the deaths or other serious side effects except to say “the safety profile is totally comparable” to what pre-marketing studies had predicted, said spokesman Gary Bruell.
“We’re very pleased with the performance of the drug thus far,” he said, noting that 1 million patients worldwide have tried Crestor, including 600,000 in the United States. The company is about to begin major television advertising for the drug.
But Wolfe contended that Crestor “has no unique advantage, but some unique risks” over other statins. He told the FDA there is growing concern about the drug, citing two major U.S. insurers who refuse to pay for it because of the muscle risk and a recent recommendation against use by Sweden’s drug advisers.
The FDA will evaluate the petition, said spokeswoman Laura Bradbard.
March 20th, 2004 at 2:04 am
Can you share your sources or case reports for this reaction to Crestor? Thank you for your time.
Dave Fuentes, Pharm. D.
March 20th, 2004 at 10:30 am
Sure, here is some study information directly from the makers of CRESTOR:
Important safety information about CRESTOR
Rare cases of rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with CRESTOR and with other drugs in this class. Patients should be advised to promptly report unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. Therapy with CRESTOR should be discontinued if markedly elevated CK levels occur or myopathy is diagnosed or suspected.1
It is recommended that liver function tests be performed before and at 12 weeks following both the initiation of therapy and any elevation of dose, and periodically (eg, semiannually) thereafter. Should an increase in ALT or AST of >3 times ULN persist, reduction of dose or withdrawal of CRESTOR is recommended.1
The effect of CRESTOR on cardiovascular morbidity and mortality has not been determined;1 long-term outcome studies are currently under way.
Prescribing Information for CRESTOR® (rosuvastatin calcium). AstraZeneca, Wilmington, Del.
Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol. 2003;93:152-160.
Schneck DW, Knopp RH, Ballantyne CM, et al. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol. 2003;91:33-41.
March 28th, 2004 at 12:22 pm
Because of high cholestorol, I was given Crestor 10MG, one tablet a day, in early November, 2003. After two weeks, I noticed some muscle pain and inability to raise my left arm. About 3 days later, I woke up during the night with EXTREME pain throughout entire body, seeming to be in all my muscles. I quit taking Crestor immediately and contacted my doctor on November 24. My muscles have not recovered. I can not raise my left arm nor reach back with it and suffer from pain in the left leg muscles, across the upper back, and right upper arm as well. It has changed my life. I can’t put on my coat without help or tuck in the back of my shirt. I am uncomfortable most of the time and in pain whenever I try to stretch. I have asked if there is any way to get my muscle movement back and understand the answer is no. It has been over four months and the pain/discomfort remains unchanged. If a patient and his/her doctor decides to try this drug, the patient should be warned that the second he/she starts experiencing muscle cramps, what appears to be muscle strain that he/she thinks might be from overexertion or “arthritis” stop taking the drug immediately. If there is ever a class action suit on this drug, I want to know about it!
April 6th, 2004 at 4:14 pm
I always had cholesterol (I think it’s genetic) and now the doctor wants me to start using statins (Lipitor). I am a bit freaked out (needless to say) when I read about these type of side effects.
Jean, I was just wondering if you have ever had any condition even remotely related to muscle pain or it this is strictly a side effect of this medication? Thanks,
July 3rd, 2004 at 4:34 am
9 june 2004
In Holland the presciption information has been adjusted for the Crestor product. The start dose has been lowered to 10 mg and can only be raised if the patient has used the 10 mg for more than four weeks. The 40 mg can only be used if the patient is under care of a specialist.
The full dutch text.
Den Haag, 9 juni 2004 – De productinformatie van de cholesterolverlager Crestor© (rosuvastatine) is aangepast om een juist en veilig gebruik van het geneesmiddel te bevorderen. De aanpassingen betreffen het startdoseringsadvies en een beperking van de indicatie voor de hoogste dosering. De voorzorgsmaatregelen zijn genomen vanwege meldingen van de bijwerking rhabdomyolyse bij gebruik van rosuvastatine. Rhabdomyolyse is een ernstige spierafbraak die leidt tot nierbeschadiging. De producent van Crestor© heeft, in overleg met alle geneesmiddelen beoordelingsautoriteiten van de Europese Unie, een brief naar artsen en apothekers gestuurd om hen hierover in te lichten. In de productinformatie van rosuvastatine wordt opgenomen dat de startdosering voor alle patiënten 10 mg per dag behoort te zijn en dat deze dosering alleen mag worden verhoogd naar 20 mg per dag als dit noodzakelijk wordt geacht na een proefperiode van 4 weken met 10 mg. Voor verdere verhoging van de dosis naar 40 mg per dag wordt controle door de specialist geadviseerd. Deze dosering mag alleen worden overwogen bij patiënten met ernstige hypercholesterolaemie die geen risicofactoren hebben voor myopathie (spierafbraak).
Myopathie is een bekende dosisgerelateerde bijwerking van statines die in zeldzame gevallen kan leiden tot rhabdomyolyse, een bijwerking die mogelijk levensbedreigend is. Recentelijk zijn er wereldwijd meldingen geweest van rhabdomyolyse bij gebruik van rosuvastatine. De productinformatie is daarom onlangs aangepast met de vermelding dat in zeldzame gevallen rhabdomyolyse kan voorkomen bij het gebruik van rosuvastatine. Een recent onderzoek naar rhabdomyolyse bij het gebruik van rosuvastatine was aanleiding voor bezorgdheid over het risico van rhabdomyolyse bij een dosis hoger dan 20 mg per dag, vooral bij patiënten met risicofactoren of met gelijktijdig gebruik van een fibraat (een ander cholesterolverlagend middel). Bij de meerderheid van de gevallen waarbij rhabdomyolyse werd geconstateerd als bijwerking van rosuvastatine, ontvingen patiënten een hogere dosis dan werd aanbevolen ofwel hadden zij risicofactoren voor myopathie.