More than a year after issuing a warning that the highest dose of the Zocor cholesterol pill could cause serious muscle damage (see here), the FDA is now saying the 80 mg dose should be avoided, except by patients who have taken this dose for 12 months or more and not experienced any muscle problems. The latest warning also applies to the highest dose of another Merck pill - Vytorin, a combe med that includes Zocor - as well as Simcor, which is sold by Abbott Laboratories.
The move was made after the agency reviewed a seven-year study conducted by Merck and other clinical trial data, as well as adverse event reports, all of which showed the highest dose had an increased risk of myopathy, or serious muscle damage. The risk was highest during the first year of treatment with the 80 mg dose and often occurred while interacting with other meds, although a genetic predisposition was also cited (here is the FDA statement).
Other regulators also issued warnings about the high dose, such as the UK's Medicines and Healthcare products Regulatory Agency (look here). Overall, though, Zocor has remained popular - the pill was prescribed 94 million times in 2010, twice the number of prescriptions in 2007, according to Forbes, which cited IMS Health research data. However, Merck says only 12 percent of patients were taking the 80 mg dose (read the statement).
The most serious form of myopathy, by the way, is rhabdomyolysis, which can lead to severe kidney damage, kidney failure, and sometimes death. A decade ago, in fact, Bayer withdrew its Baycol cholesterol pill due to this side effect. The development prompted scrutinty of all statins. Three years later, as Forbes noted, Cleveland Clinic cardiologist Steve Nissen wrote an editorial in the Journal of the American Medical Association that the 80 mg dose of Zocor "was associated with an unusually high rate of myopathy" (read here). His warning proved prescient.
Of course, the FDA is perennially stretched thin and safety reviews require a great deal of certainty and care. But the agency had been looking at the Merck study, which was called SEARCH, for the past two years. So what do you think?
Should the FDA Have Moved Faster?
- Yes (78%, 62 Votes)
- No (22%, 17 Votes)
Total Voters: 79
18 Comments
My compliments to Merck. This is the first time I've seen where the FDA notofocation and the updated PI containing the warning appeared on the same day.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021687s033s040lbl.pdf
Not that it's important, but I believe Baycol was withdrawn in 2001. The Nissen editorial was in 2004.
Hi Marilyn,
Thanks for the note pointing that out. I have corrected the text.
Regards ed
The reality is that all statins cause varying degrees of muscle weakness that increases as the dose is moved up - regardless of statin used - with rhabdo being the extreme. All statins including Lipitor, Zocor and Crestor ALL cause muscle weakness and that is a fact. I just had my dose of Lipitor cut in half (from 10 mg to 5mg - which is not even available) because my numbers were so good. You wouldn't believe the increase in strength that I have experienced at the gym. All statins should be used with caution and at the lowest possible dose. This all makes sense because statins interfere with our ability to make CoQ10.
I'm glad that 80 mg is still around for Homozygous FH patients. No one likes seeing 10 year olds get heart attacks.
Original industry insider:
Compliments to Merck?? What???? If the warning and the labeling came out on the first day it means that Merck has known about this probably had months or even YEARS to prepare. SHAME on Merck for sitting on the SEARCH data for as long as it has. I think SEARCH started in the early 2000's
ED: have you seen merck's actual SEARCH data, or are you paraphrasing news reports written elsewhere?
thanks
Hi Anger Management,
Thanks for your note. As to your question, I referred to the material released by the FDA - and provided a link - but I do not believe that contains the data. So the answer is no.
However, the FDA provided a data summary when its warning was issued in March 2010, and there is a link contained in my post at the time. And I linked to that earlier post in the first sentence of today's post.
To save time, here it is...
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm#DataSummary
As an aside, I chose to run a reader's poll because Nissen did issue his own type of warning seven years ago, ample time for the FDA to consider taking action.
And at the urging of a source, I had asked the FDA more than two months ago about the status of its review. I only recently received a reply and it was inconclusive, which is to say useless.
I hope this helps,
Regards ed
My husband has been complaining of muscle weakness for the last month. He has been taking 40 mg of simvastatin for the last 2 months. He has been on Lopid for the last 10 years, and prior to starting the simvastatin he was on Lipitor 40mg daily. It is ironic in that this study came out today, the very day he heard back from his lab work and his muscle enzyme is very high. Will the muscle deterioration (his Dr.s words) decrease now that he has stopped the simvastatin?
Anger management, it is obvious you know nothing about the process of making changes to product labeling for prescription drugs. I emphasize the word PROCESS. Labeling changes do not happen in the blink of an eye. The process of making a labeling change is probably the slowest of all of the regulatory processes because it results in a final printed labeling that is disseminated more widely than any other single document that comes out of the FDA, affecting patients, doctors pharmacists, plaintiff's lawyers and insurance companies among other interested parties, Remember also that the PI is a legal document, and so the lawyers for all parties need to have their concerns addressed.
I'm quite certain that the FDA has known about the rhabdo issue fromj Merck for a while. Starting from that point in time forward, there is a process of back and forth negotiation between FDA and the drug company until everyone is comfortable with every aspect of the labeling right down to the last semicolon.
Note the words above: NEGOTIATION and PROCESS. That's why these labeling changes cannot and should not be rushed.
I think the original industry insider didnt understand what I wrote, because his reply supports my argument. Read my comment again or have someone read it to you.
NEGOTIATION and PROCESS are obviously needed, and that obviously this takes time, but TWO YEARS??? In those two years, how many RXs for simvastatin 80 do you imagine were written that may not have been, had physicians known about the muscle risks? The PI changes DO take a long time, but a more concrete warning by the FDA could have been issued a well before the PI changes.
As an academic, I dont mind reading perspectives from people who work in the industry, but when the "original industry insider" is such an obvious shill for Merck, glad-handing them for not releasing trial information they've known about for YEARS is an embarrassment to the Merck as well your industry-biased thought process.
Even so, I believe that its an even BIGGER embarrassment for the FDA.
Am I off my rocker here? Am I incorrect in thinking this way??
Sorry, anger management, I didn't know that you required of me a conflict of interest statement. For the record, I've never received a dime from Merck, and in fact helped lead the effort to have Baycol (cerivastatin) removed from the market in 2001 for exactly the same problem of rhabdomyolysis.
You academic guys are quite amusing because I'm beginning to believe that you guys really are divorced from the reality of the American marketplace. Thank you for reminding me why I got out of academia 30 years ago.
...and in fact helped lead the effort to have Baycol (cerivastatin) removed from the market in 2001...
No, you didn't. Baycol was VOLUNTARILY withdrawn by Bayer. You didnt "remove" anything.
You industry guys are quite amusing....
Of course, anger management. It happened the way you describe exactly. The honchos at Bayer woke up one morning and decided together that they were simply making too much money with this multimillion dollar selling drug Baycol, and that it would really be in everyone's best interest if they would simply withdraw the drug voluntarily.
Permit me to educate you. ALL withdrawals for safety reasons such as Baycol are "voluntary" in nature. This is because FDA gives the company the chance to save face by offering to allow them to "voluntarily" withdraw the drug before forcing them off the market. In every case that I know of the company has taken the FDA up on the offer and has "voluntarily" withdrawn the drug.
Please keep putting your foot in your mouth. I'm enjoying this more than the choclate donut I'm eating as I tyoe.
My foot isnt in my mouth. Bayer's OWN clinical trial data got Baycol removed from the market. Period. Voluntary or non-voluntary, YOU had nothing to do with it! But my all means, keep taking credit for with with all the guys over by the water cooler.
Speaking of foot in the mouth, and getting our eye back on the ball: You are still the one congratulating Merck for taking TWO YEARS to make a PATIENT SAFETY labeling change.
This is completely unacceptable. Only you and your industry ilk would think that would be acceptable! This supports the public notion that industry stooges (like you) ONLY care about profits. Who cares how many people were hospitalized rhabdomyolysis in those two years as long as your stock price stays high and you get your bonus, right?
I am amused of the laughable visions of grandeur that you have about yourself, and am sure that I will be even more amused by your next insufferable reply.
Anger management, I can't believe how prescient your comments are. You really nailed me good this time. Please note that the time stamp on my last comment is 3:34 AM. This is because we industry executives have to get up extra early these days so that we can think of ever newer and more creative ways to use our medical and business experience to endanger the public health while raking in six figure bonuses and making unconscionable profits of the backs of the poor American populace.
Your handle is a good one, but I fear that those anger management classes aren't exactly working for you. Maybe you can work out your anger by throwing tomatoes at the screen for tonite's Republican debate while I decide which of the candididates will best cater to my industry's selfish interests.
BTW, I forgot to mention please read my comments to your students so that they will be dissuaded from going into an industry where some of us really do start our work day at 3:30 AM. That should be enough of a turnoff to this generation of GenY slackers.
You woke up and 3:34 am and replied to a blog comment. I can\'t comment on what you do all day, but I\'m not clear on how the credit-stealing, safety-dismissing rantings of an insomniac equates to \"hard work\"...
Of particular note, you reply didnt address either of the important points at hand:
1) your praising the two year time period for a SAFETY labeling change, and
2) your taking credit for a drug withdrawal you had nothing to do with.
Regardless, we both agree its a good thing that you left academia 30 years ago. I also do hope your morals arent representative of other scientists in the pharmaceutical industry.
Sorry not to address your points:
1)Rhabdomyolysis, while arguably a serious adverse event for the unfortunate victims involved is not even close to being of such epidemic proportions that the FDA will drop everything else and demand immediate action from a company. E coli outbreak? Certainly. Rhabdomyolysis, not even close.
2) I'll only take partial credit here. In the real world there exists what we call competitive intelligence. If one company spots a potentially serious problem with another company's drugs they have ways of alerting people in important places of these problems, which can contribute to the pressure to withdraw the drug.
Only an academic coming from an environment where most of you work at teaching less than 20 hours/week would accuse someone from the backbone of Corporate America of not working hard. At 3:34 AM the coffee is just starting to brew. However, even half asleep, I am capable of responding to an academic's comments with "half my brain tied behind my back just to make it fair", in the words of Rush Limbaugh. Or maybe you you can identify with the 60's types, like Paul McCartney who said "woke up, got out of bed, dragged a comb across my head". Either way I'm sure you get the point.
It's almost 11 AM. Just about time for you to be rolling out of bed to teach your one class for the day before starting to think deep thoughts, or whatever you academics think passes for real work these days.