Wednesday, June 8, 2011

Don't Take High Dose Simvastatin!

Today the FDA just announced a new warning on the highest dose of simvastatin, the most popular cholesterol medication prescription in the country.  They have issued this warning because "the highest approved dose--80 milligram (mg)--has been associated with an elevated risk of muscle injury or myopathy, particularly during the first 12 months of use."
The current recommendation is not to start simvastatin at 80mg and only to continue taking the 80mg if you "have been taking this dose for 12 months or more and have not experienced any muscle toxicity. It should not be prescribed to new patients.

First, why is this announcement so important.
As Forbes' Matthew Herper points out in A Snapshot Of The Cholesterol Drug Market, though Lipitor is the biggest selling drug in terms of dollars, generic simvastatin is actually the most commonly prescribed cholesterol lowering  medication.  As you can see from the graph below (viewed much better on the Forbes site), once Zocor became available as generic simvastatin, it became the most popular statin written (blue line) whereas Lipitor (red line) prescriptions continue to tumble. Over time, insurance companies have made it more and more difficult to write for any branded statin by increasing co-pays for patients or increasing hurdles to get prescriptions approved.

In fact, simvastatin makes sense for many patients.  Most data suggest that benefit is derived from statins when they reach about a 30% reduction in bad cholesterol, or LDL.  The folks at the NIH's NHLBI have evaluated the efficacy of all the available statins (see below) and you can see that most statins will achieve that goal at various doses.  For example 10mg of atorvastatin (Lipitor), 20-40mg of simvastatin, and 5mg of rosuvastatin (Crestor) all lower LDL cholesterol by about the same amount.  Thus, if you just need a 30% reduction in LDL, you should be fine with the generic.  Problem is that many patients need more than that amount of reduction.  Thus, if you want to stick to a generic, you would have to go to 80mg of simvastatin.

Now one might thing that the stronger, more potent the statin, the more likely it is to cause side effects.  Turns out the opposite is true.  The graph below shows that when plotting LDL reduction against number of patients developing myopathy (what the FDA is concerned about), it seems like the more potent statins (Crestor, Lipitor) not only lower cholesterol better, but have a lower risk of myopathy. Myopathy is pretty uncommon, usually only about 1/10,000 or 0.01%. Looking at both Lipitor and Crestor, you can see as the dose goes up (10, 20, 40, 80) the percent of reduction of LDL continues to improve, but rate of myopathy is pretty much the same except for a slight bump at the 80mg dose of Lipitor.  (Though not on the graph, you can see why the 80 mg dose of Crestor wasn't approved, because at that dose there was significant myopathy). However, when you jump from 40-80 mg of simvastatin, the LDL only goes up a few points, but the rate of myopathy skyrockets to over 1% (that's 1/100 instead of 1/10,000).  Finally, you can why cerivastatin or Baycol was pulled from the market.  It was pretty weak at lowering LDL, but had up to 2% incidence of myopathy at the higher doses.

The good news is that Lipitor will go generic in only a few months.  When that happens, I am sure that the graph above will change drastically.  All Lipitor scripts will likely go to the generic medication and probably many of the simvastatin prescriptions will also switch to generic atorvastin, since it is a better statin (more potent, fewer side effects).  Crestor is another option (most effective, fewest side effects), but will not go generic for a while. The other thing to note is that Pfizer, who is about to lose Lipitor, is trying to get as much business as it can by offering patient coupons, so that (as long as you are not on Medicare part D or Medicaid) a prescription of Lipitor will only cost you $4 until it goes generic. 

Bottom Line: All statins are not created equal and generic is not always best.  If you are on Simvastatin 80mg, you should seriously discuss with your doctor about switching.  In fact, if you are on simvastatin at any dose and not on Medicare part D or Medicaid, but have commercial insurance, you should consider asking your doctor about switching to Lipitor with the $4 coupon (you may actually save money by NOT taking the generic) until it too goes generic.


M. Sparacino said...

I swithced from Lipitor to simvastatin in order to save $. I took 20mg/daily Lipitor. I swithched to 20mg/daily simvastatin. My numbers went up significantly. I would need at least 80mg/daily of simvastain to be at normal levels. Thank you for your article. I will talk to my doctor about switching back to Lipitor.

M. Sparacino

terryblueeyes said...

just reading all this.. i was in hospital last year.. and was put on 80mg of simvastatin.. after about 3 month my leg musles went and i felt really ill. my voice started going and voice fatiage set in..i was weak and my breathing was bad.. after coming of them i started to feel better and flet good in my self.. just this month my doctor said my cholestol was 5.9 and put me on liptor 20mg. after one week i felt weak tired legs like led. light headed.. even had bad thoughts.. ive stoped them last night and today felt im better.. do you think it was wrong in the hospital starting me on 80gm of simvasatins in the first place..and they done me in.. plus i wonder if my body just cant stand them??? any help please..

Peter Green said...

If you want to set some modest goals for ldl reduction and at the same time limit your exposure to myopathy and other potentially harmfull interactions then taking a smaller dose is very helpful..infact i take a 5mg dose every two days but this can only be done if the drug of choice has a longer half life...for example pravastatin is 77hrs and zocor is also need to get before and after measurements and most importantly dont use these drugs as a passport to enable you to binge on fat sugary foods and booze!

vijay said...

I am very impressed with the article, I have been on 40mg simvastatin for the last 4-5 years. My doctos just do a repeat perscription ! I was having mussle pain, short of breath and above all too much of acidity ( reflux). I got fed up with life. One day, I met a friend who is in alternative medicins, suggested me that I take a spoon of anacid seeds ( Flex ) with my break fast every morning , also I started taking a capsule of Gugal herbs. Also I reduced my simvastatin from 40-20. After two months my doctor carried an other blood test. All my cholostrels went down to an unimaginable level.I also felt fresh, no mussle pains , and no short of breath.
Then for the next two months I carried on as usual, But with exclusion of Simvastatin.Sadly the levels went fractionaly up a bit. My doctors seems to be happy as it is, but I have started on 20mg simvastatins again. I am very afraid that my problems will start again.I am more worried about the acidity than any thing else. I would appriciate if any one can throw a little bit light on this. I am very scared to re start on Statins.I have been suffering with blocked arteries since I was 44 years old , I have had two grafts in my groins since. I have also a stent in my heart. I am quite careful with my diet. I am 70 years old now

profwatson said...

My total cholesterol was 227, it went down dangerously to 128 on 20mg Lipitor(I have no factors, but age of 68). My LDL went from 157 to 65. I hear that low cholesterol can make me crazy. Do you recommend a dosage of 5mg?

Dr. Matthew Mintz said...

We do need cholesterol, but research indicates LDL's below 70 are just fine (babies have LDL's in the 40's and their brains develop just fine).
I would recommend discussing with your physician your individual risks and rationale for treatment, then discuss whether a reduced dose of Lipitor makes sense for you.