Jay S. Cohen M.D.       http://medicationsense.com      1337 Camino Del Mar   Suite C       Del Mar, CA 92014       Phone: 858.345.1760       Fax: 858.509.8944


Crestor Side Effects Make More Headllines--But Underlying Causes and Preventive Measures are Again Ignored

A New Study Shows Higher Rates of Adverse Reactions with Crestor Than with Other Statins
Here's the Real Story on Super-Strong Crestor and What to Do About It

According to a new study, serious side effects with the cholesterol-lowering drug Crestor (rosuvastatin) have been reported to the FDA at a much higher rate than with other statin drugs such as Lipitor or Zocor.1  Deaths on Crestor have also been reported at a higher rate.  These findings made headlines, but problems with Crestor are no surprise.  As I told the FDA in 2002 and have stated and written many times since, problems with Crestor were predictable from the day Crestor was approved.

Super-Strong Crestor Overmedicates Patients and Causes Side Effects
AstraZeneca designed Crestor to be the strongest statin.  This would be fine if Crestor, the newest and least known statin, was reserved for use only when other statins were ineffective.  However, rosuvastatin was not marketed this way.  AstraZeneca launched an expensive, intensive marketing campaign -- which was highly criticized in some medical journals -- to convince doctors to prescribe super-strong Crestor as the first choice for people with elevated cholesterol.  The problem is, the lowest dosages of Crestor (5 and 10 mg) are still very strong.  They are much stronger than millions of patients need to achieve proper cholesterol levels.  The authors of the new study concluded that there were "concerns about the safety of this drug at the range of doses used in common clinical practice .1"  This is the key point.  An accompanying editorial stated that "the doses of statins [should] not exceed those required to achieve current goals of therapy.2"  Yet, Crestor is so strong, even its lowest doses exceed those required by many patients to reach their cholesterol goals.  Excessive dosages cause more side effects.

Most people with elevated cholesterol require reductions in their LDL levels of 25% to 30%.  This can usually be accomplished quite nicely with 20 or 40 mg of Mevacor (or its much less expensive generic, lovastatin), or 40 mg of Lescol, or 20 or 40 mg of Pravachol.3,4  These are the milder statins, and they are less likely to cause side effects. With the strong statin Lipitor, you need only 2.5 or 5 mg, but you will get 10 mg -- 100% to 400% excess medication -- because 10 mg is the lowest dosage Pfizer makes.  With strong Zocor, you need only 5 or 10 mg, but doctors routinely prescribe Merck's recommended initial dosage of 20 or 40 mg -- again much more medication that actually needed.4  With super-strong Crestor, the proper dose for reducing LDL 25%-30% is 1 mg, yet the lowest doses available are 5 mg or 10 mg -- five to ten times more medication than these people need.4-6  Such overmedication causes more frequent and more serious side effects.  This is why the FDA is receiving more reports about Crestor than any other statin drug, and why 62% of the reports about Crestor involved the 5 mg and 10 mg dosages.1

To avoid side effects with statin medications, it is vital to use the correct dosage.  If you get 10 mg of Crestor when you only need 1 mg, your risks go way up.  For example, with each doubling of a statin dosage, the risk of liver injury also doubles.7  Excessive dosages also dramatically increase the risks of other side effects such as muscle pain, kidney injury, memory problems, fatigue, or abdominal discomfort. 

Another way to look at it: 10 mg of Crestor, which is the initial dose that doctors usually prescribe, is far stronger than the maximum dose of Mevacor, which is 80 mg.  The usual initial dose of Mevacor is only 20 mg.  In other words, the usual initial dose of Crestor (10 mg ) is about six times more powerful than the usual initial dose of Mevacor (20 mg).  This extra potency comes with extra risks of side effects.

Preventive Measures You Can Take
For more complete information about these issues and about how to take statin drugs safely, see my new book What You Must Know About Statin Drugs and Their Natural Alternatives.  Remember, the key to safe treatment with statin drugs is to know exactly how much reduction of LDL you require.  The book explains how you can do this, and it then helps you determine the right statin at the right dosage to reach your LDL goal.  Many doctors today take shortcuts and just prescribe the same strong statin to everyone.  This works for some patients, but it causes side effects with others.  The imprecise use of statin medications is one big reason why side effects occur in more than 40% of patients and why 60% to 75% of statin users discontinue treatment.8,9

FDA Should Investigate Overmedication with Crestor
   Finally, it is not enough for the FDA to merely warn us about the reports involving Crestor.  The FDA should investigate these cases.  All of these people had cholesterol tests.  It is easy enough to determine whether they were overmedicated with standard dosages of super-strong Crestor.  If so, the FDA should require AstraZeneca to develop 1 and 2.5 mg dosages of Crestor for use with appropriate patients and to provide better guidelines for doctors about how to use super-strong Crestor safely. Jay S. Cohen M.D., May 2005

References
1.  Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH.  The safety of rosuvastatin as used in common clinical practice: a post-marketing analysis.  Circulation 2005;111:***.
2.  Grundy, SM.  The issue of statin safety: where do we stand?  Circulation 2005;111:***.
3.  Physicians' Desk Reference, 59th Edition.  Montvale, N.J.: Medical Economics Company, 2005.
4.  Cohen, JS.  What You Need to Know about Statin Drugs and Their Natural Alternatives.  Square One Publishers, New York: January 2005.
5.  Olsson, AG, Pears, J, McKellar, J, et al.  Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia.  American Journal of Cardiology 2001;88:504-508.
6.  Olsson, AG.  A new statin: a new standard.  The American Journal of Managed Care 2001;7:S152.
7.  Roberts, WC.  The rule of 5 and the rule of 7 in lipid-lowering by statin drugs.  American Journal of Cardiology 1997;80:106-7.
8.  Jackevicius, CA, Mamdani, M, Tu, JV.  Adherence with statin therapy in elderly patients with and without acute coronary syndromes.  JAMA 2002;288:462-467. 
9.  Benner, JS, Glynn, RJ, Mogun, H, et al.  Long-term persistence in use of statin therapy in elderly patients.  JAMA 2002;288:455-461.




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