Lipitor / Statins Using Bad Statistics

[ZippyDawg]

Released by FDA: 8/12/02. Posted by FDA: 9/4/02

Christopher A. Graham
Director, Worldwide Regulatory Strategy
Pfizer Inc.
235 Fast 42ndd Street
New York, NY 10017

RE: NDA 20-702
Lipitor (atorvastatin calcium) Tablets
MACMIS ID#: 10939

Dear Mr. Graham:

This letter notifies Pfizer Inc. (Pfizer) that the Division of Drug Marketing, Advertising, and Communications (DDMAC) has identified a direct-to-consumer (DTC) print advertisement (#LP 106204-B) for Lipitor (atorvastatin calcium) Tablets that is in violation of the Federal Food, Drug, and Cosmetic Act (Act) and applicable regulations. The ad misleadingly suggests that Lipitor is safer than other statins. The Lipitor DTC print ad has appeared in magazines with national distribution such as, Time, Reader's Digest, Good Housekeeping, Woman's Day, Cooking Light, and Health. The Lipitor "Brief Summary" part of the DTC print ad is misleading because it indicates that Lipitor may lack the side effects of other members of the statin class of lipid-lowering medications.

For the rest of the warning letter:

http://www.pharmcast.com/WarningLetters/Yr2002/August2002/Pfizer0802.htm

[rahod]

"The rates of muscle disorders observed in clinical trials of statins have not been significantly different from those with placebo,2 but wider clinical use involves individuals having multiple disease states or taking potentially interacting medication"

I guess that says it all. Those few "having multiple disease states or taking potentially interacting medication", should probably not be taking a statin. Pretty obvious you would think.

[ZippyDawg]

But that is exactly the point. These drugs aren't tested in the populations and under the conditions that they will ultimately be prescribed for in real life. If the tests were conducted using these subjects they would never receive FDA approval. Pfizer is recommending that every diabetic should be taking Lipitor. If you look at table 1 diabetes is a risk factor for muscle disorders when taking Lipitor.

Australia has a very small population taking statins. You need to extrapolate the number of known adverse effects to the much larger statin using population in the U.S. You also need to keep in mind that many adverse effects are either never reported to doctors or doctors don't bother to report them to the FDA.

Table 1: Factors increasing the risk of muscle disorders with simvastatin and atorvastatin

Substances inhibiting metabolism by CYP3A4: cyclosporin, diltiazem, verapamil, macrolide antibiotics, azole antifungals, protease inhibitors, grapefruit juice

Medicine inhibiting metabolism by other means: gemfibrozil

Disease states: diabetes, hypothyroidism, renal and hepatic disease

Advanced age: ≥ 70 years

High statin dose: ≥ 40 mg/day

ADRAC has received 91 reports of rhabdomyolysis with simvastatin and 26 with atorvastatin, as well as many reports of myalgia, myopathy or creatine kinase (CK) increase. Table 2 (top section) shows the percentage of cases with identified risk factors, as defined in Table 1. For simvastatin the factors listed most commonly in reports describing rhabdomyolysis were age ≥ 70 years (40 reports) dose ≥ 40 mg (33), cyclosporin (19), gemfibrozil (21), diltiazem (20) and diabetes (15). Over half of the simvastatin cases with rhabdomyolysis had more than one identified risk factor. Individuals with several risk factors may be at risk of developing rhabdomyolysis, rather than a less serious muscle disorder.

A feature of the cases of rhabdomyolysis is that long term statin therapy was well tolerated until after a change in medication (e.g. increase in the dose of statin, or addition of clarithromycin or diltiazem).

[rahod]

"These drugs aren't tested in the populations and under the conditions that they will ultimately be prescribed for in real life. If the tests were conducted using these subjects they would never receive FDA approval."

Statins have now been around for over 15 years and have been taken by tens of millions world wide....WITHOUT ANY SIGNIFICANT ADVERSE EFFECTS. That's a simple fact that has stood the test of time. That's what I call a REAL LIFE TEST

[ZippyDawg]

Originally Posted by rahod

Statins have now been around for over 15 years and have been taken by tens of millions world wide....WITHOUT ANY SIGNIFICANT ADVERSE EFFECTS. That's a simple fact that has stood the test of time. That's what I call a REAL LIFE TEST

No significant adverse effects of statins?


Baycol Pulled From Market as Numerous Deaths Linked to It

By David Brown

The maker of Baycol (cerivastatin), a popular cholesterol-lowering drug used by about 700,000 Americans, voluntarily pulled the medicine off the market August 8 because of numerous deaths associated with its use.

Officials at the Food and Drug Administration said 31 people have died of complications of severe muscle breakdown, a rare but well-recognized side effect of many cholesterol-lowering drugs. In about one-third of the cases, the person was on a second cholesterol drug, gemfibrozil, known to especially increase the risk of problems.

Baycol is one of six "statins," a popular family of drugs prescribed to about 12 million Americans to treat, and possibly prevent, coronary heart disease. Reports of severe side effects, including death, are at least 10 times more common for Baycol than for other drugs in the class.

The FDA is currently not considering any regulatory action with regard to the other approved statins which are lovastatin (Me****r), pravastatin (Pravachol), Zocor (Zocor), fluvastatin (Lescol) and atorvastatin (Lipitor).