The decision in August 2001 by the German Pharmaceutical giant Bayer AG to withdraw the cholesterol-lowering statin drug Baycol from the market shocked the world. For years, the public was led to believe that statin drugs lowered cholesterol and possessed other health benefits as well. Millions of statin prescriptions are written yearly in the United States alone.

Unfortunately, Baycol was linked to 31 deaths. Moreover, deaths occurred at the manufacturer's recommended initial dose (0.4 mg/day) as well as at the highest dose (0.8 mg/day). The majority of deaths occurred in elderly patients and more often in women.

There are other statin drugs on the market, such as Lipitor (the best seller).  Like Baycol, these drugs are linked to the same rare muscle weakness, known as myositis, which occurs in about 1 in 1,000 statin users. Myositis occasionally progresses to rhabdomyolysis -- a complete breakdown of muscle cells that can lead to kidney failure and death.  Some experts believe that pravastatin (Pravachol) and fluvastatin (Lescol) may have less potential for this deadly drug interactions. The data at this time are not sufficient to declare one statin drug safer or more dangerous than the others.

The Real Problem

Drug interactions and side effects with statin drugs are not new. Numerous scientific literatures have reported adverse interaction including myositis when combinations of statins and other drugs, including warfarin (used to prevent blood clotting), clarithromycin (an antibiotic), and ketoconazole (an antifungal drug), are used. Laboratory tests have shown cancer development and liver damage, in animals, when high doses statin drugs are administered.

The Baycol fiasco is just the tip of the iceberg, illustrating the growing potential for medical complications from drug interactions. Worldwide, doctors are increasingly relying on numerous pharmaceuticals to control chronic conditions , from elevated cholesterol to diabetes to high blood pressure and osteoarthritis. In about a third of the Baycol cases, deaths occurred among people who also took gemfibrozil (Lopid) - a drug used to lower triglyceride levels.

Most statin adverse effects, including the musculoskeletal (including rhabdomyolysis) and liver damage, are dose-related. That is, higher doses bring increased risks. Each doubling of the statin dosage also doubles the incidence of liver enzyme elevations that exceed three times the upper limit of normalcy.  The Food and Drug Administration earlier reported  90 cases (63 confirmed) of liver failure and more than 30 deaths linked to statin drugs. For years, numerous  researchers have been ringing the warning bell but were overruled.  The public has been led to believe that side effects of statin drugs, if any,  are minimal.  Professionals are told that the benefits outweigh the risk.


What is the proper dose?

Obviously, each person's dosage of any statin drug should be as low as possible to achieve the target LDL cholesterol.  This is particularly important for the elderly, women, and those of lesser weight.  While seniors comprise only 17% of the U.S. population, they sustain 51% of the deaths from medication reactions. Studies have shown that up to 17% of all hospitalizations of the seniors are related to medication reactions. Often overlooked are women and certain minority groups such as Asians who are smaller in size. Treating these with regular dosage could be a prescription for disaster.

According to the package insert of Baycol, the recommended initial dose is 0.4 mg/day. This dosage reduces LDL by 34% on average. But 0.3 mg -- 25% less medication -- reduces LDL by 31%.  This target is sufficient for millions with elevated cholesterol to reach. No provision is made for those of different body weight, age, or gender.

Some doctors start patients at even higher doses than manufacturers recommend due to poor information. Product inserts of  most statin drugs (including Baycol) do not include guidelines on how to titrate dosage based on the patient's weight and age. The lowest available dose of Lipitor, the best-selling statin in America,  may be stronger than millions of patients require to achieve their target LDL cholesterol level

Patients are treated like statistical averages, not like individuals -- even when many individuals probably get better than average responses and therefore need only low doses.

The end result is over-treatment, which produces predictable and avoidable problems. Overuse of statin therapy was found among 69% of patients undergoing primary prevention and among 47% of patients undergoing secondary prevention in a recent article from JAMA.  Simply put - over-treatment means increased, unnecessary risks for the patient. For some, especially those in compromised conditions,  this may put them over the edge.

The rational physician has a duty to administer the lowest rational dosing not only to achieve the target total cholesterol and LDL cholesterol levels, but also to avoid adverse effect.


What should you do?

If you are taking Baycol, talk to your doctor about switching to other drugs. Until more details are known, here is what you need to know if you take any statin drugs:

1. Watch carefully for muscle tenderness or weakness. Look for feelings of weakness that can be localized or diffuse. It can occur independent of exercise. Fever can be another symptom of muscle weakness. Be alert.

2. Seek immediate medical attention if your urine turns brown -- a symptom of muscle proteins' being excreted through the kidneys.

3. Ask about a regular liver function test.  Such tests are routinely performed before statins are started and again 10 to 12 weeks later to ensure proper liver health. A more accurate test -- either creatine kinase (CK) or creatine phosphokinase (CPK) -- should be considered if muscle cells break down are suspected.

4. Inform your doctor what other medications you take. Deaths have been reported not only in people who also took Baycol with gemfibrozil (Lopid), but also in those who took other statins with other drugs, including cyclosporin.  Those with concurrent heart disease must know that statin drugs lowers the coenzyme Q10 level in the body.  Those who are on Coumadin or other blood thinners for conditions such as atrial fibrillation must also pay extra attention for possible drug interactions.

6. Discuss with your doctor the proper dosage, remember that the best dosage is the lowest effective dosage.