Cholesterol-Lowering Drug Cerivastatin (BAYCOL) Removed from the Market

On August 8, 2001, the Bayer Pharmaceutical Division announced it was withdrawing its cholesterol-lowering “statin” drug cerivastatin (BAYCOL) from the U.S.market because of reports of sometimes fatal rhabdomyolysis, an adverse reaction involving the destruction of muscle tissue.

Rhabdomyolysis results in muscle cell breakdown and release of the contents of muscle cells into the bloodstream. Symptoms may include muscle pain, weakness, tenderness, tiredness, malaise, fever, dark urine, nausea, and vomiting. The pain may involve specific groups of muscles or may be generalized throughout the body. The muscle groups most frequently involved are in the calves and lower back; however, some patients report no symptoms of muscle injury. In some cases the muscle injury is so severe that patients develop sometimes fatal kidney or other organ failure.

Cerivastatin was initially approved in the U.S.in 1997 as a member of the family of cholesterol-lowering drugs commonly referred to as “statins.” This family lowers cholesterol levels by blocking a specific enzyme in the body that is involved in the synthesis of cholesterol.

All statins have been associated with reports of rhabdomyolysis, but reported cases of fatal rhabdo-myolysis are significantly more frequently associated with cerivastatin. The five statins still available in the U.S.are: lovastatin (MEVACOR), pravastatin (PRAVACHOL), simvastatin (ZOCOR), fluvastatin (LESCOL), and atorvastatin (LIPITOR).

We recently petitioned the Food and Drug Administration (FDA) to require stronger warnings about r habdomyolysis in the professional product labeling, or professional “package inserts,” of the five remaining statins. More importantly, the petition asks the FDA to require pharmacists to distribute patient information leaflets written in non-technical language about the risk of rhabdomyolysis telling patients how to recognize the symptoms and what steps to take should they appear. This type of FDA-mandated written patient information is known as a Medication Guide.

Reports of fatal rhabdomyolysis with cerivastatin frequently involved its use at higher doses, in elderly patients, and, particularly, in combination with gemfibrozil (LOPID), another blood-fat (lipid) lowering drug. The FDA had received reports of 31 U.S.deaths due to severe rhabdomyolysis associated with the use of cerivastatin. Twelve of these also involved the use of gemfibrozil.

Cerivastatin is the 11th new drug approved in the U.S.since 1990 that has been withdrawn from the market for safety reasons. An additional three drugs were banned during this period in other countries but remain on the market here. The majority of the banned drugs had been approved and then removed from sale since mid-1996. A remarkable six of the 38 drugs approved in 1997 in the U.S.(15.8 percent) have been withdrawn from the market in this or another country for safety reasons. Very troubling is the fact that almost all of these drugs are redundant “me-too” drugs and that the safety problems that resulted in the majority of these drugs being removed from the market were known before their approval.

The two tables below summarize safety withdrawals for drugs approved in the U.S.since 1990 and drugs removed from the market in other countries but that remain available here. Included are the brand and generic names, the FDA-approved use, and the dates of withdrawal and approval.

The most dangerous drugs on the market may be the new ones. If a drug is going to come off the market for safety reasons or be re-labeled about new adverse reactions or life-threatening interactions with other drugs it will often be within its first five years on the market.

The two tables below once again highlight the importance of our five year rule: Do Not Use any new drug until it has been on the market for at least five years unless it is one of those rare drugs that offers some documented advantage over older, better understood products. Only two of the drugs listed in these tables have been withdrawn after being on the market for more that five years, levomethadyl (ORLAAM) and cisapride (PROPULSID). However, cisapride required a number of safety labeling revisions about serious adverse reactions before it had been on the market for five years.

What You Can Do

If your doctor is going to switch you to another statin drug, read about our petition to the FDA to require additional warnings on these drugs about the risk of rhabdomyolysis.

Follow the five-year rule as given above. With FDA’s shoddy recent record, it is more important to your health now than ever before.