Our Petition To Require New Warnings on the “Statin” Family of Cholesterol-Lowering Drugs

In the wake of the withdrawal of the cholesterol-lowering “statin” drug cerivastatin (BAYCOL) from the market, the Health Research Group petitioned the Food and Drug Administration (FDA) on August 20, 2001 asking for additional warnings on the five remaining statins about muscle breakdown, an adverse reaction know as rhabdomyolysis that can be fatal. These five remaining statins are: lovastatin (MEVACOR), pravastatin (PRAVACHOL), simvastatin (ZOCOR), fluvastatin (LESCOL), and atorvastatin (LIPITOR).

The complete text of the petition can be found on our web site. Readers can also obtain a copy by writing Public Citizen Health Research Group, 1600 20th Street NW, Washington DC 20009.

Our petition requested that the FDA take the following four actions:

1. Immediately require a black box warning at the beginning of the FDA-approved professional product labeling, or “package insert” for all statins sold in the U.S. warning of the risks of rhabdomyolysis. A black box warning is the strongest type of warning the FDA can require.
2. Require that all professional product labeling for statins include an additional bold-faced warning of the risks of muscle weakness (myopathy) and the measures doctors and patients can take to reduce these risks.
3. Immediately require that pharmacists distribute an FDA-approved Medication Guide, written specifically for patients, with all new and refill statin prescriptions warning patients of the risk of muscle pain and weakness and rhabdomyolysis and informing patients to stop using the drug and contact their physicians if muscle pain, muscle tenderness, muscle weakness or tiredness develops.
4. Immediately require companies to inform all U.S. physicians through a “Dear Doctor” letter by registered mail about the risk of rhabdomyolysis with statin therapy.

In our examination of adverse drug reaction reports made to the FDA for the statins from October 1997 to December 2000, there were 772 cases of rhabdomyolysis associated with the use of statins, over 85 percent of which required hospitalization. The breakdown is: atorvastatin 86; cerivastatin 387; fluvastatin 10; lovastatin 32; pravastatin 70; and simvastatin 187 cases.

Death from rhabdomyolysis was reported in 72 of these cases (9.3 percent) including 52 deaths from statins other than cerivastatin. In a further analysis of the FDA Adverse Event reports from 1966 through October 1997 (although cerivastatin was not marketed until early 1998, the first statin, lovastatin, was marketed in 1987) we found an additional 29 deaths from rhabdomyolysis (22 with lovastatin, 6 with simvastatin, 1 with pravastatin) where the statin was listed as the “Suspect Drug” and “myopathy “ was listed as the adverse event (in the earlier data, rhabdomyolysis was not a permitted search term). Thus, the 81 total number (52+29) of rhabdomyolysis deaths with the currently remaining statins include atorvastatin 13 deaths, fluvastatin 1 death, lovastatin 27 deaths, pravastatin 10 deaths, and simvastatin 30 deaths.

The current warnings on the statins indicate an increased risk of rhabdomyolysis in patients using a statin and a fibric acid derivative or “fibrate.” However, more than two-thirds (67.9 percent) of the reported cases of statin-associated rhabdomyolysis occurred when statins were not used concurrently with a fibrate. The fibric acid derivatives include clofibrate (ATROMID-S), fenofibrate (TRICOR), and gemfibrozil (LOPID). Three-quarters (75 percent) of the reported deaths occurred in the absence of concurrent therapy with a fibrate. When cerivastatin is excluded from the analysis, 86.5 percent of reported deaths (88 percent of all cases) occurred in the absence of concurrent fibrate treatment.

Because of the increasing evidence that black box warnings and “Dear Health Professional” letters alone fail to protect patients from preventable drug-induced injury (see “More Evidence that Food and Drug Administration (FDA) Regulatory Actions Fail to Protect the Public”) the most important request made in this petition is for the FDA to require pharmacists to distribute a Medication Guide with each new refill prescription of a statin drug. The FDA can require such a guide for drugs “that pose a serious and significant public health concern” requiring immediate distribution of drug information to the public. The statins certainly rise to this level of concern.

The bottom line is that in a drug safety system that fails far too often, a Medication Guide would provide patients with the information they need to protect themselves.

The following is part of the language we suggested for inclusion in Medication Guides for all statin drugs:

At the first sign of muscle pain, muscle tenderness, muscle weakness, tiredness or darkened urine, stop taking any statin drugs to reduce the likelihood that further muscle damage might occur and contact your doctor immediately to get a blood test for creatine phosphokinase and to discuss the use of alternative treatment plans. You should refrain from excessive exercise until the diagnosis of serious muscle damage can be excluded.

What You Can Do

If you are taking one of the statin drugs, heed the advice given above in our suggested language for a statin Medication Guide.

Consumers can report adverse experiences with prescription drugs and non-prescription drugs, medical devices, and dietary supplements to the Food and Drug Administration’s Office of Emergency Operations by telephone at 301-443-1240 or on the Internet at www.fda.gov/medwatch/report/consumer/consumer.htm.