FDA Safety Office Recommends Warning About Liver Failure With The Cholesterol Lowering “Statin” Drugs

The Food and Drug Administration’s (FDA) Office of Postmarketing Drug Risk Assessment (OPDRA) recommended in a memorandum dated May 1, 2000, that liver failure be included as an adverse reaction in the professional product labeling, or “package insert” for the family of cholesterol-lowering drugs known as “statins.” The statins now being marketed in the U.S. are atorvastatin (LIPITOR), cerivastatin (BAYCOL), fluvastatin (LESCOL), lovastatin (MEVACOR), pravastatin (PRAVACHOL), and simvastatin (ZOCOR).

The current labeling for these drugs states that elevations in liver function tests, an early indication of possible liver toxicity, have been seen with the use of statins. The labeling also warns that “It is recommended that liver function tests be performed prior to and at 12 weeks following initiation of therapy or the elevation of dose.” No mention is presently made of possible liver failure.

An evaluation of reports of potential liver failure was undertaken by OPDRA in response to requests from Merck Research Laboratories and Bristol Myers Squibb to seek over-the-counter status for their statins Zocor and Pravachol, respectively. A total of 90 cases of liver failure had been reported to the FDA for the six statin drugs. Of the 90 cases, 62 were consistent with the agency’s definition of liver failure associated with statin use and more than half of these 62 patients died.

The table below lists the number of cases of liver failure reported to the FDA for each of the statins and the date that the drug was approved for use in the U.S. This table cannot be used to estimate a comparative risk of liver failure from the statins because reports of adverse reactions made to the FDA are voluntary and only 1 serious reaction in 10 is reported to the agency. Also, the drugs became available at different times. For example, lovastatin has been on the market the longest and atorvastatin, though only on the market since 1996, is a top seller primarily because of heavy promotion. There were almost 37.7 million prescriptions filled for atorvastatin in 1999, making it the third most frequently prescribed drug in the U.S., while the next closest statin was simvastatin with 19.9 million prescriptions for the year.

The symptoms of drug-induced liver toxicity are non-specific and may mimic many other illnesses. They include rash, loss of appetite, tiredness, pain on the right side just below the rib cage (where the liver is situated), dark urine or a yellowing of the skin or whites of the eyes (jaundice). The symptoms of liver toxicity may also include fever.

We agree with the OPDRA recommendation to add liver failure to the labeling of the six statin drugs as an adverse reaction. We hope the FDA’s upper management heeds the advice.

What You Can Do

You should contact your doctor immediately if you are taking a statin drug and experience the symptoms of liver toxicity listed above.