FDA Modifies Statin Label Warnings

The cholesterol-fighting drugs will have new warnings regarding the risk of diabetes and memory problems, but without recommendations for routine liver testing.

The FDA has announced changes to the labels of statins indicating an increased risk of diabetes and cognitive difficulties, but deemphasizing concerns over liver problems.

The affected medications include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), lovastatin extended-release (Altoprev), pitavastatin (Livalo), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor), as well as the combination products lovastatin/niacin extended-release (Advicor), simvastatin/niacin extended-release (Simcor), and simvastatin/ezetimibe (Vytorin).

These drugs' labels will include a new warning that statins are associated with a potential increase in blood sugar levels and the development of type 2 diabetes mellitus. This is based on a number of studies, including the JUPITER trial, which found a 27% increase in diabetes in patients taking rosuvastatin; a substudy in the PROVE-IT TIMI 22 trial, which found that high-dose atorvastatin was associated with decreased glycemic control; and a meta-analysis of 13 trials including 91,140 participants, which found that statin therapy was associated with a 9% increase in new-onset diabetes.

The labels will also include a warning that some patients have experienced memory loss and confusion in connection with the use of these cholesterol-lowering medications. This change is based on post-marketing adverse event reports, generally regarding patients older than 50 years of age who experienced memory loss or impairment that was reversed by stopping medication, with a median time of symptom resolution of 3 weeks. The FDA adds that it believes the cardiovascular benefits of statins outweigh the risks of increased blood sugar levels and cognitive problems.

In addition, statin labels will no longer indicate the need for routine periodic monitoring of liver enzymes in patients taking the drugs. Instead, the FDA recommends that patients undergo a liver enzyme test before starting statin therapy and as clinically necessary afterward. The change is based on a determination that serious liver damage with statins is unpredictable and rare—estimated at less than or equal to 2 incidents per 1 million patient-years—and that routine enzyme monitoring does not effectively detect or prevent it. Patients are urged to seek medical attention, however, if they have symptoms of liver problems, including unusual fatigue or weakness; loss of appetite; upper belly pain; dark-colored urine; or yellowing of the skin or the whites of the eyes.

The FDA also announced changes to the label of lovastatin to indicate that, due to an increased risk of muscle injury, it is contraindicated with protease inhibitors used to treat hepatitis C (boceprevir and telaprevir) and HIV, as well as drugs used to treat certain bacterial and fungal infections (itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, and telithromycin) and the antidepressant nefazodone. The label will also advise avoiding lovastatin with cyclosporine and gemfibrozil; not exceeding 20 mg of lovastatin daily with danazol, diltiazem, and verapamil; not exceeding 40 mg of lovastatin daily with amiodarone; and avoiding more than 1 quart of grapefruit juice per day with lovastatin.

The FDA requests that health care professionals and patients report any side effects associated with statin use to the FDA MedWatch program.

Check out our previous coverage of statin labeling changes:

Drug Interactions with Simvastatin: The Risk Continues (Pharmacy Times, October 2011)